bluuebunny/crossref_metadata_2025_split huggingface dataset:
U.S. Adolescent Rest-Activity patterns: insights from functional principal component analysis (NHANES 2011–2014)
Authors: Yeung Chris Ho Ching , Lu Jiachen , Soltero Erica G. , Bauer Cici , Xiao Qian 
Published: October 2023

Abstract
Background
Suboptimal rest-activity patterns in adolescence are associated with worse health outcomes in adulthood. Understanding sociodemographic factors associated with rest-activity rhythms may help identify subgroups who may benefit from interventions. This study aimed to investigate the association of rest-activity rhythm with demographic and socioeconomic characteristics in adolescents.

Methods
Using cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) 2011–2014 adolescents (N = 1814), this study derived rest-activity profiles from 7-day 24-hour accelerometer data using functional principal component analysis. Multiple linear regression was used to assess the association between participant characteristics and rest-activity profiles. Weekday and weekend specific analyses were performed in addition to the overall analysis.

Results
Four rest-activity rhythm profiles were identified, which explained a total of 82.7% of variance in the study sample, including (1) High amplitude profile; (2) Early activity window profile; (3) Early activity peak profile; and (4) Prolonged activity/reduced rest window profile. The rest-activity profiles were associated with subgroups of age, sex, race/ethnicity, and household income. On average, older age was associated with a lower value for the high amplitude and early activity window profiles, but a higher value for the early activity peak and prolonged activity/reduced rest window profiles. Compared to boys, girls had a higher value for the prolonged activity/reduced rest window profiles. When compared to Non-Hispanic White adolescents, Asian showed a lower value for the high amplitude profile, Mexican American group showed a higher value for the early activity window profile, and the Non-Hispanic Black group showed a higher value for the prolonged activity/reduced rest window profiles. Adolescents reported the lowest household income had the lowest average value for the early activity window profile.

Conclusions
This study characterized main rest-activity profiles among the US adolescents, and demonstrated that demographic and socioeconomic status factors may shape rest-activity behaviors in this population.
HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021
Authors: Hong Hang , Tang Chunlan , Liu Yuhui , Jiang Haibo , Fang Ting , Xu Guozhang 
Published: October 2023

Abstract
Background
As the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions.

Methods
Consecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013.

Results
A total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021.

Conclusions
This study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.
Adrenal schwannoma can be FDG-Avid on PET/CT: case report and review of historic institutional pathology
Authors: Fackelmayer Oliver J. , Rodriguez Eduardo D. , Sisk Anthony E. , Livhits Masha J. 
Published: October 2023

AbstractSchwannomas are benign, generally indolent tumors of neural crest origin and comprise the most common histologic tumor of peripheral nerves. Schwannomas are a rare histology for retroperitoneal tumors and very rare histologic findings for tumors of the adrenal gland with fewer than 50 cases in the reported literature. Here we present a case report of a non-hormonally functional but metabolically active adrenal tumor with indeterminate imaging characteristics with final pathology showing a 6.1 cm adrenal schwannoma as well as historical institutional pathology review revealing two additional cases.
A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis
Authors: Wang Longyan , Huang Huiming , Li Xingxing , Ouyang Lishan , Wei Xuejiao , Xie Jinxin , Liu Dongxiao , Tan Peng , Hu Zhongdong 
Published: October 2023

AbstractFerroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM.
The effectiveness of blood glucose and blood ketone measurement in identifying significant acidosis in diabetic ketoacidosis patients
Authors: Kilpatrick Eric S. , Butler Alexandra E. , Saeed Sawsan , Alamuddin Naji , Atkin Stephen L. , Sacks David B. 
Published: October 2023

Abstract
Background
Patients with diabetic ketoacidosis (DKA), a potentially fatal complication of type 1 diabetes, have hyperglycemia, ketonemia and metabolic acidosis. Blood glucose and blood ketone results are often used to triage patients with suspected DKA. This study aimed to establish how effective blood glucose and blood ketone (beta-hydroxybutyrate, BOHB) measurements are in identifying patients with significant acidosis and sought to validate existing diagnostic BOHB thresholds.

