Publications by authors named "Xiaoming Li"

1,140 Publications

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Criminalization of Sexual and Gender Minorities and Its Consequences for the HIV Epidemic in Zambia: A Critical Review and Recommendations.

J Assoc Nurses AIDS Care 2021 Jun 10. Epub 2021 Jun 10.

Valerie Yelverton, MSc, is a Doctoral Candidate, Department of Health Services Policy and Management, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA. Shan Qiao, PhD, is an Assistant Professor, Department of Health Promotion, Education, and Behavior, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA. J. Anitha Menon, PhD, is a Professor, Department of Psychology, University of Zambia, Lusaka, Zambia. Levy Ngosa, is a Board Member, Dignitate Zambia, Lusaka, Zambia. McLean Kabwe, is a Director, The Lotus Identity, Lusaka, Zambia. Sayward Harrison, PhD, is an Assistant Professor, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA. Sharon Weissman, MD, is a Professor, Department of Medicine, School of Medicine, University of South Carolina, Columbia, South Carolina, USA. Xiaoming Li, PhD, is a Professor, Department of Health Promotion, Education, and Behavior, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA. Gary W. Harper, PhD, MPH, is a Professor, Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Abstract: To elaborate the negative impacts of sexual and gender minority (SGM)-related legislation for the HIV epidemic in Zambia, we reviewed Zambian legislation that restricts the rights of SGM people and synthesized its consequences. We retrieved legal documents through the National Assembly of Zambia and the Zambia Legal Information Institute and conducted a critical review based on four academic databases following thematic synthesis methodology. Eighteen literature records and six Zambian laws were included in the review. Existing laws criminalize same-sex sexual behavior and restrict same-sex marriage and the adoption of children. Anti-SGM legislation has limited legal protections for SGM people and increased vulnerability of criminal prosecution and HIV exposure, persistent stigma/discrimination, insufficient public health resources, and lessened access to HIV-related services. We recommend enacting legal protections for SGM people, decriminalizing anti-SGM laws, rectifying misinformation to destigmatize SGM people, targeting health care for SGM people, and including SGM people in the national HIV strategy.
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http://dx.doi.org/10.1097/JNC.0000000000000281DOI Listing
June 2021

Hybrid AI-assistive diagnostic model permits rapid TBS classification of cervical liquid-based thin-layer cell smears.

Nat Commun 2021 06 10;12(1):3541. Epub 2021 Jun 10.

Department of Pathology, Guangdong Provincial Women's and Children's Dispensary, Shenzhen, Guangdong Province, PR China.

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners.
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http://dx.doi.org/10.1038/s41467-021-23913-3DOI Listing
June 2021

Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma.

Lab Invest 2021 Jun 9. Epub 2021 Jun 9.

Department of Respirology Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.

Asthma is an allergic inflammatory lung disease affecting nearly 300 million people worldwide. To better understand asthma, new regulators must be identified. We conducted a study to investigate the effect and mechanisms of action of surfactant protein A (SPA) in OVA-induced asthmatic mice. Treatment with SPA delayed the onset of asthma, decreased its severity, as well as notably suppressed pro-inflammatory cytokine production. Furthermore, SPA-treated mice possessed more leukocytes; more CD4 T cells infiltrated the spleen in the SPA-treated mice than in the control mice, and there were decreased percentages of Th1 and Th17 cells in vivo. In addition, expression levels of the T-bet (Th1 transcription factor) and RORγt (Th17 transcription factor) genes were significantly downregulated by SPA treatment. Moreover, SPA reduced the production and mRNA expression of pro-inflammatory cytokine mRNAs in activated T cells in vivo. Mechanistically, SPA could inhibit STAT1/4 and STAT3 phosphorylation, resulting in the differentiation of Th1 and suppression of Th17 cells, respectively. In the presence of CD3/CD28 expression, STAT1/4 and STAT3 were activated but suppressed by SPA, which was responsible for the augmentation of Th1 and Th17 differentiation. This result showed that SPA can effectively modulate the JAK/STAT pathway by suppressing Th1 and Th17 differentiation, thus preventing asthma. The present study reveals the novel immunomodulatory activity of SPA and highlights the importance of further investigating the effects of SPA on asthma.
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http://dx.doi.org/10.1038/s41374-021-00618-1DOI Listing
June 2021

A novel LMNA indel mutation identified in a family with atrioventricular block and atrial fibrillation.

Medicine (Baltimore) 2021 May;100(19):e25910

Shanxi Cardiovascular Hospital, Taiyuan.

Abstract: It is well known that many genetic factors are involved in the occurrence and progression of atrioventricular block (AV block) and atrial fibrillation (AF). However, the genetic variants discovered so far have only explained parts of these processes. More genes and variants remain to be identified. In the present study, a three-generation family with an autosomal dominant form of AV block and AF was enrolled. Whole exome sequencing was conducted in three affected and one unaffected family member. A total of 64 nonsynonymous variants was shared by three affected individuals and not present in the unaffected individual. By selection of variants absent in the known databases and were predicted to be deleterious, 4 novel variants were identified. Only one novel frameshift insertion in the LMNA gene (c.825_826insCAGG) was identified in another affected family member and not detected in other non-affected family members and the 100 controls. Our finding expanded the spectrum of variants associated with AV block and AF, and was valuable in the genetic diagnosis of AV block and AF.
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http://dx.doi.org/10.1097/MD.0000000000025910DOI Listing
May 2021

Enhancing methane production from anaerobic digestion of waste activated sludge with addition of sodium lauroyl sarcosinate.

