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Shear wave elastography, as a feasible tool, can be used to reflect the lower limb dysfunction in patients with chronic obstructive pulmonary disease?

UK PhD students welcome 8% pay boost, but demand more to meet rising living costs

Victimization status among persons with disabilities and its predictors: Evidence from Bangladesh National Survey on Persons with Disabilities

Background Persons with disabilities often face various forms of victimization, yet there is limited research exploring this phenomenon in Bangladesh. This study aims to investigate the victimization status among persons with disabilities and identify its predictors. Methods Data of 4293 persons with disabilities analyzed in this study were extracted from the 2021 National Survey on Persons with Disabilities. Victimization status (yes, no) was considered as the outcome variables. Explanatory variables considered were factors at the individual, household, and community levels. A multilevel mixed-effect logistic regression model was used to explore the association of the outcome variable with explanatory variables by dividing the total sample into age groups of 0–17 years, 18–59 years, and ≥ 60 years. Results The study found that 44% of persons with disabilities in Bangladesh experienced victimization, primarily involving neighbours (90.64%), relatives (43.41%), friends (28.41%), and family members (27.07%). Among persons aged 0–17 years, increasing age was associated with a higher likelihood of being victimized, while residing in the wealthiest households or in certain divisions like Khulna and Rangpur was associated with lower likelihoods. Conversely, among respondents aged 18–59 and ≥ 60 years, increasing age was associated with a lower likelihood of being victimized. Unmarried respondents aged 18–59 years had an increased likelihood of victimization compared to married individuals. For persons with disabilities aged ≥ 60 years, a higher level of schooling was associated with a reduced likelihood of being victimized. We also found divisional differences in the likelihood of victimization, with respondents residing in Chattogram, Khulna, Mymensingh, Rangpur, and Sylhet reporting lower likelihoods compared to those residing in the Barishal division, among persons with disabilities aged 18–59 and ≥ 60 years. Conclusion This study’s findings underscore that around 4 in 10 persons with disabilities are being victimized. Tailored programs and awareness-building initiatives covering neighbours, relatives, friends, and family members of persons with disabilities are important to ensure dignified lives for this population.

Intermittent hypoxia-induced enhancements in corticospinal excitability predict gains in motor learning and metabolic efficiency

Exploring cotton plant compounds for novel treatments against brain-eating Naegleria fowleri: An In-silico approach

To find potential inhibitors of Naegleria fowleri S-adenosyl-L-homocysteine hydrolase (NfSAHH), a brain-eating parasite, structure-based drug design was adopted. N. fowlerica causes primary amebic meningoencephalitis (PAM), a fatal central nervous system (CNS) disorder if untreated. NfSAHH protein (PDB ID: 5v96), involved in parasite growth and gene regulation, was targeted and screened against 163 metabolites from Gossypium hirsutum (cotton plant). With the aid of different software and web tools, the metabolites were subjected to several analyses. The RMSD was evaluated to validate our molecular docking strategy. Neplanocin A, a common anti-parasitic medication, was used as a reference to select top ligands for post-docking studies. Significant interactions were observed with residues THR-198, HIS-395, and MET-400. The drug-likeness of the top fifty hits was analyzed using Lipinski, Ghose, Veber, Egan, and Muegge rules. The top ten compounds following Lipinski’s RO5 were studied regarding medicinal chemistry, pharmacokinetic simulation, and Swiss target prediction. Advanced strategies, including molecular dynamic simulations, binding energy calculations, and principal component analysis, were employed for the top three hits, namely curcumin, heliocide H2, and piceid, which indicated that heliocide H2 is the most promising candidate, while curcumin and piceid may need further optimization to improve their stability. Overall, the top ten phytochemicals, dotriacontanol, melissic acid, curcumin, 6,6′-dimethoxygossypol, phytosphingosine 2, methyl stearate, stearic acid, piceid, heliocide H2, and 6-methoxygossypol, reported in our study, are worthy enough to be subjected to in vivo and in vitro experimentation to find a novel drug to treat PAM.

