Publications by authors named "David Miller"

2,208 Publications

  • Page 1 of 1

Comparison of transversus abdominis plane catheters with thoracic epidurals for cost and length of stay in open colorectal surgeries: a cohort study.

BMC Anesthesiol 2021 May 6;21(1):137. Epub 2021 May 6.

Department of Anesthesiology, Albany Medical Center, 43 New Scotland Avenue, Albany, NY, USA.

Background: Thoracic epidural analgesia has long been a common method of postoperative analgesia for major open abdominal surgeries and is frequently used within enhanced recovery after surgery programs. An alternative postoperative analgesia method is the single shot transversus abdominis plane block, which has shown promising outcomes with respect to total length of stay, cost, pain scores, and decreased opioid usage. However, far less is known regarding continuous transversus abdominis plane analgesia using catheters. We evaluated the total cost-effectiveness of transversus abdominis plane catheter analgesia compared to thoracic epidural analgesia for patients undergoing open colorectal surgeries within the enhanced recovery after surgery program at our institution.

Methods: This cohort study included patients booked under the colorectal surgery enhanced recovery after surgery program from November 2016 through March 2018 who received either bilateral transversus abdominis plane catheters (n = 52) or thoracic epidural analgesia (n = 24).

Results: There was no difference in total direct cost (p = 0.660) and indirect cost (p = 0.220), and median length of stay (p = 0.664) in the transversus abdominis plane catheter group compared to the thoracic epidural group. Additionally, the transversus abdominis plane catheter group received significantly less morphine equivalents compared to the thoracic epidural group (p = 0.008) and had a lower mean body mass index (p = 0.019). There was no significant difference between the two groups for age (p = 0.820), or sex (p = 0.330).

Conclusions: Transversus abdominis plane catheter analgesia is not associated with increased cost or longer hospital stays when compared to thoracic epidural analgesia in patients undergoing open colorectal surgery within an enhanced recovery after surgery program. Furthermore, transversus abdominis plane catheter analgesia led to decreased opioid consumption while maintaining similar pain scores, suggesting similar pain control between the two modalities.
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http://dx.doi.org/10.1186/s12871-021-01359-wDOI Listing
May 2021

Diagnostic criteria for apathy in neurocognitive disorders.

Alzheimers Dement 2021 May 5. Epub 2021 May 5.

Sunnybrook Research Institute, Toronto, Ontario, Canada.

Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed.

Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019.

Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies.

Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.
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http://dx.doi.org/10.1002/alz.12358DOI Listing
May 2021

Creating effective academic research teams: Two tools borrowed from business practice.

J Clin Transl Sci 2020 Nov 5;5(1):e74. Epub 2020 Nov 5.

Clinical and Translational Science Institute (CTSI), Wake Forest School of Medicine, Winston-Salem, NC, USA.

Academic Medical Centers strive to create multidisciplinary research teams to produce impactful science. However, few faculty researchers receive training in "team science," a well-established concept in business research and practice. Responding to demand for assistance developing effective research teams, the Collaboration and Team Science Program of the Clinical and Translational Science Institute (CTSI) at Wake Forest School of Medicine (WFSM) partnered with faculty from the Wake Forest University (WFU) School of Business with expertise in leadership, management, and team building. We initiated a needs assessment, including a written survey from a diverse set of 42 research scientists as well as semi-structured interviews with 8 researchers. In response to identified needs, we developed training sessions and consultations to teach teams to implement two tools known to enhance team dynamics: (1) Team charter, a document that defines the team's purpose, goals, roles, and strategies; and (2) Responsible, Accountable, Consulted, Informed (RACI) matrix, a table or spreadsheet that clarifies tasks and accountability. Since 2018, 10 teams and over 100 individuals have attended training sessions and 6 teams received personalized team consults. We describe these tools, present a formal analysis of quantitative results, and highlight the next steps being taken in response to these findings.
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http://dx.doi.org/10.1017/cts.2020.553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057410PMC
November 2020

Overutilization of surgical resection for benign colorectal polyps: analysis from a tertiary care center.

Endosc Int Open 2021 May 22;9(5):E706-E712. Epub 2021 Apr 22.

Gastroenterology, Albany Medical Center, Albany, New York, United States.

