Publications by authors named "Samantha Brown"

78 Publications

A Review of Self-Compassion as an Active Ingredient in the Prevention and Treatment of Anxiety and Depression in Young People.

Adm Policy Ment Health 2021 Sep 24. Epub 2021 Sep 24.

Discipline of Psychology, School of Population Health, Curtin University, GPO Box U1987, Perth, 6845, Australia.

Previous meta-analyses have found higher self-compassion is associated with lower anxiety and depression. The aim of this study was to investigate the efficacy of self-compassion as an active ingredient in the treatment and prevention of anxiety and depression in youth. This was conducted through (i) a systematic review of the literature and (ii) qualitative consultation with young people and researchers in self-compassion. Fifty studies met our inclusion criteria. Eight studies evaluated self-compassion interventions among youth aged 14-24, and the remaining studies measured the association between self-compassion and anxiety, and/or depression among this age group. Qualitative interviews were conducted with four self-compassion researchers. Interviews were also conducted in two rounds of consultation with 20 young people (M age = 18.85 years, age range 14-24 years). Higher self-compassion was related to lower symptoms of anxiety, r =  - 0.49, 95% CI (- 0.57, - 0.42), and depression, r =  - 0.50, 95% CI (- 0.53, - 0.47). There was evidence for self-compassion interventions in decreasing anxiety and depression in young people. Consultation with young people indicated they were interested in self-compassion interventions; however, treatment should be available in a range of formats and tailored to address diversity. Self-compassion experts emphasised the importance of decreasing self-criticism as a reason why self-compassion interventions work. The importance of targeting self-criticism is supported by the preferences of young people who said they would be more likely to engage in a treatment reducing self-criticism than increasing self-kindness. Future research is required to add to the emerging evidence for self-compassion interventions decreasing symptoms of anxiety and depression in young people.
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http://dx.doi.org/10.1007/s10488-021-01170-2DOI Listing
September 2021

The FDA approved anthelmintic Pyrvinium Pamoate inhibits pancreatic cancer cells in nutrient depleted conditions by targeting the mitochondria.

Mol Cancer Ther 2021 Aug 19. Epub 2021 Aug 19.

Dept. of Surgery, Oregon Health & Science University

Pancreatic Ductal Adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA approved anti-helminthic Pyrvinium Pamoate (PP) has been previously shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50s (9-93nM) against a panel of PDAC, patient-derived, and murine organoid cell lines. In vivo, we demonstrated that PP inhibited PDAC xenograft tumor growth with both intraperitoneal (IP; p<0.0001) and oral administration (PO; p=0.0023) of human-grade drug. Metabolomic and phosphoproteomic data identified that PP potently inhibited PDAC mitochondrial pathways including oxidative phosphorylation and fatty acid metabolism. As PP treatment reduced oxidative phosphorylation (p<0.001) leading to an increase in glycolysis (p<0.001), PP was 16.2-fold more effective in hypoglycemic conditions similar to those seen in PDAC tumors. RNA sequencing demonstrated that PP caused a decrease in mitochondrial RNA expression, an effect which was not observed with established mitochondrial inhibitors rotenone and oligomycin. Mechanistically, we determined that PP selectively bound mitochondrial G-quadruplexes and inhibited mitochondrial RNA transcription in a G-quadruplex dependent manner. This subsequently led to a 90% reduction in mitochondrial encoded gene expression. We are preparing to evaluate the efficacy of PP in PDAC in an IRB approved window of opportunity trial (IND:144822).
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0652DOI Listing
August 2021

Collagen fingerprinting traces the introduction of caprines to island Eastern Africa.

R Soc Open Sci 2021 Jul 28;8(7):202341. Epub 2021 Jul 28.

School of Social Science, The University of Queensland, St Lucia, Queensland, Australia.

The human colonization of eastern Africa's near- and offshore islands was accompanied by the translocation of several domestic, wild and commensal fauna, many of which had long-term impacts on local environments. To better understand the timing and nature of the introduction of domesticated caprines (sheep and goat) to these islands, this study applied collagen peptide fingerprinting (Zooarchaeology by Mass Spectrometry or ZooMS) to archaeological remains from eight Iron Age sites, dating between 300 and 1000 CE, in the Zanzibar, Mafia and Comoros archipelagos. Where previous zooarchaeological analyses had identified caprine remains at four of these sites, this study identified goat at seven sites and sheep at three, demonstrating that caprines were more widespread than previously known. The ZooMS results support an introduction of goats to island eastern Africa from at least the seventh century CE, while sheep in our sample arrived one-two centuries later. Goats may have been preferred because, as browsers, they were better adapted to the islands' environments. The results allow for a more accurate understanding of early caprine husbandry in the study region and provide a critical archaeological baseline for examining the potential long-term impacts of translocated fauna on island ecologies.
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http://dx.doi.org/10.1098/rsos.202341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316820PMC
July 2021

Antibody interference by a non-neutralizing antibody abrogates humoral protection against Plasmodium yoelii liver stage.

