bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Authors: Cindi Zinhle , Kawuma Aida N. , Maartens Gary , Bradford Yuki , Sokhela Simiso , Chandiwana Nomathemba , Venter Willem D. Francois , Wasmann Roeland E. , Denti Paolo , Wiesner Lubbe , Ritchie Marylyn D. , Haas David W. , Sinxadi Phumla 
Published: April 2023

Background
Tenofovir is a component of preferred combination antiretroviral therapy (ART) regimens in Africa. Few pharmacogenetic studies have been conducted on tenofovir exposure in Africa, where genetic diversity is greatest.

Objective
We characterized the pharmacogenetics of plasma tenofovir clearance in Southern Africans receiving tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF).

Methods
Adults randomized to TAF or TDF in dolutegravir-containing arms of the ADVANCE trial (NCT03122262) were studied. Linear regression models stratified by study arm examined associations with unexplained variability in tenofovir clearance. We investigated genetic associations with polymorphisms selected a priori followed by genome-wide associations.

Results
A total of 268 participants (138 and 130 in the TAF and TDF arm, respectively) were evaluable for associations. Among polymorphisms previously associated with any drug-related phenotype, IFNL4 rs12979860 was associated with more rapid tenofovir clearance in both arms (TAF: P = 0.003; TDF: P = 0.003). Genome-wide, the lowest P values for tenofovir clearance in TAF and TDF arms were LINC01684 rs9305223 (P = 3.0 × 10−8) and intergenic rs142693425 (P = 1.4 × 10−8), respectively.

Conclusion
Among Southern Africans randomized to TAF or TDF in ADVANCE, unexplained variability in tenofovir clearance was associated with a polymorphism in IFNL4, an immune-response gene. It is unclear how this gene would affect tenofovir disposition.
Comparison Between Patient and Plastic Surgeon Aesthetic Analysis in Rhinoplasty Consultation
Authors: Alosfoor Mariam , Alkhalifah Ahmad Ali , Algadiem Emran Ali , Alarfaj Abdullah A. , Alsalman Abdullah 
Published: April 2023

Background:
The surgeon’s aesthetic analysis of the nose is based on scientific measures of its proportions and dimensions. Because the primary aim of rhinoplasty is targeted at the patient’s satisfaction with self-image, patients’ perception and satisfaction are of paramount importance. The aim of this study was to evaluate surgeon versus patient nasal aesthetic analysis.

Method:
A cross-sectional study was conducted on 57 primary rhinoplasty consultations during the period June and September 2017 at the Plastic Surgery Clinic in King Fahad Hospital-Hofuf. The surgeon and the patients were handed identical questionnaires before the consultations. The questionnaire has 27 components regarding the nasal appearance.

Results:
The surgeon’s and the patients’ perceptions regarding reliability was assessed by Cohen’s Kappa and Pearson’s correlation coefficient. There was moderate agreement with the overall appearance of the nose (κ = 0.2–0.39). The most agreed-upon components were “dorsal hump” (κ = 0.6, P = 0.001) and “tip drops down” (κ = 0.41, P = 0.002). The columella and the suitability of the front part of the nose had the largest disagreement (κ = -0.06 and κ = −0.09, respectively). The level of agreement among most of the questionnaires’ components was slight or nonexistent (κ = 0.004–0.39).

Conclusions:
The surgeon and patients have a minimum agreement regarding the view of nasal appearance, mostly with the suitability of the front part and the columella. The parts of the nose agreed upon the most were “dorsal hump” and “tip drops down”. Exploring the differences between patient and surgeon aesthetic analysis of the nose will aid in addressing the discrepancies and improving surgical outcome and satisfaction.
30 Years of Experience in Musculocutaneous Latissimus Dorsi Flap Phalloplasty with Reinnervation: Optimal Principles
Authors: Adamyan Ruben T. , Startseva Olesya I. , Gabriyanchik Mark A. 
Published: April 2023

Background:
The technique of urogenital plastic surgery continues to pose difficulties for surgeons due to physical features of the anatomical region, which complicates the correction of various severe male urogenital pathologies. The goal of the surgeon is to create a neophallus that allows for urination and intercourse with minimal damage to the donor site. This special topic provides a historical overview and principles for optimal phalloplasty. To improve results in latissimus dorsi free-flap phalloplasty, we share our approach, its benefits, and the lessons we have learned.

