bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons
Authors: Kim Hyoung Woo , Shim Sang Wook , Zhao Anna Mae , Roh Dahee , Han Hye Min , Middleton Steven J. , Kim Wheedong , Chung Sena , Johnson Errin , Prentice John , Tacon Mike , Koel-Simmelink Marleen J.A. , Wieske Luuk , Teunissen Charlotte E. , Bae Yong Chul , Bennett David L.H. , Rinaldi Simon , Davies Alexander J. , Oh Seog Bae 
Published: June 2023

Abstract
Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of “painful” nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete (“full”) or incomplete (“partial”) axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.
Gross Hematuria and Lower Urinary Tract Symptoms Associated With Military Burn Pits Exposures in US Veterans Deployed to Iraq and Afghanistan
Authors: Perveen Mosammat M. , Mayo-Malasky Henry E. , Lee-Wong Mary F. , Tomaska Julie M. , Forsyth Edward , Gravely Amy , Klein Mark A. , Trembley Janeen H. , Butterick Tammy A. , Promisloff Robert A. , Ginex Pamela K. , Barach Paul , Szema Anthony M. 
Published: June 2023

Objective
The aim of the study is to describe rates of hematuria and other lower urinary tract symptoms, including self-reported cancer rates, among veterans postburn pits emissions exposure during deployment to Iraq and Afghanistan.

Methods
US post-9/11 veterans with burn pits emissions exposure confirmed via DD214 forms in the Burn Pits360.org Registry were sent a modified survey. Data were deidentified and anonymously coded.

Results
Twenty-nine percent of the 155 respondents exposed to burn pits self-reported seeing blood in their urine. The average index score of our modified American Urological Association Symptom Index Survey was 12.25 (SD, 7.48). High rates of urinary frequency (84%) and urgency (76%) were self-reported. Bladder, kidney, or lung cancers were self-reported in 3.87%.

Conclusions
US veterans exposed to burn pits are self-reporting hematuria and other lower urinary tract symptoms.
The Impact of Daily Processor Use on Adult Cochlear Implant Outcomes: Reexamining the Roles of Duration of Deafness and Age at Implantation
Authors: DeFreese Andrea J. , Lindquist Nathan R. , Shi Linjie , Holder Jourdan T. , Berg Katelyn A. , Haynes David S. , Gifford René H. 
Published: June 2023

Objective
To quantify the roles and relationships between age at implantation, duration of deafness (DoD), and daily processor use via data logging on speech recognition outcomes for postlingually deafened adults with cochlear implants.

Study Design
Retrospective case review.

Setting
Cochlear implant (CI) program at a tertiary medical center.

Patients
Six-hundred fourteen postlingually deafened adult ears with CIs (mean age, 63 yr; 44% female) were included.

Main Outcome Measure(s)
A stepwise multiple regression analysis was completed to investigate the combined effects of age, DoD, and daily processor use on CI-aided speech recognition (Consonant-Nucleus-Consonant monosyllables and AzBio sentences).

Results
Results indicated that only daily processor use was significantly related to Consonant-Nucleus-Consonant word scores (R
2 = 0.194, p < 0.001) and AzBio in quiet scores (R
2 = 0.198, p < 0.001), whereas neither age nor DoD was significantly related. In addition, there was no significant relationship between daily processor use, age at implantation, or DoD and AzBio sentences in noise (R
2 = 0.026, p = 0.005).

Conclusions
Considering the clinical factors of age at implantation, DoD, and daily processor use, only daily processor use significantly predicted the ~20% of variance in postoperative outcomes (CI-aided speech recognition) accounted for by these clinical factors.
Deep Learning Models for Severity Prediction of Acute Pancreatitis in the Early Phase From Abdominal Nonenhanced Computed Tomography Images
Authors: Chen Zhiyao , Wang Yi , Zhang Huiling , Yin Hongkun , Hu Cheng , Huang Zixing , Tan Qingyuan , Song Bin , Deng Lihui , Xia Qing 
Published: June 2023

Objectives
To develop and validate deep learning (DL) models for predicting the severity of acute pancreatitis (AP) by using abdominal nonenhanced computed tomography (CT) images.

Methods
The study included 978 AP patients admitted within 72 hours after onset and performed abdominal CT on admission. The image DL model was built by the convolutional neural networks. The combined model was developed by integrating CT images and clinical markers. The performance of the models was evaluated by using the area under the receiver operating characteristic curve.