Cell Rep 2021 Aug;36(5):109489

Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Brotman Baty Research Institute, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA. Electronic address:

Both subunit and attenuated whole-sporozoite vaccination strategies against Plasmodium infection have shown promising initial results in malaria-naive westerners but less efficacy in malaria-exposed individuals in endemic areas. Here, we demonstrate proof of concept by using a rodent malaria model in which non-neutralizing antibodies (nNAbs) can directly interfere with protective anti-circumsporozoite protein (CSP) humoral responses. We characterize a monoclonal antibody, RAM1, against Plasmodium yoelii sporozoite major surface antigen CSP. Unlike the canonical PyCSP repeat domain binding and neutralizing antibody (NAb) 2F6, RAM1 does not inhibit sporozoite traversal or entry of hepatocytes in vitro or infection in vivo. Although 2F6 and RAM1 bind non-overlapping regions of the CSP-repeat domain, pre-treatment with RAM1 abrogates the capacity of NAb to block sporozoite traversal and invasion in vitro. Importantly, RAM1 reduces the efficacy of the polyclonal humoral response against PyCSP in vivo. Collectively, our data provide a proof of concept that nNAbs can alter the efficacy of malaria vaccination.
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http://dx.doi.org/10.1016/j.celrep.2021.109489DOI Listing
August 2021

Zooarchaeology through the lens of collagen fingerprinting at Denisova Cave.

Sci Rep 2021 Jul 29;11(1):15457. Epub 2021 Jul 29.

Max Planck Institute for the Science of Human History, Jena, Germany.

Denisova Cave, a Pleistocene site in the Altai Mountains of Russian Siberia, has yielded significant fossil and lithic evidence for the Pleistocene in Northern Asia. Abundant animal and human bones have been discovered at the site, however, these tend to be highly fragmented, necessitating new approaches to identifying important hominin and faunal fossils. Here we report the results for 8253 bone fragments using ZooMS. Through the integration of this new ZooMS-based data with the previously published macroscopically-identified fauna we aim to create a holistic picture of the zooarchaeological record of the site. We identify trends associated with climate variability throughout the Middle and Upper Pleistocene as well as patterns explaining the process of bone fragmentation. Where morphological analysis of bones from the site have identified a high proportion of carnivore bones (30.2%), we find that these account for only 7.6% of the ZooMS assemblage, with large mammals between 3 and 5 more abundant overall. Our analysis suggests a cyclical pattern in fragmentation of bones which sees initial fragmentation by hominins using percussive tools and secondary carnivore action, such as gnawing and digestion, likely furthering the initial human-induced fragmentation.
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http://dx.doi.org/10.1038/s41598-021-94731-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322063PMC
July 2021

Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non-Small Cell Lung or Colorectal Cancer.

JAMA Netw Open 2021 Jul 1;4(7):e2117547. Epub 2021 Jul 1.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Contemporary observational cancer research requires associating genomic biomarkers with reproducible end points; overall survival (OS) is a key end point, but interpretation can be challenging when multiple lines of therapy and prolonged survival are common. Progression-free survival (PFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) are alternative end points, but their utility as surrogates for OS in real-world clinicogenomic data sets has not been well characterized.

Objective: To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set.

Design, Setting, And Participants: A retrospective cohort study was conducted of patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) whose tumors were genotyped at 4 academic centers from January 1, 2014, to December 31, 2017, and who initiated systemic therapy for advanced disease. Patients were followed up through August 31, 2020 (NSCLC), and October 31, 2020 (CRC). Statistical analyses were conducted on January 5, 2021.

Exposures: Candidate surrogate end points included TTD; TTNT; PFS based on imaging reports only; PFS based on medical oncologist ascertainment only; PFS based on either imaging or medical oncologist ascertainment, whichever came first; and PFS defined by a requirement that both imaging and medical oncologist ascertainment have indicated progression.

Main Outcomes And Measures: The primary outcome was the correlation between candidate surrogate end points and OS.

Results: There were 1161 patients with NSCLC (648 women [55.8%]; mean [SD] age, 63 [11] years) and 1150 with CRC (647 men [56.3%]; mean [SD] age, 54 [12] years) identified for analysis. Progression-free survival based on both imaging and medical oncologist documentation was most correlated with OS (NSCLC: ρ = 0.76; 95% CI, 0.73-0.79; CRC: ρ = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: ρ = 0.45; 95% CI, 0.40-0.50; CRC: ρ = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: ρ = 0.60; 0.55-0.64; CRC: ρ = 0.39; 95% CI, 0.32-0.46).

Conclusions And Relevance: This cohort study suggests that PFS based on both a radiologist and a treating oncologist determining that a progression event has occurred was the surrogate end point most highly correlated with OS for analysis of observational clinicogenomic data.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.17547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314138PMC
July 2021

Fractionated Infusion of Hematopoietic Progenitor Cells Does Not Improve Neutrophil Recovery or Survival in Allograft Recipients.

Transplant Cell Ther 2021 Jun 30. Epub 2021 Jun 30.

