bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia
Authors: Chear Chai Teng , Ismail Intan Hakimah , Chan Kwai Cheng , Noh Lokman Mohd , Kassim Asiah , Latiff Amir Hamzah Abdul , Gill Sandeep Singh , Ramly Nazatul Haslina , Tan Kah Kee , Sundaraj Charlotte , Choo Chong Ming , Mohamed Sharifah Adlena Syed , Baharin Mohd Farid , Zamri Amelia Suhana , Yahya Sharifah Nurul Husna Syed , Mohamad Saharuddin Bin , Ripen Adiratna Mat
Published: September 2023

Background

Bruton’s tyrosine kinase (BTK) is a cytoplasmic protein involved in the B cell development. X-linked agammaglobulinemia (XLA) is caused by mutation in the BTK gene, which results in very low or absent B cells. Affected males have markedly reduced immunoglobulin levels, which render them susceptible to recurrent and severe bacterial infections. Methods: Patients suspected with X-linked agammaglobulinemia were enrolled during the period of 2010-2018. Clinical summary, and immunological profiles of these patients were recorded. Peripheral blood samples were collected for monocyte BTK protein expression detection and BTK genetic analysis. The medical records between January 2020 and June 2023 were reviewed to investigate COVID-19 in XLA.

Results

Twenty-two patients (from 16 unrelated families) were molecularly diagnosed as XLA. Genetic testing revealed fifteen distinct mutations, including four splicing mutations, four missense mutations, three nonsense mutations, three short deletions, and one large indel mutation. These mutations scattered throughout the BTK gene and mostly affected the kinase domain. All mutations including five novel mutations were predicted to be pathogenic or deleterious by in silico prediction tools. Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo. Flow cytometric analysis showed that thirteen patients had minimal BTK expression (0-15%) while eight patients had reduced BTK expression (16-64%). One patient was not tested for monocyte BTK expression due to insufficient sample. Pneumonia (n=13) was the most common manifestation, while Pseudomonas aeruginosa was the most frequently isolated pathogen from the patients (n=4). Mild or asymptomatic COVID-19 was reported in four patients.

Conclusion

This report provides the first overview of demographic, clinical, immunological and genetic data of XLA in Malaysia. The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis.
Homologs of bacterial heat-labile enterotoxin subunit A contribute to development, stress response, and virulence in filamentous entomopathogenic fungus Beauveria bassiana
Authors: Ding Jin-Li , Wei Kang , Feng Ming-Guang , Ying Sheng-Hua
Published: September 2023

Introduction

Enterotoxigenic bacteria commonly excrete heat-labile enterotoxins (LT) as virulence factors that consist of one subunit A (LTA) and five B subunits (LTB). In fungi, there are a large number of genes encoding the homologs of LTA, but their biological roles remain largely unknown.

Methods

In this study, we identified 14 enterotoxin_A domain proteins in filamentous fungus B. bassiana in which five proteins were functionally characterized.

Results

Five proteins displayed diverse sub-cellular localizations but perform convergent functions in stress response, development, and virulence. The loss of five LTA genes resulted in significant reduction in conidial production, blastospore formation, and the increased sensitivity to oxidative and cell wall –perturbing stresses. The virulence of five disruptants was notably weakened as indicated by topical and intrahemocoel injection assays. Notably, the loss of these five proteins led to the significant changes in the carbohydrate profiles of cellular surface, which induced the enhanced host immune reactions of encapsulation and melanization.

Discussion

Thus, LTA proteins contribute to the fungus–host interaction via maintaining the carbohydrate profiles of cellular surface. This study expands our understanding of the enterotoxin_A domain proteins in fungal physiology and deepens mechanisms involved in the lifestyle of fungal insect pathogens.
Methods to get more information from sparse vessel monitoring systems data
Authors: Gerritsen Hans D.
Published: September 2023

Vessel Monitoring Systems (VMS) and other vessel tracking data have been used for many years to map the distribution of fishing activities. Mapping areas with low levels of fishing activity can be of particular interest; for example to avoid conflicts between fishing and other ocean uses like offshore renewable energy or to protect relatively pristine ecosystems from increasing fishing pressure. A particular problem when trying to delineate areas that are lightly fished, is the relative sparsity of vessel monitoring data in these areas. This paper explores three novel methods for estimating the distribution of fishing activity from VMS data, with particular focus on lightly impacted areas. The first new method divides the area of interest into a nested grid with varying cell sizes (depending on the density of data at each location); the second new method uses Voronoi diagrams to define polygons around observations and the third method applies a local regression to generate a smooth map of fishing intensity. The new methods are compared with two established methods: applying spatial grids and interpolating fishing tracks. The track interpolation method generally performs better than any of the new methods, however it is not always possible or appropriate to apply track interpolation; in those cases the local regression method is the best alternative.
Single-center experience in 127 adult patients, mono or dual artificial liver support therapy, in patients with acute liver failure
Authors: Ocak Ilhan
Published: September 2023

