bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Outcomes of Direct-Acting Antiviral Experienced Patients with Hepatitis C Undergoing Retreatment at an Essential Hospital in the United States
Authors: De La Hoz Alejandro , Pooja Amin , Kancharla Anna , Schechter-Perkins Elissa M , Ruiz-Mercado Glorimar , Baldwin Marielle , Nunes David , Taylor Jessica L 
Published: November 2024

Abstract

Background
Hepatitis C virus (HCV) guidelines recommend direct-acting antiviral (DAA) rescue regimens in cases of treatment failure, and first-line regimens for reinfection. In patients with barriers to follow-up after treatment, it is difficult to determine if HCV viremia represents failure or reinfection. Patients are often retreated with rescue regimens despite higher costs. We compared the outcome of first-line vs rescue therapy in DAA experienced patients whose prior outcome was indeterminate.

Methods
This retrospective cohort study included DAA experienced adults undergoing retreatment at a hospital in Massachusetts between January 2016 and May 2022. We used descriptive statistics to characterize the population. For patients with an indeterminate prior HCV treatment outcome, we compared the groups’ characteristics and outcomes.

Results
We included 112 patients. The mean age was 52 years (SD: 12.2), 80.4% were male, and 42.9% were White. Nearly 1 in 4 (25%) reported active substance use. Outcomes of prior DAA treatment included sustained virologic response at 12 weeks in 39.3% (n = 44) and treatment failure in 27.7% (n = 31). The prior treatment outcome was indeterminate in 33% (n = 37). We compared the outcomes of patients with an indeterminate treatment outcome retreated with first-line vs rescue therapy. Sustained virologic response at 12 weeks (66.7 vs 52.7%), treatment failure (0% vs 10.5%), and indeterminate outcome (33.3% vs 36.8%) were similar between the groups (P = .502).

Conclusions
Outcomes with first-line DAAs were comparable to rescue medications for retreatment of patients with DAA experience and an indeterminate prior treatment outcome. Our findings can help decrease treatment-level barriers for HCV treatment.
Uncomfortable knowledge, the production of ignorance, and the trustworthiness of UK policing
Authors: Fenton-O’Creevy Mark , Bowles Benjamin , Maguire Linda , Williams Emma 
Published: November 2024

Abstract
In this article, we draw on emerging theories of the production of ignorance in organizations. We conduct a qualitative analysis of two forms of secondary data on policing in England and Wales: first, documents in the public domain from the Casey Review and the Angiolini Inquiry; second, qualitative data collected as part of ‘Operation Soteria’ a UK Home Office-funded programme designed to improve the investigation of rape and serious sexual offences. We highlight the adverse effects of avoidance of uncomfortable knowledge, organizational silence, and non-learning in policing. We argue that they are both important contributors to the crisis of legitimacy faced by UK policing, and barriers to effective change. Finally, we discuss structural conditions that support the production and reproduction of ignorance and approaches to ‘undoing ignorance’.
Effects of Subanesthetic Oromucosal Dexmedetomidine on Sleep in Humans: A Randomized, Controlled Pharmacokinetics–Pharmacodynamics Study
Authors: Schnider Laura K. , Ratajczak Marta , Wespi Rafael , Kientsch Jacqueline G. , Bavato Francesco , Marten Laurenz , Kost Jonas , Puchkov Maxim , Eicher Corinne , Boxler Martina , Voegel Clarissa D. , Bosch Oliver G. , van Someren Eus , Dornbierer Dario A. , Landolt Hans-Peter 
Published: November 2024

Background:
The locus coeruleus noradrenergic system may provide a potential new target for pharmacologic insomnia treatment, particularly in patients suffering from elevated distress. The selective α2-noradrenergic agonist dexmedetomidine attenuates locus coeruleus activity in subanesthetic doses, yet no adequate nonparental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oromucosal dexmedetomidine administration, the authors developed two distinct—one sublingual and one buccal—oromucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here, the authors established the formulas’ pharmacokinetic and pharmacodynamic profiles.

Methods:
In a pilot study (sublingual formulation; n = 8 good sleepers) and a main study (buccal formulation; n = 17 poor sleepers), each following a randomized, double-blind, placebo-controlled crossover design, the authors investigated subanesthetic doses (20 and 40 µg) of the two formulas. They complemented the pharmacokinetic assessments with all-night polysomnography, nocturnal cortisol and melatonin measurements, assessments of cardiovascular functions during and after sleep, cortisol awakening response, and postawakening examination of subjective state and vigilance.

