Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption

HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination. ABSTRACT The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia. IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination.
Alcohol Withdrawal Syndrome: Improving Recognition and Treatment in the Emergency Department

Alcoholism continues to be a persistent health problem in the United States, accounting for up to 62% of emergency department (ED) visits. This quality improvement (QI) project examined whether identifying the benefit for early use of Alcohol Use Disorders Identification Test (AUDIT C) and Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIW-ar) in the ED would avoid escalation of care and offset poor outcomes of alcohol withdrawal syndrome (AWS). A preimplementation chart review (N = 99) showed an average of 12%–15% of patients requiring escalation of care at the project site. The QI project utilized a single-group, pre-/posttest design. The setting was a Southwest Veterans Affair tertiary care referral center. Thirty-five ED staff members were surveyed for baseline knowledge and attended education sessions, led by an advanced practice nurse, on the use of AUDIT-C and CIWA-ar. Posteducation, patients admitted to the hospital were screened with AUDIT-C and treated with CIWA-ar. Postimplementation, charts were reviewed for admitted patients (N = 42) on the use of AUDIT-C, CIWA-ar, length of stay (LOS), and area patient treated. Although the test scores after didactic education were statistically significant (p ⩽ 0.050), there was no significant difference in the use of AUDIT-C or CIWA-ar in the ED, nor a significant decrease in LOS for those patients with CIWA-ar ordered. However, the potential for clinical benefit could not be disavowed. Barriers to implementation included survey fatigue, inability to embed AUDIT-C in the electronic medical record, inconsistency in completing AUDIT-C, interrater reliability, and patient fear of stigmatization. Advanced practice nurses provide an integral role to augment early identification and treatment of AWS in the ED.
Bonding Performance of Simplified Adhesive Systems in Noncarious Cervical Lesions at 2-year Follow-up: A Double-blind Randomized Clinical Trial.

OBJECTIVES: This study aimed to evaluate the bonding performance of a universal adhesive used according to self-etching or etch-and-rinse protocols in noncarious cervical lesions (NCCLs) and to compare the two protocols with their respective gold standard techniques. METHODS AND MATERIALS: This randomized, double-blind clinical study enrolled 34 participants who met the inclusion criteria, 29 of whom returned after two years. They received 152 restorations bonded with one of the three adhesives (Scotchbond Universal Adhesive, Adper Single Bond 2, or Clearfil SE Bond) and one of the two bonding techniques tested. The NCCLs were restored with nanocomposite resin (Filtek Supreme). Final contours were done with a fine diamond rotary instrument and polished with rubber points. The restorations were evaluated using the FDI World Dental Federation criteria at baseline (seven days after the restoration procedure), 6, 12, and 24 months. Descriptive statistics, Kruskal-Wallis, Friedman analysis of variance, and least significant difference tests were performed. RESULTS: No statistically significant differences were found in esthetics or the functional and biological evaluated criteria among the adhesive systems and techniques. CONCLUSIONS: The Scotchbond Universal system behaved similarly to the conventional etch-and-rinse or self-etching systems in all the adhesion strategies in the evaluated periods.
Selective Emergence of the Halogen Bond in Ground and Excited States of Noble-Gas-Chlorine Systems.

Molecular-beam scattering experiments and theoretical calculations prove the nature, strength, and selectivity of the halogen bonds (XB) in the interaction of halogen molecules with the series of noble gas (Ng) atoms. The XB, accompanied by charge transfer from the Ng to the halogen, is shown to take place in, and measurably stabilize, the collinear conformation of the adducts, which thus becomes (in contrast to what happens for other Ng-molecule systems) approximately as bound as the T-shaped form. It is also shown how and why XB is inhibited when the halogen molecule is in the 3 Πu excited state. A general potential formulation fitting the experimental observables, based on few physically essential parameters, is proposed to describe the interaction accurately and is validated by ab initio computations.
1H–13C HMBC NMR experiments as a structural and analytical tool for the characterization of elusive trans/cis hydroperoxide isomers from oxidized unsaturated fatty acids in solution

