bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of local prolonged-release incisional doxycycline on surgical site infection prophylaxis in abdominal colorectal surgery: the SHIELD 1 randomized clinical trial
Authors: Zmora Oded , Fleshner Phillip , Barie Philip S. , Segev Lior , Viola George M. , Senagore Anthony J. , Spinelli Antonino , Belotserkovsky Olga , Sharoni Shmuel , Emanuel Noam ,   for the SHIELD 1 Investigators
Published: June 2024

Introduction:
Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release doxycycline-polymer-lipid encapsulation matrix (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery.

Materials and methods:
This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length greater than 10 cm were randomized 1:1 to the investigational arm (D‐PLEX+SOC) or control (SOC) arm. The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality.

Results:
A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) [risk difference estimate (RDE), −2.8%; 95% CI (−6.7%, 1.0%), P=0.1520]. In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the greater than 20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) [RDE, −9.4%; 95% CI (−15.5%, −3.2%), P=0.0032]. In the greater than 10 to less than or equal to 20 cm subgroup, no reduction was observed: 9.9% versus 7.9% [RDE, 2.0%; 95% CI (−2.8%, 6.7%), P=0.4133]. Exploratory post hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) [RDE, −4.8%; 95% CI (−9.5%, −0.1%), P=0.0472]. The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups).

Conclusions:
The SHIELD 1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.
Public Health Involvement in United States’ Vision Zero Initiatives: A Mixed-Methods Study
Authors: Evenson Kelly R. , Kintigh Jordan M. , Neuroth Lucas M. , LaJeunesse Seth , Naumann Rebecca B. 
Published: June 2024

Context:
Vision Zero (VZ) aims to reduce fatalities and serious injuries from road traffic crashes to zero through multidisciplinary coordination. While public health officials are often recognized as critical to VZ, their involvement in VZ across the United States has not been quantified.

Objective:
To explore how United States public health officials were involved in VZ development and implementation.

Design:
We used a mixed-method design including a quantitative assessment of VZ plans and in-depth interviewing with VZ coordinators.

Setting:
United States

Participants:
Twenty-two in-depth interviews with municipal (n = 12) and regional (n = 10) VZ coordinators and 43 VZ plans were reviewed.

Main Outcome Measure:
Public health involvement in VZ development and implementation.

Results:
In the United States, 64 municipalities and 21 regional entities had first-time VZ plans published between 2014 and 2022. We abstracted a sample of municipal (n = 22) and all (n = 21) regional plans. Most plans described key groups involved in plan development (municipal 81.8%, regional 100%). About two-thirds (67.4%; 59.1% municipal, 76.2% regional) of the plans noted public health officials in the plan development. Most plans described the principles forming the foundation of their plan (83.7%), but few mentioned public health as part of the plan principles (22.7% municipal, 14.3% regional). Public health officials were involved in engaging the community (9.1% municipal, 33.3% regional) and providing data (22.7% municipal, 52.4% regional) for plan development, as documented in the plans. For proposed implementation, public health officials were identified as involved in: community engagement (31.8% municipal, 42.9% regional), sharing/analyzing data (40.9% municipal, 33.3% regional), and identifying/providing funding sources (13.6% municipal, 4.8% regional). The in-depth interviews provided further context and a more detailed understanding of public health involvement in VZ.

Conclusions:
Evidence from the VZ plans and interviews provided examples of how public health officials engaged in the development and implementation of VZ initiatives.
Rapid Forehead Ossification due to a Subperiosteal Hematoma in a Patient With Neurofibromatosis Type 1
Authors: Anan Kentaro , Kadota Hideki , Oryoji Chikafumi 
Published: June 2024

