bluuebunny/crossref_metadata_2025 huggingface dataset:
Survivors of Climate Driven Abalone Mass Mortality Exhibit Declines in Health and Reproduction Following Kelp Forest Collapse
Authors: Rogers-Bennett Laura , Klamt Robert , Catton Cynthia A.
Published: August 2021

Marine ecosystems are vulnerable to climate driven events such as marine heatwaves yet we have a poor understanding of whether they will collapse or recover. Kelp forests are known to be susceptible, and there has been a rise in sea urchin barrens around the world. When temperatures increase so do physiological demands while food resources decline, tightening metabolic constraints. In this case study, we examine red abalone (Haliotis rufescens) looking at sublethal impacts and their prospects for recovery within kelp forests that have shifted to sea urchin barrens. Abalone are a recreationally fished species that once thrived in northern California’s bull kelp forests but have recently suffered mass mortalities since the 2014–2016 marine heatwave. Quantitative data exist on the health and reproduction of abalone both prior to and after the collapse. The survivors of the mass mortality show a 2-year lag in body and gonad condition indices. After the lag, body and gonad indexes decreased substantially, as did the relationship between shell length and body weight. Production of mature eggs per female declined by 99% (p< 0.001), and the number of eggs per gram of female body weight (2,984/g) declined to near zero (9/g). The number of males with sperm was reduced by 33%, and the sperm abundance score was reduced by 28% (p= 0.414). We observed that these reductions were for mature eggs and sperm while immature eggs and spermatids were still present in large numbers. In the lab, after reintroduction of kelp, weight gains were quickly lost following a second starvation period. This example illustrates how climate-driven declines in foundation species can suppress recovery of the system by impacting body condition and future reproduction of surviving individuals. Given the poor reproductive potential of the remaining abalone in northern California, coupled with ongoing mortality and low kelp abundances, we discuss the need to maintain the fishing moratorium and implement active abalone restoration measures. For fished species, such as abalone, this additional hurdle to recovery imposed by changes in climate is critical to understand and incorporate into resource management and restoration.
Production and Application of CAR T Cells: Current and Future Role of Europe
Authors: Vucinic Vladan , Quaiser Andrea , Lückemeier Philipp , Fricke Stephan , Platzbecker Uwe , Koehl Ulrike
Published: August 2021

Rapid developments in the field of CAR T cells offer important new opportunities while at the same time increasing numbers of patients pose major challenges. This review is summarizing on the one hand the state of the art in CAR T cell trials with a unique perspective on the role that Europe is playing. On the other hand, an overview of reproducible processing techniques is presented, from manual or semi-automated up to fully automated manufacturing of clinical-grade CAR T cells. Besides regulatory requirements, an outlook is given in the direction of digitally controlled automated manufacturing in order to lower cost and complexity and to address CAR T cell products for a greater number of patients and a variety of malignant diseases.
The Morphology, Taxonomy, and Phylogenetic Analyses of Five Freshwater Colonial Peritrich Ciliates (Alveolata, Ciliophora), Including the Descriptions of Two New Species
Authors: Wu Tong , Wang Zhe , Duan Lili , El-Serehy Hamed , Al-Farraj Saleh A. , Warren Alan , Liu Yujie , Wang Chundi , Lu Borong
Published: August 2021

The morphology and phylogeny of two new sessilid species, Zoothamnium weishanicum n. sp. and Epicarchesium sinense n. sp., two insufficiently known species, Zoothamnium arbusculaEhrenberg, 1831 and Zoothamnium hentscheliKahl, 1935, and a well-known species, Carchesium polypinum (Linnaeus, 1767) Ehrenberg, 1838, collected from freshwater habitats of China, were investigated. Zoothamnium weishanicum n. sp. is characterized by its inverted bell-shaped zooids, double-layered peristomial lip, alternately branched stalk, and two different-length rows in infundibular polykinety 3 (P3). Epicarchesium sinense n. sp. is recognized by its asymmetric-pyriform zooids, single-layered peristomial lip, conspicuous cortical blisters on the pellicle, dichotomously branched stalk, and P3 containing one short inner row and two long outer rows. Based on previous and newly obtained data of the three known species, improved diagnoses and redescriptions are provided including, for the first time, data on the infraciliature of Z. arbuscula and Z. hentscheli. In addition, we analyzed the phylogeny of each species based on SSU rDNA sequence data.
NAD+ Degrading Enzymes, Evidence for Roles During Infection
Authors: Tan Arnold , Doig Craig L.
Published: August 2021

