bluuebunny/crossref_metadata_2025_split huggingface dataset:
New pathways to neurogenesis: Insights from injury‐induced retinal regeneration
Authors: Blackshaw Seth , Qian Jiang , Hyde David R. 
Published: July 2024

AbstractThe vertebrate retina is a tractable system for studying control of cell neurogenesis and cell fate specification. During embryonic development, retinal neurogenesis is under strict temporal regulation, with cell types generated in fixed but overlapping temporal intervals. The temporal sequence and relative numbers of retinal cell types generated during development are robust and show minimal experience‐dependent variation. In many cold‐blooded vertebrates, acute retinal injury induces a different form of neurogenesis, where Müller glia reprogram into retinal progenitor‐like cells that selectively regenerate retinal neurons lost to injury. The extent to which the molecular mechanisms controlling developmental and injury‐induced neurogenesis resemble one another has long been unclear. However, a recent study in zebrafish has shed new light on this question, using single‐cell multiomic analysis to show that selective loss of different retinal cell types induces the formation of fate‐restricted Müller glia‐derived progenitors that differ both from one another and from progenitors in developing retina. Here, we discuss the broader implications of these findings, and their possible therapeutic relevance.
Biostatistical Aspects of Whole Genome Sequencing Studies: Preprocessing and Quality Control
Authors: Betschart Raphael O. , Riccio Cristian , Aguilera‐Garcia Domingo , Blankenberg Stefan , Guo Linlin , Moch Holger , Seidl Dagmar , Solleder Hugo , Thalén Felix , Thiéry Alexandre , Twerenbold Raphael , Zeller Tanja , Zoche Martin , Ziegler Andreas 
Published: July 2024

ABSTRACTRapid advances in high‐throughput DNA sequencing technologies have enabled large‐scale whole genome sequencing (WGS) studies. Before performing association analysis between phenotypes and genotypes, preprocessing and quality control (QC) of the raw sequence data need to be performed. Because many biostatisticians have not been working with WGS data so far, we first sketch Illumina's short‐read sequencing technology. Second, we explain the general preprocessing pipeline for WGS studies. Third, we provide an overview of important QC metrics, which are applied to WGS data: on the raw data, after mapping and alignment, after variant calling, and after multisample variant calling. Fourth, we illustrate the QC with the data from the GENEtic SequencIng Study Hamburg–Davos (GENESIS‐HD), a study involving more than 9000 human whole genomes. All samples were sequenced on an Illumina NovaSeq 6000 with an average coverage of 35× using a PCR‐free protocol. For QC, one genome in a bottle (GIAB) trio was sequenced in four replicates, and one GIAB sample was successfully sequenced 70 times in different runs. Fifth, we provide empirical data on the compression of raw data using the DRAGEN original read archive (ORA). The most important quality metrics in the application were genetic similarity, sample cross‐contamination, deviations from the expected Het/Hom ratio, relatedness, and coverage. The compression ratio of the raw files using DRAGEN ORA was 5.6:1, and compression time was linear by genome coverage. In summary, the preprocessing, joint calling, and QC of large WGS studies are feasible within a reasonable time, and efficient QC procedures are readily available.
Perillaldehyde alleviates polyQ‐induced neurodegeneration through the induction of autophagy and mitochondrial UPR in Caenorhabditis elegans
Authors: Fang Minglv , Liu Ying , Gao Xiaoyan , Yu Jing , Tu Xiaohui , Mo Xueying , Zhu Huanhu , Zou Yan , Huang Cheng , Fan Shengjie 
Published: July 2024

