bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2, single-arm trial evaluating 131I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer
Authors: Liu Richard F. , Ferrario Cristiano , Fallah Parvaneh , Rose April A.N. , Labidi Soumaya , Mamo Aline , Probst Stephan M. 
Published: May 2024

Background
Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131I-PSMA-1095 (also known as 131I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment.

Methods
We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18F-DCFPyL PET and 18F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed.

Results
Eleven patients were screened for inclusion and nine patients received 131I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia.

Conclusion

131I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131I-PSMA-1095 compared to 177Lu-PSMA-617.
Platelet lipidomics and de novo lipogenesis: impact on health and disease
Authors: Pirotton Laurence , de Cartier d’Yves Emma , Bertrand Luc , Beauloye Christophe , Horman Sandrine 
Published: May 2024

Purpose of review
Lipids play vital roles in platelet structure, signaling, and metabolism. In addition to capturing exogenous lipids, platelets possess the capacity for de novo lipogenesis, regulated by acetyl-coA carboxylase 1 (ACC1). This review aims to cover the critical roles of platelet de novo lipogenesis and lipidome in platelet production, function, and diseases.

Recent findings
Upon platelet activation, approximately 20% of the platelet lipidome undergoes significant modifications, primarily affecting arachidonic acid-containing species. Multiple studies emphasize the impact of de novo lipogenesis, with ACC1 as key player, on platelet functions. Mouse models suggest the importance of the AMPK-ACC1 axis in regulating platelet membrane arachidonic acid content, associated with TXA2 secretion, and thrombus formation. In human platelets, ACC1 inhibition leads to reduced platelet reactivity. Remodeling of the platelet lipidome, alongside with de novo lipogenesis, is also crucial for platelet biogenesis. Disruptions in the platelet lipidome are observed in various pathological conditions, including cardiovascular and inflammatory diseases, with associations between these alterations and shifts in platelet reactivity highlighted.

Summary
The platelet lipidome, partially regulated by ACC-driven de novo lipogenesis, is indispensable for platelet production and function. It is implicated in various pathological conditions involving platelets.
Prevalence and Clinical Implications of Osteosarcopenia in Patients With Acute Stroke
Authors: Kim Kyoung Tae , Lee Soyoung , Cho Jang Hyuk , Choi Yongmin 
Published: May 2024

Objective
The aim of the study is to investigate the prevalence and risk factors of osteosarcopenia in patients with acute stroke.

Design
Overall, 224 patients within 2 wks of having a stroke were enrolled. Demographic characteristics, National Institutes of Health Stroke Scale, modified Rankin Scale, modified Barthel Index, Functional Ambulation Category, Berg Balance Scale, and handgrip strength were recorded. Body composition was evaluated using dual-energy x-ray absorptiometry. Patients who met the diagnostic criteria for osteoporosis and sarcopenia were defined as having osteosarcopenia.

Results
The overall prevalence of osteoporosis and sarcopenia was 46.9% and 50.9%, respectively. The prevalence of osteoporosis without sarcopenia, sarcopenia without osteoporosis, and osteosarcopenia was 18.3%, 22.3%, and 28.6%, respectively. The proportion of female sex (71.9%), median age, and National Institutes of Health Stroke Scale score were significantly higher, and modified Rankin Scale, Berg Balance Scale, modified Barthel Index, Functional Ambulation Category, and grip strength were significantly lower in patients with osteosarcopenia. Older age (≥65 yrs) (odds ratio, 15.4), female sex (odds ratio, 6.23), and lower body mass index (<25 kg/m2) (odds ratio, 43.13) were independently associated with the likelihood of osteosarcopenia.