Background

Acute liver failure (ALF) is a serious condition characterized by sudden liver dysfunction, jaundice and hepatic encephalopathy. Its mortality rate of approximately 80% underscores the urgent need for effective treatments. Supportive extracorporeal therapies (SET), which temporarily support liver function and remove toxins, have shown promise in improving outcomes in acute liver failure (ALF). The aim of this study was to compare the outcomes of dual supportive extracorporeal therapy (SET) and mono supportive extracorporeal therapy in patients with acute liver failure.

Methods

A total of 127 patients with acute liver failure were included in this retrospective, single-center study. Of these, 62 patients received dual supportive extracorporeal therapy and 65 patients received mono supportive extracorporeal therapy. Primary endpoints were survival without the need for liver transplantation and mortality. Secondary endpoints included resolution of encephalopathy and normalization of International Normalized Ratio (INR).

Results

In the dual supportive extracorporeal therapy group, 59.6% of patients survived without the need for liver transplantation, while 27.4% achieved recovery with liver transplantation. The mortality rate in this group was 12.9%. Significant regression of encephalopathy grade was observed in 87% of patients, and the 1 year mortality rate for liver transplant recipients was 10.7%. In the mono supportive extracorporeal therapy group, 61.5% of patients experienced a successful recovery without the need for liver transplantation, with a mortality rate of 29.2%. Significant improvement in the grade of encephalopathy was observed in 70.7% of patients.

Conclusion

Both dual supportive extracorporeal therapy (CVVHDF and PE) and mono supportive extracorporeal therapy (PE) were associated with significant improvements in renal and hepatic biochemical parameters, blood ammonia levels, and neurological status in patients with acute liver failure associated with grade III-IV hepatic encephalopathy. In particular, dual support was associated with improved hemodynamic stability, lactic acidosis and acid–base balance. Survival in acute liver failure in our retrospective cohort using a protocolized approach to extracorporeal therapies is higher compared to previously published large ALF studies. This protocolized approach warrants further prospective studies.
Four new additions to Helvella (Helvellaceae, Pezizales) from Northern Thailand
Authors: Yu Feng-Ming , Lei Lei , Luangharn Thatsanee , Zhao Qi , Zhu Ying-An
Published: September 2023

Most species of Helvella have been described from temperate regions in Asia, Europe, and North America, but little is known about the genus from tropical regions. In this report, phylogenetic analyses of 11 newly collected saddle-like fungi from northern Thailand using three genetic markers [the nuclear large subunit ribosomal DNA (LSU), the heat shock protein 90 (HSP90), and the translation elongation factor 1-alpha (TEF)] confirm their assignment in Helvella. Two species were described as new, i.e., Helvella atroides and H. orentitomentosa, and two species, i.e., H. fistulosa and H. rugosa, were reported for the first time in Thailand. Details of macro- and microscopic characters and illustrations were provided for each species. To date, seven species of Helvella have been recorded in Thailand, and a key for identifying the Thai Helvella species was provided here.
Crystal structure of the lipopolysaccharide outer core galactosyltransferase WaaB involved in pathogenic bacterial invasion of host cells
Authors: Chen Yatian , Gu Jiayue , Ashworth Gareth , Wang Zhongshan , Zhang Zhengyu , Dong Changjiang
Published: September 2023