AbstractHuntington's disease (HD) is a fatal neurodegenerative disease associated with autophagy disorder and mitochondrial dysfunction. Here, we identified therapeutic potential of perillaldehyde (PAE), a monoterpene compound obtained from Perilla frutescens (L.) Britt., in the Caenorhabditis elegans (C. elegans) model of HD, which included lifespan extension, healthspan improvement, decrease in polyglutamine (polyQ) aggregation, and preservation of mitochondrial network. Further analyses indicated that PAE was able to induce autophagy and mitochondrial unfolded protein reaction (UPRmt) activation and positively regulated expression of associated genes. In lgg‐1 RNAi C. elegans or C. elegans with UPRmt‐related genes knockdown, the effects of PAE treatment on polyQ aggregation or rescue polyQ‐induced toxicity were attenuated, suggesting that its neuroprotective activity depended on autophagy and UPRmt. Moreover, we found that pharmacological and genetic activation of UPRmt generally protected C. elegans from polyQ‐induced cytotoxicity. Finally, PAE promoted serotonin synthesis by upregulating expression of TPH‐1, and serotonin synthesis and neurosecretion were required for PAE‐mediated UPRmt activation and its neuroprotective activity. In conclusion, PAE is a potential therapy for polyQ‐related diseases including HD, which is dependent on autophagy and cell‐non‐autonomous UPRmt activation.
Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures
Authors: Leong Jiayu , Tang Wen Qin , Chng Jake , Ler Wei Xuan , Manan Norhaizat Abdul , Sim Lyn Chiin , Zheng Zi Ying , Zhang Wei , Walsh Ian , Zijlstra Gerben , Pennings Maarten , Ng Say Kong 
Published: July 2024

AbstractContinuous manufacturing enables high volumetric productivities of biologics such as monoclonal antibodies. However, it is challenging to maintain both high viable cell densities and productivities at the same time for long culture durations. One of the key controls in a perfusion process is the perfusion rate which determines the nutrient availability and potentially controls the cell metabolism. Cell Specific Perfusion Rate (CSPR) is a feed rate proportional to the viable cell density while Biomass Specific Perfusion Rate (BSPR) is a feed rate proportional to the biomass (cell volume multiply by cell density). In this study, perfusion cultures were run at three BSPRs in the production phase. Low BSPR favored a growth arresting state that led to gradual increase in cell volume, which in turn led to an increase in net perfusion rate proportional to the increase in cell volume. Consequently, at low BSPR, while the cell viability and cell density decreased, high specific productivity of 55 pg per cell per day was achieved. In contrast, the specific productivity was lower in bioreactors operating at a high BSPR. The ability to modulate the cell metabolism by using BSPR was confirmed when the specific productivity increased after lowering the BSPR in one of the bioreactors that was initially operating at a high BSPR. This study demonstrated that BSPR significantly influenced cell growth, metabolism, and productivity in cultures with variable cell volumes.
Toehold region triggered CRISPR/Cas12a trans‐cleavage for detection of uracil‐DNA glycosylase activity
Authors: Cui Chenyu , Guo Guihuan , Chen Ting‐Hsuan 
Published: July 2024

AbstractDNA glycosylases are a group of enzymes that play a crucial role in the DNA repair process by recognizing and removing damaged or incorrect bases from DNA molecules, which maintains the integrity of the genetic information. The abnormal expression of uracil‐DNA glycosylase (UDG), one of significant DNA glycosylases in the base‐excision repair pathway, is linked to numerous diseases. Here, we proposed a simple UDG activity detection method based on toehold region triggered CRISPR/Cas12a trans‐cleavage. The toehold region on hairpin DNA probe (HP) produced by UDG could induce the trans‐cleavage of ssDNA with fluorophore and quencher, generating an obvious fluorescence signal. This protospacer adjacent motif (PAM)‐free approach achieves remarkable sensitivity and specificity in detecting UDG, with a detection limit as low as 0.000368 U mL−1. Moreover, this method is able to screen inhibitors and measure UDG in complex biological samples. These advantages render it highly promising for applications in clinical diagnosis and drug discovery.
Efficient CRISPR‐mediated C‐to‐T base editing in Komagataella phaffii
Authors: Wu Ling‐Yu , Xu Yan , Yu Xiao‐Wei 
Published: July 2024