Conclusions
Osteosarcopenia may occur in acute stroke survivors. Patients with osteosarcopenia have a significantly higher stroke severity and disability. A comprehensive diagnostic approach is imperative for osteosarcopenia, thereby facilitating implementation of optimal rehabilitative strategies.
The Association of Multidimensional Sleep Health With HbA1c and Depressive Symptoms in African American Adults With Type 2 Diabetes
Authors: Woo Jihun , Lehrer H. Matthew , Tabibi Doonya , Cebulske Lauren , Tanaka Hirofumi , Steinhardt Mary 
Published: May 2024

Objective
Sleep is important for diabetes-related health outcomes. Using a multidimensional sleep health framework, we examined the association of individual sleep health dimensions and a composite sleep health score with hemoglobin A1c (HbA1c) and depressive symptoms among African American adults with type 2 diabetes.

Methods
Participants (N = 257; mean age = 62.5 years) were recruited through local churches. Wrist-worn actigraphy and sleep questionnaire data assessed multidimensional sleep health using the RuSATED framework (regularity, satisfaction, alertness, timing, efficiency, duration). Individual sleep dimensions were dichotomized into poor or good sleep health and summed into a composite score. HbA1c was assessed using the DCA Vantage™ Analyzer or A1CNow® Self Check. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Regression models examined the association of individual sleep dimensions and composite sleep health with HbA1c and depressive symptoms.

Results
Higher composite sleep health scores were associated with a lower likelihood of having greater than minimal depressive symptoms (PHQ-9 ≥ 5) (odds ratio [OR] = 0.578, 95% confidence interval [CI] = 0.461–0.725). Several individual sleep dimensions, including irregularity (OR = 1.013, CI = 1.005–1.021), poor satisfaction (OR = 3.130, CI = 2.095–4.678), and lower alertness (OR = 1.866, CI = 1.230–2.833) were associated with a greater likelihood of having depressive symptoms. Neither composite sleep health scores nor individual sleep dimensions were associated with HbA1c.

Conclusions
Better multidimensional sleep health is associated with lower depressive symptoms among African American adults with type 2 diabetes. Longitudinal research is needed to determine the causal association between multidimensional sleep health and depressive symptoms in this population.

Trial Registry

ClinicalTrials.gov identifier NCT04282395.
Pre-exposure Prophylaxis Awareness and Use Among Transgender and Nonbinary Individuals in Canada
Authors: Hallarn Jason , Scheim Ayden I. , Bauer Greta R. 
Published: May 2024

Background:
Transgender and nonbinary populations are disproportionately affected by HIV and face barriers to accessing HIV-related services. Pre-exposure prophylaxis (PrEP) may benefit those at risk of HIV acquisition. However, PrEP awareness and uptake, along with potential barriers and facilitators, have not been investigated among transgender and nonbinary individuals living in Canada.

Setting:
This study analyzed data from 1965 participants of the 2019 Trans PULSE Canada survey, a national convenience sampling survey of transgender and nonbinary individuals in Canada.

Methods:
Data were analyzed to estimate levels of PrEP awareness and uptake and to identify predictors of PrEP awareness among the study population. Prevalence ratios estimated from block-wise modified Poisson regression models were used to assess predictors of PrEP awareness.

Results:
PrEP awareness, lifetime PrEP use, and current PrEP use were estimated to be 71.0%, 2.2%, and 0.9%, respectively, among the full sample, and 82.3%, 7.3%, and 3.8% among those with indications for PrEP use. Respondents who were aged 45 years or older, transfeminine, Indigenous, living in Atlantic Canada or Quebec, and had high school education or less were significantly less likely to be aware of PrEP. Lifetime sex work, past-year HIV/STI testing, being single or in a nonmonogamous relationship, and higher levels of emotional social support were positively associated with PrEP awareness.