The radical‐dependent oxidation of unsaturated fatty acids is a fundamental reaction in lipid chemistry, biochemistry, and technology. We report herein the first successful application of 1H–13C HMBC NMR experiment for the identification and quantification of complex and minor (3.9% to 0.85%) components of cis and trans primary hydroperoxide isomers of oxidized oleate and linoleate methyl esters in solution, without the need of laborious isolation of the individual components.
Towards robust distributed systems (abstract)

Current distributed systems, even the ones that work, tend to be very fragile: they are hard to keep up, hard to manage, hard to grow, hard to evolve, and hard to program. In this talk, I look at several issues in an attempt to clean up the way we think about these systems. These issues include the fault model, high availability, graceful degradation, data consistency, evolution, composition, and autonomy. These are not (yet) provable principles, but merely ways to think about the issues that simplify design in practice. They draw on experience at Berkeley and with giant-scale systems built at Inktomi, including the system that handles 50% of all web searches.
Development of a comprehensive mobile assessment of pressure (CMAP) system for pressure injury prevention for veterans with spinal cord injury

Objective: This paper reports the iterative redesign, feasibility and usability of the Comprehensive Mobile Assessment of Pressure (CMAP) system’s mobile app used by Veterans with SCI. Design: This three-year, multi-staged study used a mixed-methods approach. Setting: Minneapolis VA Health Care System, Minneapolis, Minnesota. Participants: Veterans with spinal cord injury (N = 18). Interventions: Veterans with spinal cord injury engaged in iterative focus groups and personal interviews, sharing their needs and desires for the CMAP app redesign. App developers used these data for the redesign. The redesigned CMAP app was tested for six-weeks in users’ homes. Outcome Measures: Quantitative (surveys) and qualitative (interviews) methods measured feasibility for self-management of seating pressure. Qualitative data were audio recorded, transcribed, anonymized, and coded. Survey data were analyzed using summary statistics. Results: After the CMAP system’s redesign, the in-home use interview found: (1) any tool that can assist in prevention and monitoring of skin ulcers is important; (2) the desired key features are present in the app; (3) the main barrier to CMAP use was inconsistent functionality; (4) when functioning as expected, the live pressure map was the central feature, with reminders to weight shift also of high importance. The survey found: power wheelchair users tended to score closer than manual wheelchair users to the positive response end ranges on two separate surveys. Conclusions: Overall both the power and manual wheelchair users reported that they wanted to use the system, felt confident using the system, and that the functions of the system were well integrated.
Effect of progressive resistance training on health-related quality of life in the first year after breast cancer surgery – results from a randomized controlled trial

Abstract Aims: To examine the effect of progressive resistance training (PRT) on health related quality of life and a predefined symptom cluster of pain–sleep–fatigue. Methods: This study was a planned secondary analysis of a randomized controlled trial examining the effect of PRT on prevention of arm lymphedema in a population of women between 18 and 75 years undergoing breast cancer surgery with axillary lymph node dissection. Participants were allocated by computer randomization to usual care control or a PRT intervention in a 1:1 ratio. The intervention, initiated in the third post-operative week, consisted of three times PRT per week, supervised in groups in the first 20 weeks, and self-administered in the following 30 weeks. Questionnaire assessments were made at baseline, 20 weeks and 12 months, with the European Organization for Research and Treatment in Cancer Core questionnaire (EORTC QLQ C30) and the Functional Assessment of Chronic Illness Therapy-(FACIT) fatigue questionnaire. The symptom cluster of pain–sleep–fatigue was measured with a constructed score adding EORTC C30 subscales of insomnia, pain, and fatigue. Data were treated as repeated measurements and analyzed with mixed models. Results: Among 158 recruited participants, we found a clinically relevant increased emotional functioning with nine points at both follow-ups (p = .02), and 16 and 11 points at 20 weeks and 12 months respectively (p = .04) in social functioning. Furthermore, in the subgroup of women with the symptom cluster pain–sleep–fatigue present at baseline, a significant effect was found for global health status (p = .01) and social functioning (p = .02). Conclusion: To our knowledge, this is the first study to report clinically relevant effects of PRT on social and emotional functioning in the first postoperative year after breast cancer surgery. Furthermore, a subgroup of women with the pain–sleep–fatigue symptom cluster had particular benefit from PRT on global health status and social functioning.
Prevalence and determinants of Caesarean delivery in Punjab, Pakistan.