Methods:
We performed a retrospective review of patients who underwent shaft-only, two-stage or one-stage latissimus dorsi flap phalloplasty with or without reinnervation at a single institution from 1991 through 2020. Patients with a minimum of 1 year of follow-up were included. Data on the patient’s demographics, the procedure, and the results of the operation were maintained.

Results:
In total, 592 latissimus dorsi flap phalloplasties were performed during the entire study period. Of the phalloplasties, 494 (83.5%) were performed for gender-affirming surgery, of which 470 were performed for transgender patients and 24 for intersex patients. Twenty-five patients (4.2%) had congenital malformations, 17 (2.9%) had oncologic resections, and 56 had posttraumatic loss (9.5%).

Conclusion:
Latissimus dorsi flap total phalloplasty with reinnervation is currently one of the few methods that can solve not only an aesthetic problem, but also a functional one without the use of an endoprosthesis if the level of reinnervation and muscle contraction is sufficient.
Soluble ORF2 protein enhances HEV replication and induces long-lasting antibody response and protective immunity in vivo
Authors: Ralfs Philipp , Holland Brantley , Salinas Eduardo , Bremer Bill , Wang Minghang , Zhu Jingting , Ambardekar Charuta , Blasczyk Heather , Walker Christopher M. , Feng Zongdi , Grakoui Arash 
Published: April 2023

Background and Aims:
The HEV is a small positive–sense RNA virus that encodes a cytoplasmic form of the capsid protein (ORF2c), essential for virion structure, and a secreted glycosylated form (ORF2s) that accumulates at high titer in serum and can mask neutralizing epitopes. We explored the contribution of ORF2s to HEV replication and its role in generating antibodies against ORF2 in a nonhuman primate model.

Approach and Results:
We used a recombinant HEV genotype 3 variant that does not express ORF2s due to the introduction of stop codons (ORF2smut). Rhesus macaques (RMs) were given intrahepatic injections of infectious wildtype HEV (ORF2swt) RNA or a variant lacking ORF2s expression (ORF2smut). The replication of the ORF2smut virus was delayed by ~2 weeks compared with ORF2swt, and peak titers were nearly tenfold lower. Reversions of the 3 mutations that blocked ORF2s expression were not detected in the ORF2smut genomes, indicating genetic stability. However, serum antibodies against ORF2 were transiently detected in RMs infected with ORF2smut, whereas they were long-lasting in RMs infected with ORF2swt. Moreover, RMs infected with ORF2smut were more susceptible to reinfection, as evidenced by the viral RNA detected in fecal samples and the expansion of HEV-specific CD8+ T cells.

Conclusions:
These findings indicate that ORF2s may be dispensable for viral replication in vivo but is required for long-lived antibody-mediated responses that protect against HEV re-exposure.
Long-term Outcomes After Lamellar Endothelial Keratoplasty Compared With Penetrating Keratoplasty for Corneal Endothelial Dysfunction: A Systematic Review
Authors: Lemaitre Daniel , Tourabaly Moise , Borderie Vincent , Dechartres Agnes 
Published: April 2023

Purpose:The purpose of this study is to evaluate long-term outcomes of endothelial keratoplasty (EK) compared with penetrating keratoplasty (PK) for corneal endothelial dysfunction [Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK)].Methods:In this systematic review, we searched PubMed, the Cochrane Library, and Embase up to May 2022 and considered all types of studies addressing our objective. Graft survival at 5, 10, and 15 years was the main outcome.Results:Fifty cohort studies were included. At 5 years, in FECD and BK, graft survival seemed higher after EK than PK. Two comparative studies showed either a higher 5-year graft survival after EK than PK or no significant differences. Including noncomparative studies, in FECD, the 5-year graft survival ranged from 0.69 to 0.98 for PK, from 0.93 to 1.00 for DSEK, and from 0.93 to 0.99 for Descemet membrane endothelial keratoplasty (DMEK). In BK, the 5-year graft survival ranged from 0.39 to 0.91 for PK, from 0.65 to 0.89 for DSEK, and from 0.84 to 0.95 for DMEK. The 10-year graft survival ranged from 0.20 to 0.90 for PK and from 0.62 to 0.92 for EK. The mean 5-year best spectacle-corrected visual acuity ranged from 0.73 to 0.43 LogMAR for PK, from 0.61 to 0.09 for DSEK, and from 0.31 to 0.05 for DMEK. The 5-year rejection rate ranged from 11.0% to 28.7% for PK, from 5.0% to 7.9% for DSEK, and from 1.7% to 2.6% for DMEK.Conclusions:These results suggest a higher 5-year graft survival and better secondary outcomes after EK. Nevertheless, the level of evidence was low.Prospero Registration:CRD42021260614.
Coordinating Care for People With HIV Who Have Lower Incomes and Alternative Sources of Health Care Coverage
Authors: Au Melanie , Coombs Ellie , Jones Andrew , Carley Frances , Talwar-Hebert Maya , Addison West , Mills Robert J. , Cohen Stacy M. , Klein Pamela W. , Cheever Laura , Gilman Boyd 
Published: April 2023