Adequate removal of precancerous polyps is an independent factor in colorectal cancer prevention. Despite advances in polypectomy techniques, there is an increasing rate of surgery for benign polyps. We assessed whether surgical resection is properly utilized for benign colorectal polyps. We identified 144 patients with surgical resection for benign colorectal polyps. Polyp location, size and the indication for and type of surgery were obtained. For the purposes of this analysis, we assumed that gastroenterologists should assess polyp size accurately, endoscopically resect polyps < 2 cm, and treat incompletely excised polyps on follow-up. A total of 118 patients (82 %) were referred to surgery without attempted endoscopic removal. In 26 (22 %) of 118, the macroscopic polyp size was < 2 cm (23 in right, 3 in the left colon) and 18 (15 %; 14 in the right, four in the left colon) were found to have had size overestimation during endoscopy. Twenty-two (15 %) of 144 underwent surgical resection for incomplete endoscopic resection of adenomas (16 in the right, 6 in the left colon); 12 (54.5 %) had a residual polyp size of < 2 cm (10 in the right colon; 2 in the left colon). In-hospital mortality was 0.7 % and morbidity was 20.1 %. Of the patients, 41 % could have potentially avoided surgical intervention (37 polyps < 2 cm and/or size overestimations precluding endoscopic polypectomy and 22 incomplete resections). When including polyps with size ≥ 2 to < 4 cm, the percentage of patients with avoidable surgery reached 80 %. This confirms the need to develop standardized quality metrics for endoscopic polypectomies and for better overall training of endoscopists performing these procedures. Given the risks of surgery, referral to an experienced gastroenterologist should be considered as a first step.
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http://dx.doi.org/10.1055/a-1380-3017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062229PMC
May 2021

Corrigendum to "Direct transfer of electron microscopy samples to wetted carbon and graphene films via a support floatation block" [J. Struct. Biol. 213 (2021) 107677].

J Struct Biol 2021 Apr 28:107739. Epub 2021 Apr 28.

Section for Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jsb.2021.107739DOI Listing
April 2021

Migratory strategy drives species-level variation in bird sensitivity to vegetation green-up.

Nat Ecol Evol 2021 Apr 29. Epub 2021 Apr 29.

Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA.

Animals and plants are shifting the timing of key life events in response to climate change, yet despite recent documentation of escalating phenological change, scientists lack a full understanding of how and why phenological responses vary across space and among species. Here, we used over 7 million community-contributed bird observations to derive species-specific, spatially explicit estimates of annual spring migration phenology for 56 bird species across eastern North America. We show that changes in the spring arrival of migratory birds are coarsely synchronized with fluctuations in vegetation green-up and that the sensitivity of birds to plant phenology varied extensively. Bird arrival responded more synchronously with vegetation green-up at higher latitudes, where phenological shifts over time are also greater. Critically, species' migratory traits explained variation in sensitivity to green-up, with species that migrate more slowly, arrive earlier and overwinter further north showing greater responsiveness to earlier springs. Identifying how and why species vary in their ability to shift phenological events is fundamental to predicting species' vulnerability to climate change. Such variation in sensitivity across taxa, with long-distance neotropical migrants exhibiting reduced synchrony, may help to explain substantial declines in these species over the last several decades.
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http://dx.doi.org/10.1038/s41559-021-01442-yDOI Listing
April 2021

Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents.

Sci Transl Med 2021 Apr;13(590)

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Subcortical white matter stroke (WMS) accounts for up to 30% of all stroke events. WMS damages primarily astrocytes, axons, oligodendrocytes, and myelin. We hypothesized that a therapeutic intervention targeting astrocytes would be ideally suited for brain repair after WMS. We characterize the cellular properties and in vivo tissue repair activity of glial enriched progenitor (GEP) cells differentiated from human-induced pluripotent stem cells, termed hiPSC-derived GEPs (hiPSC-GEPs). hiPSC-GEPs are derived from hiPSC-neural progenitor cells via an experimental manipulation of hypoxia inducible factor activity by brief treatment with a prolyl hydroxylase inhibitor, deferoxamine. This treatment permanently biases these cells to further differentiate toward an astrocyte fate. hiPSC-GEPs transplanted into the brain in the subacute period after WMS in mice migrated widely, matured into astrocytes with a prorepair phenotype, induced endogenous oligodendrocyte precursor proliferation and remyelination, and promoted axonal sprouting. hiPSC-GEPs enhanced motor and cognitive recovery compared to other hiPSC-differentiated cell types. This approach establishes an hiPSC-derived product with easy scale-up capabilities that might be effective for treating WMS.
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http://dx.doi.org/10.1126/scitranslmed.aaz6747DOI Listing
April 2021

Stigma, beliefs and perceptions regarding prostate cancer among Black and Latino men and women.

BMC Public Health 2021 Apr 20;21(1):758. Epub 2021 Apr 20.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, USA.

Background: Health disparities in prostate cancer (PC) are thought to reflect the complex interplay of socioeconomics, environment and biology. The potential impact of beliefs and perceptions about PC among Black and Latino populations on clinical disparities are not well understood. This qualitative study was conducted to assess current prevalent and pervasive stigma, beliefs and perceptions regarding PC among Blacks and Latinos living in a large metropolitan area, thereby identifying potentially modifiable barriers to care.

