bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases
Authors: Foliaki Simote T. , Schwarz Benjamin , Groveman Bradley R. , Walters Ryan O. , Ferreira Natalia C. , Orrù Christina D. , Smith Anna , Wood Aleksandar , Schmit Olivia M. , Freitag Phoebe , Yuan Jue , Zou Wenquan , Bosio Catharine M. , Carroll James A. , Haigh Cathryn L. 
Published: October 2021

AbstractThe neuro-physiological properties of individuals with genetic pre-disposition to neurological disorders are largely unknown. Here we aimed to explore these properties using cerebral organoids (COs) derived from fibroblasts of individuals with confirmed genetic mutations includingPRNPE200K, trisomy 21 (T21), andLRRK2G2019S, which are associated with Creutzfeldt Jakob disease, Down Syndrome, and Parkinson’s disease. We utilized no known disease/healthy COs (HC) as normal function controls. At 3–4 and 6–10 months post-differentiation, COs with mutations showed no evidence of disease-related pathology. Electrophysiology assessment showed that all COs exhibited mature neuronal firing at 6–10 months old. At this age, we observed significant changes in the electrophysiology of the COs with disease-associated mutations (dCOs) as compared with theHC, including reduced neuronal network communication, slowing neuronal oscillations, and increased coupling of delta and theta phases to the amplitudes of gamma oscillations. Such changes were linked with the detection of hypersynchronous events like spike-and-wave discharges. These dysfunctions were associated with altered production and release of neurotransmitters, compromised activity of excitatory ionotropic receptors including receptors of kainate, AMPA, and NMDA, and changed levels and function of excitatory glutamatergic synapses and inhibitory GABAergic synapses. Neuronal properties that modulate GABAergic inhibition including the activity of Na–K-Cl cotransport 1 (NKCC1) in Cl−homeostasis and the levels of synaptic and extra-synaptic localization of GABA receptors (GABARs) were altered in theT21COs only. The neurosteroid allopregnanolone, a positive modulator of GABARs, was downregulated in all the dCOs. Treatment with this neurosteroid significantly improved the neuronal communication in the dCOs, possibly through improving the GABAergic inhibition. Overall, without the manifestation of any disease-related pathology, the genetic mutationsPRNPE200K,T21, andLRRK2G2019Ssignificantly altered the neuronal network communication in dCOs by disrupting the excitatory-to-inhibitory balance.
Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis
Authors: Wang Junmei , Tierney Lydia , Mann Ranjeet , Lonsway Thomas , Walker Chandler L. 
Published: October 2021

AbstractAmyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.
Huatan Dingji Decoction intervening in atrial fibrillation: protocol for a randomized double-blind single-simulated placebo-controlled clinical trial
Authors: Xiao Ying , Wang Xinyi , Yang Jin , Liu Keke , Li Mianmian , Ma Zilin , Deng Bing , Shen Lin , Wei Yihong , Zhang Shuai , Zhang Na , Zhao Ping , Zhu Chen , Mao Meijiao , Tang Nuo , Wu Qiong 
Published: October 2021

Abstract
Background
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and can lead to heart failure (HF), stroke, pulmonary embolism (PE), and other complications, seriously affecting people’s quality of life and health. Western medicine is limited in the treatment of AF, while Traditional Chinese Medicine (TCM) has unique advantages, such as less side effects, low toxicity, long effect duration, and high compliance. The prescription of HTDJ is a common prescription for the treatment of atrial fibrillation in Longhua Hospital, Shanghai University of Traditional Chinese Medicine. It has been used for many years and has a large number of clinically effective cases. It has a good clinical application prospect, but there is a lack of effective evaluation of its clinical efficacy.

Method
This study adopts a randomized double-blind, single-simulated, placebo-controlled research method. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. Participants would take the medicine for 1 month, and the curative effect would be evaluated. Subsequently, the participants would not take TCM and only receive western medicine treatment. They would be followed up for another 8 weeks, and a clinical evaluation would be conducted. The secondary outcomes include echocardiography, Hamilton Anxiety Scale, Hamilton Depression Scale, rate of increase and decrease of anti-arrhythmia western medicine, the MOS 36-item short-form health survey, N-terminal-pro hormone B-type natriuretic peptide level, and integral TCM syndrome score. Adverse events will be monitored throughout the trial. Cases are from outpatient and inpatient with atrial fibrillation in the Cardiology Department of Longhua Hospital. Evaluations will be conducted at baseline and at weeks 4 and 12 after randomization.