Results:
Particularly buccal dexmedetomidine was rapidly absorbed and exhibited excellent dose proportionality with minimal between-subject variation in exposure. In poor sleepers, 40 µg buccal dexmedetomidine shortened the sleep latency by 11.5 min, increased the time spent in non–rapid eye movement sleep by 37.2 min, and elevated non–rapid eye movement sleep electroencephalographic slow-wave energy (0.75 to 4.0 Hz) in the first half of the night by roughly 23%. Rapid eye movement sleep latency was dose-dependently prolonged (20 µg, 55.0 min; 40 µg, 115.3 min). Nocturnal cortisol, melatonin and heart rate, and morning cortisol were not significantly affected by dexmedetomidine, nor did postawakening orthostatic regulation, subjective sleepiness and mood, and psychomotor vigilance differ among the conditions.

Conclusions:
The favorable pharmacokinetic and pharmacodynamic profile of oromucosal dexmedetomidine delivery warrants further dose-finding and clinical studies to establish the exact roles of α2 receptor agonism in pharmacologic sleep enhancement and as a possible novel mechanism to alleviate stress-related insomnia.
Intraoperative Frontal Electroencephalogram Alpha Power Is Associated with Postoperative Mortality and Other Adverse Outcomes
Authors: Mather Rory Vu , Nipp Ryan , Balanza Gustavo , Stone Tom A. D. , Gutierrez Rodrigo , Raje Praachi , Higuchi Masaya , Liu Ran , Santa Cruz Mercado Laura A. , Bittner Edward A. , Kunitake Hiroko , Purdon Patrick L. 
Published: November 2024

Background:
With estimated global postoperative mortality rates at 1% to 4% leading to approximately 3 million to 12 million deaths per year, an urgent need exists for reliable measures of perioperative risk. Existing approaches suffer from poor performance, place a high burden on clinicians to gather data, or do not incorporate intraoperative data. Previous work demonstrated that intraoperative anesthetics induce prefrontal electroencephalogram (EEG) oscillations in the alpha band (8 to 12 Hz) that correlate with postoperative cognitive outcomes.

Methods:
The authors analyzed a retrospective cohort of 1,081 patients undergoing surgery with general anesthesia at Massachusetts General Hospital (Boston, Massachusetts) with intraoperative EEG recordings. The association between EEG alpha power and adverse outcomes was characterized using statistical models that were fitted on propensity weighted data. The primary outcome was postoperative mortality, measured from date of surgery to date of death or last follow-up. Secondary outcomes included mortality within prespecified time windows (30 days, 90 days, 180 days, and 1 yr), hospital and postanesthesia care unit lengths of stay, discharge to long-term care, and 30-day hospital readmission.

Results:
Alpha power was associated with mortality risk (hazard ratio, 0.92; 95% CI, 0.85 to 0.99; P = 0.039). Within specified time windows, alpha power was associated with 30-day mortality (odds ratio, 0.81; 95% CI, 0.66 to 0.95; P = 0.010), 90-day mortality (odds ratio, 0.68; 95% CI, 0.55 to 0.79; P < 0.001), 180-day mortality (odds ratio, 0.75; 95% CI, 0.66 to 0.83; P < 0.001), and 1-yr mortality (odds ratio, 0.85; 95% CI, 0.79 to 0.91; P < 0.001). Additionally, alpha power was associated with discharge to long-term care (odds ratio, 0.91; 95% CI, 0.86 to 0.96; P < 0.001). We did not find significant associations among alpha power and 30-day readmission and hospital or postanesthesia care unit lengths of stay.

Conclusions:
Intraoperative EEG alpha power is independently associated with postoperative mortality and adverse outcomes, suggesting it could represent a broad measure of postoperative physical resilience and provide clinicians with a low-burden, personalized measure of postoperative risk.
Is Reconstructive Plastic Surgery Appropriately Valued? Comparison of Reimbursement per Unit Time for Reconstructive versus Aesthetic Procedures
Authors: De la Fuente Hagopian Alexa , Farhat Souha , Reddy Narainsai K. , Guadarrama-Sistos Vazquez Sebastian , Padilla Pablo L. , Echo Anthony 
Published: November 2024

Background:
The work relative value units (wRVUs) system was established as a quantifier of physician labor, technical skill, medical decision-making, and training time required to complete a surgical procedure; hence, more challenging operations should theoretically result in higher reimbursement or compensation. Our purpose was to highlight the discrepancies between insurance-based reconstructive and fee-for-service aesthetic procedures based upon dollar/unit time.

