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Background: Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory. Methods: Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software. Results: Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1? and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associatedpheochromocytoma. Conclusions: These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events.Methods: We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H2O2), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 microM and 1 mM).Results: After treatment with H2O2 at 250 microM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress.Conclusions: The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals. [ABSTRACT FROM AUTHOR]

Background: Type-III prostatitis is the most common prostate disease in adult males below 40 years old. The actual operation of its diagnosis process is cumbersome. Recently, a group of top Chinese urologists have proposed the theory of "prostate-pelvic syndrome (PPS)" and suggested using it to replace the traditional term for type-III prostatitis. However, the practical application effectiveness of PPS theory in clinical practice is still unclear., Objective: The aims of this study were to verify the clinical outcome of PPS theory in diagnosing the adult patients with type-III prostatitis below 40 years old and analyze the related factors for the main symptoms of PPS in adult males below 40 years old, providing references for the prevention and treatment of PPS in young adult males., Methods: The clinical medical records of 548 adult outpatients with type-III prostatitis under 40 years old between August 2018 and May 2023 were retrospectively analyzed. The patients were diagnosed retrospectively again by using PPS diagnostic criteria in this retrospective cohort study. Subsequently, the age, disease duration, prostate volume (PV), PV ≥ 20 mL detection rate and other related indicators among different symptom groups were analyzed by univariate analysis. The correlation between different symptoms of PPS patients and PV as well as disease duration was analyzed by correlation analysis. Additionally, the related factors for different main symptoms of PPS patients were analyzed by multivariate analysis., Results: Of the 548 patients, 229 patients had lower urinary tract symptoms, 159 patients had pelvic pain symptoms, and 160 patients had lower urinary tract and pelvic pain symptoms, respectively corresponding to those with voiding symptoms (VS), pain symptoms (PS), and voiding + pain symptoms (VS + PS) defined according to the concept of PPS. There were significant differences in PV and disease duration among the three main symptoms groups of PPS. PV in the VS group was larger than that in the PS group. Spearman correlation analysis showed that VS was positively correlated with PV and disease duration, while four secondary symptoms (including sexual dysfunction, psychosocial symptoms, reproductive dysfunction and other symptoms) were not related to PV. The proportion of VS patients in the PV ≥ 20 mL group was higher than that in the PV < 20 mL group. Multivariate logistic analysis showed that PV and disease duration were independent related factors for VS in adult PPS patients below 40 years old., Conclusions: Type-III prostatitis in Chinese adult males below 40 years old can be diagnosed and treated with PPS. PV and disease duration were independent related factors for VS in Chinese adult PPS patients below 40 years old. The risk of VS in PPS patients with PV ≥ 20 mL was 5.348 times as long as that in PPS patients with PV < 20 mL., Competing Interests: Declarations. Ethics approval and consent to participate: The study was in accordance with the Helsinki Declaration as revised in 2013. The ethics committee of the North District of the First Affiliated Hospital of Anhui Medical University (Anhui Public Health Clinical Center) approved the study (No: PJ-YX2023-043F1) and waived the informed consent for this retrospective analysis. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Glioblastoma (GBM) is a rare brain cancer with an exceptionally high mortality rate, which illustrates the pressing demand for more effective therapeutic options. Despite considerable research efforts on GBM, its underlying biological mechanisms remain unclear. Furthermore, none of the United States Food and Drug Administration (FDA) approved drugs used for GBM deliver satisfactory survival improvement., Methods: This study presents a novel computational pipeline by utilizing gene expression data analysis for GBM for drug repurposing to address the challenges in rare disease drug development, particularly focusing on GBM. The GBM Gene Expression Profile (GGEP) was constructed with multi-omics data to identify drugs with reversal gene expression to GGEP from the Integrated Network-Based Cellular Signatures (iLINCS) database., Results: We prioritized the candidates via hierarchical clustering of their expression signatures and quantification of their reversal strength by calculating two self-defined indices based on the GGEP genes' log2 foldchange (LFC) that the drug candidates could induce. Among five prioritized candidates, in-vitro experiments validated Clofarabine and Ciclopirox as highly efficacious in selectively targeting GBM cancer cells., Conclusions: The success of this study illustrated a promising avenue for accelerating drug development by uncovering underlying gene expression effect between drugs and diseases, which can be extended to other rare diseases and non-rare diseases., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors consent to the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) progression and metastasis. However, research comprehensively exploring tissue-derived lncRNAs for predicting peritoneal recurrence in patients with GC remains limited. This study aims to investigate the transcriptional landscape of lncRNAs in GC with peritoneal metastasis (PM) and to develop an integrated lncRNA-based score to predict peritoneal recurrence in patients with GC after radical gastrectomy., Methods: We analyzed the transcriptome profile of lncRNAs in paired peritoneal, primary gastric tumor, and normal tissue specimens from 12 patients with GC in the Sun Yat-sen University Cancer Center (SYSUCC) discovery cohort. Key lncRNAs were identified via interactive analysis with the TCGA database and SYSUCC validation cohort. A score model was constructed using the LASSO regression model and nomogram COX regression and evaluated using receiver operating characteristic curves. The role of lncRNAs in the PM of GC was then examined through wound healing, Transwell, 3D multicellular tumor spheroid invasion, and peritoneal cavity xenograft tumorigenicity assays in mice., Result: Five essential lncRNAs were screened and incorporated into the PM risk score to predict peritoneal recurrence-free survival (pRFS). We developed a comprehensive, integrated nomogram score, including the PM risk score, pT, pN, and tumor size, which could effectively predict the 5-year pRFS with an Area under the curve of 0.79 (95% CI: 0.71-0.88). Subsequently, we demonstrated that one of these lncRNAs, CASC15, promoted the invasion and migration of GC cells in vitro and facilitated the PM of GC cells in vivo, initially verifying that lncRNAs contribute to the PM of GC. Mechanistic analysis demonstrated that CASC15 promoted EMT and metastasis by activating the JNK and p38 pathways., Conclusion: A lncRNA-based integrated score was constructed in this study to predict peritoneal recurrence in patients clinically., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Institutional Review Board (IRB) of Sun Yat-Sen University Cancer Center (SYSUCC, Guangzhou, China) with the IRB number of G2021-036. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems., Results: Here, we reported a Chinese SCA48 family exhibited typical features and defined a novel missense mutation STUB1 c.755A>C (CHIP p. Y252S) through whole-exome sequencing. The variant was interpreted as a variant of uncertain significance, so we conducted a series of experiments using minigene plasmids to evaluate the pathogenicity of the variant. We found that the variant STUB1 c.755A>C caused a significant reduction of CHIP level and the loss function of ubiquitin ligase activity as the pathogenic STUB1 mutations reported before. Besides, we also found that the CHIP p. Y252S could cause tau aggregation, which is considered to contribute to the progression of neurodegenerative disorders., Conclusions: We diagnose the SCA48 pedigree in China and highlight the role of decreased ubiquitination and increased tau aggregation in the pathogenesis of the novel STUB1 c.755C>A mutation., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Fujian Medical University Union Hospital (2023-100). Informed consent was obtained from all individual participants included in the study. Consent for publication: Patients signed informed consent regarding publishing their data and photographs. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Acquired bronchobiliary fistula (BBF) is a rare but life-threatening complication that can occur as a result of oncological processes, inflammatory reactions, parasite infections, thoracoabdominal trauma, or invasive procedures associated with iatrogenic injury. However, the potential etiology of BBF caused by instrumental issues when using ultrasonic scalpels resulting in diathermy burn and its post-burn effects has never been reported., Case Presentation: Herein, we present a case of a 65-year-old woman who developed BBF one month after hepatectomy and presented with refractory irritating cough accompanied by yellow bitter sputum. The diagnosis was confirmed through detection of bile components in the sputum, fiberoptic bronchoscopy examination, and endoscopic retrograde cholangio-pancreatography (ERCP). Unfortunately, both endobronchial blocker and endoscopic nasobiliary drainage (ENBD) failed to address the condition until surgical removal of the involved subdiaphragmatic fistula followed by pedicled greater omentum tamping were performed. After closure of the fistula during a 5-month follow-up period, she did not experience any further episodes of biloptysis., Conclusions: For diathermy burn associated BBF, non-surgical management proves difficult due to inadequate or ineffective biliary drainage, so that early surgical intervention should be considered as an effective approach. Moreover, the adhesion between the atrophied liver and the diaphragm may pose a significant risk factor for diathermy burn, necessitating heightened vigilance., Competing Interests: Declarations. Ethics approval and consent to participate: There was no requirement for ethics approval for this case report. Consent for publication: The participant has consented to the submission of the case report to the journal. Competing interests: All the authors declare no conflicts of interests and financial disclosures., (© 2024. The Author(s).)

