bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrinsic and intrinsic factors drive the timing of gestation and reproductive success of Scandinavian brown bears
Authors: Lemière Lucie , Thiel Alexandra , Fuchs Boris , Gilot-Fromont Emmanuelle , Hertel Anne G. , Friebe Andrea , Kindberg Jonas , Støen Ole-Gunnar , Arnemo Jon M. , Evans Alina L.
Published: December 2022

Introduction

Climate change is altering the reproductive phenology of many organisms, but the factors that influence the timing of gestation in ursids are still poorly understood. Higher temperatures in spring are already causing an earlier den exit in some brown bear populations, and a temporal mismatch between hibernation and reproduction could have dramatic consequences for reproductive success. Therefore, understanding the factors that control the timing of these events is important to forecast the consequences of climate change on population growth rates.

Methods

In this study, we used abdominal temperature loggers and GPS collars with acceleration sensors on 23 free-ranging pregnant female brown bears living in two areas in Sweden (61°N and 67°N latitude) to pinpoint hibernation and reproductive events. We investigated how intrinsic and extrinsic factors influence the termination of embryonic diapause and parturition, as well as their impact on reproductive success.

Results

The termination of embryonic diapause was later in the northern area compared to the southern area and occurred earlier when ambient temperature at den entry was higher in both areas. In the southern area, young adults (i.e., females = 7 years old) had a delayed parturition when bilberry abundance was low the year of mating. Additionally, young adults had a lower reproductive success than adults and their probability to reproduce successfully was dependent on bilberry abundance, whereas adult females were not affected by this parameter.

Discussion

As den exit occurs later in the northern study area, we suggest that a later parturition might ensure that females lactate their cubs in the den for a reasonable amount of time while fasting. Similarly, a later parturition combined with an earlier emergence could allow young adults to spend less time in the den lactating if they could not reach an optimal body condition prior to hibernation. But as a result, their cubs are younger and more vulnerable when they leave the den leading to lower survival rates. Our results suggest that a decreased berry abundance in the fall could impact the reproductive and hibernation phenology of Scandinavian brown bear females and lead to a lower cub survival with potential consequences on the population dynamics.
Analysis of miRNA rare variants in amyotrophic lateral sclerosis and in silico prediction of their biological effects
Authors: Brusati Alberto , Ratti Antonia , Pensato Viviana , Peverelli Silvia , Gentilini Davide , Dalla Bella Eleonora , Sorce Marta Nice , Meneri Megi , Gagliardi Delia , Corti Stefania , Gellera Cinzia , Lauria Pinter Giuseppe , Ticozzi Nicola , Silani Vincenzo
Published: December 2022

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and/or lower motor neurons and characterized by complex etiology. Familial cases show high genetic heterogeneity and sporadic cases (90%) are associated with several genetic and environmental risk factors. Among the genetic risk factors, the contribution of non-coding elements, such as microRNAs (miRNAs), to ALS disease susceptibility remains largely unexplored.

Aim: This work aims to identify rare variants in miRNA genes in sporadic ALS (sALS) patients which may cause a defective miRNA maturation or altered target gene recognition by changing miRNA secondary structure or seed sequence, respectively.

Methods: Rare variants located in miRNA loci with a minor allele frequency (MAF) < 0.01 were extracted from whole genome sequencing (WGS) data of 100 sALS patients. The secondary pre-miRNA structures were predicted using MiRVas to evaluate the impact of the variants on RNA folding process. Human TargetScan was used to retrieve all the potential target genes of miRNAs with variants in the seed region. Over Representation Analysis (ORA) was conducted to compare the lists of target genes for the reference and mutated miRNAs in the seed sequence.

Results: Our analysis identified 86 rare variants in 77 distinct miRNAs and distributed in different parts of the miRNA precursors. The presence of these variants changed miRNA secondary structures in ∼70% of MiRVas predictions. By focusing on the 6 rare variants mapping within the seed sequence, the predicted target genes increased in number compared to the reference miRNA and included novel targets in a proportion ranging from 30 to 82%. Interestingly, ORA revealed significant changes in gene set enrichment only for mutated miR-509-1 and miR-941-3 for which the Gene Ontology term related to “nervous system development” was absent and present, respectively, compared to target lists of the reference miRNA.

Conclusion: We here developed a workflow to study miRNA rare variants from WGS data and to predict their biological effects on miRNA folding, maturation and target gene recognition. Although this in silico approach certainly needs functional validation in vitro and in vivo, it may help define the role of miRNA variability in ALS and complex diseases.
HIF-1α/BNIP3L induced cognitive deficits in a mouse model of sepsis-associated encephalopathy
Authors: Zhao Lina , Song Yu , Zhang Ying , Liu Haiying , Shen Yuehao , Fan Yan , Li Yun , Xie Keliang
Published: December 2022

Objective

Sepsis Associated Encephalopathy (SAE) is a common complication in critically ill patients and perioperative period, but its pathogenesis is still unclear. This study aimed to explore the effect of the HIF-1α (hypoxia-inducible factor-1α)/BNIP3L (Bcl-2/adenovirus E1B 19-kDa interaction protein) signaling pathway on SAE.