Methods:
We analyzed national data from the American College of Surgeons National Surgical Quality Improvement Program, Aesthetic Surgery Databank, and Centers for Medicare and Medicaid Services to compare reimbursement for 8 reconstructive microsurgery and 3 aesthetic procedures and assessed operative times and reimbursement rates, then calculated “relative value unit per unit time” to measure compensation efficiency.

Results:
This difference in remuneration translates to a 4.7× difference, with an overwhelming gap of $25.26 per minute between microsurgical reconstructive and aesthetic cases. These findings suggest that aesthetic cases are more profitable considering the compensation per unit time. Based on national rates of reimbursement, there is a large discrepancy between reimbursement in microsurgical reconstructive procedures and aesthetic procedures.

Conclusions:
We demonstrated that complexity and time are not directly related to compensation.
Findings Consistent with a Breast Implant–associated Somatic System Disorder (BIA-SSD) Among Patients Self-reporting Breast Implant Illness
Authors: Bresnick Stephen D. , Morris Susie , Lagman Carlito 
Published: November 2024

Background:
Self-reported breast implant illness (BII) has been found to be associated with anxiety as well as medically diagnosed anxiety and depression. Somatic symptom disorder (SSD) is a relatively common mental health condition that includes anxiety and somatic symptoms, often without a clear cause.

Methods:
We evaluated patients with BII symptoms, with or without a history of an anxiety disorder, for findings consistent with SSD. A total of 120 women were evaluated in 2 cohorts, 60 women with somatic symptoms and breast implants desiring explantation as well as 60 women desiring explantation without BII symptoms. Patient demographics, a patient survey, and validated anxiety scale and somatic symptom scale measurements were obtained.

Results:
Patients with a history of an anxiety disorder and BII symptoms had very high levels of anxiety and highly elevated somatic symptom scores. Patients with a combined diagnosis of anxiety and BII symptoms demonstrated an SSD prevalence of 70.2%, with the difference between the BII/anxiety group and other groups statistically significant (P < 0.01). Other patients with BII symptoms and no history of anxiety had a lower SSD prevalence (21.7%). Patients without a history of BII had little to no SSD inclusion.

Conclusions:
Our data suggest that a significant subset of patients with somatic symptoms have findings consistent with a breast implant–associated somatic symptom disorder. Patients with persistent or excessive thoughts about somatic symptoms will benefit from counseling and referral to an SSD specialist if they wish to maintain breast implants.
Impact of Shifting From Office Work to Telework on Workers’ Physical Health
Authors: Hoshi Rena , Kikuchi Hiroyuki , Machida Masaki , Nakanishi Yutaka , Inoue Shigeru 
Published: November 2024

Objective
The aim of the study is to clarify the longitudinal association between teleworking and physical health changes of Japanese workers before and during the COVID-19 pandemic.

Methods
Participants were in a certain company who received mandatory health examinations in 2019 and 2020. In June 2020, the participants were asked about frequency of teleworking, which was introduced owing to the COVID-19. Whether physical health differed by the frequency of teleworking was analyzed.

Results
The participants were 3689 workers. Frequency of teleworking were associated with more deleterious changes in diastolic blood pressure, antilipidemic drug use, low-density lipoprotein (LDL) cholesterol, Glutamic Oxaloacetic Transaminase(GOT), Glutamic Pyruvic Transaminase(GPT), metabolic syndrome, and insufficient walking time among men. In contrast, no significant changes were observed in women.

Conclusions
Male workers who teleworked more frequently were more likely to experience a deterioration in their physical health within 1-year compared with those who worked at the office.
The OCCHLTH Mnemonic—Construction and Content of a Tool for Increasing Awareness of Occupational Illness and Injury
Authors: Pandalai Sudha P. 
Published: November 2024

Introduction
Unidentified or nonmitigated occupational illnesses and injuries can complicate disease management. The “occupational health” (OCCHLTH) mnemonic aims to raise awareness of work-related exposures and associated illnesses and injuries.

Methods
Occupational safety and health history-taking elements were combined with peer-reviewed information [from the PubMed database (first review January 1, 2000, to February 8, 2016; updated to February 8, 2021)] about workplace exposure-outcome associations to create the mnemonic.