Objectives: The clinical decision-making regarding post hoc management of early colorectal cancer (CRC) patients who have undergone non-curative endoscopic resection (ER) remains a subject of debate. This systematic review and meta-analysis aims to compare the clinical outcomes between patients undergoing additional surgery and those receiving surveillance only., Methods: A comprehensive literature search was conducted across three major medical databases: PubMed, Embase, and the Cochrane Library. STATA software was utilized for pooling analysis. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale., Results: A total of 15 eligible studies encompassing 3,508 early CRC patients were included in this meta-analysis (additional surgery group: 1,974 cases; surveillance-only group: 1,533 cases). All included studies demonstrated good methodological quality, with Newcastle-Ottawa scores no less than 6. The results of the meta-analysis indicated that compared to the surveillance-only group, patients in the additional surgery group exhibited significantly improved overall survival (OR = 2.95, 95% CI: 2.05-4.24, P < 0.05), enhanced recurrence-free survival (OR = 2.53, 95% CI = 1.38-4.62, P < 0.05), a reduced recurrence rate (OR = 1.96, 95% CI = 1.22-3.13, P < 0.05), and a lower local recurrence rate (OR = 2.35, 95% CI = 1.12-4.95, P < 0.05). No significant sources of heterogeneity were identified among the studies analyzed; publication bias was also deemed acceptable across these investigations. Furthermore, we performed subgroup analyses based on inclusion criteria and age stratification which revealed notable differences in effect sizes between groups (JSCCR subgroup: OR = 2.09; 95% CI = 1.32-3.30 versus Non-JSCCR subgroup: OR = 1 .54; 95% CI = 0.89 -2.65, indicating negative results). Pooling analysis showed no significant difference between subgroups when stratified by age using a cutoff value of 65 years old., Conclusions: Compared to patients who underwent surveillance only, those receiving additional surgical treatment demonstrated superior outcomes in terms of overall survival, recurrence-free survival, recurrence rates, and control of local recurrences. This suggests that such an approach may represent a more optimal clinical decision for early-stage colorectal cancer (CRC) patients who have received non-curative endoscopic resection (ER). Furthermore, this study indicates that the inclusion criteria significantly influence the reported outcomes. Notably, age did not affect the recurrence rate. Overall, this is the first meta-analysis aimed at exploring and clarifying this ongoing controversy., Competing Interests: Declarations. Ethics approval and consent to participate: The formal ethical review was waived by our institutional review board. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Whether gastrointestinal hormones in patients with postprandial distress syndrome (PDS) are altered by acupuncture, and whether such alterations are related to the autonomic nervous system (ANS), remains an open question., Objective: This study aims to investigate the effects of acupuncture on symptoms, serum hormones, and ANS in PDS patients., Methods: This randomized controlled clinical trial was conducted at Beijing Hospital of Traditional Chinese Medicine affiliated with Capital Medical University. Sixty-two PDS patients were randomly assigned equally to acupuncture or sham acupuncture arm (3 sessions per week for 4-week). The main outcome measures which were evaluated at baseline and 4-week included cardinal symptoms, serum hormones including ghrelin, vasoactive intestinal peptide (VIP), substance P (SP), and ANS., Results: Among the 62 randomly assigned participants, 51 (82%) were included in the baseline characteristics and outcome analysis. Gastrointestinal symptoms including response rate (p = 0.001) and dyspepsia symptom severity (p = 0.002) were significantly improved after acupuncture treatment. Serum ghrelin concentration was significantly higher in acupuncture group than in sham acupuncture group (8.34 ± 3.00 ng/ml versus 6.52 ± 2.00 ng/ml, p = 0.022) after 4-week treatment, instead of VIP and SP (p > 0.05). The acupuncture group had significantly higher vagal activity, showing with increasing of high-frequency component (HF, p ≤ 0.001) and decreasing of the ratio of low-frequency and HF (p ≤ 0.001). In relationship analysis, the HF component exhibited a significant inverse correlation with symptom severity (R = - 0.501, p ≤ 0.001), but not with ghrelin level (R = 0.026, p = 0.865)., Conclusion: Acupuncture may improve the symptoms and increase the ghrelin level of PDS patients, the therapeutic effect of acupuncture was associated with the alteration of vagal activity., Trial Registration: The trial is registered with the ISRCTN registry, ISRCTN12511434. Registered 31 March 2017, https://www.isrctn.com/ ., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board and ethics committee of Beijing Hospital of Traditional Chinese Medicine affiliated with Capital Medical University (2016-BL-073-03). Written informed consent will be obtained from patients prior to enrolment in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Building reliable and robust quantitative structure-property relationship (QSPR) models is a challenging task. First, the experimental data needs to be obtained, analyzed and curated. Second, the number of available methods is continuously growing and evaluating different algorithms and methodologies can be arduous. Finally, the last hurdle that researchers face is to ensure the reproducibility of their models and facilitate their transferability into practice. In this work, we introduce QSPRpred, a toolkit for analysis of bioactivity data sets and QSPR modelling, which attempts to address the aforementioned challenges. QSPRpred's modular Python API enables users to intuitively describe different parts of a modelling workflow using a plethora of pre-implemented components, but also integrates customized implementations in a "plug-and-play" manner. QSPRpred data sets and models are directly serializable, which means they can be readily reproduced and put into operation after training as the models are saved with all required data pre-processing steps to make predictions on new compounds directly from SMILES strings. The general-purpose character of QSPRpred is also demonstrated by inclusion of support for multi-task and proteochemometric modelling. The package is extensively documented and comes with a large collection of tutorials to help new users. In this paper, we describe all of QSPRpred's functionalities and also conduct a small benchmarking case study to illustrate how different components can be leveraged to compare a diverse set of models. QSPRpred is fully open-source and available at https://github.com/CDDLeiden/QSPRpred .Scientific ContributionQSPRpred aims to provide a complex, but comprehensive Python API to conduct all tasks encountered in QSPR modelling from data preparation and analysis to model creation and model deployment. In contrast to similar packages, QSPRpred offers a wider and more exhaustive range of capabilities and integrations with many popular packages that also go beyond QSPR modelling. A significant contribution of QSPRpred is also in its automated and highly standardized serialization scheme, which significantly improves reproducibility and transferability of models., Competing Interests: Declarations Competing interest Not applicable., (© 2024. The Author(s).)