Methods

C57BL/6J male mice were divided into four groups, using a random number table method: control group, sham group, sepsis group, sepsis+HIF-1α activity inhibitor (echinomycin) group. Sepsis was induced by cecal ligation and puncture (CLP). At 24 h after surgery, brain tissue was sampled. HE was staining to observe changes in the hippocampus structure. Fluoroscopy observes changes in mitochondrial structure. Western blot, QT-PCR, and immunofluorescence were used to assess the amount of expression of HIF-1α and BNIP3L in the hippocampus and mitochondrion of hippocampus neurons. Observation of neuronal apoptosis by TUNEL staining. Seven days after surgery, mice were tested in a Morris water maze test to assess cognitive function after CLP.

Results

Our results show that CLP-induced hippocampus-dependent cognitive deficits were accompanied with increased HIF 1a and decreased BNIP3L, increased protein levels of TNF-α, IL-6, and IL-β, and damage to mitochondrial structures and neuronal apoptosis in the hippocampus. In addition, administration of echinomycin rescues cognitive deficits, ameliorates HIF-1α and BNIP3L-mediated neuronal pyroptosis and damaged mitochondrial structures, and decreases the expression of TNF-α and IL-6 in the hippocampus.

Conclusions

HIF-1α and the BNIP3L promote mitochondrial damage, and neuronal apoptosis and the expression of inflammatory factors may be the mechanism of SAE in critically ill patients and perioperative period
Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis
Authors: Zhang Tian-Ping , Li Rui , Wang Li-Jun , Huang Qian , Li Hong-Miao
Published: December 2022

Objective

The aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB).

Methods

A case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in METTL3 (rs1061027, rs1139130, rs1061026), three SNPs in METTL14 (rs62328061, rs4834698, rs1064034), and two SNPs in WTAP (rs1853259, rs11752345) were genotyped via the SNPscan™ technique. METTL3, METTL14, and WTAP transcription levels were determined in 78 PTB patients and 86 controls via quantitative real-time reverse-transcription PCR.

Results

Frequencies of the METTL14 rs62328061 GG genotype, WTAP rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. METTL3 gene variation was not associated with PTB risk. The METTL3 rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the METTL14 rs62328061 G allele was associated with leukopenia, a reduced frequency of the WTAP rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the METTL14 rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, METTL3, METTL14, and WTAP transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase.

Conclusion

METTL14 rs62328061 and WTAP rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.
Characterization and genomic analysis of a novel halovirus infecting Chromohalobacter beijerinckii
Authors: Yi Hao , Fu Chaoqun , Diao Kaixin , Li Zhiying , Cui Xiaolong , Xiao Wei
Published: December 2022

Bacteriophages function as a regulator of host communities and metabolism. Many phages have been isolated and sequenced in environments such as the ocean, but very little is known about hypersaline environments. Phages infecting members of the genus Chromohalobacter remain poorly understood, and no Chromohalobacter phage genome has been reported. In this study, a halovirus infecting Chromohalobacter sp. F3, YPCBV-1, was isolated from Yipinglang salt mine. YPCBV-1 could only infect host strain F3 with burst size of 6.3 PFU/cell. It could produce progeny in 5%–20% (w/v) NaCl with an optimal concentration of 10% (w/v), but the optimal adsorption NaCl concentration was 5%–8% (w/v). YPCBV-1 is sensitive to pure water and depends on NaCl or KCl solutions to survive. YPCBV-1 stability increased with increasing salinity but decreased in NaCl saturated solutions, and it has a broader salinity adaptation than the host. YPCBV-1 has a double-stranded DNA of 36,002 bp with a G + C content of 67.09% and contains a total of 55 predicted ORFs and no tRNA genes. Phylogenetic analysis and genomic network analysis suggested that YPCBV-1 is a novel Mu-like phage under the class Caudoviricetes. Auxiliary metabolic gene, SUMF1/EgtB/PvdO family non-heme iron enzyme, with possible roles in antioxidant was found in YPCBV-1. Moreover, DGR-associated genes were predicted in YPCBV-1 genome, which potentially produce hypervariable phage tail fiber. These findings shed light on the halovirus-host interaction in hypersaline environments.
A review on the bioleaching of toxic metal(loid)s from contaminated soil: Insight into the mechanism of action and the role of influencing factors
Authors: Sarkodie Emmanuel Konadu , Jiang Luhua , Li Kewei , Yang Jiejie , Guo Ziwen , Shi Jiaxin , Deng Yan , Liu Hongwei , Jiang Huidan , Liang Yili , Yin Huaqun , Liu Xueduan
Published: December 2022