Results
The clinical, Image DL, and the combined DL models were developed in 783 AP patients and validated in 195 AP patients. The combined models possessed the predictive accuracy of 90.0%, 32.4%, and 74.2% for mild, moderately severe, and severe AP. The combined DL model outperformed clinical and image DL models with 0.820 (95% confidence interval, 0.759–0.871), the sensitivity of 84.76% and the specificity of 66.67% for predicting mild AP and the area under the receiver operating characteristic curve of 0.920 (95% confidence interval, 0.873–0.954), the sensitivity of 90.32%, and the specificity of 82.93% for predicting severe AP.

Conclusions
The DL technology allows nonenhanced CT images as a novel tool for predicting the severity of AP.
Pathways From HIV-Related Stigma, Racial Discrimination, and Gender Discrimination to HIV Treatment Outcomes Among Women Living With HIV in Canada: Longitudinal Cohort Findings
Authors: Malama Kalonde , Logie Carmen H. , Sokolovic Nina , Skeritt Lashanda , O'Brien Nadia , Cardinal Claudette , Gagnier Brenda , Loutfy Mona , Kaida Angela , de Pokomandy Alexandra 
Published: June 2023

Background:
HIV-related stigma, gender discrimination, and racial discrimination harm mental health and hamper HIV treatment access for women living with HIV. Maladaptive coping strategies, such as substance use, can further worsen HIV treatment outcomes, whereas resilience can improve HIV outcomes. We examined resilience and depression as mediators of the relationship between multiple stigmas and HIV treatment outcomes among women living with HIV.

Setting:
Ontario, British Columbia, and Quebec, Canada.

Methods:
We conducted a longitudinal study with 3 waves at 18-month intervals. We used structural equation modeling to test the associations of multiple stigmas (HIV-related stigma, racial discrimination, and gender discrimination) or an intersectional construct of all 3 stigmas at wave 1 on self-reported HIV treatment cascade outcomes (≥95% antiretroviral treatment [ART] adherence, undetectable viral load) at wave 3. We tested depression and resilience at wave 2 as potential mediators and adjusted for sociodemographic factors.

Results:
There were 1422 participants at wave 1, half of whom were Black (29%) or Indigenous (20%). Most participants reported high ART adherence (74%) and viral suppression (93%). Racial discrimination was directly associated with having a detectable viral load, while intersectional stigma was directly associated with lower ART adherence. Resilience mediated associations between individual and intersectional stigmas and HIV treatment cascade outcomes, but depression did not. Racial discrimination was associated with increased resilience, while intersectional and other individual stigmas were associated with reduced resilience.

Conclusion:
Race, gender and HIV-related stigma reduction interventions are required to address intersectional stigma among women living with HIV. Including resilience-building activities in these interventions may improve HIV treatment outcomes.
Modified Drilled Extended Spreader Grafts in Asian Rhinoplasty: Clinical Application and Histopathological Analysis
Authors: Xu Yihao , Song Zhen , Zhang Xulong , Guo Junsheng , Tian Le , Zheng Ruobing , Wang Huan , You Jianjun , Fan Fei 
Published: June 2023

Background:
Extended Spreader Grafts (ESGs) are widely used for both esthetic and functional purpose in rhinoplasty. This study aims to examine the effects of drilling on ESGs in rhinoplasty and their clinical benefits, as well as to analyze their histologic characteristics.

Methods:
We conducted a retrospective review of patients undergoing esthetic rhinoplasty using drilled ESGs with autologous costal cartilage by a senior surgeon from January 2018 to April 2022.

Results:
A total of 80 patients were included, with a mean follow-up period of 26 months. Revision operations were performed on 4 patients. The phenomenon of tissue ingrowth from the septum mucoperichondrium to the septal cartilage through the holes of the drilled ESGs was observed in all 4 patients. Specimens of the ingrown tissue were taken from 3 patients during their revision surgeries. Vascular structures and connective tissue were observed in the specimens after fixation, paraffin embedding, and staining with hematoxylin-eosin. No other complications were observed except for 2 cases presenting cartilage warping after surgery.

Conclusion:
Application of the drilled ESGs is a simple but effective approach, which has 3 significant advantages in rhinoplasty: enhancing the stability of the cartilaginous framework through connective tissue ingrowth, preserving the septal cartilage, and providing septum vitality by allowing the formation of vascular structures between the perichondrium and the septal cartilage; reducing the probability of warping in early stages through release the tension force of the cartilage itself.