Abstract
As people with HIV increasingly access affordable health care coverage—enabling them to obtain medical care from private providers—understanding how they use the Ryan White HIV/AIDS Program (RWHAP), and their unmet health care needs, can enhance their overall care. We analyzed RWHAP client-level data and interviewed staff and clients at 29 provider organizations to identify trends in health care coverage and service use for clients who received medical care from private providers. The RWHAP helps cover the cost of premiums and copays for these clients and provides medical and support services that help them stay engaged in care and virally suppressed. The RWHAP plays an important role in HIV care and treatment for clients with health care coverage. The growing number of people who receive a combination of services from RWHAP providers and private providers offers opportunities for greater care coordination through communication and data sharing between these settings.
Athletes With Attention-Deficit/Hyperactivity Disorder: Position Statement of the American Medical Society for Sports Medicine
Authors: Pujalte George G.A. , Narducci Dusty Marie , Smith Michael Seth , King Rebecca , Logan Kelsey , Callender Shelley Street , Liebman Catherine A. , Kane Shawn F. , Israel Michael P. , Wolf Sigrid F. , Nuti Rathna , Khodaee Morteza 
Published: April 2023

Abstract:
Athletes of all ages may be affected by medical and mental health issues. Sports medicine physicians should be familiar with common conditions that may affect the well-being of athletes, such as attention-deficit/hyperactivity disorder (ADHD). ADHD behaviors have the potential to affect a person's ability to concentrate. It is likely that social and cognitive therapies combined with pharmacotherapy will be the most effective way to treat ADHD in athletes. Medications used for ADHD, especially stimulant types, are known to improve alertness, reaction time, anaerobic performance, and endurance, which would potentially improve athletic performance. Furthermore, stimulant medications may enable student athletes with ADHD to focus on academic studies for longer periods of time, beyond usual levels of fatigue, important for those who may be exhausted after practices and games. The purported performance enhancement effects and potential adverse effects of stimulant medications have prompted many sports governing bodies to ban prescription stimulants or establish strict rules for their use. Athletes taking physician-prescribed stimulants to treat ADHD need to provide the appropriate documentation for approval before competition or risk punitive measures. Physicians should strive to provide a high quality of care to athletes with ADHD through early diagnosis, appropriate and careful multidisciplinary treatment, and complete and timely documentation to facilitate continued sports participation.
Evaluating Burnout and Resiliency in New Graduate Nurses
Authors: Catarelli Bryce , Nobles Patrick , Aull Michael , Yi Fan 
Published: April 2023

OBJECTIVE
The aim of this study was to evaluate current levels of and factors contributing toward burnout and resiliency among new graduate nurses to identify effective mitigation strategies.

BACKGROUND
New graduate nurses are at a high risk of increased turnover in the 1st year of employment. An evidence-based, graduate-nurse centered approach is essential to improving nurse retention among this cohort.

METHODS
A cross-sectional study involving 43 new graduate nurses was completed in July 2021 (a subset of a larger sample of 390 staff nurses). Nurses were recruited to complete the Brief Resilience Scale, the Copenhagen Burnout Inventory, and a demographic survey.

RESULTS
New graduate nurses scored within “normal resiliency.” This cohort reported moderate levels of burnout overall. Higher levels were reported within personal- and work-related subgroups.

CONCLUSIONS
Strategies to reduce burnout and increase resiliency in new graduate nurses should be focused on improving personal and work-related burnout.
Long-Term Functional Outcomes at 1-Year After Hospital Discharge in Critically Ill Neonates With Congenital Diaphragmatic Hernia
Authors: O’Hara Jill E. , Buchmiller Terry L. , Bechard Lori J. , Akhondi-Asl Alireza , Visner Gary , Sheils Catherine , Becker Ronald , Studley Mollie , Lemire Lindsay , Mullen Mary P. , Vitali Sally , Mehta Nilesh M. , Dickie Belinda , Zalieckas Jill M. , Albert Ben D. 
Published: April 2023

OBJECTIVES:
Congenital diaphragmatic hernia (CDH) is a birth defect associated with long-term morbidity. Our objective was to examine longitudinal change in Functional Status Scale (FSS) after hospital discharge in CDH survivors.