AbstractThe nonconventional methylotrophic yeast Komagataella phaffii is widely applied in the production of industrial enzymes, pharmaceutical proteins, and various high‐value chemicals. The development of robust and versatile genome editing tools for K. phaffii is crucial for the design of increasingly advanced cell factories. Here, we first developed a base editing method for K. phaffii based on the CRISPR‐nCas9 system. We engineered 24 different base editor constructs, using a variety of promoters and cytidine deaminases (CDAs). The optimal base editor (PAOX2*‐KpA3A‐nCas9‐KpUGI‐DAS1TT) comprised a truncated AOX2 promoter (PAOX2*), a K. phaffii codon‐optimized human APOBEC3A CDA (KpA3A), human codon‐optimized nCas9 (D10A), and a K. phaffii codon‐optimized uracil glycosylase inhibitor (KpUGI). This optimal base editor efficiently performed C‐to‐T editing in K. phaffii, with single‐, double‐, and triple‐locus editing efficiencies of up to 96.0%, 65.0%, and 5.0%, respectively, within a 7‐nucleotide window from C‐18 to C‐12. To expand the targetable genomic region, we also replaced nCas9 in the optimal base editor with nSpG and nSpRy, and achieved 50.0%–60.0% C‐to‐T editing efficiency for NGN‐protospacer adjacent motif (PAM) sites and 20.0%–93.2% C‐to‐T editing efficiency for NRN‐PAM sites, respectively. Therefore, these constructed base editors have emerged as powerful tools for gene function research, metabolic engineering, genetic improvement, and functional genomics research in K. phaffii.
Resting‐state neural activity and cerebral blood flow alterations in type 2 diabetes mellitus: Insights from hippocampal subfields
Authors: Li Mingrui , Li Yifan , Tan Xin , Qin Chunhong , Chen Yuna , Liang Yi , Qiu Shijun , An Jie 
Published: July 2024

AbstractObjectiveIn this study, multimodal magnetic resonance imaging (MRI) imaging was used to deeply analyze the changes of hippocampal subfields perfusion and function in patients with type 2 diabetes mellitus (T2DM), aiming to provide image basis for the diagnosis of hippocampal‐related nerve injury in patients with T2DM.MethodsWe recruited 35 patients with T2DM and 40 healthy control subjects (HCs). They underwent resting‐state functional MRI (rs‐fMRI), arterial spin labeling (ASL) scans, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low‐frequency fluctuation (ALFF) value, and regional homogeneity (ReHo) value of the bilateral hippocampus subfields.ResultsThe CBF values of cornu ammonis area 1 (CA1), dentate gyrus (DG), and subiculum in the right hippocampus of T2DM group were significantly lower than those of HCs. The ALFF values of left hippocampal CA3, subiculum, and bilateral hippocampus amygdala transition area (HATA) were higher than those of HCs in T2DM group. The ReHo values of CA3, DG, subiculum, and HATA in the left hippocampus of T2DM group were higher than those of HCs. In the T2DM group, HbAc1 and FINS were negatively correlated with imaging characteristics in some hippocampal subregions.ConclusionThis study indicates that T2DM patients had decreased perfusion in the CA1, DG, and subiculum of the right hippocampus, and the right hippocampus subiculum was associated with chronic hyperglycemia. Additionally, we observed an increase in spontaneous neural activity within the left hippocampal CA3, subiculum, and bilateral HATA regions, as well as an enhanced local neural coordination in the left hippocampal CA3, DG, HATA, and subiculum among patients with type 2 diabetes, which may reflect an adaptive compensation for cognitive decline. However, this compensation may decline with the exacerbation of metabolic disorders.
Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats
Authors: Boustani Ali , Rashidy‐Pour Ali , Bozorgi Hossein , Vafaei Abbas Ali , Raise‐Abdullahi Payman 
Published: July 2024

AbstractPurposeLevothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild‐intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams.MethodTwenty‐four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6‐propyl‐2‐thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty‐four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 μg/kg, i.p.) with or without forced mild‐intensity exercise. After 14 days of interventions, anxiety‐like behaviors, spatial learning and memory, and hippocampal brain‐derived neurotrophic factor (BDNF) levels were evaluated.FindingA pre and postnatal PTU‐induced model of hypothyroidism increased anxiety‐like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety‐like behaviors. Exercise plus LEV more effectively improved anxiety‐like behaviors and spatial learning than exercise or LEV alone.ConclusionPractically, these pre‐clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.
The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta‐analysis of controlled clinical trials
Authors: Ghazanfar Shamas , Farooq Minaam , Qazi Shurjeel Uddin , Chaurasia Bipin , Kaunzner Ulrike 
Published: July 2024

AbstractIntroductionMultiple sclerosis (MS) is a debilitating neurological condition affecting nearly one million people across the United States. Among the most prominent symptoms of the condition are excessive fatigue and daytime sleepiness. Numerous clinical trials have investigated the efficacy of modafinil in addressing fatigue among these patients.ObjectiveThe objective of the present study is to assess the safety and efficacy of modafinil for the treatment of fatigue in MS.MethodologyAn electronic search of PUBMED, ScienceDirect, and Cochrane Central was conducted for articles published from inception to December 2023 using search terms such as “modafinil,” “fatigue,” and “MS.”ResultsSeven studies were included in our analysis. Modafinil leads to a meaningful reduction in fatigue when compared with placebo, as measured by Modified Fatigue Impact Scale [mean difference (MD) = −4.42 [−8.01, −.84]; I2 = 45%; p = .02] and Epworth Sleepiness Scale [MD = −.87 [−1.64, −.10]; I2 = 0%; p = .03]. Modafinil also demonstrated a greater risk of precipitating adverse events (e.g., insomnia, gastrointestinal symptoms) when compared with placebo [RR = 1.30 [1.03, 1.66]; I2 = 0%; p = .03]. In quality‐of‐life assessments, modafinil was associated with overall improvement in well‐being [standardized mean difference = .18 [.01, .35]; I2 = 56%; p = .04].ConclusionThe data indicates that modafinil confers a therapeutic benefit when treating fatigue in patients with MS and improves overall quality of life; however, there is a risk of precipitating adverse events. Ultimately, higher quality of evidence may be required to better inform clinical management.
PROTOCOL: Behavioral, information and monetary interventions to reduce energy consumption in households: A “living” systematic review
Authors: Khanna Tarun M. , Danilenko Diana , Andor Mark , Callaghan Max , Elliott Julian H. , Repke Tim , Smith Luke A. , Sanchez Jorge , Bhumika T. V. , Minx Jan C. 
Published: July 2024

AbstractThis is the protocol for a Campbell systematic review. The objectives are as follows: Our proposed systematic review and meta‐analysis will integrate the evidence available from all sources to answer the following questions: (1) to what extent can information, behavioral and monetary interventions reduce energy consumption of households in residential buildings? (average treatment effect of interventions) (2) what is the relative effectiveness of interventions? (account for heterogeneity in treatment effects across and within studies) (3) how effective are combinations of different interventions?
Early Development of the Thalamo‐Pallial Stage of the Tectofugal Visual Pathway in the Chicken (Gallus gallus)
Authors: Reyes‐Pinto Rosana , Rojas María‐José , Letelier Juan‐Carlos , Marín Gonzalo J. , Mpodozis Jorge 
Published: July 2024