Discussion
In this study, the efficacy and safety of HTDJ plus western medicine in the treatment of atrial fibrillation (qi deficiency and phlegm opacities) will be evaluated, so as to provide medical evidence of short-term and medium-term clinical efficacy for the treatment of atrial fibrillation with integrated traditional and western medicine and lay a foundation for further clinical development and application.

Trial registration
ClinicalTrials.govChiCTR2000030517. Registered on March 5, 2020, with the Chinese Clinical Trial Registry
Electronic early notification of sepsis in hospitalized ward patients: a study protocol for a stepped-wedge cluster randomized controlled trial
Authors: Arabi Yaseen M. , Alsaawi Abdulmohsen , Al Zahrani Mohammed , Al Khathaami Ali M. , AlHazme Raed H. , Al Mutrafy Abdullah , Al Qarni Ali , Al Shouabi Ahmed , Al Qasim Eman , Abdukahil Sheryl Ann , Al-Rabeah Fawaz K. , Al Ghamdi Huda , Al Ghamdi Ebtisam , Alansari Mariam , Abuelgasim Khadega A. , Alatassi Abdulaleem , Alchin John , Al-Dorzi Hasan M. , Ghamdi Abdulaziz A. , Al-Hameed Fahad , Alharbi Ahmad , Hussein Mohamed , Jastaniah Wasil , AlKatheri Mufareh Edah , AlMarhabi Hassan , Mustafa Hani T. , Jones Joan , Al-Qahtani Saad , Qahtani Shaher , Qureshi Ahmad S. , Salih Salih Bin , Alselaim Nahar , Tashkandi Nabiha , Vishwakarma Ramesh Kumar , AlWafi Emad , Alyami Ali H. , Alyousef Zeyad ,   for the SCREEN Trial Group, Al Arfaj Ahmed , Al Moammary Mohamed S. , Rasheed Soud , Alwasaidi Turki , Matroud Amal , Al Anazi Rasha Ebeid , Alhasani Amar M. , Al Shammari Haifa , Alshamrani Majid M. , Qasim Saleh , Obbed Saeed , Munshi Adnan A. , Al Tabsh Hadia , Banat Basem R. , Abuskout Omar , Marcelo Anna Liza , Alhabshi Mayadah M. , Jaber Ibrahim J. , Shahin Mohammad , Yaakob Jamielah , Al Somali Hanan , Masala Clara , Al Qarni Mohammed , Chalabi Jamal , Greyvenstein Johanna E. , Jazieh Abdul Rahman , Omaish Noha , Abdrahim Azura , Abdrabo Mohammad , Al Hamdan Abdullah , Al Qasem Abdulaziz , Esilan Hattan 
Published: October 2021

Abstract
Background
To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality.

Methods
The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of “possible sepsis alert” to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days.

Discussion
The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021.

Trial registration
ClinicalTrials.gov NCT04078594. Registered on September 6, 2019
Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial
Authors: Richard Jean-Christophe , Yonis Hodane , Bitker Laurent , Roche Sylvain , Wallet Florent , Dupuis Claire , Serrier Hassan , Argaud Laurent , Thiery Guillaume , Delannoy Bertrand , Pommier Christian , Abraham Paul , Muller Michel , Aubrun Frederic , Sigaud Florian , Rigault Guillaume , Joffredo Emilie , Mezidi Mehdi , Terzi Nicolas , Rabilloud Muriel 
Published: October 2021

Abstract
Background
Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34–50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg−1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation.

Methods
The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg−1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg−1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles.

Discussion
The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing.