The anthropogenic activities in agriculture, industrialization, mining, and metallurgy combined with the natural weathering of rocks, have led to severe contamination of soils by toxic metal(loid)s. In an attempt to remediate these polluted sites, a plethora of conventional approaches such as Solidification/Stabilization (S/S), soil washing, electrokinetic remediation, and chemical oxidation/reduction have been used for the immobilization and removal of toxic metal(loid)s in the soil. However, these conventional methods are associated with certain limitations. These limitations include high operational costs, high energy demands, post-waste disposal difficulties, and secondary pollution. Bioleaching has proven to be a promising alternative to these conventional approaches in removing toxic metal(loid)s from contaminated soil as it is cost-effective, environmentally friendly, and esthetically pleasing. The bioleaching process is influenced by factors including pH, temperature, oxygen, and carbon dioxide supply, as well as nutrients in the medium. It is crucial to monitor these parameters before and throughout the reaction since a change in any, for instance, pH during the reaction, can alter the microbial activity and, therefore, the rate of metal leaching. However, research on these influencing factors and recent innovations has brought significant progress in bioleaching over the years. This critical review, therefore, presents the current approaches to bioleaching and the mechanisms involved in removing toxic metal(loid)s from contaminated soil. We further examined and discussed the fundamental principles of various influencing factors that necessitate optimization in the bioleaching process. Additionally, the future perspectives on adding omics for bioleaching as an emerging technology are discussed.
Altered anterior cingulate cortex subregional connectivity associated with cognitions for distinguishing the spectrum of pre-clinical Alzheimer’s disease
Authors: Yuan Qianqian , Liang Xuhong , Xue Chen , Qi Wenzhang , Chen Shanshan , Song Yu , Wu Huimin , Zhang Xulian , Xiao Chaoyong , Chen Jiu
Published: December 2022

Background

Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered part of the early progression continuum of Alzheimer’s disease (AD). The anterior cingulate cortex (ACC), a hub of information processing and regulation in the brain, plays an essential role in AD pathophysiology. In the present study, we aimed to systematically identify changes in the functional connectivity (FC) of ACC subregions in patients with SCD and aMCI and evaluate the association of these changes with cognition.

Materials and methods

Functional connectivity (FC) analysis of ACC sub-regions was performed among 66 patients with SCD, 71 patients with aMCI, and 78 healthy controls (HCs). Correlation analyses were performed to examine the relationship between FC of altered ACC subnetworks and cognition.

Results

Compared to HCs, SCD patients showed increased FC of the bilateral precuneus (PCUN) and caudal ACC, left superior frontal gyrus (SFG) and subgenual ACC, left inferior parietal lobule (IPL) and dorsal ACC, left middle occipital gyrus (MOG) and dorsal ACC, and left middle temporal gyrus (MTG) and subgenual ACC, while aMCI patients showed increased FC of the left inferior frontal gyrus (IFG) and dorsal ACC and left medial frontal gyrus (MFG) and subgenual ACC. Compared to patients with SCD, patients with aMCI showed increased FC of the right MFG and dorsal ACC and left ACC and subgenual ACC, while the left posterior cingulate cortex (PCC) showed decreased FC with the caudal ACC. Moreover, some FC values among the altered ACC subnetworks were significantly correlated with episodic memory and executive function.

Conclusion

SCD and aMCI, part of the spectrum of pre-clinical AD, share some convergent and divergent altered intrinsic connectivity of ACC subregions. These results may serve as neuroimaging biomarkers of the preclinical phase of AD and provide new insights into the design of preclinical interventions.
Chronic neuroinflammation impairs waste clearance in the rat brain
Authors: Suresh Swathi , Larson Jacob , Jenrow Kenneth Allen
Published: December 2022

Background

Previous reports have established an association between impaired clearance of macromolecular waste from the brain parenchyma and a variety of brain insults for which chronic neuroinflammation is a common pathological feature. Here we investigate whether chronic neuroinflammation is sufficient to impair macromolecular waste clearance from the rat brain.

Methods

Using a rodent model of chronic neuroinflammation induced by a single high-dose injection of lipopolysaccharide, the clearance kinetics of two fluorophore-conjugated dextran tracers were assayed at 8-weeks post-induction. The expression and distribution of amyloid β and aquaporin-4 proteins within selected brain regions were assayed at 36-weeks post-induction, following open-field, novel object recognition, and contextual fear conditioning assays.

Results

Chronic neuroinflammation significantly impaired the clearance kinetics of both dextran tracers and resulted in significantly elevated levels of amyloid β within the hippocampus. Aquaporin-4 density on astrocytic endfeet processes was also reduced within multiple brain regions. These pathologies were associated with significantly enhanced contextual fear memory.

Conclusion

Our results suggest that chronic neuroinflammation is sufficient to compromise the clearance of macromolecular waste from the brain parenchyma and may be the root cause of impaired waste clearance associated with a variety of brain pathologies.
Test-retest reliability of modular-relevant analysis in brain functional network
Authors: Wen Xuyun , Yang Mengting , Hsu Liming , Zhang Daoqiang
Published: December 2022

Introduction

The human brain could be modeled as a complex network via functional magnetic resonance imaging (fMRI), and the architecture of these brain functional networks can be studied from multiple spatial scales with different graph theory tools. Detecting modules is an important mesoscale network measuring approach that has provided crucial insights for uncovering how brain organizes itself among different functional subsystems. Despite its successful application in a wide range of brain network studies, the lack of comprehensive reliability assessment prevents its potential extension to clinical trials.