Lipopolysaccharide (LPS) is essential for most gram-negative bacteria and plays an important role in serum resistance, pathogenesis, drug resistance, and protection from harsh environments. The outer core oligosaccharide of LPS is involved in bacterial recognition and invasion of host cells. The D-galactosyltransferase WaaB is responsible for the addition of D-galactose to the outer core oligosaccharide of LPS, which is essential for Salmonella typhimurium invasion. Here we report the first crystal structures of WaaB and WaaB in complex with UDP to resolutions of 1.8 and 1.9 Å, respectively. Mutagenesis and enzyme activity assays confirmed that residues V186, K195, I216, W243, E276, and E269 of WaaB are essential for the binding and hydrolysis of UDP-galactose. The elucidation of the catalytic mechanism of WaaB is of great importance and could potentially be used for the design of novel therapeutic reagents.
Effects of biochar amendment and organic fertilizer on microbial communities in the rhizosphere soil of wheat in Yellow River Delta saline-alkaline soil
Authors: Li Meng , Chen Chuanjie , Zhang Haiyang , Wang Zongshuai , Song Ningning , Li Junlin , Liang Xiaoyan , Yi Kuihua , Gu Yinyu , Guo Xiaohong
Published: September 2023

The biochar and organic fertilizer amendment have been used as an effective practice to increase soil fertility. Nevertheless, the mechanisms of microbial community response to organic fertilizer and biochar application on saline-alkali soil have not been clarified. This study investigated the effects at different concentrations of organic fertilizer and biochar on the microbial community of wheat rhizosphere soil under field experiment in the Yellow River Delta (China, YRD), using high-throughput sequencing technology. Biochar and organic fertilizer significantly influenced in most soil parameters (p < 0.05), apart from soil moisture content (M), pH, total nitrogen (TN) and soil total phosphorus (TP). Proteobacteria and Actinobacteriota were found in the rhizosphere soil as the main bacterial phyla, and the main fungal phyla were Ascomycota and Mortierellomycota. The soil bacterial and fungal communities under organic fertilizer were distinct from CK. Furthermore, redundancy analysis (RDA) directed that changes in bacterial communities were related to soil properties like pH, available phosphorus (AP), and total organic carbon (TOC), while pH, AP and TP, were crucial contributors in regulating fungal distribution. The correlation between soil parameters and bacteria or fungi varied with the application of biochar and organic fertilizers, and the interaction between the bacteria and fungi in organic fertilizer treatments formed more connections compared with biochar treatments. Our results indicated that biochar was superior to organic fertilizer under the contents set up in this study, and soil parameters increased with biochar and organic fertilizer application rate. The diversity and structure of soil bacteria and fungi differed with the application of biochar and organic fertilizer. The research provides a reference to rational application of organic fertilizer and biochar improvement in saline-alkali soil.
First report on identification and genomic analysis of a novel porcine circovirus (porcine circovirus 4) in cats
Authors: Xu Tong , Deng Li-Shuang , Jian Zhi-Jie , Xu Lei , Li Feng-Qin , Lai Si-Yuan , Ai Yan-Ru , Zhu Ling , Xu Zhi-Wen
Published: September 2023

Porcine circovirus type 4 (PCV4) is an emerging circovirus, which has been detected in domestic pigs across various provinces in China and Korea. In this study, we aimed to investigate whether cats are susceptible to PCV4. For this purpose, we collected 116 cat samples from animal hospitals in Sichuan Province, China, between 2021 and 2022. Using a SYBR Green-based real-time PCR assay, we detected PCV4 in 5 out of the 116 clinical samples, indicating a positive rate of 4.31% (5/116) and confirming the presence of PCV4 in cats from Sichuan Province, China. Moreover, we successfully sequenced and analyzed the complete genome of one PCV4 strain (SCGA-Cat) along with 60 reference sequences deposited in the GenBank database. SCGA-Cat exhibited high nucleotide homology (98.2–99.0%) with PCV4 strains from other species, including dogs, pigs, dairy cows, and fur animals. Notably, the SCGA-Cat strain from cats clustered closely with a PCV4 strain derived from a pig collected in Fujian Province, China. To the best of our knowledge, this study represents the first report on the molecular detection of PCV4 in cats worldwide, which prompted us to understand the genetic diversity and cross-species transmission of the ongoing PCV4 cases. However, further investigations are needed to explore the association between PCV4 infection and clinical syndromes in cats.
Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates
Authors: Shah Mohibullah , Anwar Amna , Qasim Aqsa , Jaan Samavia , Sarfraz Asifa , Ullah Riaz , Ali Essam A. , Nishan Umar , Shehroz Muhammad , Zaman Aqal , Ojha Suvash Chandra
Published: September 2023

The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen.
Prevalence, drug resistance, molecular typing and comparative genomics analysis of MRSA strains from a tertiary A hospital in Shanxi Province, China
Authors: Hou Zhuru , Xu Benjin , Liu Ling , Yan Rongrong , Zhang Jinjing , Yin Jiaxin , Li Peipei , Wei Jianhong
Published: September 2023