Results
Seven components constitute the OCCHLTH mnemonic. Literature results support its categories and subcategories. Three components represent symptom onset and health conditions. Four represent occupational exposures. Evaluating published occupational illness cases explored mnemonic applicability.

Conclusions
Awareness of occupational risk factors can affect clinical decision-making. The OCCHLTH mnemonic encourages consideration of occupational causes of illness and injury to optimize patient care. Further evaluation of the utility of the OCCHLTH mnemonic is needed.
Orbital Inflammatory Manifestations in a Patient With VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) Syndrome
Authors: Colman Blake D. , Smolyansky Eliot D. , Parmar Hemant A. , Puvanakumar Pratheepan , Fraser Rogan G. , Ramachandran Prashanth , Sheth Shivanand , Shuey Neil , Raviskanthan Subahari 
Published: November 2024

Abstract:
An 84-year-old man with a genetically confirmed diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome treated with tocilizumab reported with a 3-day history of left eye pain, conjunctival chemosis and injection, and horizontal binocular diplopia. Examination revealed restriction of left eye ductions in all directions with mild unilateral proptosis. MRI of his brain and orbits demonstrated abnormal enhancement of the left posterior sclera and intraorbital optic nerve sheath, without involvement of the extraocular muscles, cavernous sinus, or optic nerve parenchyma. B-scan ultrasonography heralded a positive “T-sign.” Empiric treatment with high-dose intravenous methylprednisolone led to rapid clinical improvement. Workup for alternative causes was unremarkable. Oral prednisone dose and tocilizumab ultimately resulted in complete resolution after 4 weeks. The final diagnosis was consistent with orbital inflammatory manifestations of VEXAS syndrome.
DyNDG: Identifying Leukemia-Related Genes based on the Time-Series Dynamical Network by Integrating Differential Genes
Authors: Jin A , Xiang Ju , Meng Xiangmao , Sheng Yue , Peng Hongling , Li Min 
Published: November 2024

AbstractLeukemia is a malignant disease of progressive accumulation characterized by high morbidity and mortality rates, and investigating its disease genes is crucial for understanding its etiology and pathogenesis. Network propagation methods have emerged and been widely employed in disease gene prediction, but most of them focus on static biological networks, which hinders their applicability and effectiveness in the study of progressive diseases. Moreover, there is currently a lack of special algorithms for the identification of leukemia disease genes. Here, we proposed DyNDG, a novel Dynamic Network-based model, which integrates Differentially Expressed Genes to identify leukemia-related genes. Initially, we constructed a time-series dynamic network to model the development trajectory of leukemia. Then, we built a background-temporal multilayer network by integrating both the dynamic network and the static background network, which was initialized with differentially expressed genes at each stage. To quantify the associations between genes and leukemia, we extended a random walk process to the background-temporal multilayer network. The experimental results demonstrate that DyNDG achieves superior accuracy compared to several state-of-the-art methods. Moreover, after excluding housekeeping genes, DyNDG yields a set of promising candidate genes associated with leukemia progression or potential biomarkers, indicating the value of dynamic network information in identifying leukemia-related genes. The implementation of DyNDG is available athttps://github.com/CSUBioGroup/DyNDG.
Exploiting uniqueness: seed-chain-extend alignment on elastic founder graphs
Authors: Rizzo Nicola , Cáceres Manuel , Mäkinen Veli 
Published: November 2024

AbstractSequence-to-graph alignment is a central challenge of computational pangenomics. To overcome the theoretical hardness of the problem, state-of-the-art tools useseed-and-extendorseed-chain-extendheuristics to alignment, therefore reducing the computational resources required for the task. However, two main problems still remain: on the one hand, the daunting amount of sequencing data requires us to trade alignment accuracy with computational resources; on the other hand, current graph representations of pangenomes introduce an excessive amount of spurious recombinations.In this paper, we implement a complete seed-chain-extend alignment workflow based onindexable elastic founder graphs(iEFGs), a class of graphs built from aligned sequences and supporting fast pattern matching while reducing the number of artificial recombinations. We show how to construct iEFGs from the variations to a linear reference, find high-quality seeds, and extend them usingGraphAligner, at the scale of a telomere-to-telomere assembled human chromosome.The main ingredient of our workflow is the use and the efficient computation ofsemi-repeat-free seeds(srf), a novel class of iEFG-based seeds introduced in this work. The amount of srf seeds is two orders of magnitude less than that of minimizers at the human chromosome level while maintaining comparable speed. Thanks to the uniqueness properties of iEFGs, we show that srf-based seeds suffice to maintain high accuracy while leveraging the speed of our tool. To further stress our point, we also implement chaining of seeds on the elastic degenerate string relaxation of the iEFG and show that only chained seeds suffice to achieve high accuracy alignments.Our sequence-to-graph alignment tool and the scripts to replicate our experiments are available inhttps://github.com/algbio/SRFAligner.
Immune organization in sentinel lymph nodes of melanoma patients is prognostic of distant metastases
Authors: Amitay Yael , Milo Idan , Keidar Haran Tal , Deis Saif , Truzman Guy , Elhanani Ofer , Salame Tomer-Meir , Azimov Michal , Stein Ilan , Cohen Jonathan E. , Lotem Michal , Pikarsky Eli , Keren Leeat 
Published: November 2024