Methods

To fill this gap, this paper, using resting-state test-retest fMRI data, systematically explored the reliabilities of five popular network metrics derived from modular structure. Considering the repeatability of network partition depends heavily on network size and module detection algorithm, we constructed three types of brain functional networks for each subject by using a set of coarse-to-fine brain atlases and adopted four methods for single-subject module detection and twelve methods for group-level module detection.

Results

The results reported moderate-to-good reliability in modularity, intra- and inter-modular functional connectivities, within-modular degree and participation coefficient at both individual and group levels, indicating modular-relevant network metrics can provide robust evaluation results. Further analysis identified the significant influence of module detection algorithm and node definition approach on reliabilities of network partitions and its derived network analysis results.

Discussion

This paper provides important guidance for choosing reliable modular-relevant network metrics and analysis strategies in future studies.
Lateralization of cerebral blood flow in the auditory cortex of patients with idiopathic tinnitus and healthy controls: An arterial spin labeling study
Authors: Li Xiaoshuai , Zhao Yansheng , Hui Ying , Wu Yuntao , Chen Qian , Shi Huijing , Lv Han , Li Mengning , Zhao Pengfei , Zhang Wenfei , Zhao Xinyu , Li Jing , Cui Liufu , Wang Zhenchang
Published: December 2022

Objectives

To assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL).

Methods

Thirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed.

Results

In both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left (AAC: HCs, P < 0.001; patients: P < 0.001. SAC: HCs, P < 0.001; patients: P = 0.001). Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC (right: P = 0.008; left: P = 0.022). CBF in the left PAC was positively correlated with tinnitus severity (r = 0.399, P = 0.016).

Conclusion

This study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF.
The antihyperglycemic effect of pulsed electric field-extracted polysaccharide of Kaempferia elegans officinale on streptozotocin induced diabetic mice
Authors: Lei Huan-Qing , Li Dong-Mei , Woo Meng-Wai , Zeng Xin-An , Han Zhong , Wang Ruo-Yong
Published: December 2022

Kaempferia elegans polysaccharide (KEP) was extracted using a high-voltage pulsed electric field-assisted hot water method. Its physicochemical properties, in vitro activity and hypoglycemic effect was investigated. Experiments were undertaken with diabetic mice models and the potential mechanism of KEP to improve blood glucose levels was unveiled through measurements of relevant indicators in the serum and liver of the mice. Results showed that KEP is mainly composed of glucose, rhamnose, arabinose, and galactose. It has certain DPPH and ABTS free radical scavenging ability and good α-glucosidase inhibitory ability, indicating that KEP has the potential to improve blood glucose levels in diabetes patients. The experimental results of KEP treatment on mice showed that KEP could control the continuous increase of fasting blood glucose levels. The potential mechanisms behind this blood glucose level control composes of (1) increasing the glucokinase and C peptide levels and decreasing Glucose-6-phosphatase content for improving key enzyme activity in the glucose metabolism pathway. This promotes the consumption of blood glucose during glycolysis, thereby inhibiting the production of endogenous glucose in gluconeogenesis pathway; (2) reducing triglyceride, total cholesterol, low density lipoprotein cholesterol, and increasing high density lipoprotein cholesterol content, for regulating blood lipid indicators to normal levels; and (3) by improving the activities of catalase, glutathione peroxidase, and antioxidant enzymes superoxide dismutase for further improving the antioxidant defense system in the body to reduce blood glucose.
Diagnostic performance of 99mTc-HYNIC-PSMA SPECT/CT for biochemically recurrent prostate cancer after radical prostatectomy
Authors: Li Bo , Duan Lili , Shi Jingqi , Han Yunyun , Wei Wei , Cheng Xiaoliang , Cao Yong , Kader Akeban , Ding Degang , Wu Xinyu , Gao Yongju
Published: December 2022

Objectives

99mTc-HYNIC-PSMA is a novel technetium-99m-labeled small-molecule inhibitor of prostate-specific membrane antigen (PSMA) for detection of prostate cancer. The present study investigated the diagnostic yield of 99mTc-HYNIC-PSMA Single photon emission computed tomography (SPECT)/CT in 147 patients with biochemically recurrent prostate cancer after radical prostatectomy.

Methods

147 patients with biochemical relapse after radical prostatectomy were finally eligible for this retrospective analysis. The median prostate-specific antigen (PSA) level was 8.26 ng/mL (range, 0.22-187.40 ng/mL). Of the 147 patients, 72 patients received androgen deprivation therapy (ADT) at least 6 months before the 99mTc-HYNIC-PSMA SPECT/CT. All patients underwent planar whole-body scans and subsequent SPECT/CT of the thoracic and abdominal regions after intravenous injection of 705 ± 70 MBq of 99mTc-HYNIC-PSMA. Images were evaluated for the presence and location of PSMA-positive lesions, in which SUVmax were also measured. Detection rates were stratified according to PSA levels, ADT and Gleason scores. The relationships between SUVmax and clinical characteristics were analyzed using univariate and multivariable linear regression models for patients with positive findings.

