bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfluorooctanoic acid triggers premature ovarian insufficiency by impairing NAD+ synthesis and mitochondrial function in adult zebrafish
Authors: Xu Hao , Mao Xiaoyu , Zhang Siling , Ren Jie , Jiang Shanwen , Cai Lijuan , Miao Xiaomin , Tao Yixi , Peng Chao , Lv Mengzhu , Li Yun 
Published: June 2024

Abstract
High-dose perfluorooctanoic acid (PFOA) impairs oocyte maturation and offspring quality. However, the physiological concentrations of PFOA in follicular fluids of patients with premature ovarian insufficiency (POI) were detected at lower levels, thus the relationship between physiological PFOA and reproductive disorders remains elusive. Here, we investigated whether physiological PFOA exposure affects gonad function in adult zebrafish. Physiological PFOA exposure resulted in POI-like phenotypes in adult females, which exhibited decreased spawning frequency, reduced number of ovulated eggs, abnormal gonadal index, and aberrant embryonic mortality. Meanwhile, oocytes from PFOA-exposed zebrafish showed mitochondrial disintegration and diminished mitochondrial membrane potential. Unlike the high-dose treated oocytes exhibiting high reactive oxygen species (ROS) levels and excessive apoptosis, physiological PFOA reduced the ROS levels and did not trigger apoptosis. Interestingly, physiological PFOA exposure would not affect testis function, indicating specific toxicity in females. Mechanistically, PFOA suppressed the NAD+ biosynthesis and impaired mitochondrial function in oocytes, thus disrupting oocyte maturation and ovarian fertility. Nicotinamide mononucleotide (NMN), a precursor for NAD+ biosynthesis, alleviated the PFOA-induced toxic effects in oocytes and improved the oocyte maturation and fertility upon PFOA exposure. Our findings discover new insights into PFOA-induced reproductive toxicity and provide NMN as a potential drug for POI therapy.
Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial
Authors: Hoffman Michaela , Voronin Konstantin , Book Sarah W. , Prisciandaro James , Bristol Emily J. , Anton Raymond F. 
Published: June 2024

Objectives
Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication’s effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin’s effects on alcohol consumption.

Methods
This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential “moderator” of the interaction of medication effects and alcohol withdrawal on drinking.

Results
Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [P = 0.026] and higher (PDA [P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase (P < 0.001; P = 0.002), but this did not significantly moderate gabapentin’s effectiveness.

Conclusions
Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.
Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD
Authors: Sakane Sadatsugu , Hikita Hayato , Shirai Kumiko , Sakamoto Tatsuya , Narumi Ryohei , Adachi Jun , Kakita Naruyasu , Yamada Yukinori , Toyoda Hidenori , Takahashi Hirokazu , Suda Goki , Kai Machiko , Tahata Yuki , Sakamori Ryotaro , Kumazaki Shusuke , Fukumoto Kenji , Myojin Yuta , Murai Kazuhiro , Kodama Takahiro , Tatsumi Tomohide , Tomonaga Takeshi , Sakamoto Naoya , Morii Eiichi , Takehara Tetsuo 
Published: June 2024

Background:
There is a need for novel noninvasive markers for metabolic dysfunction–associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events.

Methods:
We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis. A further evaluation was conducted on another cohort of 463 patients with MASLD with biopsy.

Results:
Eight candidate proteins were identified by proteomic analysis of serum EVs. Among them, serum levels of Fibulin-3, Fibulin-1, and Ficolin 1 correlated with their EV levels. In addition, serum Fibulin-3 and serum Fibulin-1 levels changed significantly with advanced fibrosis. Using another cohort with biopsy, we found that the serum Fibulin-3 concentration was significantly greater in those with advanced fibrosis but that the serum Fibulin-1 concentration was not significantly different. Multivariate Cox proportional hazards analysis revealed that a higher Fibrosis-4 (FIB-4) index and higher serum Fibulin-3 concentration were independent risk factors for liver-related events. When the cutoff value for the serum Fibulin-3 concentration was 6.0 µg/mL according to the Youden index of AUROCs, patients with high serum Fibulin-3 significantly more frequently developed liver-related events than did other patients. Validation using another cohort of 226 patients with clinically diagnosed MASLD confirmed that high serum Fibulin-3 levels are associated with a greater frequency of liver-related events.

Conclusions:
Serum Fibulin-3 was identified as a biomarker for predicting liver-related events in patients with MASLD.
Principal Component Analysis of a Real-World Cohort of Descemet Stripping Automated Endothelial Keratoplasty and Descemet Membrane Endothelial Keratoplasty Cases: Demonstration of a Powerful Data-Mining Technique for Identifying Areas of Research
Authors: Perone Jean-Marc , Goetz Christophe , Zevering Yinka , Derumigny Alexis 
Published: June 2024

Purpose:
Principal component analysis (PCA) is a descriptive exploratory statistical technique that is widely used in complex fields for data mining. However, it is rarely used in ophthalmology. We explored its research potential with a large series of eyes that underwent 3 keratoplasty techniques: Descemet membrane endothelial keratoplasty (DMEK), conventional Descemet stripping automated endothelial keratoplasty (ConDSAEK), or ultrathin-DSAEK (UT-DSAEK).