Declines in cellular nicotinamide adenine dinucleotide (NAD) contribute to metabolic dysfunction, increase susceptibility to disease, and occur as a result of pathogenic infection. The enzymatic cleavage of NAD+transfers ADP-ribose (ADPr) to substrate proteins generating mono-ADP-ribose (MAR), poly-ADP-ribose (PAR) or O-acetyl-ADP-ribose (OAADPr). These important post-translational modifications have roles in both immune response activation and the advancement of infection. In particular, emergent data show viral infection stimulates activation of poly (ADP-ribose) polymerase (PARP) mediated NAD+depletion and stimulates hydrolysis of existing ADP-ribosylation modifications. These studies are important for us to better understand the value of NAD+maintenance upon the biology of infection. This review focuses specifically upon the NAD+utilising enzymes, discusses existing knowledge surrounding their roles in infection, their NAD+depletion capability and their influence within pathogenic infection.
Association Between Body Mass Index and Intracranial Aneurysm Rupture: A Multicenter Retrospective Study
Authors: Chen Sifang , Mao Jianyao , Chen Xi , Li Zhangyu , Zhu Zhi , Li Yukui , Jiang Zhengye , Zhao Wenpeng , Wang Zhanxiang , Zhong Ping , Huang Qinghai
Published: August 2021

Background and Aims: It has recently emerged the concept of “obesity paradox,” a term used to describe an inverse association between obesity and clinical outcomes in cardiovascular diseases and stroke. The purpose of this study was to investigate the association between body mass index (BMI) and the risk of intracranial aneurysm rupture.

Methods: In this study, we conducted a retrospective analysis of a prospectively maintained database of patients with intracranial aneurysms from 21 medical centers in China. A total of 3,965 patients with 4,632 saccular intracranial aneurysms were enrolled. Patients were separated into unruptured (n = 1,977) and ruptured groups (n = 1,988). Univariable and multivariable logistic regression analyses were performed to determine the association between BMI and intracranial aneurysm rupture.

Results: Compared to the patients with normal BMI (18.5 to < 24.0 kg/m2), the odds of intracranial aneurysm rupture were significantly lower in patients with BMI 24.0 to < 28.0 kg/m2 (OR = 0.745, 95% CI = 0.638–0.868, P = 0.000) and patients with BMI ≥ 28.0 kg/m2 (OR = 0.628, 95% CI = 0.443–0.890, P = 0.009). Low BMI (<18.0 kg/m2) was not associated with intracranial aneurysm rupture (OR = 0.894, 95% CI = 0.483–1.657, P = 0.505). For males, both the BMI 24.0 to < 28.0 kg/m2 (OR = 0.606, 95% CI = 0.469–0.784, P = 0.000) and the BMI ≥ 28.0 kg/m2 (OR = 0.384, 95% CI = 0.224–0.658, P = 0.001) were associated with a lower rupture risk, whereas the inverse association was not observed in females. Both the BMI 24.0 to < 28.0 kg/m2 (OR = 0.722 for aged 50–60y, 95% CI = 0.554–0.938, P = 0.015; OR = 0.737 for aged >60y, 95% CI = 0.586–0.928, P = 0.009) and the BMI ≥ 28.0 kg/m2 (OR = 0.517 for aged 50–60y, 95% CI = 0.281–0.950, P = 0.0034; OR = 0.535 for aged >60y, 95% CI = 0.318–0.899, P = 0.0018) was associated with a lower rupture risk in patients aged ≥50 years, whereas the association was not significant in patients aged <50 years.

Conclusions: Increased BMI is significantly and inversely associated with saccular intracranial aneurysm rupture in males and patients aged ≥50 years.
Microarray Analysis Identifies Key Differentially Expressed Circular RNAs in Aged Mice With Postoperative Cognitive Dysfunction
Authors: Wu Yu-Qing , Liu Qiang , Wang Hai-Bi , Chen Chen , Huang Hui , Sun Yi-Man , Ma Lin-Hui , Wan Jie , Sun Yin-Ying , Miao Hui-Hui
Published: August 2021

Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients. Circular RNAs (circRNAs) may contribute to neurodegenerative diseases. However, the role of circRNAs in POCD in aged mice has not yet been reported. This study aimed to explore the potential circRNAs in a POCD model. First, a circRNA microarray was used to analyze the expression profiles. Differentially expressed circRNAs were validated using quantitative real-time polymerase chain reaction. A bioinformatics analysis was then used to construct a competing endogenous RNA (ceRNA) network. The database for annotation, visualization, and integrated discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of circRNA-related genes. Moreover, protein-protein interactions were analyzed to predict the circRNA-regulated hub genes using the STRING and molecular complex detection plug-in of Cytoscape. Microarray screen 124 predicted circRNAs in the POCD of aged mice. We found that the up/downregulated circRNAs were involved in multiple signaling pathways. Hub genes, including Egfr and Prkacb, were identified and may be regulated by ceRNA networks. These results suggest that circRNAs are dysexpressed in the hippocampus and may contribute to POCD in aged mice.
Cerebral Edema Formation After Stroke: Emphasis on Blood–Brain Barrier and the Lymphatic Drainage System of the Brain
Authors: Chen Sichao , Shao Linqian , Ma Li
Published: August 2021

Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion and may also result in transtentorial herniation. As a physical and biochemical barrier between the peripheral circulation and the central nervous system (CNS), the blood–brain barrier (BBB) plays a vital role in maintaining the stable microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the dysfunction of the BBB results in increased paracellular permeability, directly contributing to the extravasation of blood components into the brain and causing cerebral vasogenic edema. Recent studies have led to the discovery of the glymphatic system and meningeal lymphatic vessels, which provide a channel for cerebrospinal fluid (CSF) to enter the brain and drain to nearby lymph nodes and communicate with the peripheral immune system, modulating immune surveillance and brain responses. A deeper understanding of the function of the cerebral lymphatic system calls into question the known mechanisms of cerebral edema after stroke. In this review, we first discuss how BBB disruption after stroke can cause or contribute to cerebral edema from the perspective of molecular and cellular pathophysiology. Finally, we discuss how the cerebral lymphatic system participates in the formation of cerebral edema after stroke and summarize the pathophysiological process of cerebral edema formation after stroke from the two directions of the BBB and cerebral lymphatic system.
Frontotemporal Pathology in Motor Neuron Disease Phenotypes: Insights From Neuroimaging
Authors: McKenna Mary Clare , Corcia Philippe , Couratier Philippe , Siah We Fong , Pradat Pierre-Francois , Bede Peter
Published: August 2021

Frontotemporal involvement has been extensively investigated in amyotrophic lateral sclerosis (ALS) but remains relatively poorly characterized in other motor neuron disease (MND) phenotypes such as primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), spinal muscular atrophy (SMA), spinal bulbar muscular atrophy (SBMA), post poliomyelitis syndrome (PPS), and hereditary spastic paraplegia (HSP). This review focuses on insights from structural, metabolic, and functional neuroimaging studies that have advanced our understanding of extra-motor disease burden in these phenotypes. The imaging literature is limited in the majority of these conditions and frontotemporal involvement has been primarily evaluated by neuropsychology and post mortem studies. Existing imaging studies reveal that frontotemporal degeneration can be readily detected in ALS and PLS, varying degree of frontotemporal pathology may be captured in PMA, SBMA, and HSP, SMA exhibits cerebral involvement without regional predilection, and there is limited evidence for cerebral changes in PPS. Our review confirms the heterogeneity extra-motor pathology across the spectrum of MNDs and highlights the role of neuroimaging in characterizing anatomical patterns of disease burdenin vivo. Despite the contribution of neuroimaging to MND research, sample size limitations, inclusion bias, attrition rates in longitudinal studies, and methodological constraints need to be carefully considered. Frontotemporal involvement is a quintessential clinical facet of MND which has important implications for screening practices, individualized management strategies, participation in clinical trials, caregiver burden, and resource allocation. The academic relevance of imaging frontotemporal pathology in MND spans from the identification of genetic variants, through the ascertainment of presymptomatic changes to the design of future epidemiology studies.
Neural Field Theory of Evoked Response Sequences and Mismatch Negativity With Adaptation
Authors: Robinson Peter A. , Gabay Natasha C. , Babaie-Janvier Tara
Published: August 2021

Physiologically based neural field theory of the corticothalamic system is used to calculate the responses evoked by trains of auditory stimuli that correspond to different cortical locations via the tonotopic map. The results are shown to account for standard and deviant evoked responses to frequent and rare stimuli, respectively, in the auditory oddball paradigms widely used in human cognitive studies, and the so-called mismatch negativity between them. It also reproduces a wide range of other effects and variants, including the mechanism by which a change in standard responses relative to deviants can develop through adaptation, different responses when two deviants are presented in a row or a standard is presented after two deviants, relaxation of standard responses back to deviant form after a stimulus-free period, and more complex sequences. Some cases are identified in which adaptation does not account for the whole difference between standard and deviant responses. The results thus provide a systematic means to determine how much of the response is due to adaptation in the system comprising the primary auditory cortex and medial geniculate nucleus, and how much requires involvement of higher-level processing.
Driving With Distraction: Measuring Brain Activity and Oculomotor Behavior Using fMRI and Eye-Tracking
Authors: Yuen Nicole H. , Tam Fred , Churchill Nathan W. , Schweizer Tom A. , Graham Simon J.
Published: August 2021

Introduction

Driving motor vehicles is a complex task that depends heavily on how visual stimuli are received and subsequently processed by the brain. The potential impact of distraction on driving performance is well known and poses a safety concern – especially for individuals with cognitive impairments who may be clinically unfit to drive. The present study is the first to combine functional magnetic resonance imaging (fMRI) and eye-tracking during simulated driving with distraction, providing oculomotor metrics to enhance scientific understanding of the brain activity that supports driving performance.

Materials and Methods

As initial work, twelve healthy young, right-handed participants performed turns ranging in complexity, including simple right and left turns without oncoming traffic, and left turns with oncoming traffic. Distraction was introduced as an auditory task during straight driving, and during left turns with oncoming traffic. Eye-tracking data were recorded during fMRI to characterize fixations, saccades, pupil diameter and blink rate.