Results

Of the 147 patients, 99mTc-HYNIC-PSMA SPECT/CT revealed at least one positive lesion in 118 patients with a high detection rate (80.3%). The detection rates were 48.6% (17/35), 85.1% (40/47), 92.1% (35/38), and 96.3% (26/27) at PSA levels of greater than 0.2 to 2, greater than 2 to 5, greater than 5 to 10, and greater than 10 ng/mL, respectively. PSMA SPECT/CT indicated local recurrence, lymph node metastases, bone metastases, and visceral metastases in 14 (9.5%), 73 (49.7%), 48 (32.7%) and 3 (2.0%) patients. The detection rates of local recurrence and metastasis increased with increasing PSA levels. The detection rate was higher in patients treated with ADT than those without (90.3% vs. 70.7%; P =0.0029). In patients with Gleason scores ≥8, detection rate was slightly higher than those with ≤7 (81.7% vs. 78.5%), but not statistically significant (P = 0.6265). Multivariable linear regression analysis showed a significant correlation of PSA levels and ADT with SUVmax (P=0.0005 and P=0.0397).

Conclusions

99mTc-HYNIC-PSMA SPECT/CT offers high detection rates for biochemically recurrent prostate cancer after radical prostatectomy. The detection rate and SUVmax were positively correlated with PSA levels and ADT.
Implementation of multigene panel testing for breast and ovarian cancer in South Africa: A step towards excellence in oncology for the public sector
Authors: van der Merwe Nerina C. , Ntaita Kholiwe S. , Stofberg Hanri , Combrink Herkulaas MvE. , Oosthuizen Jaco , Kotze Maritha J.
Published: December 2022

Translation of genomic knowledge into public health benefits requires the implementation of evidence-based recommendations in clinical practice. In this study, we moved beyond BRCA1/2 susceptibility testing in breast and ovarian cancer patients to explore the application of pharmacogenetics across multiple genes participating in homologous recombination DNA damage repair. This involved the utilisation of next-generation sequencing (NGS) at the intersection of research and service delivery for development of a comprehensive genetic testing platform in South Africa. Lack of international consensus regarding risk categorization of established cancer susceptibility genes and the level of evidence required for prediction of drug response supported the development of a central database to facilitate clinical interpretation. Here we demonstrate the value of this approach using NGS to 1) determine the variant spectrum applicable to targeted therapy and implementation of prevention strategies using the 15-gene Oncomine™ BRCA Expanded Panel, and 2) searched for novel and known pathogenic variants in uninformative cases using whole exome sequencing (WES). Targeted NGS performed as a routine clinical service in 414 South African breast and/or ovarian cancer patients resulted in the detection of 48 actionable variants among 319 (15%) cases. BRCA1/2-associated cancers were identified in 70.8% of patients (34/48, including two double-heterozygotes), with the majority (35.3%, 12/34) representing known South African founder variants. Detection of actionable variants in established non-BRCA1/2 risk genes contributed 29% to the total percentage (14/48), distributed amongst ATM, CHEK2, BARD1, BRIP1, PALB2 and TP53. Experimental WES using a virtually constructed multi-cancer NGS panel in 16 genetically unresolved cases (and four controls) revealed novel protein truncating variants in the basal cell carcinoma gene PTCH1 (c.4187delG) and the signal transmission and transduction gene KIT (c.930delA) involved in crucial cellular processes. Based on these findings, the most cost-effective approach would be to perform BRCA1/2 founder variant testing at referral, followed by targeted multigene panel testing if clinically indicated and addition of WES in unresolved cases. This inventive step provides a constant flow of new knowledge into the diagnostic platform via a uniquely South African pathology-supported genetic approach implemented for the first time in this context to integrate research with service delivery.
Flos Puerariae-Semen Hoveniae medicinal pair extract ameliorates DSS-induced inflammatory bowel disease through regulating MAPK signaling and modulating gut microbiota composition
Authors: Chen Xiaofan , Zhang Jiahui , Li Rui , Zhang Hua , Sun Yong , Jiang Li , Wang Xiaoya , Xiong Yaokun
Published: December 2022

Background: Inflammatory bowel disease (IBD) is a global gastrointestinal disease characterized by relapsing and remitting inflammatory conditions. Flos Puerariae (the flower of Pueraria lobata [Willd.] Ohwi and P. thomsonii Benth.) and Hovenia dulcis Thunb. (Rhamnaceae) are traditional Chinese medicines. This medicinal pair has been used to treat various diseases due to its excellent anti-oxidant and anti-inflammatory activity. However, the effects of extracts from these plants on dextran sulfate sodium (DSS)-induced colitis have not been investigated; further study is needed to improve the understanding of their mechanisms of action and potential applications.