DESIGN:
Single-center retrospective cohort study.

SETTING:
Center for comprehensive CDH management at a quaternary, free-standing children’s hospital.

PATIENTS:
Infants with Bochdalek CDH were admitted to the ICU between January 2009 and December 2019 and survived until hospital discharge.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
One hundred forty-two infants (58% male, mean birth weight 3.08 kg, 80% left-sided defects) met inclusion criteria. Relevant clinical data were extracted from the medical record to calculate FSS (primary outcome) at hospital discharge and three subsequent outpatient follow-up time points. The median (interquartile range [IQR]) FSS score at hospital discharge was 8.0 (7.0–9.0); 39 patients (27.5%) had at least moderate impairment (FSS ≥ 9). Median (IQR) FSS at 0- to 6-month (n = 141), 6- to 12-month (n = 141), and over 12-month (n = 140) follow-up visits were 7.0 (7.0–8.0), 7.0 (6.0–8.0), and 6.0 (6.0–7.0), respectively. Twenty-one patients (15%) had at least moderate impairment at over 12-month follow-up; median composite FSS scores in the over 12-month time point decreased by 2.0 points from hospital discharge. Median feeding domain scores improved by 1.0 (1.0–2.0), whereas other domain scores remained without impairment. Multivariable analysis demonstrated right-sided, C- or D-size defects, extracorporeal membrane oxygenation use, cardiopulmonary resuscitation, and chromosomal anomalies were associated with impairment.

CONCLUSIONS:
The majority of CDH survivors at our center had mild functional status impairment (FSS ≤ 8) at discharge and 1-year follow-up; however, nearly 15% of patients had moderate impairment during this time period. The feeding domain had the highest level of functional impairment. We observed unchanged or improving functional status longitudinally over 1-year follow-up after hospital discharge. Longitudinal outcomes will guide interdisciplinary management strategies in CDH survivors.
A Medicolegal Perspective on the Development of Facial Hypertrophic Scars in a Child after Contact with Alkaline Battery Content
Authors: Demir Canser Yilmaz , Asirdizer Mahmut , Hekimoglu Yavuz 
Published: April 2023

<p> </p>
<p>One of the main causes of injuries in children is batteries.</p>
<p>Serious morbidity can result from ingesting batteries or rubbing their contents into the body.</p>
<p>Batteries must be labeled with child-friendly warnings.</p>
Genetic Evidence Causally Linking Pancreas Fat to Pancreatic Cancer: A Mendelian Randomization Study
Authors: Yamazaki Hajime , Streicher Samantha A. , Wu Lang , Fukuhara Shunichi , Wagner Róbert , Heni Martin , Grossman Steven R. , Lenz Heinz-Josef , Setiawan Veronica Wendy , Marchand Loic Le , Huang Brian Z. 
Published: April 2023

AbstractBackground & AimsPancreatic ductal adenocarcinoma (PDAC) is highly lethal, and any clues to understanding its elusive etiology could lead to breakthroughs in prevention, early detection, or treatment. Observational studies have shown a relationship between pancreas fat accumulation and PDAC, but the causality of this link is unclear. We therefore investigated whether pancreas fat is causally associated with PDAC using two-sample Mendelian randomization.MethodsWe leveraged eight genetic variants associated with pancreas fat (P<5×10-8) from a genome-wide association study (GWAS) in the UK Biobank (25,617 individuals), and assessed their association with PDAC in the Pancreatic Cancer Cohort Consortium I-III and the Pancreatic Cancer Case-Control Consortium dataset (8,275 PDAC cases and 6,723 non-cases). Causality was assessed using the inverse-variance weighted method. Although none of these genetic variants were associated with body mass index (BMI) at genome-wide significance, we further conducted a sensitivity analysis excluding genetic variants with a nominal BMI association in GWAS summary statistics from the UK Biobank and the Genetic Investigation of Anthropometric Traits consortium dataset (806,834 individuals).ResultsGenetically determined higher levels of pancreas fat using the eight genetic variants was associated with increased risk of PDAC. For one standard deviation increase in pancreas fat levels (i.e., 7.9% increase in pancreas fat fraction), the odds ratio of PDAC was 2.46 (95%CI:1.38-4.40, P=0.002). Similar results were obtained after excluding genetic variants nominally linked to BMI (odds ratio:3.79, 95%CI:1.66-8.65, P=0.002).ConclusionsThis study provides genetic evidence for a causal role of pancreas fat in the pathogenesis of PDAC. Thus, reducing pancreas fat could lower the risk of PDAC.
Curation and description of a blood glucose management and nutritional support cohort using the eICU collaborative research database
Authors: Fitzgerald Oisin , Perez-Concha Oscar , Gallego-Luxan Blanca , Rudd Lachlan , Jorm Louisa 
Published: April 2023