Bioresour Technol 2021 May 24;336:125321. Epub 2021 May 24.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China. Electronic address:

In this study, sodium lauroyl sarcosinate (SLS) was used to promote anaerobic digestion of waste activated sludge for producing methane. It was found maximum cumulative methane production increased from 98.1 ± 3.1 to 166.0 ± 4.3 mL/g Volatile Suspended Solids (VSS) with dosage increasing from 0 (control) to 40 mg SLS/g TSS. But the addition of SLS (>10 mg SLS/g Total Suspended Solids (TSS)) resulted in prolonged lag phase time. Microbiological analysis showed that Syntrophobacter and Syntrophomonas both got enriched in reactors fed with SLS. Furthermore, hydrogenotrophic methanogens genus got more enrichment in contrast to acetoclastic methanogens. Mechanism analysis indicated that addition SLS could decrease surface tension, and promote release of organic matters as well as improve activities of hydrolytic enzymes. Besides, SLS could be nearly degraded completely within 3 days, and its degradation intermediates could be further transformed into methane gradually, thus enhancing methane production eventually.
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http://dx.doi.org/10.1016/j.biortech.2021.125321DOI Listing
May 2021

A case study of glycogen storage disease type Ia presenting with multiple hepatocellular adenomas: an analysis by gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid magnetic resonance imaging.

Quant Imaging Med Surg 2021 Jun;11(6):2785-2791

Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Glycogen storage disease type Ia (GSD Ia) is a rare disease caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase). Here, we report a 17-year-old Chinese boy with GSD Ia. Clinical manifestations of the patient included hepatomegaly, growth retardation, doll face, and biochemical abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia. The computed tomography (CT) and gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) revealed multiple masses in the left and right hemiliver. These masses presented as different dynamic enhanced patterns in the Gd-EOB-DTPA MRI. In addition, a large amount of glycogen deposit was detected in the liver tissue biopsy. Liver puncture confirmed that the masses were hepatocellular adenomas (HCAs). Genetic analyses confirmed the presence of liver metabolic disease, and the final clinical diagnostic was GSD Ia. The patient's clinical manifestations were significantly improved following regular treatment with raw corn starch for 9 months. Unfortunately, it was suspected that parts of the adenoma had undergone malignant transformation.
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http://dx.doi.org/10.21037/qims-20-746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107322PMC
June 2021

Propensity score matching evaluation of psychological stress and hair cortisol among people living with HIV in China.

Sci Rep 2021 Jun 1;11(1):11426. Epub 2021 Jun 1.

Guangxi Center for Disease Prevention and Control, Nanning, Guangxi, China.

To compare the psychological stress level and hair cortisol level of people living with HIV (PLWH) with those without HIV in China, a total of 220 participants were initially enrolled in the study, including 200 PLWH and 20 people living without HIV. Psychological stress level, including quality of life, anxiety, perceived stress and psychological resilience, was self-reported in both groups with related scales. The cortisol in hair was extracted and assessed by LC-APCI-MS/MS method. Propensity score matching analysis was performed to balance the baseline covariates of the two groups, whereas the difference in psychological stress level and hair cortisol level between the two groups was compared. Furthermore, the associations between psychological stress level and cortisol level were examined. Two comparison groups were matched by 1:3 propensity score matching, which yielding 20 people living without HIV and 60 PLWH. Ultimately, in regarding to the psychological stress, the levels of the anxiety (34 vs. 26, p < 0.001), perceived stress (38.5 vs. 33, p = 0.001) and psychological resilience (31 vs. 26, p = 0.004) were higher among PLWH than those living without HIV, but the people without HIV showed higher quality of life (109 vs.116, p < 0. 001). The hair cortisol level (34.66 vs. 21.61, p = 0.002) in PLWH was higher than those living without HIV. However, there were no significant associations between psychological stress level and cortisol level (p > 0.05). The PLWH showed higher level of psychological stress and cortisol than those without HIV. No relationship was seen between psychological stress level and cortisol level in PLWH.
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http://dx.doi.org/10.1038/s41598-021-90922-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169931PMC
June 2021

Dysregulation of tumour microenvironment driven by circ-TPGS2/miR-7/TRAF6/NF-κB axis facilitates breast cancer cell motility.

Autoimmunity 2021 May 26:1-10. Epub 2021 May 26.

Department of Clinical Medicine, Peihua University, Xi'an, China.

Tumour microenvironment (TME) is frequently remodelled and deregulated in cancer development and progression. The underlying mechanisms are complex, multifactorial and largely unknown. Circular RNA (circRNA) is an endogenous RNA with a covalently closed loop that plays critical roles in the pathological and physiological processes of the organism. Here, we identified a TME-associated circRNA, circ-TPGS2, which promoted breast cancer (BC) cell dissemination altering TME. High circ-TPGS2 was observed in metastatic BC tissues and cell lines in comparison to respective normal controls, which was linked to poor overall and recurrence-free survival. Overexpression of circ-TPGS2 notably promoted cell migration, while silencing of circ-TPGS2 resulted in an opposite trend. Moreover, circ-TPGS2 increased pro-inflammatory chemokine production and evoked tumour-associated inflammation by recruiting neutrophils autocrine and paracrine manners. In terms of mechanism, circ-TPGS2 acted as a sponge of miR-7 and elevated TRAF6, leading to p65 phosphorylation and nuclear translocation, ultimately activating NF-κB signalling. In addition, p65 was abundantly occupied on circ-TPGS2 promoter, activating circ-TPGS2 transcription, thus, forming a positive feedback loop that amplified the pro-metastasis effect of circ-TPGS2. Taken together, our data for the first time reveal the biological implication of circ-TPGS2 in BC, it triggers TME reshaping that facilitates BC metastasis through the miR-7/TRAF6/NF-κB signalling cascade.
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http://dx.doi.org/10.1080/08916934.2021.1931843DOI Listing
May 2021

A Fifteen-Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer.