Background: Streptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported., Case Presentation: We present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient's peripheral blood whole-exome and the pathogen's whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment., Conclusions: It is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess., Competing Interests: Declarations Ethics approval and consent to participate Study approval and ethical clearance were obtained from the Children’s Hospital, Zhejiang University School of Medicine. Written informed consent was obtained from the guardian of the child and all the participants for participation before data collection. All methods were performed following the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication Written informed consent was obtained from the guardian of the child and all the participants for publication of medical images were taken from the patient. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The ecosystems of marine ranching have enhanced marine biodiversity and ecological balance and have promoted the natural recovery and enhancement of fishery resources. The microbial communities of these ecosystems, including bacteria, fungi, protists, and viruses, are the drivers of biogeochemical cycles. Although seasonal changes in microbial communities are critical for ecosystem functioning, the current understanding of microbial-driven metabolic properties and their viral communities in marine sediments remains limited. Here, we employed amplicon (16S and 18S) and metagenomic approaches aiming to reveal the seasonal patterns of microbial communities, bacterial-eukaryotic interactions, whole metabolic potential, and their coupling mechanisms with carbon (C), nitrogen (N), and sulfur (S) cycling in marine ranching sediments. Additionally, the characterization and diversity of viral communities in different seasons were explored in marine ranching sediments., Results: The current study demonstrated that seasonal variations dramatically affected the diversity of microbial communities in marine ranching sediments and the bacterial-eukaryotic interkingdom co-occurrence networks. Metabolic reconstruction of the 113 medium to high-quality metagenome-assembled genomes (MAGs) was conducted, and a total of 8 MAGs involved in key metabolic genes and pathways (methane oxidation - denitrification - S oxidation), suggesting a possible coupling effect between the C, N, and S cycles. In total, 338 viral operational taxonomic units (vOTUs) were identified, all possessing specific ecological characteristics in different seasons and primarily belonging to Caudoviricetes, revealing their widespread distribution and variety in marine sediment ecosystems. In addition, predicted virus-host linkages showed that high host specificity was observed, with few viruses associated with specific hosts., Conclusions: This finding deepens our knowledge of element cycling and viral diversity in fisheries enrichment ecosystems, providing insights into microbial-virus interactions in marine sediments and their effects on biogeochemical cycling. These findings have potential applications in marine ranching management and ecological conservation. Video Abstract., (© 2024. The Author(s).)