Staphylococcus aureus (S. aureus) is an important zoonotic pathogen that causes a high incidence rate and mortality worldwide. This study investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains in a tertiary A hospital in Shanxi Province, China, in order to determine the major epidemic clones as well as their antibiotic resistance and virulence characteristics. A total of 212 S. aureus strains were collected in this hospital, and were subjected to antimicrobial susceptibility testing, detection of virulence genes, resistance genes, and efflux pump genes. Among them, 38 MRSA strains were further subjected to detection of biofilm genes, assessment of biofilm formation ability, MLST, spa typing, SCCmec typing, and phylogenetic analysis. The majority of S. aureus strains came from the neonatology department, with secretions and purulent fluid being the main source of samples. The strains showed high resistance to penicillin (98.11%), erythromycin (64.62%) and clindamycin (59.91%), while being sensitive to vancomycin and linezolid. The detection rates of efflux pump genes and resistance genes were high, and there was a significant correlation between resistance gene types and phenotypes, with mecA showing a close correlation with oxacillin. The detection rates of virulence genes and the toxin gene profiles of MSSA and MRSA strains showed significant differences. And the detection rate of biofilm genes in MRSA strains was relatively high, with 13.16% of MRSA strains showing strong biofilm formation ability. The most common epidemic clone of MRSA was ST59-SCCmecIV-t437, followed by ST59-SCCmecV-t437. The former had a higher detection rate of resistance genes and a stronger biofilm formation ability, while the latter had a higher positive rate for pvl gene and stronger pathogenicity, making it more likely to cause systemic infections. Phylogenetic analysis showed that all MRSA strains in this study clustered into three major branches, with distinct differences in antibiotic resistance and virulence characteristics among the branches. ST59-MRSA strains from different species showed consistency and inter-species transmission, but there were differences among ST59-MRSA strains from different geographical locations. In general, most MSSA and MRSA strains exhibited multidrug resistance and carried multiple resistance genes, virulence genes, and biofilm formation genes, warranting further research to elucidate the mechanisms of drug resistance and pathogenesis.
Clinical trials in Charcot-Marie-Tooth disorders: a retrospective and preclinical assessment
Authors: Nair Malavika A. , Niu Zhiyv , Madigan Nicholas N. , Shin Alexander Y. , Brault Jeffrey S. , Staff Nathan P. , Klein Christopher J.
Published: September 2023

Objective

This study aimed to evaluate the progression of clinical and preclinical trials in Charcot-Marie-Tooth (CMT) disorders.

Background

CMT has historically been managed symptomatically and with genetic counseling. The evolution of molecular and pathologic understanding holds a therapeutic promise in gene-targeted therapies.

Methods

ClinicalTrials.gov from December 1999 to June 2022 was data extracted for CMT with preclinical animal gene therapy trials also reviewed by PubMed search.

Results

The number of active trials was 1 in 1999 and 286 in 2022. Academic settings accounted for 91% and pharmaceutical companies 9%. Of the pharmaceutical and academic trials, 38% and 28%, respectively, were controlled, randomized, and double-blinded. Thirty-two countries participated: the United States accounted for 26% (75/286). In total, 86% of the trials were classified as therapeutic: 50% procedural (21% wrist/elbow surgery; 22% shock wave and hydrodissection therapy), 23% investigational drugs, 15% devices, and 11% physical therapy. Sixty-seven therapeutic trials (49%) were designated phases 1–2 and 51% phases 3–4. The remaining 14% represent non-therapeutic trials: diagnostic testing (3%), functional outcomes (4%), natural history (4%), and standard of care (3%). One-hundred and three (36%) resulted in publications. Phase I human pharmaceutical trials are focusing on the safety of small molecule therapies (n = 8) and AAV and non-viral gene therapy (n = 3). Preclinical animal gene therapy studies include 11 different CMT forms including viral, CRISPR-Cas9, and nanoparticle delivery.

Conclusion

Current CMT trials are exploring procedural and molecular therapeutic options with substantial participation of the pharmaceutical industry worldwide. Emerging drug therapies directed at molecular pathogenesis are being advanced in human clinical trials; however, the majority remain within animal investigations.
Neuropsychiatric disturbance detecting polycythemia vera myelofibrosis: a case report and literature review
Authors: Li Li , Zhou Min , Wu Yun-Qin , Fan Wei-Nv , Li Da
Published: September 2023

Background

Neuropsychiatric disturbances and chorea are less recognized consequences of polycythemia vera (PV), and their role in post-PV myelofibrosis (MF) has not been reported. Clinical features that predict post-PV MF lack specificity.