Methods:
All consecutive DMEK/DSAEK cases conducted in 2016 to 2022 that had ≥24 months of follow-up were included. ConDSAEK and UT-DSAEK were defined as preoperative central graft thickness ≥130 and <130 μm, respectively. Seventy-six patient, disease, surgical practice, and temporal outcome variables were subjected to PCA, including preoperative anterior keratometry, the use of sulfur hexafluoride gas (SF6) versus air for primary tamponade, and postoperative best corrected visual acuity and endothelial cell density. Associations of interest that were revealed by PCA were assessed with the Welch t test or Pearson test.

Results:
A total of 331 eyes were treated with DMEK (n = 165), ConDSAEK (n = 95), or UT-DSAEK (n = 71). PCA showed that ConDSAEK and UT-DSAEK clustered closely, including regarding postoperative best corrected visual acuity, and were clearly distinct from DMEK. PCA and follow-up univariate analyses suggested that in DMEK, 1) flatter preoperative anterior keratometry (average, K1, and K2) associated with more rebubbling (P = 0.004–0.089) and graft detachment (P = 0.007–0.022); 2) graft marking did not affect postoperative endothelial cell density; and 3) lower postoperative endothelial cell density associated with SF6 use (all P > 0.001) and longer surgery (P = 0.005–0.091). All associations are currently under additional investigation in our hospital.

Conclusions:
PCA is a powerful technique that can rapidly reveal clinically relevant associations in complex ophthalmological datasets.
Learning pathways composed of core subjects with features of reducing cognitive load have better learning outcomes
Authors: Huang Shiau-Shian , Huang Anna YuQing , Lin Yu-Fan , Lin Sheng-Min , Webster Craig S. , Lin Ji-Yang , Yang Ying-Ying , Yang Stephen J.H. , Lirng Jiing-Feng , Chen Chen-Huan , Yang Albert ChihChieh , Lin Chi-Hung 
Published: June 2024

Background:
Changing the course duration or timing of subjects in learning pathways would influence medical students’ learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts.

Methods:
This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset.

Results:
We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway.

Conclusion:
An approach to finding a promising learning pathway facilitating students’ learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.
Phase angle is an indicator of GLIM-diagnosed malnutrition in patients undergoing major pancreatic and biliary surgery: a cross-sectional study
Authors: Wang Lijuan , Li Pengxue , Hu Yifu , Cheng Bo , Li Lei , Ding Lili , Song Jinghai , Wei Junmin , Xu Jingyong 
Published: June 2024

Objective:
The aim of this study is to elucidate the correlation between phase angle and malnutrition, and to determine the malnutrition cut-off points based on phase angle in patients undergoing major pancreatic and biliary surgery.

Methods:
This is a cross-sectional study analyzing the prospective database of the Department of Hepatopancreatobiliary Surgery at Beijing Hospital, China, from December 2020 to September 2023. Basal data, diet surveys, anthropometry, and body composition were recorded. Phase angle was measured with the InBody 720. The GLIM criteria were used to diagnose malnutrition. Subgroup analyses were conducted by stratifying age and pancreatic cancer.

Results:
A total of 185 consecutive cases were included, with a mean age of 63.66;±11.96 years. 63.8% (118/185) of the participants were aged 60 years or older, and 43.8% (81/185) were diagnosed with pancreatic cancer. The prevalence of malnutrition was 62.2% among all subjects, 67.8% among the elderly, and 69.1% among pancreatic cancer patients. Phase angle was significantly lower in the malnourished group than in the normal group. Positive correlations were found between phase angle and BMI, ASMI, FFMI, fat-free mass, total energy intake, grip strength, calf circumference, 6-meter timed walk speed, total protein, albumin, and prealbumin. Among all the subjects, participants with a lower phase angle were significantly more likely to suffer from malnutrition than their control group, with a 1.611 times higher risk (95% CI 1.013-2.562, P=0.044). The cut-off points of the phase angle for determining malnutrition were 4.82 in men (sensitivity 0.744, specificity 0.571, area under the curve 0.667, 95% CI 0.567-0.766, P = 0.003), and 4.54 in women (sensitivity 0.750, specificity 0.711, area under the curve 0.757, 95% CI 0.644-0.869, P < 0.001). In the subgroup analyses of elderly and pancreatic cancer patients, we obtained consistent results with statistical significance and identified corresponding cut-off points.