Trial registration
ClinicalTrials.govNCT04349618. Registered on April 16, 2020
An update on the mosquito fauna and mosquito-borne diseases distribution in Cameroon
Authors: Bamou Roland , Mayi Marie Paul Audrey , Djiappi-Tchamen Borel , Nana-Ndjangwo Stella Mariette , Nchoutpouen Elysée , Cornel Antony John , Awono-Ambene Parfait , Parola Phillipe , Tchuinkam Timoléon , Antonio-Nkondjio Christophe 
Published: October 2021

AbstractThe expansion of mosquito-borne diseases such as dengue, yellow fever, and chikungunya in the past 15 years has ignited the need for active surveillance of common and neglected mosquito-borne infectious diseases. The surveillance should be designed to detect diseases and to provide relevant field-based data for developing and implementing effective control measures to prevent outbreaks before significant public health consequences can occur. Mosquitoes are important vectors of human and animal pathogens, and knowledge on their biodiversity and distribution in the Afrotropical region is needed for the development of evidence-based vector control strategies. Following a comprehensive literature search, an inventory of the diversity and distribution of mosquitoes as well as the different mosquito-borne diseases found in Cameroon was made. A total of 290 publications/reports and the mosquito catalogue website were consulted for the review. To date, about 307 species, four subspecies and one putative new species of Culicidae, comprising 60 species and one putative new species of Anopheles, 67 species and two subspecies of Culex, 77 species and one subspecies of Aedes, 31 species and one subspecies of Eretmapodites, two Mansonia, eight Coquillettidia, and 62 species with unknown medical and veterinary importance (Toxorhynchites, Uranotaenia, Mimomyia, Malaya, Hodgesia, Ficalbia, Orthopodomyia, Aedeomyia, and Culiseta and Lutzia) have been collected in Cameroon. Multiple mosquito species implicated in the transmission of pathogens within Anopheles, Culex, Aedes, Eretmapodites, Mansonia, and Coquillettidia have been reported in Cameroon. Furthermore, the presence of 26 human and zoonotic arboviral diseases, one helminthic disease, and two protozoal diseases has been reported. Information on the bionomics, taxonomy, and distribution of mosquito species will be useful for the development of integrated vector management programmes for the surveillance and elimination of mosquito-borne diseases in Cameroon.
Influence of 2D:4D ratio on fitness parameters and accumulated training load in elite youth soccer players
Authors: Nobari Hadi , Alves Ana Ruivo , Clemente Filipe Manuel , Pérez-Gómez Jorge 
Published: October 2021

AbstractBackgroundDigit ratio (2D:4D) characterized by the length of the second digit (2D) divided by the length of the fourth digit (4D), is a powerful marker of athletic performance. Some studies showed a negative correlation between 2D:4D ratio and sports performances.ObjectivesThe purpose of the present study was three-fold: (1) to analyze the influence of anthropometric and 2D:4D ratio on variations of accumulated training load (ATL) and fitness parameters: maximal oxygen uptake (V̇O2max), countermovement jump (CMJ), isometric muscular strength of the knee extensor for hamstring (ISH) and flexor for quadriceps (ISQ) muscles; along three stages of evaluation of soccer players based on playing positions; (2) to analyze the correlations between 2D:4D ratio and aforementioned parameters; and (3) to investigate if variance in fitness levels and ATL can explain the 2D:4D ratio.MethodsTwenty-four elite players under 17 years were daily monitored for their rating perceived exertion and ATL across 24 weeks over the season. Soccer players have also measured in three stages for anthropometric traits and fitness parameters.ResultsSignificant differences were observed between playing positions for body mass, goalkeepers had higher body mass compared to centre-midfielder and winger players. Moreover, there were significant differences in ATL between early-season to mid-season in goalkeepers (P = 0.032). The 2D:4D ratio (left and right) shown largely and negatively association with muscular strength (ISQ: r =  − 0.80; r =  − 0.78,P ≤ 0.001, ISH: r =  − 0.63; r =  − 0.62,P = 0.001, respectively) and VO2maxchanges (r =  − 0.55,P = 0.005; r =  − 0.50,P = 0.013, respectively); lastly, both 2D:4D ratio significantly predicted changes in muscular strength and VO2maxin young soccer players.ConclusionsGoalkeepers tended to have higher body mass compared to centre-midfielder and winger players; and 2D:4D ratio revealed a mighty predictor of physical fitness changes in soccer players. Evidence should be helpful to professionals to highlight the usefulness of the 2D:4D into the identification of talent, but also to optimize young players' performance.
Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study
Authors: Song Min-Ae , Seffernick Anna Eames , Archer Kellie J. , Mori Kellie M. , Park Song-Yi , Chang Linda , Ernst Thomas , Tiirikainen Maarit , Peplowska Karolina , Wilkens Lynne R. , Le Marchand Loïc , Lim Unhee 
Published: October 2021

Abstract
Background
Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA).