Background: Polyploidisation often results in genome rearrangements that may involve changes in both the single-copy sequences and the repetitive genome fraction. In this study, we performed a comprehensive comparative analysis of repetitive DNA, with a particular focus on ribosomal DNA (rDNA), in Brachypodium hybridum (2n = 4x = 30, subgenome composition DDSS), an allotetraploid resulting from a natural cross between two diploid species that resemble the modern B. distachyon (2n = 10; DD) and B. stacei (2n = 20; SS). Taking advantage of the recurrent origin of B. hybridum, we investigated two genotypes, Bhyb26 and ABR113, differing markedly in their evolutionary age (1.4 and 0.14 Mya, respectively) and which resulted from opposite cross directions. To identify the origin of rDNA loci we employed cytogenetic and molecular methods (FISH, gCAPS and Southern hybridisation), phylogenetic and genomic approaches., Results: Unlike the general maintenance of doubled gene dosage in B. hybridum, the rRNA genes showed a remarkable tendency towards diploidisation at both locus and unit levels. While the partial elimination of 35S rDNA units occurred in the younger ABR113 lineage, unidirectional elimination of the entire locus was observed in the older Bhyb26 lineage. Additionally, a novel 5S rDNA family was amplified in Bhyb26 replacing the parental units. The 35S and 5S rDNA units were preferentially eliminated from the S- and D-subgenome, respectively. Thus, in the more ancient B. hybridum lineage, Bhyb26, 5S and 35S rRNA genes are likely expressed from different subgenomes, highlighting the complexity of polyploid regulatory networks., Conclusion: Comparative analyses between two B. hybridum lineages of distinct evolutionary ages revealed that although the recent lineage ABR113 exhibited an additive pattern of rDNA loci distribution, the ancient lineage Bhyb26 demonstrated a pronounced tendency toward diploidisation manifested by the reduction in the number of both 35S and 5S loci. In conclusion, the age of the allopolyploid appears to be a decisive factor in rDNA turnover in B. hybridum., (© 2024. The Author(s).)

Objective: To describe the adoption of international travel measures during the first year of the COVID-19 pandemic., Methods: To comprehensively analyze the measures adopted, we constructed a dataset based on the WHO's Public Health and Social Measures (PHSM) database, which covered 252 countries, territories, or other areas (CTAs), including all 194 WHO Member States, from December 31, 2019, to December 31, 2020. We examined the adoption of measures by type, over time, and by the implementing and targeted CTA, including their levels of income., Findings: We identified 11,431 international travel measures implemented during the first year of the pandemic. The adoption of measures was rapid and widespread: over 60% of Member States had adopted a travel measure before the WHO declared COVID-19 a Public Health Emergency of International Concern on January 30, 2020. Initially, health screening and travel restrictions were the most adopted measures; however, quarantine and testing became more widely adopted over time. Although only a small portion of the total measures adopted constituted full border closure, approximately half of all Member States implemented this measure. Many travel measures targeted all CTAs but were unlikely to have been adopted universally enough to provide public health benefits. Low-income countries relied more on more universal measures, including full border closure, and were slower in scaling up testing compared to higher-income countries., Conclusion: The adoption of international travel measures during the first year of the COVID-19 pandemic varied across jurisdictions and over time. Lower-income countries used a different mix and scaled-up measures slower than higher-income countries. Understanding what measures were used is crucial for assessing their effectiveness in controlling the spread of COVID-19, reviewing the usefulness of the International Health Regulations, and informing future pandemic preparedness and response activities., (© 2024. The Author(s).)

Background: Treatment options for the Triple-Negative Breast Cancer (TNBC) subtype remain limited and the outcome for patients with advanced TNBC is very poor. The standard of care is chemotherapy, but approximately 50% of tumors develop resistance., Methods: We performed gene expression profiling of 58 TNBC tumor samples by microarray, comparing chemosensitive with chemoresistant tumors, which revealed that one of the top upregulated genes was TGFβ2. A connectivity mapping bioinformatics analysis predicted that the SRC inhibitor Dasatinib was a potential pharmacological inhibitor of chemoresistant TNBCs. Claudin-low TNBC cell lines were selected to represent poor-outcome, chemoresistant TNBC, for in vitro experiments and in vivo models., Results: In vitro, we identified a signaling axis linking SRC, AKT and ERK2, which in turn upregulated the stability of the transcription factors, Slug and Snail. Slug was shown to repress TGFβ2-antisense 1 to promote TGFβ2 signaling, upregulating cell survival via apoptosis and DNA-damage responses. Additionally, an orthotopic allograft in vivo model demonstrated that the SRC inhibitor Dasatinib reduced tumor growth as a single agent, and enhanced responses to the TNBC mainstay drug, Epirubicin., Conclusion: Targeting the SRC-Slug-TGFβ2 axis may therefore lead to better treatment options and improve patient outcomes in this highly aggressive subpopulation of TNBCs., (© 2024. The Author(s).)

Purposes: Chronic obstructive pulmonary disease (COPD) is a major cause of the rapid decline of health-related quality of life (HRQoL), associated with accelerated frailty in older populations. This study aimed to analyse the long-term dynamic changes of HRQoL and the predictive factors for the rapid decline of HRQoL in older patients with COPD., Methods: Overall 244 patients with COPD, aged ≧ 65 years from one medical centre were enrolled between March 2012 and July 2020. Further, we prospectively assessed HRQoL scores with utility values, using EuroQol Five-Dimension (EQ-5D) questionnaires. Additionally, long-term dynamic changes in HRQoL were analysed using the Kernel smoothing method and examined the factors contributing to the deterioration of HRQoL using a linear mixed effects model., Results: Older patients with COPD with forced expiration volume (FEV1) < 50% of prediction entered the phase of rapid and continuous decline of HRQoL ~ 2 years after enrolment, but patients with FEV1 ≥ 50% of prediction without rapidly declined HRQoL during 7 years follow up. Therefore, FEV1 < 50% of prediction is a novel predictor for the rapid decline of HRQoL. The course of rapidly declining HRQoL occurred, initially in the usual activities and pain/discomfort domains, followed by the morbidity, self-care, and depression/anxiety domains ~ 2 and 4 years after enrolment, respectively. The mixed effects model indicated that both FEV1 < 50% of prediction and a history of severe acute exacerbation (SAE) requiring hospitalisation were contributing factors for deterioration in HRQoL ., Conclusions: Both FEV1 < 50% of prediction and exacerbations requiring hospitalisation were contributing factors for the deterioration of HRQoL in long-term follow up. Additionally, FEV1 < 50% of prediction was a novel predictor for patients entering the phase of rapid decline of HRQoL., (© 2024. The Author(s).)