Conclusion:
The present study suggests that the phase angle could be a valid, useful, and simple indicator of malnutrition in patients undergoing major pancreatic and biliary surgery.
N-terminal pro–B-type natriuretic peptide and pulmonary echography are predictors of acute heart failure needing early mechanical ventilation in acute coronary syndrome
Authors: Cristo-Ropero María J. , Garcia-Rubira Juan C. , Rivera-Rabanal Francisco Javier , Seoane-García Tania , Madrona-Jiménez Luis , Izquierdo-Bajo Álvaro , Hernández-Meneses Begoña , Vilches-Arenas Angel , Hidalgo-Urbano Rafael 
Published: June 2024

Aim
The aim of this study was to determine the best clinical predictors of acute heart failure needing mechanical ventilation (MV) in the first 48 h of evolution of patients admitted because of acute coronary syndrome (ACS).

Methods
We analyzed a cohort of patients admitted for ACS between February 2017 and February 2018. A pulmonary ultrasound was performed on admission and was considered positive (PE+) when there were three or more B-lines in two quadrants or more of each hemithorax. It was compared with N-terminal pro–B-type natriuretic peptide (NT-proBNP), peak troponin T-us value GRACE (Global Registry of Acute Coronary Events), CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology and American Heart Association guidelines – Bleeding Score), CACS (Canada Acute Coronary Syndrome risk score), and HAMIOT (Heart Failure after Acute Myocardial Infarction with Optimal Treatment score) scores, shock index, ejection fraction, chest X-ray, and Killip class at admission as predictors of MV in the first 48 h of admission.

Results
A total of 119 patients were included: 54.6% with ST elevation and 45.4% without ST elevation. Twelve patients (10.1%) required MV in the first 48 h of evolution. The sensitivity of PE+ was 100% (73.5–100%), specificity 91.6% (84.6–96.1%), and area under the curve was 0.96 (0.93–0.96). The sensitivity of an NT-proBNP value more than 3647 was 88.9% (51.9–99.7%), specificity 92.1% (84.5–96.8%), and area under the curve was 0.905 (0.793–1). The κ statistic between both predictors was 0.579. All the other scores were significantly worse than PE + .

Conclusion
Lung ultrasound and a high NT-proBNP (3647 ng/L in our series) on admission are the best predictors of acute heart failure needing MV in the first 48 h of ACS. The agreement between both tests was only moderate.
Compartment syndrome of arm secondary to snake bite on hand: a case report
Authors: Dahal Amartya , Basi Ashkal , Shrestha Rohit , Khadka Sushant K. , Das Arjun , Malla Manasil , Dahal Arshima , Chaudhary Aashutosh 
Published: June 2024

Introduction:
Snake bites pose a significant common public health concern, with more prevalence in rural areas. Compartment syndrome (CS) is one of the rare and severe manifestations of snake bite wherein venom-induced swelling within a closed anatomical compartment leads to increased pressure, which may result in ischemic damage to nerves and muscle. Antisnake venom and prompt fasciotomy is recommended for management of CS secondary to snake bite.

Case details:
Here, the authors report a case of 47-year-old female with Green Pit Viper bite on the left hand. Upon arrival to hospital, initial resuscitation measures were initiated. Six hours following the bite, there was severe pain on passive stretch and paresthesia. Ten vials of antisnake venom administration along with fasciotomy of hand and arm resulted in notable alleviation of pain and swelling. Eighteen pints of blood was transfused for coagulopathy and low hemoglobin. After continued care of wound and intensive physiotherapy, functional limb could be achieved.

Discussion:
Snake bite envenomation is one of the biggest hidden health crises with case fatality rate of 7.8% in the southern plains of Nepal. As in our case, snake bites commonly affect upper extremities, accounting for around two third of all cases. CS must be differentiated from acute swelling, which sometimes may be difficult. Surgical decompression is indicated in presence of signs and symptoms of CS, in case of resource limited setting.

Conclusion:
Multidisciplinary and prompt management with initial resuscitation, ASV administration, fasciotomy, and rehabilitative measures can save both life and limb in such cases.
An exploration of clinical features and factors associated with pain frequency and pain intensity in children with growing pains: a cross-sectional study from Chongqing, China
Authors: Zhang Wenni , Xu Ximing , Leng Hongyao , Shen Qiao , Lu Qiufan , Zheng Xianlan 
Published: June 2024

Abstract

Instruction:
Growing pains are the most common cause of musculoskeletal pain in children, affecting both children's and caregivers' well-being. The lack of definitive diagnostic criteria complicates diagnosis and treatment.

Objectives:
This study aims to outline the clinical features and identify factors associated with the frequency and intensity of growing pains in children in Chongqing, China.