Results

Brain activation maps for right turns, left turns without oncoming traffic, left turns with oncoming traffic, and the distraction conditions were largely consistent with previous literature reporting the neural correlates of simulated driving. When the effects of distraction were evaluated for left turns with oncoming traffic, increased activation was observed in areas involved in executive function (e.g., middle and inferior frontal gyri) as well as decreased activation in the posterior brain (e.g., middle and superior occipital gyri). Whereas driving performance remained mostly unchanged (e.g., turn speed, time to turn, collisions), the oculomotor measures showed that distraction resulted in more consistent gaze at oncoming traffic in a small area of the visual scene; less time spent gazing at off-road targets (e.g., speedometer, rear-view mirror); more time spent performing saccadic eye movements; and decreased blink rate.

Conclusion

Oculomotor behavior modulated with driving task complexity and distraction in a manner consistent with the brain activation features revealed by fMRI. The results suggest that eye-tracking technology should be included in future fMRI studies of simulated driving behavior in targeted populations, such as the elderly and individuals with cognitive complaints – ultimately toward developing better technology to assess and enhance fitness to drive.
Cortical Areas Associated With Multisensory Integration Showing Altered Morphology and Functional Connectivity in Relation to Reduced Life Quality in Vestibular Migraine
Authors: Zhe Xia , Chen Li , Zhang Dongsheng , Tang Min , Gao Jie , Ai Kai , Liu Weijun , Lei Xiaoyan , Zhang Xiaoling
Published: August 2021

Background: Increasing evidence suggests that the temporal and parietal lobes are associated with multisensory integration and vestibular migraine. However, temporal and parietal lobe structural and functional connectivity (FC) changes related to vestibular migraine need to be further investigated.

Methods: Twenty-five patients with vestibular migraine (VM) and 27 age- and sex- matched healthy controls participated in this study. Participants completed standardized questionnaires assessing migraine and vertigo-related clinical features. Cerebral cortex characteristics [i.e., thickness (CT), fractal dimension (FD), sulcus depth (SD), and the gyrification index (GI)] were evaluated using an automated Computational Anatomy Toolbox (CAT12). Regions with significant differences were used in a seed-based comparison of resting-state FC conducted with DPABI. The relationship between changes in cortical characteristics or FC and clinical features was also analyzed in the patients with VM.

Results: Relative to controls, patients with VM showed significantly thinner CT in the bilateral inferior temporal gyrus, left middle temporal gyrus, and the right superior parietal lobule. A shallower SD was observed in the right superior and inferior parietal lobule. FD and GI did not differ significantly between the two groups. A negative correlation was found between CT in the right inferior temporal gyrus, as well as the left middle temporal gyrus, and the Dizziness Handicap Inventory (DHI) score in VM patients. Furthermore, patients with VM exhibited weaker FC between the left inferior/middle temporal gyrus and the left medial superior frontal gyrus, supplementary motor area.

Conclusion: Our data revealed cortical structural and resting-state FC abnormalities associated with multisensory integration, contributing to a lower quality of life. These observations suggest a role for multisensory integration in patients with VM pathophysiology. Future research should focus on using a task-based fMRI to measure multisensory integration.
A Wireless Electro-Optic Platform for Multimodal Electrophysiology and Optogenetics in Freely Moving Rodents
Authors: Bilodeau Guillaume , Gagnon-Turcotte Gabriel , Gagnon Léonard L. , Keramidis Iason , Timofeev Igor , De Koninck Yves , Ethier Christian , Gosselin Benoit
Published: August 2021

This paper presents the design and the utilization of a wireless electro-optic platform to perform simultaneous multimodal electrophysiological recordings and optogenetic stimulation in freely moving rodents. The developed system can capture neural action potentials (AP), local field potentials (LFP) and electromyography (EMG) signals with up to 32 channels in parallel while providing four optical stimulation channels. The platform is using commercial off-the-shelf components (COTS) and a low-power digital field-programmable gate array (FPGA), to perform digital signal processing to digitally separate in real time the AP, LFP and EMG while performing signal detection and compression for mitigating wireless bandwidth and power consumption limitations. The different signal modalities collected on the 32 channels are time-multiplexed into a single data stream to decrease power consumption and optimize resource utilization. The data reduction strategy is based on signal processing and real-time data compression. Digital filtering, signal detection, and wavelet data compression are used inside the platform to separate the different electrophysiological signal modalities, namely the local field potentials (1–500 Hz), EMG (30–500 Hz), and the action potentials (300–5,000 Hz) and perform data reduction before transmitting the data. The platform achieves a measured data reduction ratio of 7.77 (for a firing rate of 50 AP/second) and weights 4.7 g with a 100-mAh battery, an on/off switch and a protective plastic enclosure. To validate the performance of the platform, we measured distinct electrophysiology signals and performed optogenetics stimulation in vivo in freely moving rondents. We recorded AP and LFP signals with the platform using a 16-microelectrode array implanted in the primary motor cortex of a Long Evans rat, both in anesthetized and freely moving conditions. EMG responses to optogenetic Channelrhodopsin-2 induced activation of motor cortex via optical fiber were also recorded in freely moving rodents.
A Modified Miniscope System for Simultaneous Electrophysiology and Calcium Imaging in vivo
Authors: Wu Xiaoting , Yang Xiangyu , Song Lulu , Wang Yang , Li Yamin , Liu Yuanyuan , Yang Xiaowei , Wang Yijun , Pei Weihua , Li Weidong
Published: August 2021