With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In this study, we isolated a series of LDPE-degrading fungi from landfill sites and carried out LDPE degradation experiments by combining highly efficient degrading fungi in pairs. The results showed that the mixed microorganisms composed of Alternaria sp. CPEF-1 and Trametes sp. PE2F-4 (H-3 group) had a greater degradation effect on heat-treated LDPE (T-LDPE). After 30 days of inoculation with combination strain H-3, the weight loss rate of the T-LDPE film was approximately 154% higher than that of the untreated LDPE (U-LDPE) film, and the weight loss rate reached 0.66 ± 0.06%. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) were used to further investigate the biodegradation impacts of T-LDPE, including the changes on the surface and depolymerization of the LDPE films during the fungal degradation process. Our findings revealed that the combined fungal treatment is more effective at degrading T-LDPE than the single strain treatment, and it is expected that properly altering the composition of the microbial community can help lessen the detrimental impact of plastics on the environment., (© 2024. The Author(s).)

Background: Sand fly females require a blood meal to develop eggs. The size of the blood meal is crucial for fecundity and affects the dose of pathogens acquired by females when feeding on infected hosts or during experimental membrane-feeding., Methods: Under standard laboratory conditions, we compared blood meal volumes taken by females of ten sand fly species from four genera: Phlebotomus, Lutzomyia, Migonomyia, and Sergentomyia. The amount of ingested blood was determined using a haemoglobin assay. Additionally, we weighed unfed sand flies to calculate the ratio between body weight and blood meal weight., Results: The mean blood meal volume ingested by sand fly females ranged from 0.47 to 1.01 µl. Five species, Phlebotomus papatasi, P. duboscqi, Lutzomyia longipalpis, Sergentomyia minuta, and S. schwetzi, consumed about double the blood meal size compared to Migonomyia migonei. The mean body weight of females ranged from 0.183 mg in S. minuta to 0.369 mg in P. duboscqi. In males, the mean body weight ranged from 0.106 mg in M. migonei to 0.242 mg in P. duboscqi. Males were always lighter than females, with the male-to-female weight ratio ranging from 75% (in Phlebotomus argentipes) to 52% (in Phlebotomus tobbi)., Conclusions: Females of most species took a blood meal 2.25-3.05 times their body weight. Notably, the relatively tiny females of P. argentipes consumed blood meals 3.34 times their body weight. The highest (Mbl/Mf) ratios were found in both Sergentomyia species studied; females of S. minuta and S. schwetzi took blood meals 4.5-5 times their body weight. This parameter is substantially higher than that reported for mosquitoes and biting midges., (© 2024. The Author(s).)

Background: Growing evidence suggests that distal regulatory elements are essential for cellular function and states. The sequences within these distal elements, especially motifs for transcription factor binding, provide critical information about the underlying regulatory programs. However, cooperativities between transcription factors that recognize these motifs are nonlinear and multiplexed, rendering traditional modeling methods insufficient to capture the underlying mechanisms. Recent development of attention mechanism, which exhibit superior performance in capturing dependencies across input sequences, makes them well-suited to uncover and decipher intricate dependencies between regulatory elements., Result: We present Transcription factors cooperativity Inference Analysis with Neural Attention (TIANA), a deep learning framework that focuses on interpretability. In this study, we demonstrated that TIANA could discover biologically relevant insights into co-occurring pairs of transcription factor motifs. Compared with existing tools, TIANA showed superior interpretability and robust performance in identifying putative transcription factor cooperativities from co-occurring motifs., Conclusion: Our results suggest that TIANA can be an effective tool to decipher transcription factor cooperativities from distal sequence data. TIANA can be accessed through: https://github.com/rzzli/TIANA ., (© 2024. The Author(s).)

Background: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies., Methods: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics., Results: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China., Conclusions: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk., (© 2024. The Author(s).)

Background: Assessment of the effective use of international travel measures during the COVID-19 pandemic has focused on public health goals, namely limiting virus introduction and onward transmission. However, risk-based approaches includes the weighing of public health goals against potential social, economic and other secondary impacts. Advancing risk-based approaches thus requires fuller understanding of available evidence on such impacts., Methods: We conducted a scoping review of existing studies of the social impacts of international travel measures during the COVID-19 pandemic. Applying a standardized typology of travel measures, and five categories of social impact, we searched 9 databases across multiple disciplines spanning public health and the social sciences. We identified 26 studies for inclusion and reviewed their scope, methods, type of travel measure, and social impacts analysed., Results: The studies cover a diverse range of national settings with a strong focus on high-income countries. A broad range of populations are studied, hindered in their outbound or inbound travel. Most studies focus on 2020 when travel restrictions were widely introduced, but limited attention is given to the broader effects of their prolonged use. Studies primarily used qualitative or mixed methods, with adaptations to comply with public health measures. Most studies focused on travel restrictions, as one type of travel measure, often combined with domestic public health measures, making it difficult to determine their specific social impacts. All five categories of social impacts were observed although there was a strong emphasis on negative social impacts including family separation, decreased work opportunities, reduced quality of life, and inability to meet cultural needs. A small number of countries identified positive social impacts such as restored work-life balance and an increase in perceptions of safety and security., Conclusions: While international travel measures were among the most controversial interventions applied during the COVID-19 pandemic, given their prolonged use and widespread impacts on individuals and populations, there remains limited study of their secondary impacts. If risk-based approaches are to be advanced, involving informed choices between public health and other policy goals, there is a need to better understand such impacts, including their differential impacts across diverse populations and settings., (© 2024. The Author(s).)