Methods: Qualitative data were collected through four separate focus groups of self-identified Black and Latino adult men and women living in Philadelphia to better understand their perceptions of PC diagnosis, screening and treatment. Each focus group was single-sex and conducted by racial/ethnic group in order to assess possible differences in beliefs about PC based on gender and racial/ethnic affiliation. Audio recordings were transcribed verbatim by trained research assistants and qualitative data analysis was conducted using modified grounded theory.

Results: There were a total of 34 participants: 19 Hispanics/Latinos and 15 Blacks, with equal numbers of men and women (n=17). Median age was 57 years (range: 18 to 85 years). Dominant themes that emerged with respect to PC diagnosis included the stigma surrounding this condition and the perceived role of an "unhealthy lifestyle" and certain sexual behaviors as risk factors for PC development. While the majority of participants acknowledged the importance of PC screening and early detection, discussion centered around the barriers to both the interest in seeking medical care and the likelihood of securing it. These barriers included misunderstanding of PC etiology, distrust of the medical profession, and financial/access limitations. Men expressed substantial confusion about PC screening guidelines. In the Black female group, the role of faith and religion in the course of disease was a major theme. Both Black and Latina females discussed the role of fear and avoidance around PC screening and treatment, as well as the prevalence of misinformation about PC in their familial and social communities.

Conclusion: Black and Latino focus groups revealed the existence of cultural beliefs, misunderstandings and fears pertaining to PC which could influence health-related behaviors. Some themes were common across groups; others suggested racial and gender predilections. Future targeted efforts focused on directly addressing prevalent misperceptions among underserved communities in urban settings could help to improve health literacy and equity in PC outcomes in these populations.
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http://dx.doi.org/10.1186/s12889-021-10793-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056613PMC
April 2021

Microsatellitosis in Merkel cell carcinoma: a staging quandary.

Dermatol Online J 2021 Mar 15;27(3). Epub 2021 Mar 15.

Harvard Medical School, Boston, Massachusetts, USA Department of Dermatology, Massachusetts General Hospital, Boston, MA.

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March 2021

A head-to-head comparison of ribodepletion and polyA selection approaches for C. elegans low input RNA-sequencing libraries.

G3 (Bethesda) 2021 Apr 15. Epub 2021 Apr 15.

Department of Genetics, Yale University School of Medicine, New Haven, CT, 06510, USA.

A recent and powerful technique is to obtain transcriptomes from rare cell populations, such as single neurons in C. elegans, by enriching dissociated cells using fluorescent sorting. However, these cell samples often have low yields of RNA that present challenges in library preparation. This can lead to PCR duplicates, noisy gene expression for lowly expressed genes, and other issues that limit endpoint analysis. Further, some common resources, such as sequence specific kits for removing ribosomal RNA, are not optimized for non-mammalian samples. To advance library construction for such challenging samples, we compared two approaches for building RNAseq libraries from less than 10 nanograms of C. elegans RNA: SMARTSeq V4 (Takara), a widely used kit for selecting poly-adenylated transcripts; and SoLo Ovation (Tecan Genomics), a newly developed ribodepletion-based approach. For ribodepletion, we used a custom kit of 200 probes designed to match C. elegans rRNA gene sequences. We found that SoLo Ovation, in combination with our custom C. elegans probe set for rRNA depletion, detects an expanded set of noncoding RNAs, shows reduced noise in lowly expressed genes, and more accurately counts expression of long genes. The approach described here should be broadly useful for similar efforts to analyze transcriptomics when RNA is limiting.
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http://dx.doi.org/10.1093/g3journal/jkab121DOI Listing
April 2021

Obesity reduces the requirement for subsequent esophageal stricture dilation in adults with eosinophilic esophagitis.

Esophagus 2021 Apr 12. Epub 2021 Apr 12.

Albany Medical Center, 43 New Scotland Avenue, Albany, NY, 12208, USA.

Background: Eosinophilic esophagitis (EoE) causes esophageal narrowing and strictures, but factors that modify the severity of strictures and requirement for subsequent dilation are not well described. The aim of this study was to identify characteristics that impact the need for repeat (> 1) esophageal dilations in EoE patients.

Methods: This was a single center retrospective cohort study over a 12-year period (September 2005-October 2017). Patients were identified using ICD9, ICD10, and CPT codes for esophageal dilation, eosinophilic esophagitis, and esophageal obstruction. Data for EoE clinical characteristics, treatments, and BMI were extracted and correlated to the number of esophageal dilations and time elapsed between dilations.

Results: Of the 21 patients who met inclusion criteria, 11 (52%) had at least two dilations and 9 (43%) had three dilations. There was no differences baseline demographics between patients who needed ≥ 2 vs. those who needed one dilation. However, patients with a BMI > 30 had a significantly longer median time to second dilation compared to non-obese patients (4.9 years vs. 1.8 years; p = 0.027). Stratification by either high dose PPI or inhaled steroid use did not change this result.