Rapid ossification due to a subperiosteal hematoma in extremities has occasionally been documented in patients with neurofibromatosis type 1, but it has not been reported in the maxillofacial region. The authors present the first case of a subperiosteal hematoma in the forehead. A 36-year-old man presented with a rapidly swelling firm, fixed, 8×10 cm forehead mass. It became evident shortly after a fine-needle aspiration biopsy. Computed tomography imaging 2 months after the biopsy showed a hematoma that was encapsulated by a surrounding layer of ossification. Magnetic resonance imaging displayed a fluid-fluid level under the ossified area. These characteristic images led us to diagnose this rare lesion as a subperiosteal hematoma with ossification. Rapid ossification is a characteristic imaging finding of subperiosteal hematoma, which makes definitive diagnosis easy. It becomes imperative to underscore the potential risks of fine-needle aspiration in proximity to the periosteum in patients with neurofibromatosis type 1.
Benefits of Aerosolized, Point-of-care, Autologous Skin Cell Suspension (ASCS) for the Closure of Full-thickness Wounds From Thermal and Nonthermal Causes
Authors: Hultman C. Scott , Adams Ursula C. , Rogers Corianne D. , Pillai Minakshi , Brown Samantha T. , McGroarty Carrie Ann , McMoon Michelle , Uberti M. Georgina 
Published: June 2024

Objective:
To determine the utility of Autologous Skin Cell Suspension (ASCS) in closing full-thickness (FT) defects from injury and infection.

Background:
Although ASCS has documented success in closing partial-thickness burns, far less is known about the efficacy of ASCS in FT defects.

Methods:
Fifty consecutive patients with FT defects (burn 17, necrotizing infection 13, crush 7, degloving 5, and other 8) underwent closure with the bilayer technique of 3:1 widely meshed, thin, split-thickness skin graft and 80:1 expanded ASCS. End points were limb salvage rate, donor site reduction, operative and hospital throughput, incidence of complications, and re-epithelialization by 4, 8, and 12 weeks.

Results:
Definitive wound closure was achieved in 76%, 94%, and 98% of patients, at 4, 8, and 12 weeks, respectively. Limb salvage occurred in 42/43 patients (10 upper and 33 lower extremities). The mean area grafted was 435 cm2; donor site size was 212 cm2, representing a potential reduction of 50%. The mean surgical time was 71 minutes; the total operating room time was 124 minutes. The mean length of stay was 26.4 days; the time from grafting to discharge was 11.2 days. Four out of 50 patients (8%) required 6 reoperations for bleeding (1), breakdown (4), and amputation (1). Four out of 50 patients (8%) developed hypertrophic scarring, which responded to silicone sheeting (2) and laser resurfacing (2). The mean follow-up was 92.7 days.

Conclusions:
When used for the closure of FT wounds, point-of-care ASCS is effective and safe. Benefits include rapid re-epithelialization, high rate of limb salvage, reduction of donor site size and morbidity, and low incidence of hypertrophic scarring.
Psychosocial Evaluation of Living Kidney Donors: A Survey of Current Practices in the United States
Authors: Clifton Erin , Winder Gerald Scott , Lentine Krista L. , Zimbrean Paula C. , Yadav Anju , Rubman Susan , Kalil Roberto , Kumar Vineeta , Prashar Rohini , Gan Geliang , Deng Yanhong , Joyce Michael , Holmes Rachel , Laflen Jennie , Bakhai Darsh , Liapakis AnnMarie , Doshi Mona D. 
Published: June 2024

Background.
Best practices in psychosocial evaluation and care of living donor candidates and donors are not well established.

Methods.
We surveyed 195 living kidney donor (LKD) transplant centers in United States from October 2021 to April 2022 querying (1) composition of psychosocial teams, (2) evaluation processes including clinical tools and domains assessed, (3) selection criteria, and (4) psychosocial follow-up post-donation.