Methods
Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60–65. Differentially methylated CpGs by race/ethnicity (DM-CpGs) were identified by linear regression (Bonferroni-corrected P < 0.1) and analyzed in relation to corresponding gene expression, a priori selected single nucleotide polymorphisms (SNPs), and blood biomarkers of inflammation and metabolism using Pearson or Spearman correlations (FDR < 0.1).

Results
We identified 174 DM-CpGs with the majority of hypermethylated in JPA compared to EUA (n = 133), often in promoter regions (n = 48). Half (51%) of the genes corresponding to the DM-CpGs were involved in liver function and liver disease, and the methylation in nine genes was significantly correlated with gene expression for DM-CpGs. A total of 156 DM-CpGs were associated with rs7489665 (SH2B1). Methylation of DM-CpGs was correlated with blood levels of the cytokine MIP1B (n = 146). We confirmed some of the DM-CpGs in the TCGA adjacent non-tumor liver tissue of Asians versus EUA.

Conclusion
We found a number of differentially methylated CpGs in blood DNA between JPA and EUA women with a potential link to liver disease, specific SNPs, and systemic inflammation. These findings may support further research on the role of DNA methylation in mediating some of the higher risk of liver disease among JPA.
Cell-based therapies for retinal diseases: a review of clinical trials and direct to consumer “cell therapy” clinics
Authors: Hinkle John W. , Mahmoudzadeh Raziyeh , Kuriyan Ajay E. 
Published: October 2021

Abstract
Background
The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven “cell therapy” treatments marketed by “cell therapy” clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside of legitimate studies are presented.

Main body
Cell-based therapies can be applied to disorders that involve the RPE via a variety of techniques. A defining characteristic of any cell therapy treatment is the cell source used: human embryonic stem cells, induced pluripotent stem cells, and human umbilical tissue-derived cells have all been studied in published trials. In addition to the cell source, various trials have evaluated particular immunosuppression regiments, surgical approaches, and outcome measures. Data from early phase studies investigating cell-based therapies in non-neovascular age-related macular degeneration (70 patients, five trials), neovascular age-related macular degeneration (12 patients, four trials), and Stargardt’s macular dystrophy (23 patients, three trials) have demonstrated safety related to the cell therapies, though evidence of significant efficacy has not been reported. This is in contrast to the multiple reports of serious complications and permanent vision loss in patients treated at “cell therapy” clinics. These interventions are marketed directly to patients, funded by the patient, lack Food and Drug Administration approval, and lack significant oversight.

Conclusion
Currently, there are no proven effective cell-based treatments for retinal diseases, although several trials have investigated potential therapies. These studies reported favorable safety profiles with multiple surgical approaches, with cells derived from multiple sources, and with utilized different immunosuppressive regiments. However, data demonstrating the efficacy and long-term safety are still pending. Nevertheless, “cell therapy” clinics continue to conduct direct-to consumer marketing for non-FDA-approved treatments with potentially blinding complications.
Study on the causes of secondary cracks of the eave wall mural of Daxiong Hall at Fengguo Temple in Yixian, Liaoning, China
Authors: Liu Cheng , He Yuan , Li Qian , Wang Fei 
Published: October 2021

Abstract
Built in Kaitai 9 years after the beginning of the Liao Dynasty (1020 A.D.), the Daxiong Hall of Fengguo Temple (Yixian County, Liaoning Province) is one of China’s largest existing ancient single-eave wooden architecture structures. In 2012, it was listed on the “Preliminary List of World Cultural Heritage in China.” Preserved Buddhist murals depicting the Yuan Dynasty cover approximately 470 m2 of the hall’s four walls. Since the in-situ reinforcement and protection of the mural, conducted in the 1980s in cooperation with the maintenance and restoration project of the main hall, seriously developed cracks—known as secondary cracks—have become a primary factor affecting the mural’s structural stability. In this study, we conducted a comprehensive investigation using a full-frame digital camera, an industrial endoscope, an infrared thermal imager, an online environmental monitoring system, and a three-dimensional laser scanner. Our results, and other relevant materials, allowed us to deepen our understanding of the existing structural features, the nature of the cracks, the deformation conditions, and the environmental characteristics of the mural. Moreover, we provide a further discussion on the macroscopic formation process of the secondary cracks.