Conclusions: EoE patients with strictures who are obese have a reduced requirement for subsequent esophageal dilation. While the mechanism for this is not clear, increased attention of non-obese patients with fibrostenotic EoE is indicated as they are at higher risk for recurrent strictures.
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http://dx.doi.org/10.1007/s10388-021-00838-wDOI Listing
April 2021

Current and time-lagged effects of climate on innate immunity in two sympatric snake species.

Ecol Evol 2021 Apr 16;11(7):3239-3250. Epub 2021 Feb 16.

Westmont College Santa Barbara CA USA.

Changing environments result in alterations at all levels of biological organization, from genetics to physiology to demography. The increasing frequency of droughts worldwide is associated with higher temperatures and reduced precipitation that can impact population persistence via effects on individual immune function and survival.We examined the effects of annual climate variation on immunity in two sympatric species of garter snakes from four populations in California over a seven-year period that included the record-breaking drought.We examined three indices of innate immunity: bactericidal competence (BC), natural antibodies (NABs), and complement-mediated lysis (CL).Precipitation was the only climatic variable explaining variation in immune function: spring precipitation of the current year was positively correlated to BC and NABs, whereas spring precipitation of the previous year was positively correlated to BC and NABs. This suggests that experiences a physiological time-lag in response to reduced precipitation, which may reflect lack of capital for investment in immunity in the year following a dry year.In general, our findings demonstrate compelling evidence that climate can influence wild populations through effects on physiological processes, suggesting that physiological indices such as these may offer valuable opportunities for monitoring the effects of climate.
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http://dx.doi.org/10.1002/ece3.7273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019058PMC
April 2021

The stability of an isolate of the SARS-CoV-2 B.1.1.7 lineage in aerosols is similar to three earlier isolates.

J Infect Dis 2021 Apr 2. Epub 2021 Apr 2.

National Biodefense Analysis and Countermeasures Center, operated by Battelle National Biodefense Institute for the US Department of Homeland Security, Frederick, Maryland, USA.

Background: Our laboratory previously examined the influence of environmental conditions on the stability of an early isolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosols generated from culture medium or simulated saliva. However, genetic differences have emerged among SARS-CoV-2 lineages, and it is possible that these differences may affect environmental stability and the potential for aerosol transmission.

Methods: The influence of temperature, relative humidity, and simulated sunlight on the decay of four SARS-CoV-2 isolates in aerosols, including one belonging to the recently emerged B.1.1.7 lineage, were compared in a rotating drum chamber. Aerosols were generated from simulated respiratory tract lining fluid to represent aerosols originating from the deep lung.

Results: No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. .

Conclusions: The stability of SARS-CoV-2 in aerosols does not vary greatly among currently circulating lineages, including B.1.1.7, suggesting that the increased transmissibility associated with recent SARS-CoV-2 lineages is not due to enhanced survival in the environment.
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http://dx.doi.org/10.1093/infdis/jiab171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083468PMC
April 2021

Reusable snorkel masks adapted as particulate respirators.

PLoS One 2021 5;16(4):e0249201. Epub 2021 Apr 5.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Introduction: During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject's face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/.

Conclusion: Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249201PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021169PMC
April 2021

Preoperative Telephone Medical Clearance for Ophthalmic Surgeries.

J Cataract Refract Surg 2021 Mar 9. Epub 2021 Mar 9.

Retina Associates of Cleveland Inc.

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http://dx.doi.org/10.1097/j.jcrs.0000000000000548DOI Listing
March 2021

The use of an Ebola virus reporter cell line in a semi-automated microtitration assay.

J Virol Methods 2021 06 6;292:114116. Epub 2021 Mar 6.

National Biodefense Analysis and Countermeasures Center, Operated by BNBI for the U.S. Department of Homeland Security Science and Technology Directorate, Frederick, MD, USA; School of Systems Biology, George Mason University, Manassas, VA, USA.

A variety of methods have been developed for quantification of infectious Ebola virus in clinical or laboratory samples, but existing methods often require extensive operator involvement, manual assay scoring, or the use of custom reagents. In this study, we utilize a recently developed Ebola-specific reporter cell line that expresses ZsGreen in response to Ebola virus infection, in conjunction with semi-automated processing and quantification techniques, to develop an unbiased, high-throughput microtitration assay for quantification of infectious Ebola virus in vitro. This assay was found to have equivalent sensitivity to a standardized plaque assay for quantifying viral titers. However, the new assay could be implemented with fewer reagents and processing steps, reduced subjectivity, and higher throughput. This assay may be useful for a variety of applications, particularly studies that require the detection or quantification of infectious Ebola virus in large numbers of samples.
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http://dx.doi.org/10.1016/j.jviromet.2021.114116DOI Listing
June 2021

Prostate Cancer Screening and Young Black Men: Can Early Communication Avoid Later Health Disparities?