Adv Sci (Weinh) 2021 05 18;8(10):2001978. Epub 2021 Mar 18.

Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Jiefang Avenue 1095# Wuhan Hubei 430030 China.

Neoadjuvant chemotherapy (NACT) remains an attractive alternative for controlling locally advanced cervical cancer. However, approximately 15-34% of women do not respond to induction therapy. To develop a risk stratification tool, 56 patients with stage IB-IIB cervical cancer are included in 2 research centers from the discovery cohort. Patient-specific somatic mutations led to NACT non-responsiveness are identified by whole-exome sequencing. Next, CRISPR/Cas9-based library screenings are performed based on these genes to confirm their biological contribution to drug resistance. A 15-gene classifier is developed by generalized linear regression analysis combined with the logistic regression model. In an independent validation cohort of 102 patients, the classifier showed good predictive ability with an area under the curve of 0.80 (95% confidence interval (CI), 0.69-0.91). Furthermore, the 15-gene classifier is significantly associated with patient responsiveness to NACT in both univariate (odds ratio, 10.8; 95% CI, 3.55-32.86; = 2.8 × 10) and multivariate analysis (odds ratio, 17.34; 95% CI, 4.04-74.40; = 1.23 × 10) in the validation set. In conclusion, the 15-gene classifier can accurately predict the clinical response to NACT before treatment, representing a promising approach for guiding the selection of appropriate treatment strategies for locally advanced cervical cancer.
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http://dx.doi.org/10.1002/advs.202001978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132153PMC
May 2021

Diagnostic performance of D-dimer in predicting pulmonary embolism in tuberculous pleural effusion patients.

BMC Pulm Med 2021 May 22;21(1):177. Epub 2021 May 22.

Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kongjiang Road, Shanghai, 200092, China.

Background: Tuberculous pleural effusion (TPE) patients usually have elevated D-dimer levels. The diagnostic performance of D-dimer in predicting pulmonary embolism (PE) in the TPE population is unclear. This study aimed to assess the diagnostic performance of D-dimer for PE in the TPE population and explore its potential mechanism.

Methods: We retrospectively analysed patients who were admitted to Xinhua Hospital and Weifang Respiratory Disease Hospital with confirmed TPE between March 2014 and January 2020. D-dimer levels were compared between patients with and without PE. To test the diagnostic performance of D-dimer in predicting PE, receiver operating characteristic curve analysis was performed. Positive predictive value (PPV) and negative predictive value (NPV) were also reported. To explore the potential mechanism of PE in TPE, inflammatory biomarkers were compared between PE and non-PE patients.

Results: This study included 248 patients (170 males and 78 females) aged 43 ± 20.6 years. Elevated D-dimer levels (≥ 0.5 mg/L) were detected in 186/248 (75%) patients. Of the 150 patients who underwent computed tomography pulmonary angiography, 29 were diagnosed with PE. Among the TPE population, the PE patients had significantly higher D-dimer levels than the non-PE patients (median, 1.06 mg/L vs. 0.84 mg/L, P < 0.05). The optimal cut-off value for D-dimer in predicting PE in TPE was 1.18 mg/L, with a sensitivity of 89.7% and a specificity of 77.8% (area under curve, 0.893; 95% confidence interval 0.839-0.947; P < 0.01). The PPV was 49.1%, while the NPV was 96.9% at a D-dimer cut-off of 1.18 mg/L for PE. PE patients had lower median WBC and interleukin (IL)-8 values (5.14 × 10/L vs. 6.1 × 10/L, P < 0.05; 30.2 pg/ml vs. 89.7 pg/ml, P < 0.05) but a higher median IL-2 receptor value (1964.8 pg/ml vs. 961.2 pg/ml, P < 0.01) than those in the non-PE patients.

Conclusions: D-dimer is an objective biomarker for predicting PE in patients with TPE. A D-dimer cut-off of 1.18 mg/L in the TPE population may reduce unnecessary radiological tests due to its excellent sensitivity, specificity, and NPV for PE. The imbalance of prothrombotic and antithrombotic cytokines may partly be attributed to the formation of pulmonary emboli in patients with TPE.
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http://dx.doi.org/10.1186/s12890-021-01546-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141242PMC
May 2021

Electrospun Polymer-Free Nanofibers Incorporating Hydroxypropyl-β-cyclodextrin/Difenoconazole via Supramolecular Assembly for Antifungal Activity.

J Agric Food Chem 2021 Jun 20;69(21):5871-5881. Epub 2021 May 20.

Department of Chemistry, Northeast Agricultural University, Harbin 150030, China.

In this study, flexible and self-standing hydroxypropyl-β-cyclodextrin/difenoconazole inclusion complex (HPβCD/DZ-IC) nanofibers were prepared by polymer-free electrospinning, which exhibited potential to be a new fast-dissolving pesticide formulation. Scanning electron microscopy and optical microscopy were applied to evaluate the morphology of nanofibers, which showed that the resulting HPβCD/DZ-IC nanofibers were bead-free and uniform. In addition, the proton nuclear magnetic resonance (H NMR) spectrum suggested a stoichiometric ratio of 1:0.9 (HPβCD/DZ). Other characterization methods, such as UV-vis absorption, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA), were applied in this study. On the one hand, UV-vis absorption, fluorescence spectroscopy, FT-IR, XRD, and TGA provided useful information for the successful formation of an inclusion complex; on the other hand, the results of TGA indicated the thermal stability of DZ was enhanced after the formation of inclusion complexes. Besides, the phase solubility test could explain the increased water solubility of the nanofibers of inclusion complexes formed by DZ and HPβCD. The results of molecular docking studies demonstrated the most favorable binding interactions when HPβCD combined with DZ. The dissolution test and the antifungal performance test exhibited the characteristics of fast dissolution and the excellent antifungal performance of HPβCD/DZ-IC nanofibers, respectively.
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http://dx.doi.org/10.1021/acs.jafc.1c01351DOI Listing
June 2021

The relationship between crosslinking structure and silk fibroin scaffold performance for soft tissue engineering.