Adult Blood and Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Allogeneic hematopoietic cell transplantation (HCT) offers a potentially curative therapy in patients with hematologic malignancies; however, nonrelapse mortality (NRM) remains a concern. Strategies to improve neutrophil recovery and immune reconstitution are needed to decrease NRM. Murine models of allogeneic HCT suggest that fractionated hematopoietic progenitor cell (HPC) infusion may improve engraftment through improved access of HPCs to a viable hematopoietic niche. The primary objective of the present study was to determine the impact of fractionated infusion versus unfractionated (bulk) infusion of HPCs on the time to achieve neutrophil engraftment. Secondary objectives included the effect of fractionated versus bulk infusion of HPCs on platelet engraftment, immune reconstitution, the incidence of acute graft-versus-host disease (GVHD) grade II-IV, NRM, and overall survival (OS). In this randomized phase 2 study, patients with hematologic malignancies undergoing allogeneic HCT were randomized to receive HPC infusion as a bulk (bulk arm) or in fractions (fractionated arm): 4 × 10 CD34 cells/kg recipient weight infused on day 0, with the remaining HPCs CD34 cell-selected then infused in equally distributed aliquots on days 2, 4, and 6 post-HCT. Randomization was stratified by type of transplant, unmodified (i.e. T cell-replete graft) versus CD34 cell-selected (T cell-depleted graft). Patients whose donor failed to collect at least 7 × 10 CD34 cells/kg of recipient weight received bulk HPC infusions regardless of randomization, for safety. These patients continued the HCT process on study but were replaced until each arm reached the prespecified accrual target. Per protocol, these patients were not included in this modified intention-to-treat analysis. A total of 116 patients were enrolled. Donors of 42 patients failed to mobilize the minimum CD34 cell dose (7 × 10 cells/kg recipient weight) and were excluded from the analysis. The 74 evaluable patients included 38 randomized to the bulk arm and 36 randomized to the fractionated arm. All patients engrafted. The median time to an absolute neutrophil count of ≥0.5 × 10/L was 11 days on both arms. The day +180 median CD4 cell count was 179 cells/µL in the bulk arm and 111 cells/µL in the fractionated arm (P = .779). The cumulative incidence of grade II-IV acute GVHD on post-transplant day +100 was 32% in the bulk arm and 17% in the fractionated arm (P = .131). Two patients in the bulk arm, but none in the fractionated arm, experienced grade III-IV GVHD. The 4-year OS was 60% in the bulk arm and 62% in the fractionated arm (P = .414), whereas the 4-year cumulative incidences of NRM and relapse were similar in the 2 arms. Fractionated infusion of HPCs in allogeneic HCT recipients did not impact neutrophil or CD4 cell recovery, NRM, relapse, or OS when compared with bulk HPC infusion. We also observed that with current mobilization techniques, it was unlikely that more than 60% of healthy donors would be able to collect >7 × 10 CD34 cells/kg recipient weight for adult recipients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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http://dx.doi.org/10.1016/j.jtct.2021.06.022DOI Listing
June 2021

Unguided low intensity cognitive behaviour therapy for anxiety and depression during the COVID-19 pandemic: A randomised trial.

Behav Res Ther 2021 09 13;144:103902. Epub 2021 Jun 13.

Institute of Child Health, University College London, United Kingdom.

The COVID-19 pandemic has had a severe impact on mental health worldwide, with increased rates of anxiety and depression widely documented. The aim of this study was to examine unguided low intensity cognitive behaviour therapy for anxiety and depression during the pandemic. A sample of 225 individuals in Australia and the United Kingdom (M age 37.79, SD = 14.02, range 18-80 years; 85% female) were randomised into intervention or waitlist control. The intervention group demonstrated significant decreases in anxiety (d = 0.36 [0.18, 0.54]) and depression (d = 0.28 [0.11, 0.45]) compared to controls. The majority of participants (96%) rated the intervention as useful, and most (83%) reported they spent 30 min or less reading the guide, with 83% agreeing the intervention was easy to read. The results indicate that low intensity cognitive behaviour therapy has efficacy in reducing anxiety and depression during the COVID-19 pandemic. There is an urgent need to disseminate low intensity psychological therapies to improve mental health in this challenging time.
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http://dx.doi.org/10.1016/j.brat.2021.103902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197681PMC
September 2021

The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes.

J Neurooncol 2021 Jul 19;153(3):507-518. Epub 2021 Jun 19.

Department of Neurological Surgery and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Objective: Radiation therapy is a cornerstone of brain metastasis (BrM) management but carries the risk of radiation necrosis (RN), which can require resection for palliation or diagnosis. We sought to determine the relationship between extent of resection (EOR) of pathologically-confirmed RN and postoperative radiographic and symptomatic outcomes.

Methods: A single-center retrospective review was performed at an NCI-designated Comprehensive Cancer Center to identify all surgically-resected, previously-irradiated necrotic BrM without admixed recurrent malignancy from 2003 to 2018. Clinical, pathologic and radiographic parameters were collected. Volumetric analysis determined EOR and longitudinally evaluated perilesional T2-FLAIR signal preoperatively, postoperatively, and at 3-, 6-, 12-, and 24-months postoperatively when available. Rates of time to 50% T2-FLAIR reduction was calculated using cumulative incidence in the competing risks setting with last follow-up and death as competing events. The Spearman method was used to calculate correlation coefficients, and continuous variables for T2-FLAIR signal change, including EOR, were compared across groups.

Results: Forty-six patients were included. Most underwent prior stereotactic radiosurgery with or without whole-brain irradiation (N = 42, 91%). Twenty-seven operations resulted in gross-total resection (59%; GTR). For the full cohort, T2-FLAIR edema decreased by a mean of 78% by 6 months postoperatively that was durable to last follow-up (p < 0.05). EOR correlated with edema reduction at last follow-up, with significantly greater T2-FLAIR reduction with GTR versus subtotal resection (p < 0.05). Among surviving patients, a significant proportion were able to decrease their steroid use: steroid-dependency decreased from 54% preoperatively to 15% at 12 months postoperatively (p = 0.001).

Conclusions: RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR; and reduced steroid dependency.
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http://dx.doi.org/10.1007/s11060-021-03790-yDOI Listing
July 2021

Distinguishing African bovids using Zooarchaeology by Mass Spectrometry (ZooMS): New peptide markers and insights into Iron Age economies in Zambia.

PLoS One 2021 18;16(5):e0251061. Epub 2021 May 18.

Department of Archaeology, Max-Planck Institute for the Science of Human History, Jena, Germany.