The miniscope system is one of the calcium (Ca2+) imaging tools with small size and lightweight and can realize the deep-brain Ca2+ imaging not confined to the cerebral cortex. Combining Ca2+ imaging and electrophysiology recording has been an efficient method for extracting high temporal-spatial resolution signals in the brain. In this study, a particular electrode probe was developed and assembled on the imaging lens to modify the miniscope system. The electrode probe can be tightly integrated into the lens of the miniscope without increasing the volume, weight, and implantation complexity. In vivo tests verified that the proposed modified system has realized the simultaneous recording of Ca2+ signals and local field potential (LFP) signal in the hippocampus CA1 region of an adult mouse.
Held Up in Traffic—Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease
Authors: Markworth Ronja , Bähr Mathias , Burk Katja
Published: August 2021

Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments.
Effects of New Bayesian Penalized Likelihood Reconstruction Algorithm on Visualization and Quantification of Upper Abdominal Malignant Tumors in Clinical FDG PET/CT Examinations
Authors: Tatsumi Mitsuaki , Soeda Fumihiko , Kamiya Takashi , Ueda Junpei , Katayama Daisuke , Matsunaga Keiko , Watabe Tadashi , Kato Hiroki , Tomiyama Noriyuki
Published: August 2021

Purpose

This study evaluated the effects of new Bayesian penalized likelihood (BPL) reconstruction algorithm on visualization and quantification of upper abdominal malignant tumors in clinical FDG PET/CT examinations, comparing the results to those obtained by an ordered subset expectation maximization (OSEM) reconstruction algorithm. Metabolic tumor volume (MTV) and texture features (TFs), as well as SUV-related metrics, were evaluated to clarify the BPL effects on quantification.

Materials and Methods

A total of 153 upper abdominal lesions (82 liver metastatic and 71 pancreatic cancers) were included in this study. FDG PET/CT images were acquired with a GE Discovery 710 scanner equipped with a time-of-flight system. Images were reconstructed using OSEM and BPL (beta 700) algorithms. In 58 lesions <1.5 cm in greatest diameter (small-lesion group), visual image quality of each lesion was evaluated using a four-point scale. SUVmax was obtained for quantitative metrics. Visual scores and SUVmax were compared between OSEM and BPL images. In 95 lesions >2.0 cm in greatest diameter (larger-lesion group), SUVmax, SUVpeak, MTV, and six TFs were compared between OSEM and BPL images. In addition to the size-based analyses, an increase of SUVmax with BPL was evaluated according to the original SUVmax in OSEM images.

Results

In the small-lesion group, both visual score and SUVmax were significantly higher in the BPL than OSEM images. The increase in visual score was observed in 20 (34%) of all 58 lesions. In the larger-lesion group, no statistical difference was observed in SUVmax, SUVpeak, or MTV between OSEM and BPL images. BPL increased high gray-level zone emphasis and decreased low gray-level zone emphasis among six TFs compared to OSEM with statistical significance. No statistical differences were observed in other TFs. SUVmax-based analysis demonstrated that BPL increased and decreased SUVmax in lesions with low (<5) and high (>10) SUVmax in original OSEM images, respectively.

Conclusion

This study demonstrated that BPL improved conspicuity of small or low-count upper abdominal malignant lesions in clinical FDG PET/CT examinations. Only two TFs represented significant differences between OSEM and BPL images of all quantitative metrics in larger lesions.
Effectiveness of Pharmacological Intervention Among Men with Infertility: A Systematic Review and Network Meta-Analysis
Authors: Shahid Muhammad Nabeel , Khan Tahir Mehmood , Neoh Chin Fen , Lean Qi Ying , Bukhsh Allah , Karuppannan Mahmathi
Published: August 2021

Background.Infertility is an emerging health issue for men. Comparative efficacy of different pharmacological interventions on male infertility is not clear. The aim of this review is to investigate the efficacy of various pharmacological interventions among men with idiopathic male infertility. All randomized control trials evaluating the effectuality of interventions on male infertility were included for network meta-analysis (NMA) from inception to 31 April 2020, systematically performed using STATA through the random effect model. The protocol was registered at PROSPERO (CRD42020152891).