Results.
We received 161 responses from 104 programs, representing 53% of active LKD programs and 67% of LKD transplant volume in 2019. Most respondents (63%) were social workers/independent living donor advocates. Over 90% of respondents indicated donor candidates with known mental health or substance use disorders were initially evaluated by the psychosocial team. Validated psychometric or transplant-specific tools were rarely utilized but domains assessed were consistent. Active suicidality, self-harm, and psychosis were considered absolute contraindications in >90% of programs. Active depression was absolute contraindication in 50% of programs; active anxiety disorder was excluded 27%. Conditions not contraindicated to donation include those in remission: anxiety (56%), depression (53%), and posttraumatic stress disorder (41%). There was acceptance of donor candidates using alcohol, tobacco, or cannabis recreationally, but not if pattern met criteria for active use disorder. Seventy-one percent of programs conducted post-donation psychosocial assessment and use local resources to support donors.

Conclusions.
There was variation in acceptance of donor candidates with mental health or substance use disorders. Although most programs conducted psychosocial screening post-donation, support is not standardized and unclear if adequate. Future studies are needed for consensus building among transplant centers to form guidelines for donor evaluation, acceptance, and support.
Alzheimer’s disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression
Authors: Ropri Ali S. , Lam Tiffany G. , Kalia Vrinda , Buchanan Heather M. , Bartosch Anne Marie W. , Youth Elliot H. H. , Xiao Harrison , Ross Sophie K. , Jain Anu , Chakrabarty Jayanta K. , Kang Min Suk , Boyett Deborah , Spinazzi Eleonora F. , Iodice Gail , McGovern Robert A. , Honig Lawrence S. , Brown Lewis M. , Miller Gary W. , McKhann Guy M. , Teich Andrew F. 
Published: June 2024

AbstractINTRODUCTIONNormal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact.METHODSWe analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.RESULTSAD pathology on biopsy correlates with CSF β-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data..DISCUSSIONAs additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.
Global access to speech hearing tests
Authors: Polspoel Sigrid , Moore David R. , Swanepoel De Wet , Kramer Sophia E. , Smits Cas 
Published: June 2024

ABSTRACTUnderstanding speech in noisy settings is one of the biggest challenges for individuals with hearing loss. Traditional speech-in-noise tests play a crucial role in screening for and diagnosing hearing loss, but are resource-intensive to develop, limiting accessibility, particularly in low and middle-income countries. This four-part study introduces an innovative approach using artificial intelligence (AI) to automate the development of such tests. By leveraging text-to-speech (TTS) and automatic speech recognition (ASR) technologies, this approach significantly reduces the cost, time, and resources required for high-quality speech-in-noise testing accessible worldwide. The procedure, named “Aladdin” (Automatic LAnguage-independent Development of the Digits-In-Noise test), creates digits-in-noise (DIN) hearing tests through synthetic speech material and ASR-based level corrections to perceptually equalize the digits, demonstrating characteristics comparable to traditional tests. Notably, Aladdin provides a universal guideline for developing DIN tests across languages, addressing the challenge of comparing test results across variants. This approach, with its potential for broad application in audiology, represents a significant advancement in test development and offers a cost-effective and efficient enhancement to global screening and treatment for hearing loss.
A protocol for the co-creation and usability/acceptability testing of an evidence-based, patient-centred intervention for self-management of urinary incontinence in older men
Authors: Olagundoye Olawunmi , Gibson William , Wagg Adrian 
Published: June 2024

AbstractMale urinary incontinence (UI) is most prevalent in older men, with one in three men aged 65 and above having problems maintaining continence. Addressing health inequalities, male-female disparities in continence services, and low health-seeking behavior among men emphasizes the necessity for co-creating an intervention that empowers them to self-manage their UI.We aim to co-create a self-management intervention with an older men and Health care provider (HCP) group and assess its usability/acceptability among older men with UI.The intervention mapping (IM) framework, a co-creation strategy, will be used to co-create a self-management tool, followed by usability/acceptability testing. The study will be guided by the first four IM steps: the logic model of the problem, the logic model of change, program/intervention design, and program/intervention production, followed by preliminary testing. A participatory group of older men with UI recruited from an existing group of patient partners, and continence care experts will be involved in all steps of the IM process. Usability/acceptability testing will be conducted on a sample of 20 users recruited through seniors’ associations and retirement living facilities. After accessing the self-management tool for a week, participants will complete a product usability testing scale (aka System Usability Scale-SUS) and/or an acceptability test, depending on the preferred mode(s) of intervention delivery. Data will be analyzed using descriptive statistics. A benchmark overall mean usability score of 70 represents a good/usable product, based on the large database of SUS scores.
Differential contribution of direct and indirect pathways from dorsolateral and dorsomedial striatum to motor symptoms in Huntington’s disease mice
Authors: Conde-Berriozabal Sara , Sitjà-Roqueta Laia , García-García Esther , García-Gilabert Lia , Sancho-Balsells Anna , Fernández-García Sara , Rodriguez-Urgellés Ened , Giralt Albert , López-Gil Javier , Muñoz-Moreno Emma , Castañé Anna , Soria Guadalupe , Rodríguez Manuel J , Alberch Jordi , Masana Mercè 
Published: June 2024