Assessing past foodways, subsistence strategies, and environments depends on the accurate identification of animals in the archaeological record. The high rates of fragmentation and often poor preservation of animal bones at many archaeological sites across sub-Saharan Africa have rendered archaeofaunal specimens unidentifiable beyond broad categories, such as "large mammal" or "medium bovid". Identification of archaeofaunal specimens through Zooarchaeology by Mass Spectrometry (ZooMS), or peptide mass fingerprinting of bone collagen, offers an avenue for identification of morphologically ambiguous or unidentifiable bone fragments from such assemblages. However, application of ZooMS analysis has been hindered by a lack of complete reference peptide markers for African taxa, particularly bovids. Here we present the complete set of confirmed ZooMS peptide markers for members of all African bovid tribes. We also identify two novel peptide markers that can be used to further distinguish between bovid groups. We demonstrate that nearly all African bovid subfamilies are distinguishable using ZooMS methods, and some differences exist between tribes or sub-tribes, as is the case for Bovina (cattle) vs. Bubalina (African buffalo) within the subfamily Bovinae. We use ZooMS analysis to identify specimens from extremely fragmented faunal assemblages from six Late Holocene archaeological sites in Zambia. ZooMS-based identifications reveal greater taxonomic richness than analyses based solely on morphology, and these new identifications illuminate Iron Age subsistence economies c. 2200-500 cal BP. While the Iron Age in Zambia is associated with the transition from hunting and foraging to the development of farming and herding, our results demonstrate the continued reliance on wild bovids among Iron Age communities in central and southwestern Zambia Iron Age and herding focused primarily on cattle. We also outline further potential applications of ZooMS in African archaeology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251061PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130928PMC
May 2021

The Impact of the COVID-19 Pandemic on Child Protection System Referrals and Responses in Colorado, USA.

Child Maltreat 2021 Apr 26:10775595211012476. Epub 2021 Apr 26.

129263University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Although the coronavirus disease 2019 (COVID-19) has amplified risk factors known to increase children's vulnerability to abuse and neglect, emerging evidence suggests declines in maltreatment reporting and responding following COVID-19 social distancing protocols in the United States. Using statewide administrative data, this study builds on the current state of knowledge to better understand the volume of child protection system (CPS) referrals and responses in Colorado, USA before and during the early phase of the COVID-19 pandemic and to determine whether there were differences in referral and response rates by case characteristics. Results indicated an overall decline in referrals and responses during COVID-19 when compared to the previous year. Declines were specific to case characteristics, such as reporter and maltreatment type. Implications regarding the impact of the COVID-19 pandemic on child maltreatment reporting and CPS response are discussed.
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http://dx.doi.org/10.1177/10775595211012476DOI Listing
April 2021

Economic choice between remifentanil and food in squirrel monkeys.

Neuropsychopharmacology 2021 Apr 8. Epub 2021 Apr 8.

Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.

Traditional approaches for evaluating if compounds are reinforcing, and thus a risk for abuse, include preclinical self-administration procedures conducted in the absence of alternative reinforcers. While the track record of this approach for determining abuse potential is good, that for predicting efficacy of addiction treatments is not. An alternate approach would be economic choice between drug and nondrug rewards, with parametrically varied options from trial to trial. This would promote goal-directed decisions between reward modalities and should provide metrics that reflect changes in internal state that influence desirability of a given option. We report herein a high throughput economic choice procedure in which squirrel monkeys choose between a short-lived opiate, remifentanil, and a palatable food reward. Stimuli on touchscreens indicate the amount of each reward type offered by varying the number of reward-specific elements. The rapid clearance of remifentanil avoids accumulation of confounding levels of drug, and permits a large number of trials with a wide range of offers of each reward modality. The use of a single metric encompassing multiple values of each reward type within a session enables estimation of indifference values using logistic regression. This indifference value is sensitive to reward devaluation within each reward domain, and is therefore a useful metric for determining shifts in reward preference, as shown with satiation and pharmacological treatment approaches.
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http://dx.doi.org/10.1038/s41386-021-00996-6DOI Listing
April 2021

Injury inequalities among U.S. construction workers.

J Occup Environ Hyg 2021 Apr-May;18(4-5):159-168. Epub 2021 Mar 16.

Data Center, CPWR - The Center for Construction Research and Training, Silver Spring, Maryland.

This study explores racial/ethnic inequalities in work-related injuries among U.S. construction workers. Data from the 2004-2017 National Health Interview Survey were used to estimate work-related injuries by race/ethnicity in construction. Disparities in demographic, socioeconomic, and injury status among construction workers were examined by race/ethnicity. Injury differences were also evaluated in multiple logistic regression analyses controlling for potential confounders. Compared to white, non-Hispanic workers, minority workers were more likely to have lower socioeconomic statuses (e.g., lower educational attainment, lack of health insurance coverage, and family income below the poverty level), which considerably increased the likelihood of work-related injuries. The odds of work-related injuries were 70% higher among racial/ethnic minorities than white, non-Hispanics in construction. Injuries were also more severe among minorities than white, non-Hispanic workers. Among workers with a work-related injury, nearly 85% of Hispanics reported missing at least one workday due to injury, 45.6% higher than the proportion of 57.9% for their white, non-Hispanic counterparts. After adjusting for major demographic and socioeconomic factors, the work-related injury difference between race/ethnicity was no longer statistically significant. However, the odds of work-related injury remained significantly higher among workers who were younger (35-54 years vs. ≥ 55 years: aOR = 2.2, 95% CI: 1.3-3.6); male (aOR = 5.3, 95% CI: 2.9-9.8); not college-educated (aOR = 1.5, 95% CI: 1.0-2.2); had a family income below the poverty threshold (aOR = 1.8, 95% CI: 1.2-2.8); or held a blue-collar occupation (aOR = 2.0, 95% CI: 1.2-3.4). These findings suggest that the injury differences between race/ethnicity were strongly associated with demographics and socioeconomic inequalities in these worker groups. The identified injury disparities should be reduced or eliminated, following the hierarchy of controls paradigm.
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http://dx.doi.org/10.1080/15459624.2021.1888958DOI Listing
March 2021

Misinformation tactics protect rare birds from problem predators.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia.