Conclusions:
There is a need to improve PrEP awareness and particularly uptake among transgender and nonbinary individuals in Canada. This study revealed inequities in PrEP awareness within this population, which may serve as targets for future public health initiatives.
Brief Report: Youth Who Acquired HIV Perinatally Have Poorer Viral Suppression Than Those Who Acquired HIV Later in Life: Findings From a Population Survey in Zimbabwe
Authors: Simms Victoria , Kranzer Katharina , Dziva Chikwari Chido , Dauya Ethel , Bandason Tsitsi , Dzavakwa Nyasha , Ferrand Rashida A. 
Published: May 2024

Background:
Perinatally acquired HIV may lead to worse health outcomes than later acquisition. We compared the demographic and clinical characteristics of youth diagnosed with HIV in childhood and adulthood, as a proxy for acquisition route (perinatal vs. horizontal).

Setting:
Youth aged 18–24 years in 3 provinces in Zimbabwe were included.

Methods:
In a representative population-based survey, participants were asked their HIV status, date of HIV diagnosis if positive, and whether they were diagnosed in childhood. A dried blood spot was taken to measure viral load. Multilevel mixed-effects generalized linear modelling was used to estimate the association between HIV acquisition time and viral nonsuppression (≥1000 copies/mL).

Results:
A total of 17,682 participants (60.8% female) were enrolled, 17,553 (99.3%) gave a dried blood spot sample, 1200 (6.8%) tested HIV antibody–positive (7 indeterminate results), and 26 reported being HIV-positive without confirmation. Of the 1226 participants living with HIV, 435 (35.5%) self-reported that they were HIV-positive, of whom 196 (45.1%) were diagnosed in childhood (median age 7 years). A higher proportion of adult-diagnosed than child-diagnosed participants were female (91.2% vs. 76.5%), had ever had sex (93.3% vs. 61.5%), had been married/cohabiting (59.4% vs. 19.4%), and had been pregnant (78.9% of women vs. 40.0%). A lower proportion had viral suppression (39.3% vs. 52.5%). Adjusting for sex, age, marital status, and education, those diagnosed in childhood had higher odds of viral nonsuppression (adjusted odds ratio = 1.83, 95% confidence interval: 1.17 to 2.85, P = 0.008).

Conclusions:
Youth who acquired HIV perinatally have differentiated care needs and greater risk of viral nonsuppression compared with those who acquired HIV later.
Outcomes and Complications of Sole Reconstruction Using Lateral Thoracic Free Tissue Transfer
Authors: Zhang Ran , Wang Hyung Woo , Kim Youn Hwan , Park Seong Oh 
Published: May 2024

Background
The complex structure of the sole of the foot makes the repair of extensive defects challenging. The present study, therefore, aimed to address a gap in current research by evaluating the potential of the lateral thoracic free flap, including perforator options and chimeric configurations, to be used as an advanced solution for comprehensive sole reconstruction.

Patients and Methods
We retrospectively collected the following data from the charts of patients with sole defects, due to various causes, who underwent lateral thoracic free tissue transfers: patient demographics; etiologies; comorbidities; flap types and dimensions; pedicle length; operative time; follow-up period; complications; and management.

Results
The present study included 54 patients who underwent lateral thoracic free tissue transfer, citing infection, trauma, tumor, and posttraumatic sequelae as the major etiologies. We used the following techniques for the reconstruction of sole defects: thoracodorsal artery perforator free flap (83.3%); latissimus dorsi musculocutaneous free flap (1.9%); and various chimeric pattern flaps (14.8%). Free tissue transfer in the lateral thoracic region offers versatility for reconstruction, as well as low donor site morbidity. Complications observed in the present study included wound dehiscence (9.3%), partial necrosis (9.3%), and pressure ulcers (22.2%), although most patients healed favorably without flap loss.