Int J Biol Macromol 2021 May 10;182:1268-1277. Epub 2021 May 10.

International Research Center for Advanced Structural and Biomaterials, School of Materials Science & Engineering, Beihang University, Beijing 100191, China. Electronic address:

Biologically active scaffolds with tunable mechano- and bio-performance remain desirable for soft tissue engineering. Previously, highly elastic and robust silk fibroin (SF) scaffolds were prepared via cryogelation. In order to get more insight into the role of ethylene glycol diglycidyl ether (EGDE) on the structure and properties of SF scaffolds, we investigated the fate of SF scaffolds with different usages of the crosslinking agent in vitro and in vivo. Although SF scaffolds with varied EGDE contents showed similar micro-morphology, increasing EGDE from 1 mmol/g to 5 mmol/g resulted in firstly increased and later decreased content of β-sheet conformation, and linearly increased tensile modulus and decreased elasticity. The dual-crosslinked SF scaffolds with EGDE up to 5 mmol/g did not show in vitro cytotoxicity for NIH3T3 fibroblasts. In vivo subcutaneous implantation of SF scaffolds with <3 mmol/g EGDE displayed excellent degradation behavior and tissue ingrowth after 28 days of implantation. However, with ≥3 mmol/g EGDE, SF scaffolds exhibited obvious post-implantation foreign body reactions, probably associated with slow degradation due to excess chemical crosslinks and less mechanical compatibility. These results suggest that an appropriate dosage of crosslinking agent was critical to achieve balanced mechanical properties, degradability in vivo and immuno-properties of the SF scaffold platform for soft tissue engineering.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.058DOI Listing
May 2021

The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension.

Respir Res 2021 May 4;22(1):134. Epub 2021 May 4.

Department of Pathophysiology, School of Basic Medicine, Fourth Military Medical University, 169 Changle Western Street, Xi'an, Shaanxi, 710032, People's Republic of China.

Background: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.

Methods: In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (HO), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.

Results: Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (HO) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.

Conclusion: The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine HO into the pulmonary vascular microenvironment.
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http://dx.doi.org/10.1186/s12931-021-01708-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094493PMC
May 2021

Association of Hair Concentrations of Antiretrovirals with Virologic Outcomes Among People Living with HIV in Guangxi, China.

Patient Prefer Adherence 2021 23;15:853-861. Epub 2021 Apr 23.

Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi, People's Republic of China.

Background: Hair concentrations of antiretrovirals are an innovative and non-invasive method for measuring cumulative antiretroviral exposure and assessing long-term antiretroviral adherence. This study aimed to examine hair concentrations of antiretrovirals in relation to virologic outcomes among PLHIV in Guangxi, China.

Methods: Cross-sectional data of hair concentrations of antiretrovirals and HIV viral load were collected from 215 PLHIV in Guangxi, China. Multivariate logistic regression analyses were used to examine the association of hair concentrations of antiretrovirals with virologic outcomes.

Results: Of the 215 participants, 215, 67, and 163 PLHIV are receiving lamivudine, zidovudine, and efavirenz, respectively. Multivariate analysis revealed that hair concentrations of lamivudine [odds ratio = 16.52, 95% CI 2.51-108.60, = 0.004] and efavirenz [odds ratio = 14.26, 95% CI 1.18-172.01, = 0.036], but not zidovudine [odds ratio = 1.77, 95% CI 0.06-56.14, = 0.747], were the strongest independent predictor of virologic suppression when controlling for sociodemographic and other HIV-related characteristics.

Conclusion: Hair concentrations of lamivudine and efavirenz were the strongest independent predictor of virologic suppression among Chinese PLHIV. Hair analysis of antiretrovirals may provide a non-invasive, cost-effective tool that predicts virologic suppression among PLHIV in China.
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http://dx.doi.org/10.2147/PPA.S277965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080155PMC
April 2021

Auxin-induced AUXIN RESPONSE FACTOR4 activates APETALA1 and FRUITFULL to promote flowering in woodland strawberry.

Hortic Res 2021 May 1;8(1):115. Epub 2021 May 1.

Liaoning Key Laboratory of Strawberry Breeding and Cultivation, College of Horticulture, Shenyang Agricultural University, Shenyang, 110866, China.

Flowering time is known to be regulated by numerous pathways, such as the autonomous, gibberellin, aging, photoperiod-mediated, and vernalization pathways. These regulatory mechanisms involve both environmental triggers and endogenous hormonal cues. Additional flowering control mechanisms mediated by other phytohormones, such as auxin, are less well understood. We found that in cultivated strawberry (Fragaria × ananassa), the expression of auxin response factor4 (FaARF4) was higher in the flowering stage than in the vegetative stage. Overexpression of FaARF4 in Arabidopsis thaliana and woodland strawberry (Fragaria vesca) resulted in transgenic plants flowering earlier than control plants. In addition, FveARF4-silenced strawberry plants showed delayed flowering compared to control plants, indicating that FaARF4 and FveARF4 function similarly in regulating flowering. Further studies showed that ARF4 can bind to the promoters of the floral meristem identity genes APETALA1 (AP1) and FRUITFULL (FUL), inducing their expression and, consequently, flowering in woodland strawberry. Our studies reveal an auxin-mediated flowering pathway in strawberry involving the induction of ARF4 expression.
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http://dx.doi.org/10.1038/s41438-021-00550-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087778PMC
May 2021

Association between hair cortisol, hair cortisone, and fatigue in people living with HIV.