J Cancer Educ 2021 Mar 10. Epub 2021 Mar 10.

Servant Voice Technologies Consulting LLC, Apex, NC, USA.

This study aims to determine if younger men, across racial and ethnic groups, discussed the benefits/risks/harms of PSA screening with health care professionals. Publicly available data were obtained from the Health Information National Trends Survey https://hints.cancer.gov/ in March 2019. Cross-sectional analysis of 518 men between the ages of 18 and 49 years from men who completed the survey between October 2011 and February 2012 (HINTS cycle 4) was performed. We used logistic regression to evaluate the association between race/ethnicity and discussions around PSA. Less than 10% of the participants reported a prior PSA; Black and Hispanic men were more likely compared with White men. Compared with White men, Black and other race men reported receiving less communications from some doctors recommending PSA screening (OR: 0.16, 95% CI: 0.07-0.38; OR: 0.10, 95% CI: 0.04-0.25), and that no one is sure PSA testing saves lives (OR: 0.49, 95% CI: 0.04-6.91; OR: 0.17, 95% CI: 0.06-0.48). Minority men, while more likely to have had a PSA, were less likely to be told of the harms and benefits of PSA testing, compared with White men. Increasing communication surrounding screening advantages and disadvantages between providers and patients can increase awareness and knowledge among younger men. In a post-COVID-19 environment, communication regarding the return to preventative screenings within vulnerable populations is an important message to convey. Research shows preventive screenings have dropped across all population groups due to the pandemic yet the decline disproportionately affects Black and other minority men.
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http://dx.doi.org/10.1007/s13187-021-01984-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943410PMC
March 2021

Association of a Health Equity Curriculum With Medical Students' Knowledge of Social Determinants of Health and Confidence in Working With Underserved Populations.

JAMA Netw Open 2021 Mar 1;4(3):e210297. Epub 2021 Mar 1.

Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Importance: National organizations recommend that medical schools train students in the social determinants of health.

Objective: To develop and evaluate a longitudinal health equity curriculum that was integrated into third-year clinical clerkships and provided experiential learning in partnership with community organizations.

Design, Setting, And Participants: This longitudinal cohort study was conducted from June 2017 to October 2020 to evaluate the association of the curriculum with medical students' self-reported knowledge of social determinants of health and confidence working with underserved populations. Students from 1 large medical school in the southeastern US were included. Students in the class of 2019 and class of 2020 were surveyed at baseline (before the start of their third year), end of the third year, and graduation. The class of 2018 (No curriculum) was surveyed at graduation to serve as a control. Data analysis was conducted from June to September 2020.

Exposures: The curriculum began with a health equity simulation followed by a series of modules. The class of 2019 participated in the simulation and piloted the initial 3 modules (pilot), and the class of 2020 participated in the simulation and the full 9 modules (full).

Main Outcomes And Measures: A linear mixed-effects model was used to evaluate the change in the self-reported knowledge and confidence scores over time (potential scores ranged from 0 to 32, with higher scores indicating higher self-reported knowledge and confidence working with underserved populations). In secondary analyses, a Kruskal-Wallis test was conducted to compare graduation scores between the no, pilot, and full curriculum classes.

Results: A total of 314 students (160 women [51.0%], 205 [65.3%] non-Hispanic White participants) completed at least 1 survey, including 125 students in the pilot, 121 in the full, and 68 in the no curriculum classes. One hundred forty-one students (44.9%) were interested in primary care. Total self-reported knowledge and confidence scores increased between baseline and end of clerkship (15.4 vs 23.7, P = .001) and baseline and graduation (15.4 vs 23.7, P = .001) for the pilot and full curriculum classes. Total scores at graduation were higher for the pilot curriculum (median, 24.0; interquartile range [IQR], 21.0-27.0; P = .001) and full curriculum classes (median, 23.0; IQR, 20.0-26.0; P = .01) compared with the no curriculum class (median, 20.5; IQR, 16.25-24.0).

Conclusions And Relevance: In this cohort study of medical students, a dedicated health equity curriculum was associated with a significant improvement in students' self-reported knowledge of social determinants of health and confidence working with underserved populations.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921901PMC
March 2021

Accommodating the role of site memory in dynamic species distribution models.

Ecology 2021 May 22;102(5):e03315. Epub 2021 Apr 22.

U.S. Geological Survey, Patuxent Wildlife Research Center, 1 Migratory Way, Turners Falls, Massachusetts, 01376, USA.