Case presentation

We describe an elderly patient with PV who developed acute-onset reversible neuropsychiatric disturbances accompanied by generalized chorea and was finally diagnosed with post-PV MF after a bone marrow examination. We also reviewed four cases of late PV associated with neuropsychiatric symptoms since 1966 and analyzed their clinical characteristics and therapeutic effects.

Conclusion

Our case indicates that Janus kinase 2 (JAK2)-related PV is a treatable cause of late-onset chorea and that chorea may herald the deterioration of hematological parameters. Our case provides a clinically specific representation of post-PV MF. Patients with a long course of PV are recommended to undergo bone marrow re-examinations when they present with neuropsychiatric symptoms to achieve an early diagnosis of post-PV MF.
Treatment of insomnia in myasthenia gravis—A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia
Authors: Yan Jingwen , Yang Minhui , Li Michael Ke , Huang Yangyu , Tan Ying , Shi Jiayu , Fan Qianqian , Zhu Zhu , Guan Yuzhou , Cui Liying
Published: September 2023

Objectives

This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia.

Methods

This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4–5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication.

Results

A total of 75 MG patients with insomnia were included in this study. After 4–5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders.

Conclusion

Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.
Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson’s Disease patients
Authors: Zapata Amaya Valentina , Aman Joshua E. , Johnson Luke A. , Wang Jing , Patriat Remi , Hill Meghan E. , MacKinnon Colum D. , Cooper Scott E. , Darrow David , McGovern Robert , Harel Noam , Molnar Gregory F. , Park Michael C. , Vitek Jerrold L. , Escobar Sanabria David
Published: September 2023

Introduction

Evidence suggests that spontaneous beta band (11–35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson’s disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined.

Methods

We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery.

Results

Our analyses show that low-frequency (2–4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization.

Discussion

Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.
Multiple regions of sensorimotor cortex encode bite force and gape
Authors: Arce-McShane Fritzie I. , Sessle Barry J. , Ram Yasheshvini , Ross Callum F. , Hatsopoulos Nicholas G.
Published: September 2023

The precise control of bite force and gape is vital for safe and effective breakdown and manipulation of food inside the oral cavity during feeding. Yet, the role of the orofacial sensorimotor cortex (OSMcx) in the control of bite force and gape is still largely unknown. The aim of this study was to elucidate how individual neurons and populations of neurons in multiple regions of OSMcx differentially encode bite force and static gape when subjects (Macaca mulatta) generated different levels of bite force at varying gapes. We examined neuronal activity recorded simultaneously from three microelectrode arrays implanted chronically in the primary motor (MIo), primary somatosensory (SIo), and cortical masticatory (CMA) areas of OSMcx. We used generalized linear models to evaluate encoding properties of individual neurons and utilized dimensionality reduction techniques to decompose population activity into components related to specific task parameters. Individual neurons encoded bite force more strongly than gape in all three OSMCx areas although bite force was a better predictor of spiking activity in MIo vs. SIo. Population activity differentiated between levels of bite force and gape while preserving task-independent temporal modulation across the behavioral trial. While activation patterns of neuronal populations were comparable across OSMCx areas, the total variance explained by task parameters was context-dependent and differed across areas. These findings suggest that the cortical control of static gape during biting may rely on computations at the population level whereas the strong encoding of bite force at the individual neuron level allows for the precise and rapid control of bite force.
Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma
Authors: Huang Yi , Liu Fangfang , Xu Ruiping , Zhou Fuyou , Yang Wenlei , He Yu , Liu Zhen , Hou Bolin , Liang Linlin , Zhang Lixin , Liu Mengfei , Pan Yaqi , Liu Ying , He Zhonghu , Ke Yang
Published: September 2023

Background

Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood.

Methods

This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions.

Results

With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable.