Methods:
A cross-sectional study was conducted in a children's hospital using its Internet hospital follow-up platform. Children initially diagnosed with growing pains between July and September 2022 were enrolled. Sociodemographics, pain locations, duration, frequency, intensity, and potentially related factors were collected.

Results:
Eight hundred sixty-three children were enrolled (average age: 8.19 ± 3.24 years; 455 boys [52.72%]). Pain frequency was reported as quarterly (62.11%), monthly (24.80%), biweekly (1.74%), weekly (10.08%), and daily (1.27%). The prevalence of mild, moderate, and severe pain was 26.65%, 55.74%, and 17.61%, respectively. The knee was the most common pain location (63.85%), mostly encountered between 4 pm and 5 pm (20.51%). Multivariate analysis revealed that pain frequency negatively correlated with vitamin supplementation during pregnancy, positively correlated with underweight, bad temper, increased exercise, and cold lower extremities. Pain intensity positively correlated with irritability, increased exercise, and pain sensitivity but negatively correlated with age and vitamin supplementation during lactation.

Conclusion:
Growing pains typically occur on a quarterly basis, predominantly affecting the knees during 4 pm to 5 pm. Factors in sociodemographics, maternal aspect, temperament, and exercise levels can influence pain frequency and intensity. Clinicians should consider these aspects when developing comprehensive strategies for pain management.
Freezing of gait: pharmacological and surgical options
Authors: Gámez-Leyva Gonzalo , Cubo Esther 
Published: June 2024

Purpose of review
The primary aim of this review is to describe and update the pathophysiological and relevant therapeutic strategies for freezing of gait (FoG) in patients with Parkinson's disease (PD).

Recent findings
FoG presumably involves dysfunction of multiple cortical and subcortical components, including dopaminergic and nondopaminergic circuits. In this regard, levodopa and physical therapy represent the first-choice therapeutic options for PD patients with FoG. However, the relationship between FoG and levodopa is not fully predictable. For those patients with levodopa-resistant FoG, there is promising but still controversial data on the benefits of bilateral high-frequency transcranial magnetic stimulation and deep brain stimulation on the subthalamic nuclei, substantia nigra pars reticulata, pedunculopontine nucleus, and the Fields of Forel. On the other hand, general exercise, gait training with a treadmill, focus attention on gait training, and conventional physiotherapy have demonstrated moderate to large benefits in FoG.

Summary
FOG requires different treatment strategies. The inclusion of adequate detection and prediction of FoG combined with double-blind, and statistically powered protocols are needed to improve patients’ quality of life, the motor and nonmotor symptoms and societal burden associated with FoG.
Tormentor: An obelisk prediction and annotation pipeline
Authors: Kremer Frederico Schmitt , de Barros Danielle Ribeiro 
Published: June 2024

AbstractObelisks are circular RNA viroid-like elements first described in January 2024 and identified through RNA-Seq data analysis. These elements are widespread in human gut samples. and characterized by their rod-like secondary structure reminiscent of obelisk monuments, exhibiting an average size of approximately 1,000 base pairs. Despite their initial identification, little is known about their biogenesis and their potential impact on human physiology and the microbiome. To facilitate further exploration in this emerging field, we developed Tormentor, an automated pipeline designed for the identification and annotation of Obelisks from stranded RNA-Seq data, leveraging methodologies similar to those employed in their initial discovery. To our knowledge, this is the first tool specialized for the identification of these elements.
ScSNViz: a user-friendly toolset for visualization and analysis of Cell-Specific Expressed SNVs
Authors: Kim Allen , Martinez Siera , Edwards Nathan , Horvath Anelia 
Published: June 2024

AbstractMotivationUnderstanding genetic variation at the single-cell level is crucial for insights into cellular heterogeneity, clonal evolution, and gene expression regulation, but there is a scarcity of tools for visualizing and analyzing cell-level genetic variants.ResultsWe introduce scSNViz, a comprehensive R-based toolset for visualization and analysis of cell-specific expressed Single Nucleotide Variants (sceSNVs) within cell-barcoded single-cell RNA-sequencing (scRNA-seq) data. ScSNViz offers 3D sceSNV visualization capabilities for dimensionally reduced scRNA-seq gene expression data, compatibility with popular scRNA-seq processing tools like Seurat, cell-type classification tools such as SingleR and scType, and trajectory inference computation using Slingshot. Furthermore, scSNViz conducts estimation, summary, and graphical representation of statistical metrics pertaining to sceSNVs distribution and expression across individual cells. It also provides support for the analysis of individual sceSNVs as well as sets comprising multiple expressed sceSNVs of interest.AvailabilityScSNViz is implemented as user-friendly R-scripts, freely available onhttps://horvathlab.github.io/NGS/scSNViz, supported by help utilities, and requiring no specialized bioinformatics skills for use.