Results.The outcomes of interest were semen and hormonal parameters. Treatment effects (p< 0.05) were estimated through WMD at the confidence interval of 95%. Upon applying exclusion criteria, n=28 RCTs were found eligible for NMA. Results from NMA indicated that consumption of supplements increases sperm concentration levels [6.26, 95% CI 3.32, 9.21] in comparison to SERMs [4.97, 95% CI 1.61, 8.32], hormones [4.14, 95% CI 1.83, 6.46], and vitamins [0.15, 95% CI −20.86, 21.15)] with placebo, whereas the use of SERMs increased percentage sperm motility [6.69, 95% CI 2.38, 10.99] in comparison to supplements [6.46, 95% CI 2.57, 10.06], hormones [3.47, 95% CI 0.40, 6.54], and vitamins [−1.24, 95% CI −11.84, 9.43] with placebo. Consumption of hormones increased the sperm morphology [3.71, 95% CI, 1.34, 6.07] in contrast to supplements [2.22, 95% CI 0.12, 4.55], SERMs [2.21, 95% CI −0.78, 5.20], and vitamins [0.51, 95% CI −3.60, 4.62] with placebo. Supplements boosted the total testosterone levels [2.70, 95% CI 1.34, 4.07] in comparison to SERMs [1.83, 95% CI 1.16, 2.50], hormones [0.40, 95% CI −0.49, 1.29], and vitamins [−0.70, 95% CI −6.71, 5.31] with placebo. SERMs increase the serum FSH levels [3.63, 95% CI 1.48, 5.79] better than hormones [1.29, 95% CI −0.79, 3.36], vitamins [0.03, 95% CI −2.69, 2.76], and supplements [−4.45, 95% CI −7.15, −1.76] in comparison with placebo.

Conclusion.This review establishes that all interventions had a significantly positive effect on male infertility. Statistically significant increased sperm parameters were noted in combinations of zinc sulfate (220 mg BID), clomiphene citrate (50 mg BID), and testosterone undecanoate and CoQ10; tamoxifen citrate and FSH were shown to improve the hormonal profile in infertile males.
Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration
Authors: Baratta Robert O. , Del Buono Brian J. , Schlumpf Eric , Ceresa Brian P. , Calkins David J.
Published: August 2021

The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barrier to environmental, microbial, and other insults. Renewal and migration of basal epithelial cells from the limbus involve critical interactions between secreted basement membranes, composed primarily of type IV collagen, and underlying Bowman’s and stromal layers, which contain primarily type I collagen. This process is challenged in many diseases and conditions that insult the ocular surface and damage underlying collagen. We investigated the capacity of a collagen mimetic peptide (CMP), representing a fraction of a single strand of the damaged triple helix human type I collagen, to promote epithelial healing following an acute corneal wound. In vitro, the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an in vivo mouse model, topical application of a CMP-containing formulation following a 360° lamellar keratectomy targeting the corneal epithelial layer accelerated wound closure during a 24 h period, compared to vehicle. We found that the CMP increased adherence of the basal epithelium to the underlying substrate and enhanced density of epithelial cells, while reducing variability in the regenerating layer. These results suggest that CMPs may represent a novel therapeutic to heal corneal tissue by repairing underlying collagen in conditions that damage the ocular surface.
Advances in the Molecular Genetics of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Song Junxia , Luo Yanhong , Jiang Ying , He Jianfeng
Published: August 2021

Catecholaminergic polymorphic ventricular tachycardia is a primary arrhythmogenic syndrome with genetic features most commonly seen in adolescents, with syncope and sudden death following exercise or agitation as the main clinical manifestations. The mechanism of its occurrence is related to the aberrant release of Ca2+ from cardiomyocytes caused by abnormal RyR2 channels or CASQ2 proteins under conditions of sympathetic excitation, thus inducing a delayed posterior exertional pole, manifested by sympathetic excitation inducing adrenaline secretion, resulting in bidirectional or polymorphic ventricular tachycardia. The mortality rate of the disease is high, but patients usually do not have organic heart disease, the clinical manifestations may not be obvious, and no significant abnormal changes in the QT interval are often observed on electrocardiography. Therefore, the disease is often easily missed and misdiagnosed. A number of genetic mutations have been linked to the development of this disease, and the mechanisms are different. In this paper, we would like to summarize the possible genes related to catecholaminergic polymorphic ventricular tachycardia in order to review the genetic tests currently performed, and to further promote the development of genetic testing techniques and deepen the research on the molecular level of this disease.
Interference With the AMPKα/mTOR/NLRP3 Signaling and the IL-23/IL-17 Axis Effectively Protects Against the Dextran Sulfate Sodium Intoxication in Rats: A New Paradigm in Empagliflozin and Metformin Reprofiling for the Management of Ulcerative Colitis
Authors: Youssef Mahmoud E. , Abd El-Fattah Eslam E. , Abdelhamid Amir M. , Eissa Hanan , El-Ahwany Eman , Amin Noha A. , Hetta Helal F. , Mahmoud Mohamed H. , Batiha Gaber El-Saber , Gobba Naglaa , Ahmed Gaafar Ahmed Gaafar , Saber Sameh
Published: August 2021