ABSTRACTThe alterations in the basal ganglia circuitry associated with motor symptoms in Huntington’s Disease (HD) have been extensively investigated. Yet, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor dysfunction is still not fully understood. Here, using the symptomatic R6/1 male mouse model of HD, strong functional connectivity alterations between DMS and DLS regions with the rest of brain were observed by fMRI, particularly pronounced in the DLS. Then, we systematically evaluated how the selective optogenetic stimulation of the direct and indirect pathways from DLS and DMS influences locomotion, exploratory behavior, and motor learning. In wild type (WT) mice, optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS elicited subtle locomotor enhancements, while exploratory behavior remained unaltered. Additionally, stimulation of the indirect pathway from DLS improved the performance in the accelerated rotarod task. In contrast, in HD mice, optogenetic stimulation of the distinct striatal pathways did not modulate these behaviors. Overall, this study points to deficits in the integration of neuronal activity in HD mice, while it contributes to deeper understanding of the complexity of motor control by the diverse striatal subcircuits.
Scale matters: Large language models with billions (rather than millions) of parameters better match neural representations of natural language
Authors: Hong Zhuoqiao , Wang Haocheng , Zada Zaid , Gazula Harshvardhan , Turner David , Aubrey Bobbi , Niekerken Leonard , Doyle Werner , Devore Sasha , Dugan Patricia , Friedman Daniel , Devinsky Orrin , Flinker Adeen , Hasson Uri , Nastase Samuel A. , Goldstein Ariel 
Published: June 2024

AbstractRecent research has used large language models (LLMs) to study the neural basis of naturalistic language processing in the human brain. LLMs have rapidly grown in complexity, leading to improved language processing capabilities. However, neuroscience researchers haven’t kept up with the quick progress in LLM development. Here, we utilized several families of transformer-based LLMs to investigate the relationship between model size and their ability to capture linguistic information in the human brain. Crucially, a subset of LLMs were trained on a fixed training set, enabling us to dissociate model size from architecture and training set size. We used electrocorticography (ECoG) to measure neural activity in epilepsy patients while they listened to a 30-minute naturalistic audio story. We fit electrode-wise encoding models using contextual embeddings extracted from each hidden layer of the LLMs to predict word-level neural signals. In line with prior work, we found that larger LLMs better capture the structure of natural language and better predict neural activity. We also found a log-linear relationship where the encoding performance peaks in relatively earlier layers as model size increases. We also observed variations in the best-performing layer across different brain regions, corresponding to an organized language processing hierarchy.
Interactively Integrating Reach and Grasp Information in Macaque Premotor Cortex
Authors: Chen Junjun , Sun Guanghao , Zhang Yiwei , Chen Weidong , Zheng Xiaoxiang , Zhang Shaomin , Hao Yaoyao 
Published: June 2024