Efficient decision-making integrates previous experience with new information. Tactical use of misinformation can alter choice in humans. Whether misinformation affects decision-making in other free-living species, including problem species, is unknown. Here, we show that sensory misinformation tactics can reduce the impacts of predators on vulnerable bird populations as effectively as lethal control. We repeatedly exposed invasive mammalian predators to unprofitable bird odors for 5 weeks before native shorebirds arrived for nesting and for 8 weeks thereafter. Chick production increased 1.7-fold at odor-treated sites over 25 to 35 days, with doubled or tripled odds of successful hatching, resulting in a 127% increase in modeled population size in 25 years. We demonstrate that decision-making processes that respond to changes in information reliability are vulnerable to tactical manipulation by misinformation. Altering perceptions of prey availability offers an innovative, nonlethal approach to managing problem predators and improving conservation outcomes for threatened species.
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http://dx.doi.org/10.1126/sciadv.abe4164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946364PMC
March 2021

Ancient proteins provide evidence of dairy consumption in eastern Africa.

Nat Commun 2021 01 27;12(1):632. Epub 2021 Jan 27.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Consuming the milk of other species is a unique adaptation of Homo sapiens, with implications for health, birth spacing and evolution. Key questions nonetheless remain regarding the origins of dairying and its relationship to the genetically-determined ability to drink milk into adulthood through lactase persistence (LP). As a major centre of LP diversity, Africa is of significant interest to the evolution of dairying. Here we report proteomic evidence for milk consumption in ancient Africa. Using liquid chromatography tandem mass spectrometry (LC-MS/MS) we identify dairy proteins in human dental calculus from northeastern Africa, directly demonstrating milk consumption at least six millennia ago. Our findings indicate that pastoralist groups were drinking milk as soon as herding spread into eastern Africa, at a time when the genetic adaptation for milk digestion was absent or rare. Our study links LP status in specific ancient individuals with direct evidence for their consumption of dairy products.
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http://dx.doi.org/10.1038/s41467-020-20682-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841170PMC
January 2021

The Co-Occurrence of Child Maltreatment and Intimate Partner Violence in Families: Effects on Children's Externalizing Behavior Problems.

Child Maltreat 2021 Jan 13:1077559520985934. Epub 2021 Jan 13.

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Children exposed to maltreatment are at risk of experiencing intimate partner violence (IPV) and behavioral problems. This study examined different forms of family violence that co-occur and their relationship to children's externalizing behaviors across developmental stages (early childhood, middle childhood, adolescence). Longitudinal data ( = 1,987) at baseline and 18 months and 36 months post-baseline from the NSCAW II were used. Mixture modeling was employed in which latent class models estimated subgroups of children who experienced co-occurring forms of family violence; regression models estimated which subgroups of children were at risk of externalizing behaviors. Three latent classes were identified across developmental stages: high family violence, low family violence, and child physical abuse and psychological aggression. For children in early childhood, a fourth class was identified: partner and child physical abuse and child psychological aggression. Results from regression models revealed differences in externalizing scores by class membership across developmental age groups and over time. That distinct classes of child maltreatment and IPV co-occur and differentially impact children's behavior suggests a need for strong prevention and intervention responses to address children's dual maltreatment and IPV exposure.
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http://dx.doi.org/10.1177/1077559520985934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275675PMC
January 2021

Parental buffering in the context of poverty: positive parenting behaviors differentiate young children's stress reactivity profiles.

Dev Psychopathol 2020 12;32(5):1778-1787

Department of Psychology, University of Denver, CO, USA.

Experiencing poverty increases vulnerability for dysregulated hypothalamic-pituitary-adrenal (HPA) axis functioning and compromises long-term health. Positive parenting buffers children from HPA axis reactivity, yet this has primarily been documented among families not experiencing poverty. We tested the theorized power of positive parenting in 124 parent-child dyads recruited from Early Head Start (Mage = 25.21 months) by examining child cortisol trajectories using five samples collected across a standardized stress paradigm. Piecewise latent growth models revealed that positive parenting buffered children's stress responses when controlling for time of day, last stress task completed, and demographics. Positive parenting also interacted with income such that positive parenting was especially protective for cortisol reactivity in families experiencing greater poverty. Findings suggest that positive parenting behaviors are important for protecting children in families experiencing low income from heightened or prolonged physiologic stress reactivity to an acute stressor.
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http://dx.doi.org/10.1017/S0954579420001224DOI Listing
December 2020

Magdalenian and Epimagdalenian chronology and palaeoenvironments at Kůlna Cave, Moravia, Czech Republic.

Archaeol Anthropol Sci 2021 17;13(1). Epub 2020 Dec 17.

Institute of Archaeology, University College London, London, UK.