Methods: The chemical constitution of extracts from Flos Puerariae and Semen Hoveniae (PHE) was analyzed using UPLC-LTQ-Orbitrap-MS/MS. The protective effects of PHE on mice with DSS-induced colitis were evaluated through assessment of body weight loss, disease activity index (DAI) score, colon length shortening, and pathological changes. The levels of inflammatory cytokines were determined by ELISA and RT-qPCR. Biomarkers of oxidative stress (ROS, CAT, SOD, MDA, and T-AOC) were analyzed using biochemical kits. The expression of MAPK proteins was determined by Western blotting analysis. Gut microbiota were analyzed via 16S rRNA sequencing.

Results: Chemical composition analysis indicated that PHE contains various bioactive compounds, including puerarin, kakkalide, tectoridin, and genistin. The findings from this study suggest that PHE could effectively modulate histopathological score, inflammatory cell infiltration, and inflammatory factor secretion. Notably, PHE ameliorated oxidative stress by inhibiting activation of the MAPK pathway, leading to decreased inflammatory mediators and restored antioxidant enzyme activity. Furthermore, PHE treatment regulated the composition of the gut microbiota by increasing the abundance of benign bacteria, such as Akkermansia, and reducing the abundance of harmful bacteria, such as Proteobacteria.

Conclusion: The findings from this study demonstrate the mechanism underlying the amelioration of DSS-induced intestinal oxidative stress by PHE and its positive impact on the restoration of the composition of gut microbiota.
γ-Aminobutyric acid treatment induced chilling tolerance in postharvest peach fruit by upregulating ascorbic acid and glutathione contents at the molecular level
Authors: Zhou Chujiang , Dong Wanqi , Jin Shuwan , Liu Qingli , Shi Liyu , Cao Shifeng , Li Saisai , Chen Wei , Yang Zhenfeng
Published: December 2022

Peach fruit was treated with 5 mM γ-aminobutyric acid (GABA) to further investigate the mechanism by which GABA induced chilling tolerance. Here, we found that GABA not only inhibited the occurrence of chilling injury in peach fruit during cold storage but also maintained fruit quality. Most of the ascorbic acid (AsA) and glutathione (GSH) biosynthetic genes were up-regulated by GABA treatment, and their levels were increased accordingly, thus reducing chilling damage in treated peaches. Meanwhile, the increased transcript of genes in the AsA-GSH cycle by GABA treatment was also related to the induced tolerance against chilling. GABA treatment also increased the expression levels of several candidate ERF transcription factors involved in AsA and GSH biosynthesis. In conclusion, our study found that GABA reduced chilling injury in peach fruit during cold storage due to the higher AsA and GSH contents by positively regulating their modifying genes and candidate transcription factors.
The impact of teacher feedback on students’ decisions to stay on or change course after math failure in a Confucian cultural context
Authors: Fwu Bih-Jen , Yang Tong-Rong , Chen Yi-Kai , Chen Rong
Published: December 2022

Previous research indicated that instructors holding entity belief tended to judge students to have low ability and provided ability-comforting feedback following math failure. Students receiving such feedback tended to quit and change course, creating a potential decrease in the pool of students pursuing math related fields. In Confucian heritage cultures (CHCs), the ideal society is primarily based on fulfillment of duties. Thus, the ability-based findings, derived from WEIRD samples, may not apply to duty-based CHCs. We hypothesized that CHC’s teachers holding obligation belief tend to attribute students’ failure to lack of duty fulfillment and provide duty-based feedback, including duty-comforting and duty-advising feedback, which motivates students to stay on rather than change course. To validate our hypothesis, we conducted three scenario experiments with 160 college students with teaching experiences, 273 high school students, and 369 pre-service teachers in Taiwan. Results showed that while ability-based paradigm may be culture-free, duty-based paradigm seems to be culture-bound. Consistent with previous research, teachers with entity belief tended to give ability-comforting feedback, pushing students to pursue non-math related fields. In contrast, teachers with obligation belief were likely to offer duty-comforting and duty-advising feedback, contributing to students’ persistent pursuit in math. Furthermore, three fifths of teachers were inclined to provide ability-comforting, duty-comforting and duty-advising feedback concurrently, thus putting students in an unpleasant predicament that might be detrimental to their psychological well-being. Theoretical and practical implications are discussed.
The impact of digital transformation on corporate total factor productivity
Authors: Li Na , Wang Xiaohong , Wang Zeren , Luan Xiangyu
Published: December 2022

Introduction

Corporates need to break through the dilemma of system and efficiency with the help of digital transformation in the digital economy era. This paper aims to examine the influence of digital transformation on corporate total factor productivity by investigating whether and how corporate technical cooperation and ESG performance mediate and moderate the relationship between them.

Methods

This study choose Chinese A-share listed manufacturing firms from 2016–2020 as the research sample and use the FGLS regression model to test the proposed hypotheses.

Results

Results show that digital transformation has a positive effect on corporate total factor productivity, and this positive impact is more pronounced when corporates have higher ESG performance. Corporate technical cooperation plays a mediating role between digital transformation and total factor productivity. ESG performance also plays a positive moderating role in the relationship between digital transformation and corporate technical cooperation.