First-order dynamic occupancy models (FODOMs) are a class of state-space model in which the true state (occurrence) is observed imperfectly. An important assumption of FODOMs is that site dynamics only depend on the current state and that variations in dynamic processes are adequately captured with covariates or random effects. However, it is often difficult to understand and/or measure the covariates that generate ecological data, which are typically spatiotemporally correlated. Consequently, the non-independent error structure of correlated data causes underestimation of parameter uncertainty and poor ecological inference. Here, we extend the FODOM framework with a second-order Markov process to accommodate site memory when covariates are not available. Our modeling framework can be used to make reliable inference about site occupancy, colonization, extinction, turnover, and detection probabilities. We present a series of simulations to illustrate the data requirements and model performance. We then applied our modeling framework to 13 yr of data from an amphibian community in southern Arizona, USA. In this analysis, we found residual temporal autocorrelation of population processes for most species, even after accounting for long-term drought dynamics. Our approach represents a valuable advance in obtaining inference on population dynamics, especially as they relate to metapopulations.
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http://dx.doi.org/10.1002/ecy.3315DOI Listing
May 2021

The Value of Family History in Colorectal Screening Decisions for Oldest Old Geriatric Populations.

Cureus 2021 Jan 20;13(1):e12815. Epub 2021 Jan 20.

Gastroenterology, Albany Medical Center, Albany, USA.

Introduction: Colorectal cancer (CRC) is the second most common form of cancer affecting both men and women. Extensive screening guidelines have been developed to help reduce the incidence of disease. Currently, United States Preventative Service Task Force guidelines recommend against routine screening in those 85 years and older. However, octogenarians and nonagenarians continue to be screened for CRC with no consensus on indications. The aim of this study is to examine family history of CRC as a risk factor and clinical indication for providing screening colonoscopies to the "oldest old" geriatric population, defined as aged 80 years and above.

Methods: We conducted a retrospective review of a Veterans' Health Administration database to identify male veterans aged 80 years and older who underwent screening colonoscopy. Subsequently, we examined those who tested positive for CRC with a family history of CRC.

Results: Of the 458,224 patients who are 80 years and older in the Veterans Affairs (VA) database, 17.8% underwent a screening colonoscopy; 11.42% of these individuals were further diagnosed with CRC; and 8.89% of those with diagnosed CRC had a documented family history of CRC.

Conclusion: Family history should not be used as an inclusionary criterion for CRC screening in the 80 years and above age group as the rate of CRC in these patients with a family history of CRC is significantly lower than that in the younger age groups with a family history of CRC.
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http://dx.doi.org/10.7759/cureus.12815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894966PMC
January 2021

Sex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial Cancer.

Cancer Epidemiol Biomarkers Prev 2021 Apr 23;30(4):719-726. Epub 2021 Feb 23.

Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

Background: The influence of sex hormone and insulin/insulin-like growth factor (IGF) axis signaling on endometrial cancer recurrence is unknown. We evaluated these pathways in a prospective cohort of Gynecologic Oncology Group (GOG)0210 trial endometrial adenocarcinoma patients.

Methods: Stage II-IV patients ( = 816) were included in this study. Pretreatment specimens were tested for tumor mRNA and protein expression of , IGF-binding proteins () and , insulin (IR) and IGF-I receptors (IGF1R), phosphorylated IR/IGF1R (pIGF1R/pIR), and estrogen (ER) and progesterone receptors (PR) using qPCR and IHC. Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone, and sex hormone binding globulin were measured. HRs and 95% confidence intervals (CI) for progression-free survival were calculated from Cox models adjusting for age, stage, and grade.

Results: Recurrence occurred in 280 (34%) cases during a median of 4.6 years of follow-up. ER positivity (HR, 0.67; 95% CI, 0.47-0.95), IR positivity (HR, 0.53; 95% CI, 0.29-0.98), and circulating IGF-I (highest vs. lowest quartile: HR, 0.66; 95% CI, 0.47-0.92) were inversely associated with recurrence risk. Circulating estradiol (highest vs. lowest tertile: HR, 1.55; 95% CI, 1.02-2.36) and pIGF1R/pIR positivity (HR, 1.40; 95% CI, 1.02-1.92) were associated with increased recurrence risk.

Conclusions: Circulating estradiol and tumor tissue phosphorylated (activated) IGR1R/IR were independently associated with higher risk of recurrence in patients with endometrial cancer.

Impact: This study may inform future clinical trials of endocrine-targeted adjuvant therapies in patients with endometrial cancer that could include baseline assessment of serum and tissue biomarkers of estradiol and insulin signaling pathways.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026669PMC
April 2021

Conservation and turnover of miRNAs and their highly complementary targets in early branching animals.

Proc Biol Sci 2021 Feb 24;288(1945):20203169. Epub 2021 Feb 24.

Department of Neurosciences and Developmental Biology; Faculty of Life Sciences, University of Vienna, Vienna, Austria.