Conclusion

Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.
Optimization of small molecule degraders and antagonists for targeting estrogen receptor based on breast cancer: current status and future
Authors: Yao Jiaqi , Tao Yiran , Hu Zelin , Li Junjie , Xue Ziyi , Zhang Ya , Lei Yi
Published: September 2023

The estrogen receptor (ER) is a classical receptor protein that plays a crucial role in mediating multiple signaling pathways in various target organs. It has been shown that ER-targeting therapies inhibit breast cancer cell proliferation, enhance neuronal protection, and promote osteoclast formation. Several drugs have been designed to specifically target ER in ER-positive (ER+) breast cancer, including selective estrogen receptor modulators (SERM) such as Tamoxifen. However, the emergence of drug resistance in ER+ breast cancer and the potential side effects on the endometrium which has high ER expression has posed significant challenges in clinical practice. Recently, novel ER-targeted drugs, namely, selective estrogen receptor degrader (SERD) and selective estrogen receptor covalent antagonist (SERCA) have shown promise in addressing these concerns. This paper provides a comprehensive review of the structural functions of ER and highlights recent advancements in SERD and SERCA-related small molecule drugs, especially focusing on their structural optimization strategies and future optimization directions. Additionally, the therapeutic potential and challenges of novel SERDs and SERCAs in breast cancer and other ER-related diseases have been discussed.
Genome-wide association studies for phenological and agronomic traits in mungbean (Vigna radiata L. Wilczek)
Authors: Manjunatha P. B. , Aski Muraleedhar S. , Mishra Gyan Prakash , Gupta Soma , Devate Narayana Bhat , Singh Akanksha , Bansal Ruchi , Kumar Shiv , Nair Ramakrishnan Madhavan , Dikshit Harsh Kumar
Published: September 2023

Mungbean (Vigna radiata L. Wilczek) is one of the important warm-season food legumes, contributing substantially to nutritional security and environmental sustainability. The genetic complexity of yield-associated agronomic traits in mungbean is not well understood. To dissect the genetic basis of phenological and agronomic traits, we evaluated 153 diverse mungbean genotypes for two phenological (days to heading and days to maturity) and eight agronomic traits (leaf nitrogen status using SPAD, plant height, number of primary branches, pod length, number of pods per plant, seeds per pod, 100-seed weight, and yield per plant) under two environmental conditions. A wide array of phenotypic variability was apparent among the studied genotypes for all the studied traits. The broad sense of heritability of traits ranged from 0.31 to 0.95 and 0.21 to 0.94 at the Delhi and Ludhiana locations, respectively. A total of 55,634 genome-wide single nucleotide polymorphisms (SNPs) were obtained by the genotyping-by-sequencing method, of which 15,926 SNPs were retained for genome-wide association studies (GWAS). GWAS with Bayesian information and linkage-disequilibrium iteratively nested keyway (BLINK) model identified 50 SNPs significantly associated with phenological and agronomic traits. In total, 12 SNPs were found to be significantly associated with phenological traits across environments, explaining 7%–18.5% of phenotypic variability, and 38 SNPs were significantly associated with agronomic traits, explaining 4.7%–27.6% of the phenotypic variability. The maximum number of SNPs (15) were located on chromosome 1, followed by seven SNPs each on chromosomes 2 and 8. The BLAST search identified 19 putative candidate genes that were involved in light signaling, nitrogen responses, phosphorus (P) transport and remobilization, photosynthesis, respiration, metabolic pathways, and regulating growth and development. Digital expression analysis of 19 genes revealed significantly higher expression of 12 genes, viz. VRADI01G08170, VRADI11G09170, VRADI02G00450, VRADI01G00700, VRADI07G14240, VRADI03G06030, VRADI02G14230, VRADI08G01540, VRADI09G02590, VRADI08G00110, VRADI02G14240, and VRADI02G00430 in the roots, cotyledons, seeds, leaves, shoot apical meristems, and flowers. The identified SNPs and putative candidate genes provide valuable genetic information for fostering genomic studies and marker-assisted breeding programs that improve yield and agronomic traits in mungbean.
Fungal volatile organic compounds: mechanisms involved in their sensing and dynamic communication with plants
Authors: Razo-Belmán Rosario , Ángeles-López Yesenia Ithaí , García-Ortega Luis Fernando , León-Ramírez Claudia Geraldine , Ortiz-Castellanos Lucila , Yu Houlin , Martínez-Soto Domingo
Published: September 2023