Discussion

Our results contribute to the literature on digital transformation and corporate total factor productivity at the micro-corporate level. Further, our findings offer insights to decision-makers and regulatory bodies regarding the current practices of digital transformation and its potential economic impact.
Face-to-trait inferences in Japanese children and adults based on Caucasian faces
Authors: Sakuta Yuiko
Published: December 2022

Recently, many studies have indicated that humans make social evaluations from facial appearances instantaneously and automatically. Furthermore, such judgments play an important role in several social contexts. However, the mechanisms involved in the ability to form impressions from faces are still unknown, as is the extent to which these can be regarded as universal in perceiving impressions. In the current study, computer-generated Caucasian faces were used to assess the universality or cultural differences in impression formation among Japanese children and adults. This study hypothesized that impressions of trustworthiness and dominance may be more fundamental and universal, whereas the impression of competence may be more complex and culture-dependent. In Experiment 1a, 42 children aged 3–6 years were presented with 10 pairs of face images and asked which image in each pair was more trustworthy, dominant, or competent. Overall, it was found that as age increased, the rate of agreement of Japanese participants with the judgment of American participants, obtained in a previous study, increased. However, the agreement rate for competence was relatively low. Experiment 1b, conducted with 46 children, was a replication of Experiment 1a, and the results showed the same tendency. In Experiment 2, 45 Japanese adults made impression judgments on 19 pairs of face images identical to those used in Experiment 1b. The results suggested that while dominance was a dimension not easily influenced by developmental changes or culture, trustworthiness could be influenced by cultural differences in facial expression recognition. Therefore, different judgment criteria are used for children and adults. For competence, the agreement rate with Americans was relatively stable and low among the different age groups. This suggests that depending on the dimension of the trait, certain judgments are influenced by cultural context and, therefore, change criteria, while others are based on more universal criteria.
Telehealth Listening Visits for emotionally distressed mothers of hospitalized newborns: Proof-of-concept
Authors: Segre Lisa S. , McCabe Jennifer E. , Chuffo Davila Rebecca , Arndt Stephan
Published: December 2022

Problem

Newborn admission to the neonatal intensive care unit (NICU) is stressful. Yet in clinical practice, at best, NICU mothers are screened for depression and if indicated, referred to a mental-health specialist. At worst, no action is taken. Listening Visits, an empirically supported nurse-delivered intervention addressing emotional distress, can be conveniently provided by a NICU nurse. Prompted by the need to minimize face-to-face contacts during the pandemic, the primary purpose of this small pilot trial was to assess the feasibility of having nurses provide Listening Visits to NICU mothers over Zoom. Secondarily, we assessed pre-to post-Listening Visits depression symptom scores as a preliminary evaluation of the effectiveness of this type of support.

Materials and methods

Nine NICU mothers with mildly to moderately severe depression symptoms received up to six Listening Visits sessions from a NICU nurse via Zoom. Participants completed the Inventory Depression and Anxiety Symptoms-General Depression scale (IDAS-GD) at study entry and 4- and 8-weeks post enrollment. They completed the Client Satisfaction Questionnaire (CSQ) at the 8-week assessment.

Results

Using an intent-to-treat approach, the effect of time from the mixed model analysis of IDAS-GD was statistically significant (F(2,26) = 10.50, p < 0.001), indicating improvement in IDAS-GD scores from baseline to follow-up. The average CSQ score was high (M = 29.0, SD = 3.3), with 75% of participants rating the quality of help they received as “excellent”.

Discussion

In this pilot trial, we learned it is feasible to provide Listening Visits over Zoom, that this mode of delivery is associated with a significant decrease in depression symptom scores, and that women value this approach.

Clinical trial registration

[https://clinicaltrials.gov/], identifier [#201805961].
Concentric regulatory zones failed to halt surging COVID-19: Brooklyn 2020
Authors: Harris Jeffrey E.
Published: December 2022

Methods

We relied on reports of confirmed case incidence and test positivity, along with data on the movements of devices with location-tracking software, to evaluate a novel scheme of three concentric regulatory zones introduced by then New York Governor Cuomo to address an outbreak of COVID-19 in South Brooklyn in the fall of 2020. The regulatory scheme imposed differential controls on access to eating places, schools, houses of worship, large gatherings and other businesses within the three zones, but without restrictions on mobility.

Results

Within the central red zone, COVID-19 incidence temporarily declined from 131.2 per 100,000 population during the week ending October 3 to 62.5 per 100,000 by the week ending October 31, but then rebounded to 153.6 per 100,000 by the week ending November 28. Within the intermediate orange and peripheral yellow zones combined, incidence steadily rose from 28.8 per 100,000 during the week ending October 3 to 109.9 per 100,000 by the week ending November 28. Data on device visits to pairs of eating establishments straddling the red-orange boundary confirmed compliance with access controls. More general analysis of device movements showed stable patterns of movement between and beyond zones unaffected by the Governor's orders. A geospatial regression model of COVID-19 incidence in relation to device movements across zip code tabulation areas identified a cluster of five high-movement ZCTAs with estimated reproduction number 1.91 (95% confidence interval, 1.27–2.55).