Spleen volume in relation to ulcerative colitis and Crohn’s disease: a Mendelian randomization study

Daily briefing: What science photos do that AI-generated images can’t

Field-based investigation of failure modes and thresholds of granite residual soil slopes under heavy rainfall conditions

Rainfall is a primary coefficient of slope instability. To study patterns of slope failure mode and key index threshold values of slope instability under varying rainfall intensities, real-time data from in-situ monitoring tests of an engineering slope were utilized. This data facilitated the analysis of the temporal and spatial responses of a rainfall infiltration slope. Four field tests were conducted under four different rainfall intensities, namely 75mm/h, 125mm/h, 150mm/h, and 175mm/h, to study the progressive failure characteristics of the granite residual soil slope. These characteristics were studied based on water-time and displacement-time curves, and the rainfall duration and threshold for slope instability were proposed. The result revealed that the granite residual soil slope undergoes progressive failure under rainfall conditions, which can be categorized into four modes: “shallow local sliding”,“shallow global sliding and collapse”, “deep local sliding”, and“deep global sliding”. It takes 25 ~ 135min for the shallow sliding failure characteristics from significant deformation to instability, while the deep sliding only lasts for 18 ~ 20min. A significant correlation was observed between soil moisture content and slope instability. Instability symptoms such as cracking and peristaltic deformation begin to appear when the soil moisture content in the shallow layer of the slope increases to 42 ~ 45%. When the soil moisture content escalates to 47 ~ 50%, the slope begins to disintegrate, leading to rapid landslides and collapses.

Comparative metabolomic analysis reveals shared and unique features of COVID-19 cytokine storm and surgical sepsis

Outcomes of percutaneous transhepatic gallbladder drainage versus percutaneous transhepatic biliary drainage for obstructive jaundice

Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative to percutaneous transhepatic biliary drainage (PTBD) for cases with obstructive jaundice in which the bile duct obstruction is below the confluence of the cystic ducts. This retrospective study aimed to evaluate the usefulness of PTGBD and PTBD in patients with obstructive jaundice. We recruited patients who had undergone percutaneous biliary drainage for acute cholangitis and obstructive jaundice at two institutions between January 2017 and March 2024. In principle, PTBD was the first choice. PTGBD was selected for cases where the intrahepatic bile duct diameter was ≤ 5 mm or ≥ 6 mm with significant respiratory-related variability of the positioning of the bile ducts. In other cases, PTBD was chosen. Fifty-five patients were included in this analysis. However, patients with intrahepatic or hilar bile duct stenosis, post choledocholithiasis, complex cholecystitis, total bilirubin levels of < 2.0 mg/dL, and uncorrectable bleeding tendency and those who had undergone the procedure and later discontinued without puncture were excluded. The technical success rates, clinical success rates, and complication rates of the procedure were evaluated. The technical success rates were 96.3% (26/27) and 82.1% (23/28) in the PTGBD and PTBD groups, respectively. The clinical success rates were 85.2% (23/27) and 67.9% (19/28) in the PTGBD and PTBD groups, respectively. The complication rates were 18.5% (5/27) and 25.0% (7/28) in the PTGBD and PTBD groups, respectively. No serious complications were observed in either group. Hence, the two groups did not significantly differ in any of the endpoints. The outcomes of PTGBD were comparable to those of PTBD in patients with obstructive jaundice. Hence, PTGBD is a reasonable treatment option for cases of obstructive jaundice in which PTBD is not feasible.

The c.119-123dup5bp mutation in human γC-crystallin destabilizes the protein and activates the unfolded protein response to cause highly variable cataracts