Methods
Initial Emergency Department results on 161 presumptive DKA episodes in 95 patients (42 F, 53 M, age range 14–89 years) containing a complete dataset of D (glucose), K (BOHB) and A (Bicarbonate [HCO3] and pH) results.

Results
Blood glucose correlated poorly with BOHB (r = 0.28 p = 0.0003), pH (r= -0.25, p = 0.002) and HCO3 (r= -0.17, p = 0.04). BOHB, though better, was still limited in predicting pH (r = -0.44, p < 0.0001) and HCO3 (r = -0.49, p < 0.0001). A HCO3 of 18mmol/L equated to a BOHB concentration of 4.3mmol/L, whilst a HCO3 of 15mmol/L equated to a BOHB of 4.7mmol/L. Of the 133 of 161 events with HCO3 < 18mmol/L, 22 were not hyperglycemic (> 13.9mmol/L, n = 8), ketonemic (≤ 3mmol/L, n = 9) or either (n = 5).

Conclusions
The commonly employed BOHB diagnostic cutoff of 3mmol/L could not be verified. Since acid-base status was poorly predicted by both glucose and BOHB, this highlights that, regardless of their results, pH and/or HCO3 should also be tested in any patient suspected of DKA.
“Publish or Perish”: barriers to research publication in an undergraduate medical research program
Authors: Alsulami Abdulrahman F , Khaimi Zeyad O , Hadi Mohammed A , Aljabri Yazeed H , Mayet Talha S , Althubaiti Alaa 
Published: October 2023

Abstract
Objectives
Publication is one of the crucial parameters in research, and the inability to publish has been noted in many medical students’ projects due to different reasons. This cross-sectional study aimed to determine the obstacles that prevented medical students in a health science university from publishing their research from 2018 to 2021. First, an online survey was distributed to assess the obstacles to publication perceived by the medical students. Second, a total of 81 research projects were evaluated by scientific reviewers and their final decision about the publication was recorded.

Results
In total, 162 students filled out the survey. The barriers faced by the students were various. They included an unsupportive research supervisor, a lack of time, an insufficient sample size, and many others. In the reviewer’s evaluation, out of 81 projects, 70 projects (86.4%) were recommended to be published after minor or major modifications, while 11 projects (13.6%) were rejected due to poor writing style, poor results interpretation, and incorrect methodology.

Conclusion
Articulating the barriers to undergraduate medical research publication is important in boosting publication rates and research experience of graduating medical students. Medical research educators and research supervisors should strongly consider creating a framework that tackles existing obstacles and any future matters.
Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats
Authors: Hector Audrey , Provost Chloé , Delignat-Lavaud Benoît , Bouamira Khadija , Menaouar Chahinez-Anissa , Mongrain Valérie , Brouillette Jonathan 
Published: October 2023

Abstract
Background
Soluble amyloid-beta oligomers (Aβo) begin to accumulate in the human brain one to two decades before a clinical diagnosis of Alzheimer’s disease (AD). The literature supports that soluble Aβo are implicated in synapse and neuronal losses in the brain regions such as the hippocampus. This region importantly contributes to explicit memory, the first type of memory affected in AD. During AD preclinical and prodromal stages, people are also experiencing wake/sleep alterations such as insomnia (e.g., difficulty initiating sleep, decreased sleep duration), excessive daytime sleepiness, and sleep schedule modifications. In addition, changes in electroencephalographic (EEG) activity during wake and sleep have been reported in AD patients and animal models. However, the specific contribution of Aβo to wake/sleep alterations is poorly understood and was investigated in the present study.

Methods
Chronic hippocampal injections of soluble Aβo were conducted in male rats and combined with EEG recording to determine the progressive impact of Aβ pathology specifically on wake/sleep architecture and EEG activity. Bilateral injections were conducted for 6 consecutive days, and EEG acquisition was done before, during, and after Aβo injections. Immunohistochemistry was used to assess neuron numbers in the hippocampal dentate gyrus (DG).