Conclusions
The lateral thoracic free flap is a viable option for the reconstruction of the sole of the foot and allows for the effective reconstruction of complex defects. It contains a sustainable skin paddle, and multiple components can be easily included as a chimeric type. Further studies should seek to identify ways to prevent pressure ulcers, which was the only known long-term complication in the present study.
Comparative Analysis of Silicone Tube Intubation Versus Probing and Balloon Dilation for Congenital Nasolacrimal Duct Obstruction: A Systematic Review and Meta-Analysis
Authors: Alruwaili Rahaf , Alanazi Farhan , Alrashidi Ali , Hazazi Mohammed , Alenezi Mazyad 
Published: May 2024

Objective:
Congenital nasolacrimal duct obstruction (CNLDO) is a pediatric disorder with a wide range of pathology. If untreated, the condition may end up with serious complications. Multiple treatment options for CNLDO exist throughout the literature, and there is an ongoing debate on the best intervention for each disease subgroup and the best timing of such interventions. This study compares the success and failure rates of silicone tube intubation (STI) against probing and balloon dilation (BD).

Methods:
The authors searched the literature for relevant articles using PubMed, Scopus, web of Science, and Cochrane Library until January 2024. Using RevMan 5.4, the authors compared STI’s success and failure rates to probing and BD using risk ratios (RRs) and a random-effect model. In addition, the complication rate of monocanalicular intubation (MCI) versus bicanalicular intubation (BCI) was investigated. The authors used the leave-one-out method to check for influential studies and to resolve heterogeneity.

Results:
The screening process resulted in 23 eligible articles for inclusion in the authors’ review. Silicone tube intubation had a higher chance of resolving the symptoms of CNLDO than probing (RR = 1.11; 95% CI: 1.04, 1.20; P = 0.004) while having less risk of surgical failure (RR = 0.48; 95% CI: 0.30, 0.76; P = 0.002]. Monocanalicular intubation showed no statistically significant difference when compared with BCI in terms of surgical success and failure; however, MCI had a lower risk of complications (RR = 0.68; 95% CI: 0.48, 0.97; P = 0.04). In addition, STI did not demonstrate any significant difference from BD.

Conclusion:
There was no significant difference in success/failure between MCI and BCI; monocanalicular had fewer complications. Silicone tube intubation did better in terms of surgical success than probing, especially in children over 12 months, suggesting that it is the preferred intervention for older patients with CNLDO.
Outcomes from 871,441 Consecutive Surgical Procedures without Overlap or with Maximally Permissible Non-Concurrent Overlap
Authors: Borja Austin J. , Karsalia Ritesh , Gallagher Ryan S. , Strouz Krista , Na Jianbo , McClintock Scott D. , DeMatteo Ronald P. , Malhotra Neil R. 
Published: May 2024

Objective:
To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes.

Summary Background Data:
The American College of Surgeons recently recommended the elimination of “concurrent surgery” with overlap during a procedure’s critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined.

Methods:
All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations.

Results:
Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon.

Conclusions:
Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.
Value in acute care surgery, part 3: Defining value in acute surgical care—It depends on the perspective
Authors: Ayoung-Chee Patricia R. , Gore Amy V. , Bruns Brandon , Knowlton Lisa M. , Nahmias Jeffry , Davis Kimberly A. , Leichtle Stefan , Ross Samuel W. , Scherer L. R. , Velopulos Catherine , Martin R. Shayn , Staudenmayer Kristan L. ,   the AAST Health Economics Committee
Published: May 2024

ABSTRACT
The prior articles in this series have focused on measuring cost and quality in acute care surgery. This third article in the series explains the current ways of defining value in acute care surgery, based on different stakeholders in the health care system—the patient, the health care organization, the payer and society. The heterogenous valuations of the different stakeholders require that the framework for determining high-value care in acute care surgery incorporates all viewpoints.

LEVEL OF EVIDENCE
Expert Opinion; Level V.
The nature and characteristics of problem gaming, with a focus on ICD-11 diagnoses
Authors: Saunders John B. , Chan Gary , Leung Janni , Stjepanović Daniel , Connor Jason P. 
Published: May 2024

Purpose of review
This review describes the diagnoses related to problem gaming that are included in ICD-11, published by the WHO in 2022. It summarizes the recent literature on the prevalence of Gaming Disorder, its structure, antecedents and comorbidities, and explores whether the range of diagnoses currently available adequately covers the range of experiences seen with problem gaming.