AbstractSentinel lymph node (sLN) biopsy is part of melanoma staging, as involved LNs indicate a higher risk of recurrence. However, how the sLN is shaped by the tumor and reciprocally affects metastatic progression is poorly understood. Here, we mapped immune organization in involved and non-involved sLNs of 69 melanoma patients using high-resolution spatial proteomics, spatial transcriptomics and deep learning, leveraging the data for prognostic evaluation. In patients with involved LNs, a robust T cell response correlated with absence of recurrence. In non-involved LNs, protection from metastases was linked to expanded sinuses colocalized with plasmablasts whereas CCR7+ cells and Tregs correlated with future development of distant metastases. We trained a model that predicts development of distant metastases with 79% and 93% AUC for non-metastatic and metastatic LNs, respectively. Our findings reveal conserved immune patterns in sLNs that prospectively identify patients at risk for metastatic disease and may aid in therapeutic decisions.
Promoting Polarization and Differentiation of Primary Human Salivary Gland Stem/Progenitor Cells in Protease-Degradable Hydrogels via ROCK Inhibition
Authors: Metkari Apoorva S. , Witt Robert L. , Cognetti David M. , Dhong Charles , Jia Xinqiao 
Published: November 2024

ABSTRACTTowards the goal ofin vitroengineering of functional salivary gland tissues, we cultured primary human salivary stem/progenitor cells (hS/PCs) in hyaluronic acid-based matrices with varying percentages of proteolytically degradable crosslinks in the presence of Rho kinase (ROCK) inhibitor. Single cells encapsulated in the hydrogel grew into organized multicellular structures by day 15, and over 60% of the structures developed in the non-degradable and 50% degradable hydrogels contained a central lumen. Importantly, ROCK inhibition led to the establishment of multicellular structures that were correctly polarized, as evidenced by apical localization of a Golgi marker GM130, apical/lateral localization of tight junction protein zonula occludens-1 (ZO-1), and basal localization of integrin β1 and basement membrane proteins laminin α1 and collagen IV. Cultures maintained in 50% degradable gels with ROCK inhibition exhibited an increased expression of acinar markersAQP5andSLC12A2(at the transcript level) and AQP5 and NKCC1 (at the protein level) as compared to those without ROCK inhibition. Upon stimulation with isoproterenol, α-amylase secretion into the lumen was observed. Particle-tracking microrheology was employed to analyze the stiffness of cells using mitochondria as the passive tracer particles. Our results indicated that cells grown in 100% degradable gels were stiffer than those maintained in non-degradable gels, and cells cultured with the ROCK inhibitor were softer than those maintained without the inhibitor. We conclude that reducing cellular contractility via ROCK inhibition while retaining some degree of matrix confinement promotes the establishment of multicellular structures containing pro-acinar cells with correct apicobasal polarization.
HIV Pre-Exposure Prophylaxis Scale-Up in Mozambique from October 2021 to December 2023
Authors: Maibaze Gonçalves , Gaspar Nuno , Seleme Jessica , Swor Meghan , Couto Aleny , Malimane Inacio , Canda Marcos , Simbine Ana Paula , Troger Mark , Namburete Evangelina 
Published: November 2024

SummaryIn 2021, The Mozambique Ministry of Health began offering HIV pre-exposure prophylaxis (PrEP) in all provinces. The number of new clients increased more than three-fold within two years. Among 51,848 new people receiving PrEP by December 2023, the largest groups were females and adolescent young adults.