MicroRNAs (miRNAs) are crucial post-transcriptional regulators that have been extensively studied in Bilateria, a group comprising the majority of extant animals, where more than 30 conserved miRNA families have been identified. By contrast, bilaterian miRNA targets are largely not conserved. Cnidaria is the sister group to Bilateria and thus provides a unique opportunity for comparative studies. Strikingly, like their plant counterparts, cnidarian miRNAs have been shown to predominantly have highly complementary targets leading to transcript cleavage by Argonaute proteins. Here, we assess the conservation of miRNAs and their targets by small RNA sequencing followed by miRNA target prediction in eight species of Anthozoa (sea anemones and corals), the earliest-branching cnidarian class. We uncover dozens of novel miRNAs but only a few conserved ones. Further, given their high complementarity, we were able to computationally identify miRNA targets in each species. Besides evidence for conservation of specific miRNA target sites, which are maintained between sea anemones and stony corals across 500 Myr of evolution, we also find indications for convergent evolution of target regulation by different miRNAs. Our data indicate that cnidarians have only few conserved miRNAs and corresponding targets, despite their high complementarity, suggesting a high evolutionary turnover.
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http://dx.doi.org/10.1098/rspb.2020.3169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935066PMC
February 2021

Detecting Scene-Plausible Perceptible Backdoors in Trained DNNs without Access to the Training Set.

Neural Comput 2021 Feb 22:1-43. Epub 2021 Feb 22.

School of Electrical Engineering and Computer Science, College of Engineering, The Pennsylvania State University, University Park, PA 16802, U.S.A.

Backdoor data poisoning attacks add mislabeled examples to the training set, with an embedded backdoor pattern, so that the classifier learns to classify to a target class whenever the backdoor pattern is present in a test sample. Here, we address posttraining detection of scene-plausible perceptible backdoors, a type of backdoor attack that can be relatively easily fashioned, particularly against DNN image classifiers. A posttraining defender does not have access to the potentially poisoned training set, only to the trained classifier, as well as some unpoisoned examples that need not be training samples. Without the poisoned training set, the only information about a backdoor pattern is encoded in the DNN's trained weights. This detection scenario is of great import considering legacy and proprietary systems, cell phone apps, as well as training outsourcing, where the user of the classifier will not have access to the entire training set. We identify two important properties of scene-plausible perceptible backdoor patterns, spatial invariance and robustness, based on which we propose a novel detector using the maximum achievable misclassification fraction (MAMF) statistic. We detect whether the trained DNN has been backdoor-attacked and infer the source and target classes. Our detector outperforms existing detectors and, coupled with an imperceptible backdoor detector, helps achieve posttraining detection of most evasive backdoors of interest.
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http://dx.doi.org/10.1162/neco_a_01376DOI Listing
February 2021

Redesigning the Molecular Choreography to Prevent Hydroxylation in Germacradien-11-ol Synthase Catalysis.

ACS Catal 2021 Feb 7;11(3):1033-1041. Epub 2021 Jan 7.

School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, United Kingdom.

Natural sesquiterpene synthases have evolved to make complex terpenoids by quenching reactive carbocations either by proton transfer or by hydroxylation (water capture), depending on their active site. Germacradien-11-ol synthase (Gd11olS) from catalyzes the cyclization of farnesyl diphosphate (FDP) into the hydroxylated sesquiterpene germacradien-11-ol. Here, we combine experiment and simulation to guide the redesign of its active site pocket to avoid hydroxylation of the product. Molecular dynamics simulations indicate two regions between which water molecules can flow that are responsible for hydroxylation. Point mutations of selected residues result in variants that predominantly form a complex nonhydroxylated product, which we identify as isolepidozene. Our results indicate how these mutations subtly change the molecular choreography in the Gd11olS active site and thereby pave the way for the engineering of terpene synthases to make complex terpenoid products.
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http://dx.doi.org/10.1021/acscatal.0c04647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886051PMC
February 2021

Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of mRNA COVID-19 Vaccines?

Pain Med 2021 04;22(4):994-1000

University of Utah, Division of Physical Medicine and Rehabilitation, Salt Lake City, Utah, USA.

Myth: Corticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19).

Fact: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine.However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.
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http://dx.doi.org/10.1093/pm/pnab063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928682PMC
April 2021

Progesterone induces porcine sperm release from oviduct glycans in a proteasome-dependent manner.