AbstractSuccessful reach-to-grasp movements necessitate the integration of both object location and grip type information. However, how these two types of information are encoded in a single brain region and to what extend they interact with each other, remain largely unknown. We designed a novel experimental paradigm that sequentially prompted reach and grasp cues to monkeys and recorded neural activity in the dorsal premotor cortex (PMd) to investigate how the encoding structures change and interact during arm reaching and hand grasping movements. This paradigm required monkeys to retain the first prompted cue when the second one arrived, and integrate both to accomplish a final goal movement. PMd neurons represented both reach and grasp to similar extend, yet the encodings were not independent. Upon the arrival of second cue, PMd continued to encode the first cue, albeit with a significantly altered structure, as evidenced by more than half of the neurons displaying incongruent modulation. At a population level, the encoding structure formed a distinct subspace that differed from, but was not entirely orthogonal to, the original one. Employing canonical correlation analysis, we identified a subspace that consistently preserved the encoding of the initial cue, potentially serving as a mechanism for downstream brain regions to extract coherent information. Furthermore, this shared subspace comprised a diverse population of neurons, including both congruent and incongruent units. these findings support the argument that reach and grasp information are interactively integrated within PMd, with a shared subspace likely underpinning a consistent encoding framework.
Transcriptomics and proteomics of projection neurons in a circuit linking hippocampus with dorsolateral prefrontal cortex in human brain
Authors: Bharadwaj Rahul A. , Borcuk Christopher , Kikidis Gianluca C. , Sportelli Leonardo , Bertolino Alessandro , Cole Robert N. , DeVine Lauren , Kleinman Joel E. , Maher Brady , Sripathy Srinidhi R. , Mallepalli Vamshi , Parihar Madhur , Shin Joo Heon , Lee Yong Kyu , Montoya Carly , Deep-Soboslay Amy , Hyde Thomas M. , Weinberger Daniel R. , Pergola Giulio 
Published: June 2024

AbstractRNA-sequencing studies of brain tissue homogenates have shed light on the molecular processes underlying schizophrenia (SCZ) but lack biological granularity at the cell type level. Laser capture microdissection (LCM) can isolate selective cell populations with intact cell bodies to allow complementary gene expression analyses of mRNA and protein. We used LCM to collect excitatory neuron-enriched samples from CA1 and subiculum (SUB) of the hippocampus and layer III of the dorsolateral prefrontal cortex (DLPFC), from which we generated gene, transcript, and peptide level data. In a machine learning framework, LCM-derived expression achieved superior regional identity predictions as compared to bulk tissue, with further improvements when using isoform-level transcript and protein quantifications. LCM-derived co-expression also had increased co-expression strength of neuronal gene sets compared to tissue homogenates. SCZ risk co-expression pathways were identified and replicated across transcript and protein networks and were consistently enriched for glutamate receptor complex and post-synaptic functions. Finally, through inter-regional co-expression analyses, we show that CA1 to SUB transcriptomic connectivity may be altered in SCZ.
Mitochondrial damage triggers concerted degradation of negative regulators of neuronal autophagy
Authors: Basak Bishal , Holzbaur Erika L.F. 
Published: June 2024

ABSTRACTMutations in genes that regulate mitophagy, a key mitochondrial quality control pathway, are causative for neurological disorders including Parkinson’s. Here, we identify a novel stress response pathway activated by mitochondrial damage that regulates mitophagy in neurons. We find that increasing levels of mitochondrial stress triggers a graded, concerted response that induces proteasomal degradation of negative regulators of autophagy. These include Myotubularin-related phosphatase 5 (MTMR5), MTMR2 and Rubicon. This ‘MitophagicStressResponse’ (MitoSR) pathway is neuron-specific and acts in parallel to the classical Pink1/Parkin-mediated mitophagy pathway. While MTMR5/MTMR2 inhibits autophagosome biogenesis, we find that Rubicon inhibits lysosomal function and thus blocks autophagosome maturation. Targeted depletion of these negative regulators is sufficient to enhance mitophagy, promoting autophagosome biogenesis and facilitating the fusion of mitophagosomes with lysosomes. Our work suggests that therapeutic activation of the MitoSR pathway to induce degradation of negative regulators of autophagy may enhance mitochondrial quality control in stressed neurons.