Kůlna Cave is the only site in Moravia, Czech Republic, from which large assemblages of both Magdalenian and Epimagdalenian archaeological materials have been excavated from relatively secure stratified deposits. The site therefore offers the unrivalled opportunity to explore the relationship between these two archaeological phases. In this study, we undertake radiocarbon, stable isotope (carbon, nitrogen and sulphur), and ZooMS analysis of the archaeological faunal assemblage to explore the chronological and environmental context of the Magdalenian and Epimagdalenian deposits. Our results show that the Magdalenian and Epimagdalenian deposits can be understood as discrete units from one another, dating to the Late Glacial between c. 15,630 cal. BP and 14,610 cal. BP, and c. 14,140 cal. BP and 12,680 cal. BP, respectively. Stable isotope results (δC, δN, δS) indicate that Magdalenian and Epimagdalenian activity at Kůlna Cave occurred in very different environmental settings. Magdalenian occupation took place within a nutrient-poor landscape that was experiencing rapid changes to environmental moisture, potentially linked to permafrost thaw. In contrast, Epimagdalenian occupation occurred in a relatively stable, temperate environment composed of a mosaic of woodland and grassland habitats. The potential chronological gap between the two phases, and their associations with very different environmental conditions, calls into question whether the Epimagdalenian should be seen as a local, gradual development of the Magdalenian. It also raises the question of whether the gap in occupation at Kůlna Cave could represent a change in settlement dynamics and/or behavioural adaptations to changing environmental conditions.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-020-01254-4.
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http://dx.doi.org/10.1007/s12520-020-01254-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746568PMC
December 2020

Testing the efficacy and comparability of ZooMS protocols on archaeological bone.

J Proteomics 2021 02 15;233:104078. Epub 2020 Dec 15.

Department of Archaeology, Max Planck Institute for the Science of Human History (MPI-SHH), Kahlaische Straße 10, 07745 Jena, Germany. Electronic address:

Collagen peptide mass fingerprinting, best known as Zooarchaeology by Mass Spectrometry (or ZooMS) when applied to archaeology, has become invaluable for the taxonomic identification of archaeological collagenous materials, in particular fragmentary and modified bone remains. Prior to MALDI-based spectrometric analysis, collagen needs to be extracted from the bone's inorganic matrix, isolated and purified. Several protocols are currently employed for ZooMS analysis, however their efficacy and comparability has not been directly tested. Here, we use four different ZooMS protocols to analyze 400 bone samples from seven archaeological sites, dating to between ~500,000-2000 years ago. One of them, single-pot solid-phase-enhance sample preparation (SP3), is used for the first time as a ZooMS protocol. Our results indicate that the least-destructive ZooMS protocol which uses an ammonium bicarbonate buffer as a means of extracting collagen is most suitable for bones with good collagen preservation, whereas the acid-based methodologies can improve success rates for bones with low-to-medium collagen preservation. Since preservation of biomolecules in archaeological bones is highly variable due to age and environmental conditions, we use the percent nitrogen by weight (%N) value as an independent semi-quantitative proxy for assessing collagen content and for predicting which bones will likely result in a successful ZooMS-based identification. We find that 0.26%N as a threshold for screening material could optimize the number of spectra which produce identifications using ZooMS. SIGNIFICANCE STATEMENT: We present a direct comparison of three previously published ZooMS protocols for the analyses of archaeological bones, and the first use of an SP3-based approach to ZooMS analysis. Our results show that the acid-based ZooMS protocols increase the success rate for bones with low-medium collagen preservation. We identify 0.26%N as a threshold for optimizing the number of samples with enough collagen for successful peptide mass fingerprinting.
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http://dx.doi.org/10.1016/j.jprot.2020.104078DOI Listing
February 2021

Meiotic Cells Counteract Programmed Retrotransposon Activation via RNA-Binding Translational Repressor Assemblies.

Dev Cell 2021 01 4;56(1):22-35.e7. Epub 2020 Dec 4.

Department of Genetics and Development, Hammer Health Sciences Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Retrotransposon proliferation poses a threat to germline integrity. While retrotransposons must be activated in developing germ cells in order to survive and propagate, how they are selectively activated in the context of meiosis is unclear. We demonstrate that the transcriptional activation of Ty3/Gypsy retrotransposons and host defense are controlled by master meiotic regulators. We show that budding yeast Ty3/Gypsy co-opts binding sites of the essential meiotic transcription factor Ndt80 upstream of the integration site, thereby tightly linking its transcriptional activation to meiotic progression. We also elucidate how yeast cells thwart Ty3/Gypsy proliferation by blocking translation of the retrotransposon mRNA using amyloid-like assemblies of the RNA-binding protein Rim4. In mammals, several inactive Ty3/Gypsy elements are undergoing domestication. We show that mammals utilize equivalent master meiotic regulators (Stra8, Mybl1, Dazl) to regulate Ty3/Gypsy-derived genes in developing gametes. Our findings inform how genes that are evolving from retrotransposons can build upon existing regulatory networks during domestication.
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http://dx.doi.org/10.1016/j.devcel.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116619PMC
January 2021

Impact of C-Terminal Chemistry on Self-Assembled Morphology of Guanosine Containing Nucleopeptides.

Molecules 2020 Nov 24;25(23). Epub 2020 Nov 24.

Department of Chemistry and Biochemistry, Fairfield University, 1073 N. Benson Rd, Fairfield, CT 06824, USA.

Herein, we report the design and characterization of guanosine-containing self-assembling nucleopeptides that form nanosheets and nanofibers. Through spectroscopy and microscopy analysis, we propose that the peptide component of the nucleopeptide drives the assembly into β-sheet structures with hydrogen-bonded guanosine forming additional secondary structures cooperatively within the peptide framework. Interestingly, the distinct supramolecular morphologies are driven not by metal cation responsiveness common to guanine-based materials, but by the C-terminal peptide chemistry. This work highlights the structural diversity of self-assembling nucleopeptides and will help advance the development of applications for these supramolecular guanosine-containing nucleopeptides.
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http://dx.doi.org/10.3390/molecules25235493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727710PMC
November 2020

On the standardization of ZooMS nomenclature.

J Proteomics 2021 03 5;235:104041. Epub 2020 Nov 5.