AbstractFreely available electronic medical record (EMR) data collections have transformed data science and observational research in critical care medicine. Descriptive characterisation of these data collections can aid in highlighting variation in clinical practice and patient outcomes across Intensive Care Units (ICUs). Glycaemic control and nutritional management are important aspects of patient management in the ICU. Blood glucose on admission has a well-known U-shaped relationship with mortality and morbidity, with both hypo- and hyper-glycemia being associated with poor patient outcomes. The importance of nutritional support has been highlighted in critical care guidelines. However, both areas have open research questions and highly variable clinical practices that observational data may help highlight and inform. To aid in this research, we curated a database of patients using the eICU collaborative research data (eICU-CRD), which we describe in the current paper, focusing on patient blood glucose, insulin therapy and enteral nutrition. The eICU-CRD is derived from a telehealth EMR covering 208 United States hospitals from 2014-2015. In addition to descriptive statistics and graphical analysis, we highlight any limitations in data quality. Our results are in line with previous research suggesting the eICU-CRD cohort is of lower illness severity than the average ICU patient cohort and so receive less invasive interventions. Examinations of data missingness revealed issues with medication orders and non-reporting of nutrition by several hospitals. Overall, with care around missingness we believe the eICU-CRD to be a valuable resource in evidence generation for critical care research.
Polyethylene Glycol-Mediated Directional Conjugation of Biological Molecules for Enhanced Immunoassays at the Point-of-Care
Authors: Battalapalli Dheerendranath , Chakraborty Purbali , Jain Disha , Obaro Stephen K. , Gurkan Umut , Bonomo Robert A. , Draz Mohamed 
Published: April 2023

AbstractRapid and reliable point-of-care (POC) diagnostic tests can make a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. Here, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes is first modified with thiolated PEG molecules, leaving the hydrazide groups available to react with the aldehyde group in Fc fragments of the oxidized IgG antibodies. UsingKlebsiella pneumoniaecarbapenemase-2 (KPC2) antibody as a model antibody used for antimicrobial resistance (AMR) testing, our results demonstrate a ∼10-fold increase in antibody coupling, compared with the standardN-hydroxysuccinimide (NHS)-based conjugation chemistry, and effective capture (> 94%) of the target KPC2 enzyme antigen on the surface of modified electrodes. This straightforward and easy-to-perform strategy of site-directed antibody conjugation can be engineered for coupling other protein and non-protein-based biological molecules commonly used in POC testing and development, thus enhancing the potential for improved diagnostic accuracy and performance.
An information-theoretic analysis of agrammatism in Broca’s aphasia
Authors: Rezaii Neguine 
Published: April 2023

AbstractRecently we proposed and tested a novel framework based on information theory about the features of agrammatism in patients with the nonfluent variant of primary progressive aphasia (nfvPPA). These features include short sentences, simplified structures, the omission of function words, reduced use of verbs, and increased use of heavy verbs. After distinguishing the syntactic and lexical features of agrammatism, we proposed that the lexical features are not defects but rather a compensatory response to structural deficits. We showed that although patients with nfvPPA have difficulty using complex structures, they use more informative words to facilitate the transfer of their intended message. In this work, we demonstrated the generalizability of our findings to patients with Broca’s aphasia who share similar neuroanatomical involvements with patients with nfvPPA. We found that patients with Broca’s aphasia use simpler syntactic structures as measured by higher syntax frequency. We also found that the use of simpler syntax predicts the use of lower-frequency words. Furthermore, our study showed that producing sentences of lower word frequency is likely achieved through the canonical features of agrammatism, i.e., higher proportions of content words over function words, nouns over verbs, and heavy verbs over light verbs.