Reproduction 2021 Apr;161(4):449-457

Department of Animal Sciences and Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

In mammals, the oviduct retains sperm, forming a reservoir from which they are released in synchrony with ovulation. However, the mechanisms underlying sperm release are unclear. Herein, we first examined in greater detail the release of sperm from the oviduct reservoir by sex steroids, and secondly, if the ubiquitin-proteasome system (UPS) mediates this release in vitro. Sperm were allowed to bind to oviductal cells or immobilized oviduct glycans, either bi-SiaLN or a suLeX, and channeled with steroids in the presence or absence of proteasome inhibitors. Previously, we have demonstrated progesterone-induced sperm release from oviduct cells and immobilized glycans in a steroid-specific manner. Herein, we found that the release of sperm from an immobilized oviduct glycan, a six-sialylated branched structure, and from immobilized fibronectin was inhibited by the CatSper blocker NNC 055-0396, akin to the previously reported ability of NNC 055-0396 to inhibit sperm release from another oviduct glycan, sulfated Lewis-X trisaccharide. Thus, CatSper may be required for release of sperm from a variety of adhesion systems. One possible mechanism for sperm release is that glycan receptors on sperm are degraded by proteasomes or shed from the sperm surface by proteasomal degradation. Accordingly, the inhibition of proteasomal degradation blocked sperm release from oviduct cell aggregates both immobilized oviduct glycans as well as fibronectin. In summary, progesterone-induced sperm release requires both active CatSper channels and proteasomal degradation, suggesting that hyperactivation and proteolysis are vital parts of the mechanism by which sperm move from the oviduct reservoir to the site of fertilization.
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http://dx.doi.org/10.1530/REP-20-0474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006895PMC
April 2021

Clinical Syndromic Phenotypes and the Potential Role of Genetics in Pulmonary Vein Stenosis.

Children (Basel) 2021 Feb 10;8(2). Epub 2021 Feb 10.

Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.

Pulmonary vein stenosis (PVS) is a rare, frequently lethal disease with heterogeneous phenotypes and an unclear etiology. Limited studies have reported associations between PVS and congenital heart disease (CHD), chronic lung disease (CLD), and/or prematurity; however, to date, there have been no studies that report detailed clinical syndromic phenotypes and the potential role of genetics in PVS. An existing registry of multivessel PVS patients seen at Boston Children's Hospital (BCH) was queried between August 2006 and January 2017 for all existing genetic testing data on these patients. PVS was defined as an intraluminal pulmonary venous obstruction in ≥2 vessels with mean pressure gradients > 4 mmHg. One-hundred-and-fifty-seven patients (46% female, with a median age at PVS diagnosis of 3 months) formed the cohort. Seventy-one (45%) patients had available genetic testing information. Of the 71 patients, a likely genetic diagnosis was found in 23 (32%) patients: 13 (57%) were diagnosed with Trisomy 21 (T21), five (22%) with Smith-Lemli-Opitz Syndrome, five (22%) had other pathologic genetic disease, and 24 (33%) had variants of unknown significance. The majority of 13 patients with T21 and PVS had common atrioventricular canal (CAVC) (10, 77%) and all had severe pulmonary hypertension (PHTN), which led to their PVS diagnosis. In our study, PVS was associated with T21, the majority of whom also had CAVC and PHTN. Therefore, complete assessment of the pulmonary veins should be considered for all T21 patients, especially those with CAVC presenting with PHTN. Furthermore, prospective standardized genetic testing with detailed clinical phenotyping may prove informative about potential genetic etiologies of PVS.
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http://dx.doi.org/10.3390/children8020128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916466PMC
February 2021

SARS-CoV-2 is rapidly inactivated at high temperature.

Environ Chem Lett 2021 Feb 3:1-5. Epub 2021 Feb 3.

National Biodefense Analysis and Countermeasures Center (NBACC), Operated By Battelle National Biodefense Institute (BNBI) for the U.S. Department of Homeland Security Science and Technology Directorate, Fort Detrick, MD 21702 USA.

In the absence of a vaccine, preventing the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the primary means to reduce the impact of the 2019 coronavirus disease (COVID-19). Multiple studies have reported the presence of SARS-CoV-2 genetic material on surfaces suggesting that fomite transmission of SARS-CoV-2 is feasible. High temperature inactivation of virus has been previously suggested, but not shown. In the present study, we investigated the environmental stability of SARS-CoV-2 in a clinically relevant matrix dried onto stainless steel at a high temperature. The results show that at 54.5 °C, the virus half-life was 10.8 ± 3.0 min and the time for a 90% decrease in infectivity was 35.4 ± 9.0 min. These findings suggest that in instances where the environment can reach temperatures of at least 54.5 °C, such as in vehicle interior cabins when parked in warmer ambient air, that the potential for exposure to infectious virus on surfaces could be decreased substantially in under an hour.
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http://dx.doi.org/10.1007/s10311-021-01187-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856623PMC
February 2021

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2021 02 2;19(2):191-226. Epub 2021 Feb 2.

Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.
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http://dx.doi.org/10.6004/jnccn.2021.0007DOI Listing
February 2021

Sperm binding to hyaluronan is an excellent predictor of Nili-Ravi buffalo bull fertility.

Andrologia 2021 Apr 2;53(3):e13991. Epub 2021 Feb 2.

Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan.

This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r  = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = -.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r  = .861, p < .01) and 85.9% (r  = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility.
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http://dx.doi.org/10.1111/and.13991DOI Listing
April 2021