Background: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them., Methods: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis., Results: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females., Conclusions: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE., (© 2024. The Author(s).)

Background: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition., Methods: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria., Results: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice., Conclusions: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques., (© 2024. The Author(s).)

Background: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc., Methods: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed., Results: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found., Conclusion: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice., (© 2024. The Author(s).)

Background: Magnesium is a micronutrient and an intracellular cation responsible for different biochemical reactions involved in energy production and storage, control of neuronal and vasomotor activity, cardiac excitability, and muscle contraction. Magnesium deficiency may result in impaired physical performance. Moreover, magnesium plays an important role on delayed onset muscle soreness after training. Thus, physically active individuals and sport specialists have to pay attention to magnesium supplementation (MgS). However, the type, timing and dosage of magnesium intake are not well elucidated yet. Hence, we aimed to systematically review the literature regarding the effects of MgS on muscle soreness in physically active individuals. We focused exclusively on MgS, excluding those studies in which magnesium was administered together with other substances., Methods: Three electronic databases and literature sources (PUBMED, SCOPUS and Web of Sciences-Core Collection) were searched, in accordance with PRISMA guidelines. After the database search, 1254 articles were identified, and after excluding duplicates, 960 articles remained. Among these, 955 were excluded following the title and abstract screening. The remaining 5 articles were screened in full text and 4 study met the eligibility criteria., Results: These studies showed that MgS reduced muscle soreness, improved performance, recovery and induced a protective effect on muscle damage., Conclusion: To reach these positive effects, individuals engaged in intense exercise should have a Mg requirement 10-20% higher than sedentary people, to be taken in capsules and 2 h before training. Moreover, it is suggested to maintain magnesium levels in the recommended range during the off-season., Systematic Review Registration: PROSPERO registration number: CRD42024501822., (© 2024. The Author(s).)

Background: The relationship between obstructive sleep apnea (OSA) and the occurrence of arrhythmias and heart rate variability (HRV) in hypertensive patients is not elucidated. Our study investigates the association between OSA, arrhythmias, and HRV in hypertensive patients., Methods: We conducted a cross-sectional analysis involving hypertensive patients divided based on their apnea-hypopnea index (AHI) into two groups: the AHI ≤ 15 and the AHI > 15. All participants underwent polysomnography (PSG), 24-hour dynamic electrocardiography (DCG), cardiac Doppler ultrasound, and other relevant evaluations., Results: The AHI > 15 group showed a significantly higher prevalence of frequent atrial premature beats and atrial tachycardia (P = 0.030 and P = 0.035, respectively) than the AHI ≤ 15 group. Time-domain analysis indicated that the standard deviation of normal-to-normal R-R intervals (SDNN) and the standard deviation of every 5-minute normal-to-normal R-R intervals (SDANN) were significantly higher in the AHI > 15 group (P = 0.020 and P = 0.033, respectively). Frequency domain analysis revealed that the low-frequency (LF), high-frequency (HF) components, and the LF/HF ratio were also significantly elevated in the AHI > 15 group (P < 0.001, P = 0.031, and P = 0.028, respectively). Furthermore, left atrial diameter (LAD) was significantly larger in the AHI > 15 group (P < 0.001). Both univariate and multivariable linear regression analyses confirmed a significant association between PSG-derived independent variables and the dependent HRV parameters SDNN, LF, and LF/HF ratio (F = 8.929, P < 0.001; F = 14.832, P < 0.001; F = 5.917, P = 0.016, respectively)., Conclusions: Hypertensive patients with AHI > 15 are at an increased risk for atrial arrhythmias and left atrial dilation, with HRV significantly correlating with OSA severity., (© 2024. The Author(s).)

Objective: To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner., Methods: This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients' operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively., Results: The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group (P < 0.05). The differences in complication rate, intraoperative bleeding volume, 24-h postoperative pain index and recurrence rate were not statistically significant between the two groups (P > 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up (P < 0.05). The differences at the 6- and 12-month postoperative follow-ups were not statistically significant (P > 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P < 0.05). The experimental group had better social adaptability, greater total medical costs, and better overall patient medical satisfaction than did the control group (P < 0.05). The acceptance of TAWISL was greater than that of COACAS (P < 0.05)., Conclusion: Compared with COACLAS, TAWISES is safe and effective and better meets the cosmetic, psychological and social adaptation needs of patients. TAWISES is also more cost effective and can be better utilized for the population in our region, filling the gap in surgical modalities for thyroid cancer in in our region., (© 2024. The Author(s).)

Background: Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children., Methods: The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index)., Results: In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children., Conclusion: Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD., (© 2024. The Author(s).)

Background: Surgical site infections (SSI) are characterized by infections occurring in the surgical incision site, organ or cavity in the postoperative period. Adherence to surgical antimicrobial prophylaxis (SAP) is paramount in mitigating the occurrence of SSIs. In this study, we aimed to evaluate the appropriateness of SAP use in patients undergoing surgical procedures in the field of general surgery according to the American Society of Health-System Pharmacists (ASHP) guideline and to determine the difference between the pre-training period (pre-TP) and the post-training period (post-TP) organized according to this guideline., Methods: It is a single-center prospective study conducted in general surgery wards between January 2022 and May 2023, with 404 patients pre-TP and 406 patients post-TP., Results: Cefazolin emerged as the predominant agent for SAP, favored in 86.8% (703/810) of cases. Appropriate cefazolin dosage increased significantly from 41% (129 patients) in pre-TP to 92.6% (276 patients) in post-TP (p < 0.001), along with a rise in adherence to recommended timing of administration from 42.2% (133 patients) to 62.8% (187 patients) (p < 0.001). The proportion of patients receiving antibiotics during hospitalization in the ward postoperatively decreased post-TP (21-14.3%; p = 0.012), as did antibiotic prescription at discharge (16.8-10.3%; p = 0.008). The incidence of SSI showed a slight increase from 9.9% in pre-TP to 13.3% in post-TP (p = 0.131)., Conclusions: Routine training sessions for surgeons emerged as crucial strategies to optimize patient care and enhance SAP compliance rates, particularly given the burden of clinical responsibilities faced by surgical teams., (© 2024. The Author(s).)