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.
USP5 Sustains the Proliferation of Glioblastoma Through Stabilization of CyclinD1
Authors: Li Gen , Yang Tianquan , Chen Yanling , Bao Jianping , Wu Di , Hu Xiaohan , Feng Chenxi , Xu Lixiao , Li Mei , Li Gang , Jin Meifang , Xu Yunyun , Zhang Rui , Qian Guanghui , Pan Jian
Published: August 2021

Glioblastoma multiforme (GBM) is one of the most malignant primary tumors in humans. Despite standard therapeutic strategy with tumor resection combined with radiochemotherapy, the prognosis remains disappointed. Recently, deubiquitinating enzymes (DUBs) has been reported as potential cancer therapy targets due to their multifunctions involved in the regulation of tumorigenesis, cell cycle, apoptosis, and autophagy. In this study, we found that knockdown of ubiquitin specific protease (USP5), a family member of DUB, could significantly suppress GBM cell line U251 and DBTRG-05MG proliferation and colony formation by inducing cell cycle G1/S arrest, which was correlated with downregulation of CyclinD1 protein level. CyclinD1 had been reported to play a critical role in the tumorigenesis and development of GBM via regulating cell cycle transition. Overexpression of USP5 could significantly extend the half-life of CyclinD1, while knockdown of USP5 decreased the protein level of CyclinD1, which could be restored by proteasome inhibitor MG-132. Indeed, USP5 was found to directly interact with CyclinD1, and decrease its K48-linked polyubiquitination level. Furthermore, knockdown of USP5 in U251 cells remarkably inhibited tumor growth in vivo. Taken together, these findings demonstrate that USP5 plays a critical role in tumorigenesis and progression of GBM by stabilizing CyclinD1 protein. Targeting USP5 could be a potential therapeutic strategy for GBM.
Multi-Locus Genome-Wide Association Study of Four Yield-Related Traits in Chinese Wheat Landraces
Authors: Lin Yu , Zhou Kunyu , Hu Haiyan , Jiang Xiaojun , Yu Shifan , Wang Qing , Li Caixia , Ma Jian , Chen Guangdeng , Yang Zisong , Liu Yaxi
Published: August 2021

Wheat (Triticum aestivum L.) is one of the most important crops in the world. Here, four yield-related traits, namely, spike length, spikelets number, tillers number, and thousand-kernel weight, were evaluated in 272 Chinese wheat landraces in multiple environments. Five multi-locus genome-wide association studies (FASTmrEMMA, ISIS EN-BLASSO, mrMLM, pKWmEB, and pLARmEB) were performed using 172,711 single-nucleotide polymorphisms (SNPs) to identify yield-related quantitative trait loci (QTL). A total of 27 robust QTL were identified by more than three models. Nine of these QTL were consistent with those in previous studies. The remaining 18 QTL may be novel. We identified a major QTL, QTkw.sicau-4B, with up to 18.78% of phenotypic variation explained. The developed kompetitive allele-specific polymerase chain reaction marker for QTkw.sicau-4B was validated in two recombinant inbred line populations with an average phenotypic difference of 16.07%. After combined homologous function annotation and expression analysis, TraesCS4B01G272300 was the most likely candidate gene for QTkw.sicau-4B. Our findings provide new insights into the genetic basis of yield-related traits and offer valuable QTL to breed wheat cultivars via marker-assisted selection.
Breeding Driven Enrichment of Genetic Variation for Key Yield Components and Grain Starch Content Under Drought Stress in Winter Wheat
Authors: Koua Ahossi Patrice , Oyiga Benedict Chijioke , Baig Mirza Majid , Léon Jens , Ballvora Agim
Published: August 2021

Drought is one of the major abiotic stress factors limiting wheat production worldwide, thus threatening food security. The dissection of the genetic footprint of drought stress response offers strong opportunities toward understanding and improving drought tolerance (DT) in wheat. In this study, we investigated the genotypic variability for drought response among 200 diverse wheat cultivars (genotypes) using agronomic, developmental, and grain quality traits (GQT), and conducted genome-wide association studies (GWAS) to uncover the genetic architectures of these important traits. Results indicated significant effects of genotype, water regime and their interactions for all agronomic traits. Grain yield (GY) was the most drought-responsive trait and was highly correlated with kernels number per meter square (KN). Genome-wide association studies revealed 17 and 20 QTL regions under rainfed and drought conditions, respectively, and identified one LD block on chromosome 3A and two others on 5D associated with breeding progress (BP). The major haplotypes of these LD blocks have been positively selected through breeding and are associated with higher starch accumulation and GY under drought conditions. Upon validation, the identified QTL regions caring favorable alleles for high starch and yield will shed light on mechanisms of tolerance to drought and can be used to develop drought resistant cultivars.
Responsiveness of Early Response to Dehydration Six-Like Transporter Genes to Water Deficit in Arabidopsis thaliana Leaves
Authors: Slawinski Lucie , Israel Abir , Artault Caroline , Thibault Florence , Atanassova Rossitza , Laloi Maryse , Dédaldéchamp Fabienne
Published: August 2021

