Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Emergency room visits (ERVs) among occupational groups associated with ambient conditions in Taiwan.

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

Clinical outcomes of carbapenem-resistant gram-negative bacterial bloodstream infection in patients with end-stage renal disease in intensive care units: a multicenter retrospective observational study.

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

Variant Impact Predictor database (VIPdb), version 2: Trends from 25 years of genetic variant impact predictors.

Background: Variant interpretation is essential for identifying patients' disease-causing genetic variants amongst the millions detected in their genomes. Hundreds of Variant Impact Predictors (VIPs), also known as Variant Effect Predictors (VEPs), have been developed for this purpose, with a variety of methodologies and goals. To facilitate the exploration of available VIP options, we have created the Variant Impact Predictor database (VIPdb). Results: The Variant Impact Predictor database (VIPdb) version 2 presents a collection of VIPs developed over the past 25 years, summarizing their characteristics, ClinGen calibrated scores, CAGI assessment results, publication details, access information, and citation patterns. We previously summarized 217 VIPs and their features in VIPdb in 2019. Building upon this foundation, we identified and categorized an additional 186 VIPs, resulting in a total of 403 VIPs in VIPdb version 2. The majority of the VIPs have the capacity to predict the impacts of single nucleotide variants and nonsynonymous variants. More VIPs tailored to predict the impacts of insertions and deletions have been developed since the 2010s. In contrast, relatively few VIPs are dedicated to the prediction of splicing, structural, synonymous, and regulatory variants. The increasing rate of citations to VIPs reflects the ongoing growth in their use, and the evolving trends in citations reveal development in the field and individual methods. Conclusions: VIPdb version 2 summarizes 403 VIPs and their features, potentially facilitating VIP exploration for various variant interpretation applications. Availability: VIPdb version 2 is available at https://genomeinterpretation.org/vipdb.

Enhancing pediatric asthma management through multifaceted health education.

BACKGROUND: Pediatric asthma is a significant public health issue that impacts the quality of life of children globally. Traditional management approaches focus on symptom control and medication adherence but often overlook the comprehensive educational needs of patients and their families. A multifaceted health education approach may offer a more holistic strategy in managing pediatric asthma, especially in outpatient settings. AIM: To evaluate the efficacy of a comprehensive health education strategy in improving disease management, medication adherence, and quality of life among children with asthma in outpatient settings. METHODS: In total, 100 pediatric patients with severe asthma were enrolled from January 2021 to November 2022 and randomly allocated to a control group (n = 50) or an observation group (n = 50). The control group received standard nursing care, including basic nursing interventions and health education upon admission. In contrast, the observation group was exposed to a broad spectrum of health education methodologies, including internet-based hospital systems, social media channels, one-on-one verbal education, informational brochures, slide presentations, telephone check-ins, animated videos, and illustrated health education manuals. Data on asthma management knowledge, symptom control, quality of life [St. George's Respiratory Questionnaire (SGRQ)], treatment adherence, and nursing satisfaction were collected and analyzed. RESULTS: The scores of the observation group in knowledge areas, such as medication, home care, disease understanding, symptom management, prevention strategies, and nutritional guidance, were significantly higher than those of the control group (P < 0.05). In addition, the observation group exhibited greater symptom control, improved quality of life based on their SGRQ scores, and higher treatment adherence post-intervention (P < 0.05). Nursing satisfaction was also rated higher in the observation group across all evaluated areas (P < 0.05). CONCLUSION: Implementing a diversified health education approach in pediatric asthma management significantly enhances disease understanding, symptom management, and treatment adherence, leading to improved quality of life for affected children. These findings underscore the importance of multifaceted clinical health education in augmenting disease awareness and facilitating continuous improvements in asthma control rates, highlighting the potential benefits of incorporating comprehensive educational strategies into pediatric asthma care protocols.

Guardian Reasons for Accessing Their Transgender and Gender-Diverse Adolescent's Patient Portal Account.

PURPOSE: To understand if and why guardians access their adolescent child's electronic health record patient portal account. METHODS: Guardians of transgender and gender-diverse adolescents completed a survey regarding patient portal use. Descriptive statistics were used to describe items related to guardian access to adolescent portal accounts. RESULTS: Of 82 respondents, 37.8% indicated they had used their child's login to access the patient portal. Most indicated they accessed their adolescent's account because their child asked them to do so. Other common reasons included being worried they might miss important health information and not realizing there was a difference between patient and proxy accounts. DISCUSSION: Results of this study provide a more detailed understanding regarding guardian access to adolescent patient portals. Findings can be used to inform adolescent patient portal design and enrollment practices that protect adolescent confidentiality.

Repurposing Type I-A CRISPR-Cas3 for a robust diagnosis of human papillomavirus (HPV).