Recent findings
Overall, between 3 and 6% of the population worldwide are reported to have a gaming disorder as defined by ICD-11 or DSM-5. However, most studies are constrained by methodological issues such as nonrepresentative samples and the use of brief questionnaires to determine prevalence. ICD-11 Gaming Disorder is a psychometrically sound diagnosis. There is no diagnosis that currently captures the experience of harm from gaming, where the requirements for the diagnosis of Gaming Disorder are not reached.

Summary
There is evidence in support of the proposed new entity of ‘Harmful Gaming’, which encompasses mental and physical harm/impairment due to a repeated pattern of gaming, but where requirements for the diagnosis of Gaming Disorder are not met. Such a diagnosis would complete the spectrum of diagnoses available for problem or unhealthy gaming, similar to those for unhealthy substance use, and would provide a framework for a public health approach to reducing the overall harm from unhealthy gaming.
Anti-tetanus vaccination is associated with reduced occurrence and slower progression of Parkinson’s disease
Authors: Israel Ariel , Magen Eli , Merzon Eugene , Ruppin Eytan , Vinker Shlomo , Giladi Nir 
Published: May 2024

AbstractParkinson’s disease (PD) is characterized by progressive neurodegeneration in the autonomic and central nervous systems, manifesting with hallmark symptoms of resting tremor, bradykinesia and rigidity. The etiology of PD remains elusive, and currently available treatments do not halt disease progression.In this study, conducted within a national health provider, we examined the impact of vaccination and medication purchase on PD occurrence and severity, using an innovative machine learning algorithm to track disease progression.Our findings reveal a significant reduction in PD occurrence following anti-tetanus vaccination, with a time-dependent association between the elapsed time since vaccination and both the rate and progression of PD. These results are supported by evidence that antimicrobial treatments significantly alter disease severity, suggesting the actual involvement ofClostridium Tetaniin PD pathology.Thus, tetanus vaccination andC. tetanieradication could be promising strategies for preventing PD and slowing its progression, pending controlled clinical trials.
Exonic splice variant discovery using in vitro models of inherited retinal disease
Authors: Mullin Nathaniel Kevin , Bohrer Laura R. , Anfinson Kristin R. , Andorf Jeaneen L. , Mullins Robert F. , Tucker Budd A. , Stone Edwin M. 
Published: May 2024

ABSTRACTCorrect identification of the molecular consequences of pathogenic genetic variants is essential to the development of allele-specific therapies. However, in some cases, such molecular effects may be ambiguous following genetic sequence analysis alone. One such case is exonic, codon-altering variants that are also predicted to disrupt normal RNA splicing. Here, we identify such cases in the context of inherited retinal disease.NR2E3c.932G>A (p.Arg311Gln) is a variant commonly associated with Enhanced S Cone Syndrome (ESCS). Previous studies using mutagenized cDNA constructs have shown that the arginine to glutamine substitution at position 311 of NR2E3 does not meaningfully diminish function of the rod-specific transcription factor. Using retinal organoids, we explored the molecular consequences ofNR2E3c.932G>A when expressed endogenously during human rod photoreceptor cell development. Retinal organoids carrying theNR2E3c.932G>A allele expressed a transcript containing a 186-nucleotide deletion of exon 6 within the ligand binding domain. This short transcript was not detected in control organoids or control human donor retina samples. A minigene containing exons 5 and 6 ofNR2E3showed sufficiency of the c.932G>A variant to cause the observed splicing defect. These results support the hypothesis that the pathogenicNR2E3c.932G>A variant leads to photoreceptor disease by causing a splice defect and not through an amino acid substitution as previously supposed. They also explain the relatively mild effect of Arg311Gln on NR2E3 functionin vitro. We also usedin silicoprediction tools to show that similar changes are likely to affect other inherited retinal disease variants in genes such asCEP290, ABCA4, andBEST1.