Level of Evidence:
Level IV.
GRPa-PRS: A risk stratification method to identify genetically-regulated pathways in polygenic diseases
Authors: Li Xiaoyang , Fernandes Brisa S. , Liu Andi , Chen Jingchun , Chen Xiangning , Zhao Zhongming , Dai Yulin 
Published: June 2023

ABSTRACTBackgroundPolygenic risk scores (PRS) are tools used to evaluate an individual’s susceptibility to polygenic diseases based on their genetic profile. A considerable proportion of people carry a high genetic risk but evade the disease. On the other hand, some individuals with a low risk of eventually developing the disease. We hypothesized that unknown counterfactors might be involved in reversing the PRS prediction, which might provide new insights into the pathogenesis, prevention, and early intervention of diseases.MethodsWe built a novel computational framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification for each cohort. We curated two AD cohorts with genotyping data; the discovery (disc) and the replication (rep) datasets include 2722 and 2854 individuals, respectively. First, we calculated the optimized PRS model based on the three recent AD GWAS summary statistics for each cohort. Then, we stratified the individuals by their PRS and clinical diagnosis into six biologically meaningful PRS strata, such as AD cases with low/high risk and cognitively normal (CN) with low/high risk. Lastly, we imputed individual genetically-regulated expression (GReX) and identified differential GReX and GRPas between risk strata using gene-set enrichment and variational analyses in two models, with and withoutAPOEeffects. An orthogonality test was further conducted to verify those GRPas are independent of PRS risk. To verify the generalizability of other polygenic diseases, we further applied a default model of GRPa-PRS for schizophrenia (SCZ).ResultsFor each stratum, we conducted the same procedures in both the disc and rep datasets for comparison. In AD, we identified several well-known AD-related pathways, including amyloid-beta clearance, tau protein binding, and astrocyte response to oxidative stress. Additionally, we discovered resilience-related GRPs that are orthogonal to AD PRS, such as the calcium signaling pathway and divalent inorganic cation homeostasis. In SCZ, pathways related to mitochondrial function and muscle development were highlighted. Finally, our GRPa-PRS method identified more consistent differential pathways compared to another variant-based pathway PRS method.ConclusionsWe developed a framework, GRPa-PRS, to systematically explore the differential GReX and GRPas among individuals stratified by their estimated PRS. The GReX-level comparison among those strata unveiled new insights into the pathways associated with disease risk and resilience. Our framework is extendable to other polygenic complex diseases.
Service delivery in acute ischemic stroke patients: Does sex matter?
Authors: Medlin Friedrich , Strambo Davide , Lambrou Dimitris , Caso Valeria , Michel Patrik 
Published: June 2023

AbstractBackgroundWomen with acute ischemic stroke (AIS) are older and have higher preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients.MethodssWe analyzed all patients from the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 03/2003-12/2019. Multivariate analyses were performed on acute time metrics, revascularization therapies, ancillary exams for stroke work-up, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care) and length of hospital stay.ResultsOf the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio (aHR):1.09, 95% confidence interval (CI) 1.04-1.14) and door-to-endovascular-puncture intervals (aHR:1.15, 95%CI:1.05-1.25). Women underwent less diagnostic exams (adjusted odds ratio (aOR): 0.94, 95%CI:0.85-1.04), fewer subacute carotid revascularizations (aOR:0.69, 95% CI:0.33-1.18) and had longer hospital stays (aHR:1.03, 95%CI:0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments.ConclusionsIn this retrospective analysis of a large, consecutive AIS cohort, female sex was associated with unfavorable pre- and inhospital time metrics, and lesser diagnostic exam and carotid revascularization rates. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention.
MATERNAL DETERMINANTS OF ADVERSE NEONATAL OUTCOMES IN A RURAL DISTRICT HOSPITAL IN EAST AFRICA
Authors: Ogah Adenike Oluwakemi , Ogbole James Aaron 
Published: June 2023