Max Planck Institute for the Science of Human History, Jena, Germany. Electronic address:

Zooarchaeology by Mass Spectrometry (ZooMS) is rapidly becoming a staple in archaeological and cultural heritage science. Developed a decade ago, this peptide mass fingerprinting technique is expanding from a small group of researchers mainly involved in method development to a broader group of scientists using it as another tool in their toolboxes. With new researchers beginning to use the method, it is imperative that a user-friendly, standardized approach be established. A major barrier has been the often haphazard and changing nomenclature used to label peptide markers necessary for taxonomic identification. Consistent, reliable, and easy-to-understand nomenclature is key to the growth of ZooMS, particularly as the reference library continues to expand. We propose a new set of standardized guidelines for peptide markers based on their position in the type I collagen sequence from the beginning of the highly conserved, helical region. Since this region has no insertions or deletions over a wide range of taxonomic groups, the proposed nomenclature system can be used reliably and consistently across all vertebrate taxa. We propose to label ZooMS peptide markers with the gene, followed by the position of the first and last amino acid of the marker from the start of the helical region. SIGNIFICANCE STATEMENT: We propose a standardized nomenclature system for ZooMS peptide markers that provides consistent labels across multiple, broad taxonomic groups. This system unambiguously locates the marker peptides in the type I collagen sequence, avoids duplication of marker names, and facilitates the creation of large ZooMS databases which can include all vertebrates.
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http://dx.doi.org/10.1016/j.jprot.2020.104041DOI Listing
March 2021

Method for mapping Hg emissions from gold shops in artisanal and small-scale gold mining communities.

MethodsX 2020 9;7:101060. Epub 2020 Sep 9.

Department of Chemistry, Mercer University Macon, GA, United States.

Gold shops in artisanal and small-scale gold mining communities represent major point sources of airborne mercury pollution. Concentrations of elemental mercury (Hg) emitted by these shops can be determined using a portable atomic absorbance spectrometer (AAS) with Zeeman correction. These measured Hg concentrations can then be correlated to position as determined by a hand-held GPS unit, and the resulting data mapped using a Geographic Information System (GIS). A detailed method for obtaining and analyzing data collected near gold shops in Mazuko, Peru is provided. Maps generated using this method were employed to identify point sources of Hg contamination originating from gold shops in ASGM communities and were shared with local city managers to assist in urban planning.•A detailed method is provided to collect and process data, ultimately generating a map that allows for the screening of a community to identify point sources of Hg contamination.•Raw data is provided, as well as a video detailing data processing and mapping using a common spreadsheet program and an open-source GIS.•The generated map can be used for determining areas where people may be exposed to elevated Hg concentrations and/or occupational mercury vapor exposure, targeted enforcement, or outreach to limit Hg pollution.
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http://dx.doi.org/10.1016/j.mex.2020.101060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516184PMC
September 2020

Musculoskeletal Disorders and Prescription Opioid Use Among U.S. Construction Workers.

J Occup Environ Med 2020 11;62(11):973-979

CPWR-The Center for Construction Research and Training, Data Center, 8484 Georgia Ave, Suite 1000, Silver Spring, Maryland.

Background: Musculoskeletal disorders (MSDs) and opioid use are a combined burden for construction safety and health. This study examines both issues among construction workers using a large population-based survey.

Methods: The prevalence of MSDs in construction was estimated using multi-year data from the Medical Expenditure Panel Survey. Prescription opioid use among workers with MSDs was compared to those without MSDs.

Results: About 34% of construction workers had at least one MSD symptom. Compared to those without MSDs, prescription opioid use tripled (aOR = 3.28, 95% CI: 2.44 to 4.41) among construction workers with MSDs.

Conclusions: MSDs are prevalent among construction workers, and prescription opioid use significantly increased among workers with MSDs. It is critical to adopt ergonomic solutions in construction to reduce MSDs, and support workers in injury recovery with effective pain management.
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http://dx.doi.org/10.1097/JOM.0000000000002017DOI Listing
November 2020

The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning.

J Mammary Gland Biol Neoplasia 2020 09 8;25(3):181-189. Epub 2020 Sep 8.

Department of Medicine, Division of Hematology/ Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, 10029, USA.

Insulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus on Pregnancy-Associated Plasma Protein A (PAPP-A), a protease involved in the degradation of IGFBP-5. PAPP-A is overexpressed in the majority of breast cancers but its role in cancer has only begun to be explored. More specifically, this review aims at highlighting the role of post-partum involution in the oncogenic function of PAPP-A. Notably, we summarize recent studies indicating that PAPP-A plays a role not only in the degradation of IGFBP-5 but also in the deposition of collagen and activation of the collagen receptor discoidin 2 (DDR2) during post-partum involution. Finally, considering the immunosuppressive microenvironment of post-partum involution, we also discuss the unexpected finding made in Ewing Sarcoma that PAPP-A plays a role in immune evasion. While the immunosuppressive role of PAPP-A in breast cancer remains to be determined, collectively these studies highlight the multifaced role of PAPP-A in cancer that extends well beyond its effect on IGF-signaling.
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http://dx.doi.org/10.1007/s10911-020-09456-1DOI Listing
September 2020

Stress and parenting during the global COVID-19 pandemic.

Child Abuse Negl 2020 12 20;110(Pt 2):104699. Epub 2020 Aug 20.

School of Social Work, Colorado State University, 1586 Campus Delivery, Fort Collins, CO, 80523, USA. Electronic address:

Background: Stress and compromised parenting often place children at risk of abuse and neglect. Child maltreatment has generally been viewed as a highly individualistic problem by focusing on stressors and parenting behaviors that impact individual families. However, because of the global coronavirus disease 2019 (COVID-19), families across the world are experiencing a new range of stressors that threaten their health, safety, and economic well-being.