Abstract Ordered cellular architecture and high concentrations of stable crystallins are required for the lens to maintain transparency. Here we investigate the molecular mechanism of cataractogenesis of the CRYGC c.119-123dupGCGGC (p.Cys42AlafsX63) (CRYGC5bpdup) mutation. Lenses were extracted from wild type and transgenic mice carrying the CRYGC5bpdup minigene and RNA was isolated and converted into cDNA. Expression of genes in the unfolded protein response (UPR) pathways was estimated by qRT-PCR and RNA seq and pathway analysis was carried out using the Qiagen IPA website. Postnatal 3 weeks (P3W) Transgenic mice exhibited phenotypic diversity with a dimorphic population of severe and clear lenses. PCA of RNA seq data showed separate clustering of wild-type, clear CRYGC5bpdup, and severe CRYGC5bpdup lenses. Transgenic mice showed differential upregulation in Master regulator Grp78 (Hspa5) and downstream targets in the PERK-dependent UPR pathway including Atf4 and Chop (Ddit3), but not GADD34 (Ppp1r15a). Thus, high levels of CRYGC5bpdup transgene expression in severely affected lenses induces UPRer and UPRmt stress responses primarily through the PERK-dependent and Atf4/Atf5/Ddit3 pathways respectively, inducing autophagy and apoptosis and thence congenital nuclear cataracts. This effect is correlated to CRYGC5bpdup transgene expression, offering insight into cataract pathogenic pathways and recapitulating the variation in cataract severity in humans.

A structured, home-based exercise programme in kidney transplant recipients (ECSERT): A randomised controlled feasibility study

Background Cardiometabolic diseases are a major cause of morbidity and mortality in kidney transplant recipients (KTR) due to clustering of traditional and non-traditional risk factors including poor physical fitness and physical inactivity. Exercise may mitigate the risk of these diseases in this population but evidence is limited, and physical activity levels are low. The ECSERT randomised controlled trial assessed the feasibility of delivering a structured, home-based exercise intervention in KTR at increased cardiometabolic risk. Methods Fifty KTR (>1-year post-transplant) were randomised 1:1 to: intervention (INT: a 12-week home-based combined aerobic and resistance exercise programme) or control (CTR: guideline-directed care). The a-priori thresholds for feasibility were: recruitment of 20% of eligible participants (≥2 participants per month); adherence (an average of ≥ 3 exercise sessions per week); and attrition (≤30%). Results One hundred and seventy-one patients were screened and 94 (55%) were eligible and invited to take part in the study. Fifty of those invited (53%) were recruited across 22 months of recruitment. Consented participant characteristics were: age 50 ± 14 years (INT 49 ± 13; CTR 51 ± 15), 23 male (INT 10; CTR 13), eGFR 59 ± 19 ml/min/1.73m2 (INT 60 ± 20; CTR 61 ± 21), 35 White British (WB), 13 South Asian (SA), 1 Caribbean, and 1 Mixed ethnicity (INT 17 WB, 7 SA, 1 Mixed; CTR 18 WB, 6 SA, 1 Caribbean). Intervention participants (n = 22 completed) recorded an average of 4.4 ± 1.4 exercise sessions per week (aerobic 2.8 ± 1.1; strength 1.6 ± 0.5). Three participants withdrew from the intervention group (1 COVID-19 infection, 1 recurrent urine infections unrelated to the trial, 1 time/family circumstances) and one from the control group (lost to follow-up; 8% attrition). There were no serious adverse events reported. Conclusion Despite previous evidence showing physical fitness and activity levels are low in KTR, the present results support that a structured, home-based exercise programme is feasible in this population. Specifically, a-priory recruitment, adherence, and retention thresholds were all exceeded. The groups were well matched and there was encouraging representation of female participants and participants from a non-white background. Thus, this study supports further development and testing of home-based programmes of exercise and activity for KTR. Trial registration ClinicalTrials.gov NCT04123951

In vitro synthetic polyploidization and enhancement of anticancer compounds in Catharanthus Roseus (L.) G. Don important cultivars

Message framing materials applied to healthy eating decision-making for pregnant women with gestational diabetes mellitus: An exploratory study

Aims To develop and initially validate message framing materials for promoting healthy dietary decisions in GDM populations. Methods The Delphi survey involved 17 experts, and consensus was obtained after two rounds. In Pre-survey I, 30 participants randomly selected one material (gain framing vs. loss framing) and complete a manipulation check item to ensure that the stimulus material manipulation was valid. Pre-survey II involved 60 participants who rated all messages using a Likert 5 rating questionnaire, a Wilcoxon signed rank sum test was used to examine the message framing effects. Results After two rounds of Delphi surveys, experts reached consensus on the final materials, which contained two message framings, each containing 11 entries. The manipulation test for materials achieved 100% validity. The findings indicated significant message framing effects on healthy eating decisions among GDM populations, with loss-framed messages proving more persuasive. Conclusion Scientifically valid message framing materials were developed and initially applied, providing an empirical basis and direction for future related research.