Background: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method., Methods: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively., Results: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method., Conclusions: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment., (© 2024. The Author(s).)

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function., (© 2024. The Author(s).)

Objectives: Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia., Methods: Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed., Results: CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic., Conclusions: The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia., (© 2024. The Author(s).)

Background: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear., Patients and Methods: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated., Results: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients., Conclusions: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy., (© 2024. The Author(s).)

Background: Semi-dwarfing alleles are used widely in cereals to confer improved lodging resistance and assimilate partitioning. The most widely deployed semi-dwarfing alleles in rice and barley encode the gibberellin (GA)-biosynthetic enzyme GA 20-OXIDASE2 (GA20OX2). The hexaploid wheat genome carries three homoeologous copies of GA20OX2, and because of functional redundancy, loss-of-function alleles of a single homoeologue would not be selected in wheat breeding programmes. Instead, approximately 70% of wheat cultivars carry gain-of-function mutations in REDUCED HEIGHT 1 (RHT1) genes that encode negative growth regulators and are degraded in response to GA. Semi-dwarf Rht-B1b or Rht-D1b alleles encode proteins that are insensitive to GA-mediated degradation. However, because RHT1 is expressed ubiquitously these alleles have pleiotropic effects that confer undesirable traits in some environments., Results: We have applied reverse genetics to combine loss-of-function alleles in all three homoeologues of wheat GA20OX2 and its paralogue GA20OX1 and evaluated their performance in three years of field trials. ga20ox1 mutants exhibited a mild height reduction (approximately 3%) suggesting GA20OX1 plays a minor role in stem elongation in wheat. ga20ox2 mutants have reduced GA 1 content and are 12-32% shorter than their wild-type segregants, comparable to the effect of the Rht-D1b 'Green Revolution' allele. The ga20ox2 mutants showed no significant negative effects on yield components in the spring wheat variety 'Cadenza'., Conclusions: Our study demonstrates that chemical mutagenesis can expand genetic variation in polyploid crops to uncover novel alleles despite the difficulty in identifying appropriate mutations for some target genes and the negative effects of background mutations. Field experiments demonstrate that mutations in GA20OX2 reduce height in wheat, but it will be necessary to evaluate the effect of these alleles in different genetic backgrounds and environments to determine their value in wheat breeding as alternative semi-dwarfing alleles., (© 2024. The Author(s).)

Background: Preoperative carbohydrate loading in Enhanced Recovery After Surgery is an independent predictor of postoperative outcomes. By reducing the impact of surgical stress response, fasting-induced insulin resistance is modulated. As a clear fluid, consuming carbohydrate drink is safe up to 2 h preoperatively. Widely practiced in abdominal surgeries, its implementation in hip fracture surgeries is yet to be recognized. This study aimed to identify the feasibility of preoperative carbohydrate loading in hip fracture surgery and assess its clinical effects., Methods: This was a randomized controlled, open labelled trial. Patients ≥ 65 years old without diabetes mellitus, has hip fracture were recruited in a tertiary hospital between November 2020 and May 2021. The intervention was carbohydrate loading versus standard preoperative fasting., Results: Thirty-four ASA I-III patients (carbohydrate loading and control, n = 17 each), mean age 78 years (SEM ± 1.5), mean body mass index 23.7 (SEM ± 0.6 kg/m 2 ) were recruited. Analysis for feasibility of carbohydrate loading (n = 17) demonstrated attrition rate of 29% (n = 5). Otherwise, all recruited patients were compliant (100% compliance) with no adverse events reported. There was no significant difference among groups in the postoperative nausea and vomiting, pain score, fatigue level, muscle strength, postoperative infection and length of hospital stay assessed at 24-48 h postoperatively., Conclusion: The implementation of preoperative carbohydrate loading was found to be feasible preoperatively in hip fracture surgeries but requires careful coordination among multidisciplinary teams. An adequately powered randomized controlled study is needed to examine the full benefits of preoperative carbohydrate loading in this group of patients., Trial Registration: This study was registered in ClinicalTrial.gov (ClinicalTrials.gov identifier: NCT04614181, date of registration: 03/11/2020)., (© 2024. The Author(s).)

Background: Maternal and neonatal mortality remains a major concern in the Democratic Republic of Congo (DRC), and the country's protracted crisis context exacerbates the problem. This political economy analysis examines the maternal and newborn health (MNH) prioritization in the DRC, focussing specifically on the conflict-affected regions of North and South Kivu. The aim is to understand the factors that facilitate or hinder the prioritization of MNH policy development and implementation by the Congolese government and other key actors at national level and in the provinces of North and South Kivu., Methods: Using a health policy triangle framework, data collection consisted of in-depth interviews with key actors at different levels of the health system, combined with a desk review. Qualitative data were analysed using inductive and then deductive approaches, exploring the content, process, actor dynamics, contextual factors and gender-related factors influencing MNH policy development and implementation., Results: The study highlighted the challenges of prioritizing policies in the face of competing health and security emergencies, limited resources and governance issues. The universal health coverage policy seems to offer hope for improving access to MNH services. Results also revealed the importance of international partnerships and global financial mechanisms in the development of MNH strategies. They reveal huge gender disparities in the MNH sector at all levels, and the need to consider cultural factors that can positively or negatively impact the success of MNH policies in crisis zones., Conclusions: MNH is a high priority in DRC, yet implementation faces hurdles due to financial constraints, political influences, conflicts and gender disparities. Addressing these challenges requires tailored community-based strategies, political engagement, support for health personnel and empowerment of women in crisis areas for better MNH outcomes., (© 2024. The Author(s).)