Stress 2021 Apr 29:1-8. Epub 2021 Apr 29.

Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China.

Cumulative evidence to date largely supports an association between dysregulation of the activity of the hypothalamic-pituitary-adrenal (HPA) axis and fatigue. People living with HIV (PLHIV), in particular, are vulnerable to both HPA axis dysregulation and fatigue. Few investigations have examined the possible role of HPA-axis dysfunction in the occurrence of fatigue in PLHIV. This cross-sectional study aimed to investigate the association between glucocorticoids in hair, retrospective indicators of long-term HPA axis activity and biomarkers of chronic stress, and fatigue in PLHIV. A total of 446 PLHIV from Guangxi China provided hair samples for cortisol and cortisone assay and provided information on fatigue levels, sociodemographic, lifestyle, and HIV-related characteristics. Results showed that before and after controlling sociodemographic, lifestyle, and HIV-related characteristics, hair cortisone levels, but not hair cortisol levels, were associated with fatigue levels in PLHIV. In conclusion, we found that higher cortisone levels are associated with greater fatigue levels in a large cohort of Chinese PLHIV.LAY SUMMARYWe found that hair cortisone levels were significantly associated with fatigue levels in a large cohort of Chinese PLHIV. Hair cortisol levels were, however, not associated with fatigue levels in the PLHIV studied. We thus show that Chinese PLHIV who have higher cortisone levels are associated with higher fatigue levels.
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http://dx.doi.org/10.1080/10253890.2021.1919616DOI Listing
April 2021

Comparison of properties of dust in alveolar of rats and the workplace.

Exp Lung Res 2021 May-Jun;47(5):239-249. Epub 2021 Apr 26.

Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, P.R. China.

Objectives: The purpose of this study was to analyze the α-SiO content, composition, dispersion, morphology, and free radical content of dust between the alveolar and the workplace, to explore the possible changes in the properties (especially the pathogenicity) of dust after it enters the lung.

Methods: We collected the dust in the workplace in HANDAN Coal mine. They were selected by a 400 mesh sieve and was made a suspension of 50 mg/ml, which would be used to perfuse into the trachea of rats. When one week, four weeks, eight weeks, fourteen weeks, twenty weeks after perfusing, we harvested dust in rats alveolar through lung lavage for further processing.

Results: In the animal test, typical fibrous nodules appeared 20 weeks after dust exposure. No inflammatory reaction was observed in the saline group. The results of animal experiments showed that there was no significant difference in the content of α-SiO between dust in the workplace and the lung lavage ( > 0.05). The content of the Fe element gradually increased with dust exposure time. The 12 elements of Al, Mg, Si, Pb, Mn, Ni, Zn, Cu, Cr, Sb, Cd, and AS were reduced in the experiment group compared with the workplace group. The shape of the dust in the workplace was mostly spherical. The shape of the dust extracted from the lung lavage fluid was mostly blocky and angular, and a few dust edges were sharp, and more than 80% of the particle size was smaller than 5 μm, while less than 1% of the particle size was larger than 10 μm. The amount of hydroxyl radical released by lung lavage dust in phosphate buffer was higher than that of the workplace dust.

Conclusions: After the dust entered the alveoli, the content of α-SiO in the dust did not change with dust exposure time, while the content of elements in the dust, the morphology, and dispersion of the dust changed. The ability of dust in alveoli to produce hydroxyl radicals in phosphate buffer was higher than that in the workplace.
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http://dx.doi.org/10.1080/01902148.2021.1916649DOI Listing
April 2021

Mindfulness-based interventions for social anxiety disorder: A systematic review and meta-analysis.

Psychiatry Res 2021 Jun 20;300:113935. Epub 2021 Apr 20.

Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China. Electronic address:

Various psychiatric disorders are treated with mindfulness-based interventions (MBIs), although the efficacy of MBIs in patients with social anxiety disorder (SAD) is unclear. In this meta-analysis, we investigated the efficacy of MBIs on SAD symptoms. Systematic searches were performed in various databases, and 11 eligible randomized controlled trials (RCTs) and 5 single-arm trials were identified. The between-groups analysis of the 11 RCTs showed that Hedges' g = 0.00, while the within-group analysis showed a large pre-post effect size (g = 1.20).MBIs were superior to the no-treatment comparator (g = 0.89), equivalent to specific active treatment (g = -0.19), and less effective than evidence-based treatment (i.e., cognitive behavioral therapies) (g = -0.29).MBIs significantly alleviated depressive symptoms and improved mindfulness, quality of life, and self-compassion. Meta-regression analysis showed a dose-response relationship between the alleviation of SAD symptoms and the duration of the MBIs (β = 0.659). Follow-up analysis showed that the effects of MBIs on SAD persisted for 12 months (g = 0.231). An analysis of the 5 single-arm trials found that MBIs had a medium effect in alleviating SAD symptoms (g = 0.48). Future research is needed regarding the design of large RCTs of MBIs on SAD patients.
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http://dx.doi.org/10.1016/j.psychres.2021.113935DOI Listing
June 2021

Potential of the tumor‑derived extracellular vesicles carrying the miR‑125b‑5p target TNFAIP3 in reducing the sensitivity of diffuse large B cell lymphoma to rituximab.

Int J Oncol 2021 Jun 23;58(6). Epub 2021 Apr 23.

Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Diffuse large B‑cell lymphoma (DLBCL) is the most common and aggressive form of non‑Hodgkin's lymphoma. Extracellular vesicles (EVs) derived from cancer cells are known to modify the tumor microenvironment. The aim of the present study was to investigate the role of miR‑125b‑3p carried by EVs in DLBCL and . TNFAIP3 expression in patient lesions was measured and the upstream miR that regulates TNFAIP3 was predicted using the starBase database. EVs were isolated from DLBCL cells and identified. DLBCL cells were transfected with pcDNA to overexpress TNFAIP3 or inhibit miR‑125b‑5p expression, incubated with EVs, and treated with rituximab to compare cell growth and TNFAIP3/CD20 expression. DLBCL model mice were administered EVs, conditioned medium, and rituximab to observe changes in tumor size, volume, and weight. TNFAIP3 was downregulated in patients with DLBCL and its levels further decreased in patients with drug‑resistant DLBCL. Overexpression of TNFAIP3 in DLBCL cells enhanced the inhibitory effect of rituximab and increased CD20 expression. miR‑125b‑5p targeted TNFAIP3. Inhibition of miR‑125b‑5p enhanced the inhibitory effect of rituximab in DLBCL cells. The EV‑carried miR‑125b‑5p reduced the sensitivity of DLBCL cells to rituximab, which was averted by overexpression of TNFAIP3. EVs reduced the sensitivity of DLBCL model mice to rituximab via the miR‑125b‑5p/TNFAIP3 axis. The study findings indicate that the tumor‑derived EVs carrying miR‑125b‑5p can enter DLBCL cells and target TNFAIP3, thus reducing the sensitivity of DLBCL to rituximab, which may provide a novel therapeutic approach for DLBCL.
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http://dx.doi.org/10.3892/ijo.2021.5211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078569PMC
June 2021

Nonmedical use of prescription drugs and biopsychosocial correlates among females who are sex workers in China.

Subst Abus 2021 Apr 19:1-7. Epub 2021 Apr 19.

Research Institute for Environment and Health, Nanjing University of Information Science and Technology, Nanjing, China.

Nonmedical use of prescription drugs (NMPUD) has become a critical public health concern. Chinese literature has paid growing attention to NMUPD, but scarce research has focused on females who are sex workers (FSWs), who have a high risk of substance use. The current study aimed to examine NMUPD and its biopsychosocial correlates in Chinese FSWs. A total of 410 FSWs (mean age = 33.58 years) from Guangxi, China, completed an anonymous, self-administered survey evaluating NMUPD, somatic symptoms, and psychosocial distress. Overall, 46.6% of FSWs reported lifetime NMUPD and 17.6% reported past-3-month NMUPD. The most commonly reported medications that were used nonmedically were analgesics (46.3%, lifetime; 17.6%, past 3 months). A majority of FSWs (69.1%) reported "relieving pain" as the motive of their NMUPD. FSWs reporting NMUPD were more likely to be younger, be unmarried, have higher income, and work in multiple venues/high-paying venues. Somatic symptoms and psychosocial distress were associated with NMUPD in Chinese FSWs. NMUPD was prevalent in Chinese FSWs and was associated with biopsychosocial factors. Critical attention should be paid to NMUPD in FSWs. Future NMUPD prevention intervention among FSWs may benefit from attending to biopsychosocial factors.
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http://dx.doi.org/10.1080/08897077.2021.1903655DOI Listing
April 2021

Occupational stress, burnout, and organizational readiness for change: A longitudinal study among HIV HCPs in China.

Psychol Health Med 2021 Apr 19:1-12. Epub 2021 Apr 19.

Guangxi Center of Disease Control and Prevention, Nanning, Guangxi, China.

Literature suggests that organizational readiness for change (ORC) could facilitate adaptation and implementation of new projects or practices in clinical settings. Limited data are available regarding the longitudinal associations between ORC and psychosocial conditions of HCPs. Using six waves of longitudinal data collected between 2013 and 2016 from 357 HIV HCPs in Guangxi, China, we identify sociodemographic and occupational characteristics that impact ORC and examine how occupational stress and burnout affect ORC adjusting for potential cofounders. A mixed effect model was used to assess the associations of ORC with psychosocial variables controlling for key background variables, and within-cluster and within-subject correlation over time. The ORC level was stable over time. Ethnical minority HCPs reported lower ORC compared with those of Han ethnicity. HCPs with administrative responsibility reported significantly lower ORC compared with the ones without administrative responsibility. HCPs with high school education attainment showed lower ORC compared to those with some college education. The ORC level was negatively associated with occupational stress and burnout controlling all the background variables. It is important to integrate reducing stress and alleviating burnout in the workplace into efforts to promote the acceptance and adaptation of new intervention.
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http://dx.doi.org/10.1080/13548506.2021.1903059DOI Listing
April 2021

Building a social media-based HIV risk behavior index to inform the prediction of HIV new diagnosis: a feasibility study.

AIDS 2021 05;35(Suppl 1):S91-S99

Big Data Health Science Center, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA.

Objective: Analysis of geolocation-based social media Big Data provides unprecedented opportunities for a broad range of domains including health as health is intrinsically linked to the geographic characteristics of places. HIV infection is largely driven by HIV risk behaviors, such as unsafe sexual behavior and drug abuse/addiction. This study explores the feasibility of building a Social media-based HIV Risk Behavior (SRB) index at the United States county level for informing HIV surveillance and prevention, considering social determinants of health and geographic locations.

Methods: The SRB index, defined as the proportion of risk behavior related Twitter users among all Twitter users, was calculated at the county level for each year. To evaluate the performance of the new SRB index, the relationships between the county-level SRB and rate of new HIV diagnoses from AIDSVu were analyzed using multivariate regression while simultaneously considering five socioeconomic status (SES) factors (percentage uninsured, median household income, Gini coefficient, percentage living in poverty, percentage high school graduates) in the model. Moran's I and geographically weighted regression analyses (GWR) were leveraged to examine spatial autocorrelations and reveal the potential spatial heterogeneity (geographical variability) of the associations.