AbstractBackgroundMaternal predisposing factors to adverse birth outcomes are often times assumed to be similar in rural and urban settings. This assumption have led to many failed or failing interventions. This study investigated the maternal risk factors of adverse birth outcomes in a remote community and compared with existing literature of similar studies done in urban areas or developed settings.Subject and methodsThis was the baseline data of a prospective cohort study, carried out in Gitwe village, Rwanda, 2019. Healthy, 529 mother-singleton infant pairs were recruited consecutively from Gitwe district hospital.ResultsThe burden of adverse neonatal outcomes of significance in this rural study (cesarean section delivery, low birth weight, small for gestational age and prematurity) were 38.8%, 10.6%, 21.4% and 4.9%, respectively. Significant (p<0.05) maternal characteristics associated with cesarean section delivery were obesity, high number of antenatal visits (>6), non-christian religion, university education, entrepreneurs, positive HIV status and short stature. Unmarried mothers were likely to produce LBW and preterm babies, while primips were prone to deliver SGA babies. The magnitude of adverse birth outcomes in this rural study was unexpectedly higher than what exist at and their drivers were not exactly the same as in urban settings and at national level.Conclusion and RecommendationsThe burden of adverse birth outcomes in this study was higher than that of several countries in the world. Therefore, mothers (not neglecting their marital, HIV, parity and religion status), residing in these rural areas should be priortised for health care interventions, in order to lower the short-and long-term effects of these adverse birth outcomes.
Identification of novel variants, genes and pathways potentially linked to Parkinson’s disease using machine learning
Authors: Yu Eric , Larivière Roxanne , Thomas Rhalena A. , Liu Lang , Senkevich Konstantin , Rahayel Shady , Trempe Jean-François , Fon Edward A. , Gan-Or Ziv 
Published: June 2023

AbstractThere are 78 loci associated with Parkinson’s disease (PD) in the most recent genome-wide association study (GWAS), yet the specific genes driving these associations are mostly unknown. Herein, we aimed to nominate the top candidate gene from each PD locus, and identify variants and pathways potentially involved in PD. We trained a machine learning model to predict PD-associated genes from GWAS loci using genomic, transcriptomic, and epigenomic data from brain tissues and dopaminergic neurons. We nominated candidate genes in each locus, identified novel pathways potentially involved in PD, such as the inositol phosphate biosynthetic pathway (INPP5F,IP6K2,ITPKB, PPIP5K2). Specific common coding variants inSPNS1andMLXmay be involved in PD, and burden tests of rare variants further support thatCNIP3,LSM7,NUCKS1and the polyol/inositol phosphate biosynthetic pathway are associated with PD. Functional studies are needed to further analyze the involvements of these genes and pathways in PD.
Improving irregular temporal modeling by integrating synthetic data to the electronic medical record using conditional GANs: a case study of fluid overload prediction in the intensive care unit
Authors: Rafiei Alireza , Rad Milad Ghiasi , Sikora Andrea , Kamaleswaran Rishikesan 
Published: June 2023

AbstractObjectiveThe challenge of irregular temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload.Materials and MethodsThis retrospective cohort study evaluated patients admitted to an ICU≥72 hours. Four machine learning algorithms to predict fluid overload after 48-72 hours of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CT-GAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets.ResultsTraining machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the metamodel trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios.DiscussionThe integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.
Genetic relationships between chronic pain, psychopathologies, and neuroticism
Authors: Zorina-Lichtenwalter Katerina , Bango Carmen I. , Čeko Marta , Ashar Yoni K. , Keller Matthew C. , Wager Tor D. , Friedman Naomi P. 
Published: June 2023

AbstractChronic pain and psychiatric conditions have consistently demonstrated substantial overlap in risk factors, epidemiology, and effective treatments. Previous work has identified cross-condition latent factors underlying shared genetic risk for several distinct psychiatric conditions and pain conditions. Here, we sought to examine the relationships between these latent genetic factors to determine biological mechanisms common to both pain and psy-chiatric conditions. We combined two previously published genetic struc-turl equation models. The first model consisted of 24 pain conditions and their two latent factors: General and Musculoskeletal pain-specific. The second model consisted of 11 psychiatric conditions and their four latent factors: Externalizing, Internalizing, Compulsive Thought, and Psychotic Thought. The combined model of six factors and 35 conditions allowed us to estimate correlations between all factors and between conditions of one domain (pain) and factors of the other (psychiatric). We then added three measures of neuroticism (depressive affect subscale, worrying subscale, and total neuroticism score) to this model to examine correlations with all conditions and factors and test for possible explanation of pain-mental disorder relationships by neuroticism. We found that genetic associations between pain and psychiatric conditions were selective to the General Pain factor (and not Musculoskeletal) and Internalizing and Externalizing, but not Thought disorder factors. Neuroticism was associated with pain conditions to the extent that they loaded onto the General Pain factor (i.e., were associated with other pain conditions). Neuroticism also explained a substantial proportion of shared genetic variance between General Pain and Externalizing and between General Pain and Internalizing factors. Overall, the genetic risks shared among chronic pain and psychiatric conditions and neuroticism suggest shared biological mechanisms and underscore the importance of clinical assessment and treatment programs that leverage these commonalities.