Microbial volatile organic compounds (MVOCs) are mixtures of gas-phase hydrophobic carbon-based molecules produced by microorganisms such as bacteria and fungi. They can act as airborne signals sensed by plants being crucial players in triggering signaling cascades influencing their secondary metabolism, development, and growth. The role of fungal volatile organic compounds (FVOCs) from beneficial or detrimental species to influence the physiology and priming effect of plants has been well studied. However, the plants mechanisms to discern between FVOCs from friend or foe remains significantly understudied. Under this outlook, we present an overview of the VOCs produced by plant-associate fungal species, with a particular focus on the challenges faced in VOCs research: i) understanding how plants could perceive FVOCs, ii) investigating the differential responses of plants to VOCs from beneficial or detrimental fungal strains, and finally, iii) exploring practical aspects related to the collection of VOCs and their eco-friendly application in agriculture.
Intuitive thinking predicts false memory formation due to a decrease in inhibitory efficiency
Authors: Gronchi Giorgio , Righi Stefania , Gavazzi Gioele , Giganti Fiorenza , Viggiano Maria Pia
Published: September 2023

False memory formation is usually studied using the Deese-Roediger-McDermott paradigm (DRM), in which individuals incorrectly remember words that were not originally presented. In this paper, we systematically investigated how two modes of thinking (analytical vs. intuitive) can influence the tendency to create false memories. The increased propensity of intuitive thinkers to generate more false memories can be explained by one or both of the following hypotheses: a decrease in the inhibition of the lure words that come to mind, or an increased reliance on the familiarity heuristic to determine if the word has been previously studied. In two studies, we conducted tests of both recognition and recall using the DRM paradigm. Our observations indicate that a decrease in inhibitory efficiency plays a larger role in false memory formation compared to the use of the familiarity heuristic.
Different dose series of human papillomavirus vaccine in young females: a pair-wise meta-analysis and network meta-analysis from randomized controlled trials
Authors: Kemin Li , Mengpei Zhang , Jing Zeng , Rutie Yin
Published: September 2023

Objective

To investigate the application value of different dose of HPV vaccine in young females.

Data sources

The following databases were searched: Cochrane Library, PubMed, Embase, Web of Science, SINOMED, and Wanfang Data, from the establishment of the database to August 1st, 2022.

Study eligibility criteria

The inclusion criterias were: healthy young women younger than 25 years old as the research object, randomized controlled study as the research type, and the efficacy and safety of single-dose, two-dose or three-dose HPV vaccines as the intervention measures and research endpoints.

Study appraisal and synthesis methods

Meta-analysis was performed to analyze the protective effects of single-dose, 2-dose and 3-dose HPV vaccine series on young females.

Results

A total of eight eligible studies involving 16 publications were included. There is no difference in the immunogenicity between the 2-dose and 3-dose series within 12 months after the last dose of HPV vaccine. However, 3-dose series was better than the 2-dose series, which performed better than the single-dose vaccine, after 12 months. With respect to the prevention of HPV16/18 infection or HPV31/33/45 infection, the single-dose vaccine worked better than 2-dose or 3-dose series.

Conclusions

The present study showed that the immunogenicity of low-dose HPV vaccine was significantly less, but it reduced the risk of high-risk HPV infection. The low-dose HPV vaccine series may not offer a preventive effect on cervical lesions, though it needs to be further confirmed by additional studies.
Measurement and evaluation of the coupling degree between National Fitness and National Health in the Yangtze River Economic Belt region of China
Authors: Cai Changwen , Ye Songzhong
Published: September 2023

Clarifying the integrated development mechanism of the National Fitness Program and National Health Program has positive and practical significance for the efficient implementation of the healthy China strategy. In order to analyze and study the integrated development mechanism of the National Fitness Program and National Health Program, we established a coupling-coordination measurement model. Based on two dimensions of space and time, we first analyzed the coupling degree between National Fitness System and National Health System in the Yangtze River Economic Belt region of China from 2016 to 2020, and studied and analyzed the coupling mechanism between the two. The research results show that the National Fitness Program and National Health Program have a development model of mutual promotion and mutual benefit. The National Fitness Program promotes the National Health Program by improving the fitness environment, increasing fitness participation, and health investment. The National Health Program optimizes environmental construction, health education, and healthy populations, thereby driving national fitness. Overall, there is stable development and balanced promotion in the integration of the National Fitness Program and National Health Program. In addition, the integrated development of the National Fitness Program and National Health Program is positively affected by economic level and regional marketization. The coupling- coordination model adopted in this study has practical value in measuring the coupling degree between the National Fitness System and National Health System. The results of this study also provide an important reference basis for the integrated and coordinated development of the National Fitness Program and National Health Program and the implementation of the Healthy China strategy.
Developing a policy brief on physical activity promotion for children and adolescents
Authors: Messing Sven , Gelius Peter , Abu-Omar Karim , Marzi Isabel , Beck Franziska , Geidl Wolfgang , Grüne Eva , Tcymbal Antonina , Reimers Anne Kerstin , Pfeifer Klaus
Published: September 2023