Results: County-level multivariate regression results revealed that SRB has the strongest association with new HIV diagnosis rate (r > 0.36; P < 0.0001) in both years compared with the five SES factors. Hierarchical regression analysis suggested that the SRB index explains significant additional variance in addition to the five SES factors. The results from GWR analysis not only greatly improved the model explanation power (bringing the adjusted r-square from 0.25 to 0.47 in 2016 and 0.26 to 0.55 in 2017) but also revealed SRB index is the most spatially consistent measurement compared with the five SES factors in terms of impact direction (negative or positive correlation).

Conclusion: It is feasible to build a social media-based HIV risk behavior index (SRB) as a new indicator for HIV surveillance at county level. The SRB index improves the regression model explanation power of new HIV diagnosis by providing additional information beyond the traditional social determinant measures, such as SES indicators. SRB index will allow researchers to utilize data captured within existing social media platforms to better understand the geospatial patterns of HIV risk behavior and to inform population-based HIV surveillance and other efforts of HIV prevention and control.
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http://dx.doi.org/10.1097/QAD.0000000000002787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172091PMC
May 2021

Adolescent HIV-related behavioural prediction using machine learning: a foundation for precision HIV prevention.

AIDS 2021 05;35(Suppl 1):S75-S84

Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.

Background: Precision prevention is increasingly important in HIV prevention research to move beyond universal interventions to those tailored for high-risk individuals. The current study was designed to develop machine learning algorithms for predicting adolescent HIV risk behaviours.

Methods: Comprehensive longitudinal data on adolescent risk behaviours, perceptions, peer and family influence, and neighbourhood risk factors were collected from 2564 grade-10 students at baseline followed for 24 months over 2008-2012. Machine learning techniques [support vector machine (SVM) and random forests] were applied to innovatively leverage longitudinal data for robust HIV risk behaviour prediction. In this study, we focused on two adolescent risk behaviours: had ever had sex and had multiple sex partners. Twenty percent of the data were withheld for model testing.

Results: The SVM model with cost-sensitive learning achieved the highest sensitivity, at 79.1%, specificity of 75.4% with AUC of 0.86 in predicting multiple sex partners on the training data (10-fold cross-validation), and sensitivity of 79.7%, specificity of 76.5% with AUC of 0.86 on the testing data. The random forest model obtained the best performance in predicting had ever had sex, yielding the sensitivity of 78.5%, specificity of 73.1% with AUC of 0.84 on the training data and sensitivity of 82.7%, specificity of 75.3% with AUC of 0.87 on the testing data.

Conclusion: Machine learning methods can be used to build effective prediction model(s) to identify adolescents who are likely to engage in HIV risk behaviours. This study builds a foundation for targeted intervention strategies and informs precision prevention efforts in school-setting.
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http://dx.doi.org/10.1097/QAD.0000000000002867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133351PMC
May 2021

County-level predictors of retention in care status among people living with HIV in South Carolina from 2010 to 2016: a data-driven approach.

AIDS 2021 05;35(Suppl 1):S53-S64

South Carolina SmartState Center for Healthcare Quality.

Objective: The aim of this study was to examine the geospatial variation of retention in care (RIC) across the counties in South Carolina (SC) from 2010 to 2016 and identify the relevant county-level predictors.

Design: Aggregated data on county-level RIC among HIV patients from 2010 to 2016 were retrieved from an electronic HIV/AIDS reporting system in SC Department of Health and Environmental Control. Sociological framework of health was used to select potential county-level predictors from multiple public datasets.

Methods: Geospatial mapping was used to display the spatial heterogeneity of county-level RIC rate in SC. Generalized linear mixed effect regression with least absolute shrinkage and selection operator (LASSO) was employed to identify county-level predictors related to the change of RIC status over time. Confusion matrix and area under the curve statistics were used to evaluate model performance.

Results: More than half of the counties had their RIC rates lower than the national average. The change of county-level RIC rate from 2010 to 2016 was not significant, and spatial heterogeneity in RIC rate was identified. A total of 22 of the 31 county-level predictors were selected by LASSO for predicting county-level RIC status. Counties with lower collective efficacy, larger proportions of men and/or persons with high education were more likely to have their RIC rates lower than the national average. In contrast, numbers of accessible mental health centres were positively related to county-level RIC status.

Conclusion: Spatial variation in RIC could be identified, and county-level factors associated with accessible healthcare facilities and social capital significantly contributed to these variations. Structural and individual interventions targeting these factors are needed to improve the county-level RIC and reduce the spatial variation in HIV care.
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http://dx.doi.org/10.1097/QAD.0000000000002832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098716PMC
May 2021

Utilizing electronic health record data to understand comorbidity burden among people living with HIV: a machine learning approach.

AIDS 2021 05;35(Suppl 1):S39-S51

South Carolina SmartState Center for Healthcare Quality.

Objectives: An understanding of the predictors of comorbidity among people living with HIV (PLWH) is critical for effective HIV care management. In this study, we identified predictors of comorbidity burden among PLWH based on machine learning models with electronic health record (EHR) data.

Methods: The study population are individuals with a HIV diagnosis between January 2005 and December 2016 in South Carolina (SC). The change of comorbidity burden, represented by the Charlson Comorbidity Index (CCI) score, was measured by the score difference between pre- and post-HIV diagnosis, and dichotomized into a binary outcome variable. Thirty-five risk predictors from multiple domains were used to predict the increase in comorbidity burden based on the logistic least absolute shrinkage and selection operator (Lasso) regression analysis using 80% data for model development and 20% data for validation.