Background Caesarean section (C-section) is a life-saving obstetric procedure that reduces maternal mortality and improves reproductive health. Although, vaginal delivery is still an important safe and low-cost method of delivery, C-section is sometimes performed when it is not even required, which creates health challenges for pregnant women and their newborn infants. Aims To estimate the effect of a set of institutional, demographic, socioeconomic and spatial variables on C-section delivery (n = 2424) in Punjab, Pakistan. Methods We used data from the Multiple Indicator Cluster Survey Punjab 2014 and multiple logistic regression analysis. Analysis was carried out using STATA version 12. Results Higher maternal age at first marriage, higher number of antenatal care visits, and higher wealth quintiles were associated with higher risk of C-section. Women in Punjab were more likely to deliver through C-section in private health facilities and there was no significant difference between urban and rural areas. There was a significant difference in the risk of C-section in different divisions of Punjab, for example, DG Khan and Rawalpindi showed the lowest risk compared with the reference division of Bahawalpur, which is partially explained by the developmental disparities and access to public healthcare facilities. Conclusions The government should facilitate access to healthcare facilities in areas that are easily accessible, especially, to rural women.
Prescription opioid misuse and comorbid substance use: Past 30‐day prevalence, correlates and co‐occurring behavioral indicators in the 2016 National Survey on Drug Use and Health

BACKGROUND AND OBJECTIVES Prescription opioid misuse has not been well examined in the context of comorbid substance use in representative samples of substance users. Past 30-day comorbid prescription opioid misuse and recreational substance use (eg, alcohol, marijuana, cocaine, etc.) was studied in a representative sample of substance users in the United States using the 2016 National Survey on Drug Use and Health (NSDUH). METHODS Prevalence of prescription opioid misuse with and without comorbid substance use was estimated with the 2016 NSDUH. Generalized linear modeling was used to describe demographic correlates of opioid and comorbid substance use and explore the relation of opioid and comorbid substance use with social and behavioral health indicators. RESULTS The majority of past month prescription opioid misusers reported use of other substances including cigarettes, alcohol, marijuana, or hard drugs (cocaine, methamphetamine, etc.). Males and younger respondents had a significantly higher risk of reporting past month prescription opioid misuse with illicit drug or polydrug use (p's < .01). Prescription opioid and polydrug users had the greatest odds of stealing property, selling drugs, having suicidal ideations, major depressive episode, and perceived treatment need in the past year compared to all other categories of prescription opioid misuse categories. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Prescription opioid misuse is likely a part of a larger set of psychological, behavioral, and mental health problems. More attention should be given to the profiles of recreational (non-medical) substance use involving prescription opioids to curtail the current opioid crisis and prevent other similar epidemics in the future. (Am J Addict 2019;XX:1-8).
Smad3 Mediates Cardiac Inflammation and Fibrosis in Angiotensin II–Induced Hypertensive Cardiac Remodeling

Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-&bgr;/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin II infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P<0.05), an increase in left ventricular mass (P<0.05), and the development of cardiac fibrosis and inflammation, including upregulation of transforming growth factor-&bgr;1, connective tissue growth factor, collagen I/III, &agr;-smooth muscle actin, interleukin 1&bgr;, tumor necrosis factor-&agr;, monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and an increase in macrophage and T-cell infiltration in left ventricular tissues (all P<0.01, respectively). Additional studies in vitro also revealed that angiotensin II–induced cardiac fibrosis and inflammation were prevented in Smad3 KO cardiac fibroblasts. Inactivation of both Smad3 and nuclear factor &kgr;B/p65 signaling pathways was a key mechanism by which Smad3 KO mice were protected from angiotensin II–mediated hypertensive cardiac remodeling. In conclusion, Smad3 plays an essential role in hypertensive cardiac remodeling. Results from this study suggest that targeting Smad3 may be a novel therapeutic strategy for hypertensive cardiovascular disease.
Swimming Fast When it Counts: A 7-Year Analysis of Olympic and World Championships Performance.