Results
Aβo injections did not affect the time spent in wakefulness, slow wave sleep (SWS), and paradoxical sleep but altered EEG activity during wake and SWS. More precisely, Aβo increased slow-wave activity (SWA; 0.5–5 Hz) and low-beta activity (16–20 Hz) during wake and decreased theta (5–9 Hz) and alpha (9–12 Hz) activities during SWS. Moreover, the theta activity/SWA ratio during wake and SWS was decreased by Aβo. These effects were significant only after 6 days of Aβo injections and were found with alterations in neuron counts in the DG.

Conclusions
We found multiple modifications of the wake and SWS EEG following Aβo delivery to the hippocampus. These findings expose a specific EEG signature of Aβ pathology and can serve the development of non-invasive and cost-effective markers for the early diagnosis of AD or other amyloid-related diseases.
Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling
Authors: Jin Jing , Zhao Qijie , Wei Zhigong , Chen Keliang , Su Yonglin , Hu Xiaolin , Peng Xingchen 
Published: October 2023

AbstractCell proliferation and function require nutrients, energy, and biosynthesis activity to duplicate repertoires for each daughter. It is therefore not surprising that tumor microenvironment (TME) metabolic reprogramming primarily orchestrates the interaction between tumor and immune cells. Tumor metabolic reprogramming affords bioenergetic, signaling intermediates, and biosynthesis requirements for both malignant and immune cells. Different immune cell subsets are recruited into the TME, and these manifestations have distinct effects on tumor progression and therapeutic outcomes, especially the mutual contribution of glycolysis and cholesterol metabolism. In particularly, glycolysis-cholesterol metabolic axis interconnection plays a critical role in the TME modulation, and their changes in tumor metabolism appear to be a double-edged sword in regulating various immune cell responses and immunotherapy efficacy. Hence, we discussed the signature manifestation of the glycolysis-cholesterol metabolic axis and its pivotal role in tumor immune regulation. We also highlight how hypothetical combinations of immunotherapy and glycolysis/cholesterol-related metabolic interventions unleash the potential of anti-tumor immunotherapies, as well as developing more effective personalized treatment strategies.
Epigenetic mechanism of Gtl2-miRNAs causes the primitive sheep characteristics found in purebred Merino sheep
Authors: Wang Jiankui , Hua Guoying , Chen Jianfei , Cui Kai , Yang Zu , Han Deping , Yang Xue , Dong Xianggui , Ma Yuhao , Cai Ganxian , Zhang Yuanyuan , Li Jinnan , Tai Yurong , Da Lai , Li Xinhai , Ma Lina , Ma Qing , Li Rui , Liu Jianbin , Darwish Hesham Y. A. , Wu Keliang , Rong Weiheng , Liu Wansheng , Zhao Yaofeng , Deng Xuemei 
Published: October 2023

Abstract
Background
It is not uncommon for some individuals to retain certain primitive characteristics even after domestication or long-term intensive selection. Wild ancestors or original varieties of animals typically possess strong adaptability to environmental preservation, a trait that is often lacking in highly artificially selected populations. In the case of the Merino population, a world-renowned fine wool sheep breed, a phenotype with primitive coarse wool characteristic has re-emerged. It is currently unclear whether this characteristic is detrimental to the production of fine wool or whether it is linked to the adaptability of sheep. The underlying genetic/epigenetic mechanisms behind this trait are also poorly understood.