Introduction

While there are several approaches to collect basic information on physical activity (PA) promotion policies, some governments require more in-depth overviews on the situation in their country. In Germany, the Federal Ministry of Health expressed its interest in collecting detailed data on target group specific PA promotion, as relevant competences are distributed across a wide range of political levels and sectors. This study describes the development of a policy brief on physical activity promotion for children and adolescents in Germany. In particular, it addresses two major gaps in the current literature by systematically assessing good practice examples and “routine practices,” i.e., PA promotion activities already taking place on large scale and regular basis.

Materials and methods

Based on relevant national and international guidelines, the TARGET:PA tool was co-produced by researchers and ministry officials. It includes (1) PA recommendations, (2) national prevalence rates, (3) recommendations for PA promotion, and data on national (4) routine practices, (5) good practice projects and (6) policies. Data were collected for children and adolescents in Germany using desk research, semi-structured interviews and secondary data analysis.

Results

A policy brief and scientific background document were developed. Results showed that 46% of the 4–5-year-olds fulfil WHO recommendations but only 15% of the 11–17-year-olds, and that girls are less active than boys. Currently, in Germany no valid data are available on the PA behaviour of children under the age of three. An overview of routine practices for PA promotion for children and adolescents was compiled, and experts were asked to critically assess their effectiveness, reach and durability. Overall, 339 target group specific projects for PA promotion were found, with 22 classified as examples of good practice. National PA policies for children and adolescents were identified across different sectors and settings.

Conclusion

The study provides a comprehensive overview of the current status of PA promotion for children and adolescents in Germany. The co-production of the policy brief was a strength of the study, as it allowed researchers to take the needs of ministry officials into account, and as it supported the immediate uptake of results in the policymaking process. Future studies should test the applicability of the TARGET:PA tool to different target groups and countries.
Public safety network design for broadband wireless access
Authors: Sümer Ahmet Sacid , Yılmaz Talha , Memisoglu Ebubekir , Akkurt Arif , Arslan Hüseyin
Published: September 2023

Public protection and disaster relief (PPDR) agencies rely on wireless communications to respond in the event of emergencies. Public safety networks (PSNs) provide the wireless network used by emergency services. PSN is used to support push-to-talk services with some data transmission by employing land mobile radios. However, PPDR agencies are increasingly relying on additional information such as videos that require higher bandwidths. Therefore, many countries are transitioning or integrating their public safety networks with advanced broadband wireless communication systems such as fourth-generation (4G) long-term evolution (LTE) and planning to evolve to fifth-generation (5G) new radio (NR) in the future. The paper investigates infrastructure sharing mechanisms and deployment strategies in the transition of PSNs to a 4G LTE network, including a roadmap for cost analysis. Additionally, the paper examines LTE-based PSN deployment scenarios in various countries and engages in a discussion of the advantages and disadvantages of different sharing mechanisms and coexistence schemes. Finally, the challenges within the Public Safety Broadband Network (PSBN) are addressed and potential future research directions in this domain are deliberated.
Ensuring food safety with molecularly imprinted polymers: innovative methods for the detection of aflatoxins in food and feed samples
Authors: Ali Asghar , Sadiqa Aqsa , Ilyas Hamna , Bibi Ayesha , Hussain Urvah , Iqbal Naseer , Mujahid Adnan , Afzal Adeel
Published: September 2023

Aflatoxins, a group of mycotoxins, represent a heterogeneous class of secondary metabolites that pose a significant risk to food safety and public health due to their potent toxicity. Aflatoxins are widely distributed in the environment, with high levels frequently observed in hot and humid conditions. There is an ongoing development of various methods for detecting aflatoxins in food and feed samples. Herein, a review of these methods is presented with special emphasis on molecularly imprinted polymers (MIPs) as selective materials for aflatoxins’ detection. The key findings of various methods for real-time analysis of food and feed samples are presented and analyzed, providing a comparative assessment of their performance. Furthermore, the challenges and limitations of these methods are discussed, considering their commercialization prospects and real-world requirements.