ABSTRACTThe tectofugal pathway is a highly conserved visual pathway in all amniotes. In birds and mammals, retinorecipient neurons located in the midbrain roof (optic tectum/superior colliculus) are the source of ascending projections to thalamic relays (nucleus rotundus/caudal pulvinar), which in turn project to specific pallial regions (visual dorsal ventricular ridge [vDVR]/temporal cortex) organized according to a columnar recurrent arrangement of interlaminar circuits. Whether or to which extent these striking hodological correspondences arise from comparable developmental processes is at present an open question, mainly due to the scarcity of data about the ontogeny of the avian tectofugal system. Most of the previous developmental studies of this system in birds have focused on the establishment of the retino‐tecto‐thalamic connectivity, overlooking the development of the thalamo‐pallial‐intrapallial circuit. In this work, we studied the latter in chicken embryos by means of immunohistochemical assays and precise ex vivo crystalline injections of biocytin and DiI. We found that the layered organization of the vDVR as well as the system of homotopic reciprocal connections between vDVR layers were present as early as E8. A highly organized thalamo‐vDVR projection was also present at this stage. Our immunohistochemical assays suggest that both systems of projections emerge simultaneously even earlier. Combined with previous findings, these results reveal that, in striking contrast with mammals, the peripheral and central stages of the avian tectofugal pathway develop along different timelines, with a tecto‐thalamo‐intrapallial organization arising before and possibly independently of the retino‐isthmo‐tectal circuit.
Highthroughput Screening of CuBi Bimetallic Catalyst Array for Electrocatalytic CO2 Reduction Reaction by Scanning Electrochemical Microscope
Authors: Gu Xiaofeng , Wang Zhen , Li Jie , Ni Gang , Liu Limin , Zhan Dongping , Peng Juan 
Published: July 2024

AbstractThe testing and evaluation of catalysts in CO2 electroreduction is a very tedious process. To study the catalytic system of CO2 reduction more quickly and efficiently, it is necessary to establish a method that can detect multiple catalysts at the same time. Herein, a series of CuBi bimetallic catalysts have been successfully prepared on a single glass carbon electrode by a scanning micropieptte contact method. The application of scanning electrochemical microscopy (SECM) enabled the visualization of the CO2 reduction activity in diverse catalyst micro‐points. The SECM imaging with Substrate generation/tip collection (SG/TC) mode was conducted on CuBi bimetallic micro‐points, revealing that HER reaction emerged as the prevailing reaction when a low overpotential was employed. While the applied potential was lower than −1.5 V vs. Ag/AgCl, the reduction of CO2 to formic acid became dominant. Increasing the bismuth proportion in the bimetallic catalyst can inhibit the hydrogen evolution reaction at low potential and enhances the selectivity of the CO product at high cathode overpotential. This research offers a novel approach to examining arrays of catalysts for CO2 reduction.
Improved gray prediction parameter identification sliding mode current control of experimental advanced superconducting tokamak fast control power supply
Authors: Chen Zhao , Huang Haihong , Wang Haixin 
Published: July 2024

AbstractExperimental advanced superconducting tokamak (EAST) fast control power supply (FCPS) is an essential device to realize balance control of plasma vertical displacement during controllable nuclear fusion process. The primary control purpose of EAST FCPS is to quickly output current to track reference current. Change of load inductance parameters due to plasma motion poses higher robustness requirements for fast tracking control of output current. Therefore, an improved gray prediction parameter identification sliding mode control method is proposed to achieve fast tracking and robust control of output current under changes in load inductance parameters. Parameter identification sliding mode control method applied to identify load inductance parameters in real‐time, accurate EAST FCPS output current tracking sliding mode control model is established. High‐order terms are added to discrete exponential convergence reaching law, and a new smooth saturation function is designed to replace traditional sign function to achieve chattering suppression and accelerate system convergence speed. Gray prediction used in current sampling to achieve output current trajectory advanced prediction to further accelerate output current response speed. Four times equal interval time sampling within a fixed switching period and new information priority period by period prediction is proposed to improving gray prediction, achieving digital control delay compensation, and improving prediction accuracy of output current trajectory at abrupt edge. Simulation and experimental verification show that the proposed improved gray prediction parameter identification sliding mode control method has good output current tracking control performance under changes in load parameters. Compared with PI control method currently used in engineering, the proposed control method performs better in output current fast response and overshoot suppression.