Background: Stroke remains a major cause of long-term adult disability in the United States, necessitating the need for effective rehabilitation strategies for post-stroke gait impairments. Despite advancements in post-stroke care, existing rehabilitation often falls short, prompting the development of devices like robots and exoskeletons. However, these technologies often lack crucial input from end-users, such as clinicians, patients, and caregivers, hindering their clinical utility. Employing a human-centered design approach can enhance the design process and address user-specific needs., Objective: To establish a proof-of-concept of the human-centered design approach by refining the NewGait® exosuit device for post-stroke gait rehabilitation., Methods: Using iterative design sprints, the research focused on understanding the perspectives of clinicians, stroke survivors, and caregivers. Two design sprints were conducted, including empathy interviews at the beginning of the design sprint to integrate end-users' insights. After each design sprint, the NewGait device underwent refinements based on emerging issues and recommendations. The final prototype underwent mechanical testing for durability, biomechanical simulation testing for clinical feasibility, and a system usability evaluation, where the new stroke-specific NewGait device was compared with the original NewGait device and a commercial product, Theratogs®., Results: Affinity mapping from the design sprints identified crucial categories for stakeholder adoption, including fit for females, ease of donning and doffing, and usability during barefoot walking. To address these issues, a system redesign was implemented within weeks, incorporating features like a loop-backed neoprene, a novel closure mechanism for the shoulder harness, and a hook-and-loop design for the waist belt. Additional improvements included reconstructing anchors with rigid hook materials and replacing latex elastic bands with non-latex silicone-based bands for enhanced durability. Further, changes to the dorsiflexion anchor were made to allow for barefoot walking. Mechanical testing revealed a remarkable 10-fold increase in durability, enduring 500,000 cycles without notable degradation. Biomechanical simulation established the modularity of the NewGait device and indicated that it could be configured to assist or resist different muscles during walking. Usability testing indicated superior performance of the stroke-specific NewGait device, scoring 84.3 on the system usability scale compared to 62.7 for the original NewGait device and 46.9 for Theratogs., Conclusion: This study successfully establishes the proof-of-concept for a human-centered design approach using design sprints to rapidly develop a stroke-specific gait rehabilitation system. Future research should focus on evaluating the clinical efficacy and effectiveness of the NewGait device for post-stroke rehabilitation., (© 2024. The Author(s).)

Background: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy., Methods: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores., Results: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes., Conclusion: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup., (© 2024. The Author(s).)

Background: There has been a precipitous decline in authorizations for medical cannabis since non-medical cannabis was legalized in Canada in 2018. This study examines the demographic and health- and medical cannabis-related factors associated with authorization as well as the differences in medical cannabis use, side effects, and sources of medical cannabis and information by authorization status., Methods: Individuals who were taking cannabis for therapeutic purposes completed an online survey in early 2022. Multivariable logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) of demographic and health- and medical cannabis-related variables associated with holding medical cannabis authorization. The differences in medical cannabis use, side effects, and sources of information by authorization status were determined via t-tests and chi-squared analysis., Results: A total of 5433 individuals who were currently taking cannabis for therapeutic purposes completed the study, of which 2941 (54.1%) currently held medical authorization. Individuals with authorization were more likely to be older (OR ≥ 70 years vs. < 30 years, 4.85 (95% CI, 3.49-6.76)), identify as a man (OR man vs. woman, 1.53 (1.34-1.74)), have a higher income (OR > $100,000/year vs. < $50,000 year, 1.55 (1.30-1.84)), and less likely to live in a small town (OR small town/rural vs. large city, 0.69 (0.59-0.81)). They were significantly more likely to report not experiencing any side effects (29.9% vs. 23.4%; p < 0.001), knowing the amount of cannabis they were taking (32.1% vs. 17.7%; p < 0.001), obtaining cannabis from regulated sources (74.1% vs. 47.5%; p < 0.001), and seeking information about medical cannabis from healthcare professionals (67.8% vs. 48.2%; p < 0.01) than individuals without authorization., Conclusions: These findings offer insight into the possible issues regarding equitable access to medical cannabis and how authorization may support and influence individuals in a jurisdiction where recreational cannabis is legalized, highlighting the value of a formal medical cannabis authorization process., (© 2024. The Author(s).)

Background: In Sierra Leone, adolescents are increasingly engaging in risky activities, including cannabis use, which can lead to substance abuse, poor academic performance, and psychotic symptoms. This study aims to investigate the prevalence and associated factors of cannabis use among school-going adolescents in the country., Method: Data for the study was sourced from the 2017 Sierra Leone Global School-based Student Health Survey (GSHS), a nationally representative survey conducted among adolescents aged 10-19 years using a multistage sampling methodology. A weighted sample of 1,467 adolescents in Sierra Leone was included in the study. The study utilised bivariate and multivariable logistic regression analysis to identify factors linked to cannabis use, presenting results using adjusted odds ratios and 95% confidence intervals., Results: The prevalence of cannabis use was 5.1% [3.0,8.6] among school-going adolescents in Sierra Leone. School-going adolescents who attempted suicide [aOR = 6.34, 95% CI = 1.71-23.45], used amphetamine [aOR = 15.84, 95% CI = 7.94-31.62] and were involved in sexual risk behaviour [aOR = 5.56, 95% CI = 2.18-14.20] were more likely to be associated with cannabis use., Conclusion: In Sierra Leone, a small but non-trivial minority of students use cannabis. Ever-used amphetamines or methamphetamines, suicidal attempts, and sexual risk behaviour were the factors associated with cannabis use in Sierra Leone. The development of school-based health intervention programmes is crucial to address the risk factors associated with cannabis use among school-going adolescents., (© 2024. The Author(s).)

Background: Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0-20 µg/cm 2 ) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-κB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles., Results: In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1α and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment., Conclusions: Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lung fibrosis adverse outcome pathway., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)