Results
This study identified lambs with an ancestral-like coarse (ALC) wool type that emerged during the purebred breeding of Merino fine wool sheep. The presence of this primitive sheep characteristic resulted in better environmental adaptability in lambs, as well as improved fine wool yield in adulthood. Reciprocal cross experiments revealed that the ALC phenotype exhibited maternal genetic characteristics. Transcriptomic SNP analysis indicated that the ALC phenotype was localized to the imprinted Gtl2-miRNAs locus, and a significant correlation was found between the ALC wool type and a newly identified short Interstitial Telomeric Sequences (s-ITSs) at this locus. We further confirmed that a novel 38-nt small RNA transcribed from these s-ITSs, in combination with the previously reported 22-nt small RNAs cluster from the Gtl2-miRNAs locus, synergistically inhibited PI3K/AKT/Metabolic/Oxidative stress and subsequent apoptotic pathways in wool follicle stem cells, resulting in the ALC wool type. The necessity of Gtl2-miRNAs in controlling primary hair follicle morphogenesis, as well as the wool follicle type for ALC wool lambs, was verified using intergenic differentially methylated region-knockout mice.

Conclusion
The ALC wool type of Merino sheep, which does not reduce wool quality but increases yield and adaptability, is regulated by epigenetic mechanisms in the imprinted Gtl2-miRNAs region on sheep chromosome 18, with the maternally expressed imprinted gene responsible for the ALC phenotype. This study highlights the significance of epigenetic regulation during embryonic and juvenile stages and emphasizes the advantages of early adaptation breeding for maternal parents in enhancing the overall performance of their offspring.
Prognosis of critically ill immunocompromised patients with virus-detected acute respiratory failure
Authors: Dumas Guillaume , Bertrand Maxime , Lemiale Virginie , Canet Emmanuel , Barbier François , Kouatchet Achille , Demoule Alexandre , Klouche Kada , Moreau Anne-Sophie , Argaud Laurent , Wallet Florent , Raphalen Jean-Herlé , Mokart Djamel , Bruneel Fabrice , Pène Frédéric , Azoulay Elie 
Published: October 2023

Abstract
Background
Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie’s database (2003–2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins.

Results
Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05–2.89]), poor performance status (OR = 1.84, CI [1.12–3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14–3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60–0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33–0.88]).

Conclusions
In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza.
MGS2AMR: a gene-centric mining of metagenomic sequencing data for pathogens and their antimicrobial resistance profile
Authors: Van Camp Pieter-Jan , Prasath V. B. Surya , Haslam David B. , Porollo Aleksey 
Published: October 2023

Abstract
Background
Identification of pathogenic bacteria from clinical specimens and evaluating their antimicrobial resistance (AMR) are laborious tasks that involve in vitro cultivation, isolation, and susceptibility testing. Recently, a number of methods have been developed that use machine learning algorithms applied to the whole-genome sequencing data of isolates to approach this problem. However, making AMR assessments from more easily available metagenomic sequencing data remains a big challenge.

Results
We present the Metagenomic Sequencing to Antimicrobial Resistance (MGS2AMR) pipeline, which detects antibiotic resistance genes (ARG) and their possible organism of origin within a sequenced metagenomics sample. This in silico method allows for the evaluation of bacterial AMR directly from clinical specimens, such as stool samples. We have developed two new algorithms to optimize and annotate the genomic assembly paths within the raw Graphical Fragment Assembly (GFA): the GFA Linear Optimal Path through seed segments (GLOPS) algorithm and the Adapted Dijkstra Algorithm for GFA (ADAG). These novel algorithms improve the sensitivity of ARG detection and aid in species annotation. Tests based on 1200 microbiome samples show a high ARG recall rate and correct assignment of the ARG origin. The MGS2AMR output can further be used in many downstream applications, such as evaluating AMR to specific antibiotics in samples from emerging intestinal infections. We demonstrate that the MGS2AMR-derived data is as informative for the entailing prediction models as the whole-genome sequencing (WGS) data. The performance of these models is on par with our previously published method (WGS2AMR), which is based on the sequencing data of bacterial isolates.

Conclusions
MGS2AMR can provide researchers with valuable insights into the AMR content of microbiome environments and may potentially improve patient care by providing faster quantification of resistance against specific antibiotics, thereby reducing the use of broad-spectrum antibiotics. The presented pipeline also has potential applications in other metagenome analyses focused on the defined sets of genes.