Results: Of 8253 PLWH, the mean value of the CCI score difference was 0.8 ± 1.9 (range from 0 to 21) with 2328 (28.2%) patients showing an increase in CCI score after HIV diagnosis. Top predictors for an increase in CCI score using the LASSO model included older age at HIV diagnosis, positive family history of chronic conditions, tobacco use, longer duration with retention in care, having PEBA insurance, having low recent CD4+ cell count and duration of viral suppression.

Conclusion: The application of machine learning methods to EHR data could identify important predictors of increased comorbidity burden among PLWH with high accuracy. Results may enhance the understanding of comorbidities and provide the evidence based data for integrated HIV and comorbidity care management of PLWH.
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http://dx.doi.org/10.1097/QAD.0000000000002736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058944PMC
May 2021

Application of machine-learning techniques in classification of HIV medical care status for people living with HIV in South Carolina.

AIDS 2021 05;35(Suppl 1):S19-S28

Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, Columbia, South Carolina, USA.

Objectives: Ending the HIV epidemic requires innovative use of data for intelligent decision-making from surveillance through treatment. This study sought to examine the usefulness of using linked integrated PLWH health data to predict PLWH's future HIV care status and compare the performance of machine-learning methods for predicting future HIV care status for SC PLWH.

Design: We employed supervised machine learning for its ability to predict PLWH's future care status by synthesizing and learning from PLWH's existing health data. This method is appropriate for the nature of integrated PLWH data because of its high volume and dimensionality.

Methods: A data set of 8888 distinct PLWH's health records were retrieved from an integrated PLWH data repository. We experimented and scored seven representative machine-learning models including Bayesian Network, Automated Neural Network, Support Vector Machine, Logistic Regression, LASSO, Decision Trees and Random Forest to best predict PLWH's care status. We further identified principal factors that can predict the retention-in-care based on the champion model.

Results: Bayesian Network (F = 0.87, AUC = 0.94, precision = 0.87, recall = 0.86) was the best predictive model, followed by Random Forest (F = 0.78, AUC = 0.81, precision = 0.72, recall = 0.85), Decision Tree (F = 0.76, AUC = 0.75, precision = 0.70, recall = 0.82) and Neural Network (cluster) (F = 0.75, AUC = 0.71, precision = 0.69, recall = 0.81).

Conclusion: These algorithmic applications of Bayesian Networks and other machine-learning algorithms hold promise for predicting future HIV care status at the individual level. Prediction of future care patterns for SC PLWH can help optimize health service resources for effective interventions. Predictions can also help improve retention across the HIV continuum.
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http://dx.doi.org/10.1097/QAD.0000000000002814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162887PMC
May 2021

Using a machine learning approach to explore predictors of healthcare visits as missed opportunities for HIV diagnosis.

AIDS 2021 05;35(Suppl 1):S7-S18

South Carolina SmartState Center for Healthcare Quality.

Objectives: A significant number of individuals with a new HIV diagnosis are still late presenters despite numerous healthcare encounters prior to HIV diagnosis. We employed a machine learning approach to identify the predictors for the missed opportunities for earlier HIV diagnosis.

Methods: The cohort comprised of individuals who were diagnosed with HIV in South Carolina from January 2008 to December 2016. Late presenters (LPs) (initial CD4 ≤200 cells/mm3 within one month of HIV diagnosis) with any healthcare visit during three years prior to HIV diagnosis were defined as patients with a missed opportunity. Using least absolute shrinkage and selection operator (LASSO) regression, two prediction models were developed to capture the impact of facility type (model 1) and physician specialty (model 2) of healthcare visits on missed opportunities.

Results: Among 4,725 eligible participants, 72.2% had at least one healthcare visit prior to their HIV diagnosis, with most of the healthcare visits (78.5%) happening in the emergency departments (ED). A total of 1,148 individuals were LPs, resulting in an overall prevalence of 24.3% for the missed opportunities for earlier HIV diagnosis. Common predictors in both models included ED visit, older age, male gender, and alcohol use.

Conclusions: The findings underscored the need to reinforce the universal HIV testing strategy ED remains an important venue for HIV screening, especially for medically underserved or elder population. An improved and timely HIV screening strategy in clinical settings can be a key for early HIV diagnosis and play an increasingly important role in ending HIV epidemic.
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http://dx.doi.org/10.1097/QAD.0000000000002735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172090PMC
May 2021

Power of Big Data in ending HIV.

AIDS 2021 05;35(Suppl 1):S1-S5

Big Data Health Science Center.

The articles in this special issue of AIDS focus on the application of the so-called Big Data science (BDS) as applied to a variety of HIV-applied research questions in the sphere of health services and epidemiology. Recent advances in technology means that a critical mass of HIV-related health data with actionable intelligence is available for optimizing health outcomes, improving and informing surveillance. Data science will play a key but complementary role in supporting current efforts in prevention, diagnosis, treatment, and response needed to end the HIV epidemic. This collection provides a glimpse of the promise inherent in leveraging the digital age and improved methods in Big Data science to reimagine HIV treatment and prevention in a digital age.
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http://dx.doi.org/10.1097/QAD.0000000000002888DOI Listing
May 2021

Targeting adenosine with adenosine deaminase 2 to inhibit growth of solid tumors.

Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Halozyme Therapeutics, Inc.

Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Here we show that increased ADA2 expression is associated with increased patient survival and enrichment of adaptive immune response pathways in several solid tumor types. Several ADA2 variants were created to improve catalytic efficiency, and PEGylation was used to prolong systemic exposure. In mice, PEGylated ADA2 (PEGADA2) inhibited tumor growth by targeting adenosine in an enzyme activity-dependent manner and thereby modulating immune responses. These findings introduce endogenous ADA2 expression as a prognostic factor and PEGADA2 as a novel immunotherapy for cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0340DOI Listing
April 2021