PURPOSE: To quantify the pattern of change in performance between season best qualifying time and the major championships of the year, and assess the influence of time between performance peaks, ranking at the major events, stroke, event distance, sex, age, and country. METHODS: A total of 7,832 official competition times recorded at 4 FINA World Championships and 2 Olympic Games between 2011 and 2017 were compared with each swimmer's season best time prior to the major event of the year. Percentage change in performance was related with the time elapsed between season best and major competition, race event, sex, age and country using linear mixed modelling. RESULTS: Faster performance (-0.79±0.67%; mean ± SD) at the major competition of the year occurred in 38% of all observations vs. 62% no change or regression (1.10±0.88%). The timing between performance peaks (<34 to >130 days) had little effect on performance progressions (P=0.83). Only medal winners (-0.87±0.91%), finalists (-0.16±0.97%), and U.S.A. swimmers (-0.44±1.08%) progressed between competitions. Stroke, event distance, sex and age had trivial impact on performance progression. CONCLUSIONS: Performance progressions at Olympic Games and World Championships were not determined by timing between performance peaks. Performance progression at a major competition appears necessary to win a medal or make the final, independent of race event, sex and age.
The complete mitochondrial genome of David’s myotis, Myotis davidii (Myotis, Vespertilionidae)

Abstract In this study, we report the complete mitochondrial genome sequence of David's myotis, Myotis davidii. The genome is found to be 17,531 bp in length and has a base composition of A (33.8%), G (13.2%), C (23.2%), and T (29.8%). Similar to other bats, it contains a typically conserved structure including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). Most of the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes. All protein-coding genes start with an ATG codon except for ND2, ND3 and ND5, which initiate with ATT or ATA instead, and terminate with the typical stop codon (TAA/TAG) or a single T (T–) or an unexpected codon of AGA. The complete mitochondrial genome sequence provided here would be useful for further phylogenetic analysis and population genetic studies in M. davidii.
Effects of Measurement Timing on Subgroup Identification Using Growth Mixture Modeling: An Empirical Application to Alcohol Use

Growth mixture modeling (GMM) identifies latent classes exhibiting distinct longitudinal patterns on an outcome. Subgroups identified by GMM may be artifactually influenced by measurement timing (e.g., timing of the initial assessment, length of the interval from the first to the last assessment, and total number of assessments) as well as the theoretically posited developmental patterns of the behavior. The current study investigated this possibility using alcohol data from the 1997 National Longitudinal Survey of Youth (n = 2686; 49.44% female; 71.84% White). Three assessment configurations were examined: all 12 waves, first 6 waves, and last 7 waves. Five subgroups were identified using all 12 waves: Normative (71.33%), Low-Increasing (8.45%), Low-Steady (8.97%), High-Slowly Decreasing (7.67%), and Extreme-Sharply Decreasing (3.57%). When comparing participants’ subgroup membership for all 12 waves to the first six waves, 14% of the sample was differentially classified. When comparing all 12 waves to the last seven waves, 62% of the sample was differentially classified. Alterations in the timing of the initial assessment had a substantial impact on latent class estimation, underscoring the importance of selecting the developmental window a priori based on theory and empirical knowledge. The time-bounded nature of mixture modeling solutions (i.e., a selected developmental window within the course of a phenomenon) suggests that the latent subgroups should not be interpreted as representing subgroups that are present in the population. Future directions and strategies for testing alternative interpretations are presented.
Intersection of immune checkpoints and CD8+ T cell noncytolytic suppression of HIV-1 infection: putting on the brakes versus the nuclear option.

In healthy donors, cytotoxic granules are found in about 95% of memory CD8þ T cells in blood. These cytotoxic granules can be detected by the mAb to T cell intracellular antigen (TIA)-1, alsoknownas anti-GMP17, fromthegene nkg7 [3]. However, most immunophenotyping studies have used mAb to perforin and granzyme B to visualize CD8 cytotoxic T lymphocytes (CTLs), finding these effector molecules in CD45RAþCD62L CD27 CD28 terminally differentiated CD8þ T cells in blood [4], with less expression in other subsets of CD8þ T cells. Over the last few years, it has been found that many CD28þ memory CD8þT cells can be positive for granzymes A and K, without granzyme B, and have intermediate staining for TIA-1 and perforin [5,6], particularly including tetramerpositive cells for influenza and EBV peptide antigens [5].