Discussion

In the highly populous area of South Brooklyn, controls on access alone, without restrictions on movement, were inadequate to halt an advancing COVID-19 outbreak.
Combining a non-immersive virtual reality gaming with motor-assisted elliptical exercise increases engagement and physiologic effort in children
Authors: Huang Chun-Kai , Buster Thad W. , Siu Ka-Chun , Burnfield Judith M.
Published: December 2022

Virtual reality (VR) gaming is promising in sustaining children’s participation during intensive physical rehabilitation. This study investigated how integration of a custom active serious gaming with a robot-motorized elliptical impacted children’s perception of engagement (Intrinsic Motivation Inventory), physiologic effort (i.e., exercise speed, heart rate, lower extremity muscle activation), and joint kinematics while overriding the motor’s assistance. Compared to Non-VR condition, during the VR-enhanced condition participants’ perceived engagement was 23% greater (p = 0.01), self-selected speed was 10% faster (p = 0.02), heart rate was 7% higher (p = 0.08) and muscle demands increased. Sagittal plane kinematics demonstrated only a small change at the knee. This study demonstrated that VR plays an essential role in promoting greater engagement and physiologic effort in children performing a cyclic locomotor rehabilitation task, without causing any adverse events or substantial disruption in lower extremity joint kinematics. The outcomes of this study provide a foundation for understanding the role of future VR-enhanced interventions and research studies that weigh/balance the need to physiologically challenge a child during training with the value of promoting task-related training to help promote recovery of walking.
An economic assessment of adoption of hybrid rice: Micro-level evidence from southern China
Authors: Yan Zedong , Chen Fengbo , Mishra Ashok K. , Sha Wenbiao
Published: December 2022

The hybrid rice technology could be considered a boon for food security for many in South and Southeast Asia to increase rice productivity. In China, the birthplace of hybrid rice (HR), the diffusion of hybrid rice started in 1976. About 28% rice-growing area in China is planted with hybrid rice. However, the proportion of HR area in China has been declining in recent years, and farmers in surrounding countries are reluctant to adopt it because of high seed costs, farm management practices, and quality issues. Most previous research on the evaluation of hybrid rice variety on yield does not control input level. This study uses the endogenous switching regression method to analyze the impacts of HR adoption on rice yield and net rice income. The study uses plot- and household-level data from four southern provinces of China. Findings show a significant effect of HR adoption on rice yields. On the same HR plots, compared to CR adopters, rice yield increases by 4.86% for HR adopters. Rice yield would increase by 4.72% if the HR variety was adopted on the same conventional rice (CR) plots. Additionally, findings show a significant effect of HR adoption on net rice incomes. On the same HR plots, compared to CR adopters, net rice income decreases by 43.61% for HR adopters. Similarly, net rice income would reduce by 10.95% if the HR variety was adopted on the same CR plots. Thus, adopting HR increases rice productivity, but Chinese farming households that adopted CR would not benefit from adopting HR. Policymakers can formulate a systematic and comprehensive rice breeding plan to guide the simultaneous development of rice variety yield and quality improvement. Additionally, policymakers, in conjunction with private companies, could enact policies to reduce the cost of hybrid rice seed or improve the production efficiency of HR. For example, they could incentivize the development of HR varieties suitable for direct seeding and seed-saving sowing methods (rice trans-planter).
Subchronic toxicity of oral deltamethrin in laying chickens
Authors: Liu Yiming , Han Mingyue , Liu Chunshuang , Tang Yaoxin , Jia Ming , Chen Xiaojie , Liang Haijun , Gao Yunfeng , Gu Xu
Published: December 2022

Pyrethroid pesticides, with low toxicity to birds and mammals and short persistence in the environment, are widely used now. With the development of intensive poultry farming, pesticide application leads to residues in poultry products and pollution in ecological environment. The aim of the present study was to examine deltamethrin subchronic toxicity in laying chickens. One hundred and twelve laying chickens were randomly assigned to 14 groups including 13 groups medicated with deltamethrin (n = 8) and one unmedicated group used as control (n = 8). Tissue samples were collected during and after administration for weighing and histopathological analysis. A single dose of deltamethrin (20 mg·kg−1·BW·d) was administered orally to laying chickens for 14 days. The results showed that deltamethrin has no significant effect on the relative organ weight of laying chickens (p > 0.05). The activities of aspartate aminotransferase and cholinesterase in the plasma gradually decreased over time in the medicated group (p < 0.05). Plasma concentrations of urea nitrogen, uric acid, cholesterol, triglycerides, and creatinine significantly increased during treatment (p < 0.05), and significant liver damage and loss of intestinal villous epithelium were observed. The intestinal wall thickness, villus height, and crypt depth of laying chickens were altered by deltamethrin treatment. During treatment was withdrawn, the intestinal repair was more extensive than the liver repair.