Objective: This study examined the impacts of the COVID-19 pandemic in relation to parental perceived stress and child abuse potential.

Participants And Setting: Participants included parents (N = 183) with a child under the age of 18 years in the western United States.

Method: Tests of group differences and hierarchical multiple regression analyses were employed to assess the relationships among demographic characteristics, COVID-19 risk factors, mental health risk factors, protective factors, parental perceived stress, and child abuse potential.

Results: Greater COVID-19 related stressors and high anxiety and depressive symptoms are associated with higher parental perceived stress. Receipt of financial assistance and high anxiety and depressive symptoms are associated with higher child abuse potential. Conversely, greater parental support and perceived control during the pandemic are associated with lower perceived stress and child abuse potential. Results also indicate racial and ethnic differences in COVID-19 related stressors, but not in mental health risk, protective factors, perceived stress, or child abuse potential.

Conclusion: Findings suggest that although families experience elevated stressors from COVID-19, providing parental support and increasing perceived control may be promising intervention targets.
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http://dx.doi.org/10.1016/j.chiabu.2020.104699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440155PMC
December 2020

Maternal health training priorities for nursing and allied professions in Haiti.

Rev Panam Salud Publica 2020 15;44:e67. Epub 2020 Jul 15.

Pan American Health Organization/World Health Organization Washington DC United States of America Pan American Health Organization/World Health Organization, Washington DC, United States of America.

Objectives: This study summarizes the findings of a training needs and priority assessment completed in Haiti. Its objective is to describe the characteristics of nursing and allied professions providing first level maternal health care and identify training needs and priorities to inform planning of Human Resources for Health interventions.

Methods: A cross-sectional survey was completed between October 2016 and March 2017 by the Pan American Health Organization/World Health Organization Haiti office in collaboration with national health authorities. Participants reached consensus to submit one finalized version of the survey. Data were collected on composition, capacities, and training needs and priorities of traditional birth attendants, community health workers, registered nurses, professional midwives, and auxiliary nurses.

Results: Haiti relies heavily on community level workers including community health workers, auxiliary nurses, and traditional birth attendants. Traditional birth attendants attend the majority of Haiti's births, despite having low education levels and not being regulated by the Ministry of Public Health and Population. All professional categories prioritize preventive capacities such as timely identification of complications, while none are trained to manage postpartum hemorrhage, preeclampsia, or eclampsia. Management of obstetric emergencies is a training priority for Haiti but is not part of the scope of work of the nursing and allied health professions included in this study.

Conclusions: Community level health workers are key in providing preventive care and referral of complicated pregnancies, but lack of access to providers qualified to treat obstetric complications remains a challenge to reducing maternal mortality.
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http://dx.doi.org/10.26633/RPSP.2020.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363286PMC
July 2020

Invasive mammalian predators habituate to and generalize avian prey cues: a mechanism for conserving native prey.

Ecol Appl 2020 12 3;30(8):e02200. Epub 2020 Aug 3.

Manaaki Whenua Landcare Research, PO Box 282, Alexandra, 9340, New Zealand.

Invasive mammalian predators can cause the decline and extinction of vulnerable native species. Many invasive mammalian predators are dietary generalists that hunt a variety of prey. These predators often rely upon olfaction when foraging, particularly at night. Little is understood about how prey odor cues are used to inform foraging decisions. Prey cues can vary spatially and temporally in their association with prey and can either reveal the location of prey or lead to unsuccessful foraging. Here we examine how two wild-caught invasive mammalian bird predator species (European hedgehogs Erinaceus europaeus and ferrets Mustela putorius furo) respond to unrewarded bird odors over successive exposures, first demonstrating that the odors are perceptually different using house mice (Mus musculus) as a biological olfactometer. We aim to test if introduced predators categorize odor cues of similar prey together, a tactic that could increase foraging efficiency. We exposed house mice to the odors using a standard habituation/dishabituation test in a laboratory setting, and wild-caught European hedgehogs and ferrets in an outdoor enclosure using a similar procedure. Mice discriminated among all bird odors presented, showing more interest in chicken odor than quail or gull odor. Both predator species showed a decline in interest toward unrewarded prey odor (i.e., habituation), but only ferrets generalized their response from one unrewarded bird odor to another bird odor. Hedgehog responses to unrewarded bird odors were highly variable between individuals. Taken together, our results reveal interspecific and intraspecific differences in response to prey odors, which we argue are a consequence of different diet breadth, life and evolutionary histories, and the conditions in each experiment. Generalization of prey odors may have enabled some species of invasive predators to efficiently hunt a range of intraguild prey species, for example, ground-nesting shorebirds. Olfactory manipulation of predators may be a useful conservation tool for threatened prey if it reduces the conspicuousness of vulnerable prey.
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http://dx.doi.org/10.1002/eap.2200DOI Listing
December 2020

Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.

J Am Coll Surg 2020 04 11;230(4):659-667. Epub 2020 Feb 11.

Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, PA.

Background: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO) on development of pancreatic ductal adenocarcinoma (PDAC) and drug resistance.

Study Design: Two PDAC cell lines were exposed to normocapnic (5% CO) and hypercapnic (continuous/intermittent 10% CO) conditions, physiologically similar to patients with active ORD. Cells were assessed for proliferation rate, colony formation, and chemo-/radiotherapeutic efficacy. In a retrospective clinical study design, patients with PDAC who had undergone pancreatic resection between 2002 and 2014 were reviewed. Active smokers were excluded to remove possible smoking-related protumorigenic influence. Clinical data, pathologic findings, and survival end points were recorded. Kaplan-Meier and Cox regression analyses were performed.

Results: Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p < 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67).

Conclusions: PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498306PMC
April 2020
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