Drought is one of the main abiotic stresses, which affects plant growth, development, and crop yield. Plant response to drought implies carbon allocation to sink organs and sugar partitioning between different cell compartments, and thereby requires the involvement of sugar transporters (SUTs). Among them, the early response to dehydration six-like (ESL), with 19 members in Arabidopsis thaliana, form the largest subfamily of monosaccharide transporters (MSTs) still poorly characterized. A common feature of these genes is their involvement in plant response to abiotic stresses, including water deficit. In this context, we carried out morphological and physiological phenotyping of A. thaliana plants grown under well-watered (WW) and water-deprived (WD) conditions, together with the expression profiling of 17 AtESL genes in rosette leaves. The drought responsiveness of 12 ESL genes, 4 upregulated and 8 downregulated, was correlated to different water statuses of rosette leaves. The differential expression of each of the tandem duplicated AtESL genes in response to water stress is in favor of their plausible functional diversity. Furthermore, transfer DNA (T-DNA) insertional mutants for each of the four upregulated ESLs in response to water deprivation were identified and characterized under WW and WD conditions. To gain insights into global sugar exchanges between vacuole and cytosol under water deficit, the gene expression of other vacuolar SUTs and invertases (AtTMT, AtSUC, AtSWEET, and AtβFRUCT) was analyzed and discussed.
Meaning of Gaze Behaviors in Individuals' Perception and Interpretation of Commercial Interior Environments: An Experimental Phenomenology Approach Involving Eye-Tracking
Authors: Kwon Jain , Kim Ju Yeon
Published: August 2021

A critical question in interior design is how multisensory information is integrated into occupant perception and interpretation of the environmental contexts and meanings. Although there have been efforts to identify and theorize visual perception of interior factors or features (e.g., colors, fixtures, and signs), the hidden meanings behind visual attention and behaviors have been neglected in interior design research. This experimental phenomenological study investigates the impact of auditory stimuli on the gaze behaviors of individuals and the hidden meanings of their audio-visual perceptions of commercial interiors. Implementing eye-tracking and open-ended interviews, this study explored how the neurophysiological and phenomenological methods in complementary can serve for interior design research on the meaning of gaze behaviors. The study used a convenience sample of 26 participants, three coffee shop interior images, and two musical stimuli. Essential to this study is the interpretive analysis of corresponding eye-tracking and interview data. The results show that visual perception is affected by auditory stimuli and other interior elements and factors associated with personal experiences; however, no distinct gaze pattern is identified by the type of auditory stimuli. The fixation patterns showed mixed reflections of the participants' perceptions, e.g., a single fixation pattern reflecting participants' likes and dislikes. Findings included six essential meanings of participants' gaze behaviors. This study suggested that auditory and visual stimuli are reciprocal in individuals' perceptions. Rather than one affects the other, the interaction between sensory stimuli contributes to the complexity and intensity of multisensory stimuli people associate with their experiences and conceptualize with meanings they establish.
Consequences of Sensory Modality for Perspective-Taking: Comparing Visual, Olfactory and Gustatory Perception
Authors: Kaiser Elsi
Published: August 2021

Perspective-taking is fundamental for language comprehension, including the interpretation of subjective adjectives (e.g.,fun, tasty, andamazing). To understand these adjectives, one needs to know whose opinion is being conveyed—in other words, who is the attitude-holder or perspectival center. Although the perspective-sensitivity of subjective adjectives has received considerable attention in prior work in formal semantics, potential effects of sensory modality (e.g., sight, taste, and smell) on the process of attitude-holder identification have not been systematically investigated. This paper reports a series of studies testing whether interpretation of subjective adjectives depends on whether they refer to the visual, olfactory (smell) vs. gustatory (taste) domains. The results provide evidence that sensory modality has a significant impact on the process of identifying the attitude-holder. This outcome suggests that perspective-sensitivity is highly context-dependent, and the observed modality effects align well with the biological and social properties of sight, taste, and smell.
Effects of Labor Values on Subjective Well-Being: The Mediating Role of Altruistic Tendencies
Authors: Chao Xiaomei , Gu Yuliang
Published: August 2021

This study examined the mediating role of altruistic tendency in the association between labor values and subjective well-being (SWB). About 2,691 Chinese students (1,504 males and 1,187 females) completed the labor values scale (LVS), the Positive Affect and Negative Affect Scale, the Satisfaction With Life Scale, and the altruistic tendency scale. Results demonstrated that labor values were positively associated with life satisfaction and positive affect, while negatively with negative affect. The altruistic tendency was positively correlated with labor values, and positive affect, while negatively correlated with negative affect. Furthermore, altruistic tendency served as a mediator linking labor values and positive/negative affect. These results confirmed the relationship between labor values and SWB and revealed the mechanism of altruism tendency between the two.