R-loop-triggered collateral single-stranded DNA (ssDNA) nuclease activity within Class 1 Type I CRISPR-Cas systems holds immense potential for nucleic acid detection. However, the hyperactive ssDNase activity of Cas3 introduces unwanted noise and false-positive results. In this study, we identified a novel Type I-A Cas3 variant derived from Thermococcus siculi, which remains in an auto-inhibited state until it is triggered by Cascade complex and R-loop formation. This Type I-A CRISPR-Cas3 system not only exhibits an expanded protospacer adjacent motif (PAM) recognition capability but also demonstrates remarkable intolerance towards mismatched sequences. Furthermore, it exhibits dual activation modes-responding to both DNA and RNA targets. The culmination of our research efforts has led to the development of the Hyper-Active-Verification Establishment (HAVE, ). This innovation enables swift and precise human papillomavirus (HPV) diagnosis in clinical samples, providing a robust molecular diagnostic tool based on the Type I-A CRISPR-Cas3 system. Our findings contribute to understanding type I-A CRISPR-Cas3 system regulation and facilitate the creation of advanced diagnostic solutions with broad clinical applicability.

The efficacy of early office hysteroscopy in preventing intrauterine adhesions after abortion: a randomized controlled trial.

BACKGROUND: Intrauterine adhesions (IUA) are a challenging clinical problem in reproductive infertility. The most common causes are intrauterine surgery and abortions. We aimed to investigate whether early second-look office hysteroscopy can prevent IUA. METHODS: A single-center, prospective, two-armed, randomized controlled trial was designed to explore the efficacy of early office hysteroscopy after first-trimester induced abortion (suction dilatation and curettage [D&C]) and to further analyze fertility outcomes. Women aged 20-45 years undergoing suction D&C and desiring to conceive were recruited. Between October 2019 and September 2022, 66 women were enrolled, of whom 33 were allocated to group A (early hysteroscopy intervention). The women in intervention group A were planned to receive 2 times of hysteroscopies (early and late). In group B, women only underwent late (6 months post suction D&C) hysteroscopy. RESULTS: The primary outcome was the IUA rate assessed using office hysteroscopy 6 months after artificial abortion. Secondary outcomes included menstrual amount/durations and fertility outcomes. In intervention group A, 31 women underwent the first hysteroscopy examination, and 15 completed the second. In group B (late hysteroscopy intervention, 33 patients), 16 completed the hysteroscopic exam 6 months after an artificial abortion. Twenty-one women did not receive late hysteroscopy due to pregnancy. The IUA rate was 16.1% (5/31) at the first hysteroscopy in group A, and no IUA was detected during late hysteroscopy. Neither group showed statistically significant differences in the follow-up pregnancy and live birth rates. CONCLUSIONS: Early hysteroscopy following suction D&C can detect intrauterine lesions. IUA detected early by hysteroscopy can disappear on late examination and become insignificant for future pregnancies. Notably, the pregnancy outcomes showed a favorable trend in the early hysteroscopy group, but there were no statistically significant differences. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04166500. Registered on 2019-11-10. https://clinicaltrials.gov/ct2/show/NCT04166500 .

Insight into enhancing the performance of sludge dewatering using a novel flocculant CS-TA prepared through free radical-mediated conjugation.

Flocculation is one of the most significant conditioning methods for sludge dewatering. In the study, a novel flocculant CS-TA, prepared through free radical-mediated conjugation of tannic acid (TA) and chitosan (CS), was proposed to improve sludge dewatering. The characterisation using Fourier transform infra-red spectroscopy and X-ray diffraction analysis shows that the CS chain was the backbone of CS-TA, and the presence of CS-TA aromatic rings confirmed the conjugation of CS with TA. Moreover, the conditioning of CS-TA yielded the best dewatering performance at 30 mg g TS-1 with the water content of sludge cake by press filtration (Wsc) of 59.78% ± 0.3% and capillary suction time (CST) of 11.8s ± 0.35 s, compared to 98.2% ± 0.15% and 56.2 s ± 0.16 in raw sludge. The results of different influencing factors (e.g. pH and temperature) on flocculation efficiency indicated that CS-TA possessed the capacity for enhancing sludge dewaterability over a wide range of pH, and the optimal temperature was observed to be 35 °C. Furthermore, the increase of particle size and zeta potential implied the addition of CS-TA favoured the formation of larger particles charge neutralisation and adsorption bridging effect. In addition, extracellular polymer substances (EPS) analysis indicated that the decrease in the polysaccharide and protein contents in EPS after CS-TA addition could increase the relative hydrophobicity of sludge. Moreover, the contents of heavy metals in sludge and their leaching toxicity and environmental risk were reduced. This study provides comprehensive insights into the exploration of CS-TA for sludge dewatering and the maintenance of ecological security in an eco-friendly.

Age-related impairment in testosterone elevation after anterior fibromuscular stroma preserved enucleation.

OBJECTIVES: This study aims to evaluate the impact of anterior fibromuscular stroma preserved enucleation (AFSPE) of the prostate on serum testosterone levels in patients with benign prostatic obstruction (BPO) and to explore age-related differences in postoperative testosterone elevation. METHODS: In a retrospective analysis, 304 patients from a pool of 560 who underwent AFSPE at Linkou Chang Gung Memorial Hospital between January 2018 and December 2021 were evaluated. Patients were stratified based on preoperative testosterone levels into low (<3.5 ng/mL) and normal (≥3.5 ng/mL) groups. Serum testosterone levels were measured preoperatively, at 1.5 and 3-6 months postoperatively. Age and other demographic data were analyzed as potential factors influencing testosterone changes. RESULTS: The low-testosterone group (n = 90) showed significant testosterone increases, from an average of 2.61 ng/mL preoperatively to 3.3 ng/mL at 1.5 months and 3.59 ng/mL at 3-6 months postoperatively (p < 0.0001). The normal-testosterone group (n = 214) maintained stable testosterone levels at 1.5 months but exhibited a significant rise to 6.06 ng/mL by 3-6 months (p = 0.0079). Older age was inversely associated with postoperative testosterone elevation in both groups. Improvements in nocturia were notable in both groups. CONCLUSIONS: AFSPE of the prostate significantly elevates serum testosterone levels in men with BPO, particularly benefiting those initially with low levels. Age is a crucial factor influencing postoperative testosterone changes, indicating that younger patients may benefit more from this intervention. AFSPE offers a promising approach for improving hormonal health in BPO patients, alongside alleviating urinary symptoms.

[Diagnostic Value of Ultrasound for Thyroid Nodules With a Spoke-Wheel Blood Flow Pattern].

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (χ2=5.968,P=0.015),while central coarse calcification was more common in benign nodules (χ2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both P<0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

The association between acute myocardial infarction and subsequent diagnosis of breast cancer: a nationwide, population-based cohort study.

Coronary artery disease (CAD) such as acute myocardial infarction (MI) share several common risk factors with cancers, and each disease may influence the prognosis of the other. Recently, acute MI was demonstrated to accelerate the outgrowth of preexisting breast cancer cells but the risk of breast cancer after MI remains unclear. This study aimed to investigate the association between acute MI and a subsequent diagnosis of breast cancer. Female patients with and without a history of acute MI were identified from nationwide databases in Taiwan. Patients with a diagnosis of cancer, MI or CAD prior to the study period were excluded. After reducing confounding through inverse probability of treatment weighting, we compared the incidence of newly diagnosed breast cancer between patients with a history of acute MI and those without. As a result, a total of 66,445 female patients were obtained, including 15,263 patients with a history of acute MI and 51,182 patients without. The incidences of breast cancer during follow-up were 1.93 (95% confidence interval [CI] 1.78-2.09) and 1.80 (95% CI 1.67-1.93) per 1,000 person-years for patients with and without a history of acute MI, respectively. The hazard ratio (HR) was 1.05 (95% CI 0.78-1.41, P = 0.756). In subgroup analysis, breast cancer risk was significantly associated with acute MI in patients using antidiabetic drugs (HR 1.27; 95% CI 1.02-1.58) and in low to moderate urbanization levels (HR 1.28; 95% CI 1.06-1.53). In conclusion, the risk of newly diagnosed breast cancer was not increased in patients with acute MI when compared to general population without MI or CAD.

Phylogenomics identifies parents of naturally occurring tetraploid bananas.

BACKGROUND: Triploid bananas are almost sterile. However, we succeeded in harvesting seeds from two edible triploid banana individuals (Genotype: ABB) in our conservation repository where various wild diploid bananas were also grown. The resulting rare offspring survived to seedling stages. DNA content analyses reveal that they are tetraploid. Since bananas contain maternally inherited plastids and paternally inherited mitochondria, we sequenced and assembled plastomes and mitogenomes of these seedlings to trace their hybridization history. RESULTS: The coding sequences of both organellar genomic scaffolds were extracted, aligned, and concatenated for constructing phylogenetic trees. Our results suggest that these tetraploid seedlings be derived from hybridization between edible triploid bananas and wild diploid Musa balbisiana (BB) individuals. We propose that generating female triploid gametes via apomeiosis may allow the triploid maternal bananas to produce viable seeds. CONCLUSIONS: Our study suggests a practical avenue towards expanding genetic recombination and increasing genetic diversity of banana breeding programs. Further cellular studies are needed to understand the fusion and developmental processes that lead to formation of hybrid embryos in banana reproduction, polyploidization, and evolution.