Impact of formal credit and social capital on the scalability of agricultural operations

Combined immunoinformatic approaches with computational biochemistry for development of subunit-based vaccine against Lawsonia intracellularis

Lawsonia intracellularis (LI) are obligate intracellular bacteria and the causative agent of proliferative hemorrhagic enteropathy that significantly impacts the health of piglets and the profitability of the swine industry. In this study, we used immunoinformatic and computational methodologies such as homology modelling, molecular docking, molecular dynamic (MD) simulation, and free energy calculations in a novel three stage approach to identify strong T and B cell epitopes in the LI proteome. From ∼ 1342 LI proteins, we narrowed our focus to 256 proteins that were either not well-identified (unknown role) or were expressed at a higher frequency in pathogenic strains relative to non-pathogenic strains. At stage 1, these proteins were analyzed for predicted virulence, antigenicity, solubility, and probability of residing within a membrane. At stage 2, we used NetMHCPan4-1 to identify over ten thousand cytotoxic T lymphocyte epitopes (CTLEs) and 286 CTLEs were ranked as having high predicted binding affinity for the SLA-1 and SLA-2 complexes. At stage 3, we used homology modeling to predict the structures of the top ranked CTLEs and we subjected each of them to molecular docking analysis with SLA-1*0401 and SLA-2*0402. The top ranked 25 SLA–CTLE complexes were selected to be an input for subsequent MD simulations to fully investigate the atomic-level dynamics of proteins under the natural thermal fluctuation of water and thus potentially provide deep insight into the CTLE-SLA interaction. We also performed free energy evaluation by Molecular Mechanics/Poisson−Boltzmann Surface Area to predict epitope interactions and binding affinities to the SLA-1 and SLA-2. We identified the top five CTLEs having the strongest binding energy to the indicated SLAs (-305.6 kJ/mol, -219.5 kJ/mol, -214.8 kJ/mol, -139.5 kJ/mol and -92.6 kJ/mol, respectively.) W also performed B-cell epitope prediction and the top-ranked 5 CTLEs and 3 B-cell epitopes were organized into a multi-epitope subunit antigen vaccine construct joined using EAAAK, AAY, KK, and GGGGG linkers with 40 residues of the LI DnaK protein attached to the N-terminus to further enhance the antigenicity of the vaccine construct. Blind docking studies showed strong interactions between our vaccine construct with swine Toll-like receptor 5. Collectively, these molecular modeling and immunoinformatic analyses present a useful in silico protocol for the discovery of candidate antigen in many viral and bacterial pathogens.

Deciphering the prognostic impact of aberrant DNA methylation on ANGPT1 gene in breast cancer

Protective effects of psychiatric medications against COVID-19 mortality before vaccines

The coronavirus disease pandemic caused by the coronavirus SARS-CoV-2, which emerged in the United States in late 2019 to early 2020 and quickly escalated into a national public health crisis. Research has identified psychiatric conditions as possible risk factors associated with COVID-19 infection and symptom severity. This study aims to determine whether specific classes of psychiatric medications could reduce the likelihood of infection and alleviate the severity of the disease. The objective of this study is to investigate the relationship between neuropsychiatric medication usage and COVID-19 outcomes before the widespread utilization of COVID-19 vaccines. This cross-sectional study used Optum’s de-identified Clinformatics Data Mart Database to identify patients diagnosed with COVID-19 in 2020 and their psychiatric medication prescriptions in the United States. Ordered logistic regression was used to predict the likelihood of a higher COVID-19 severity level for long-term and new users. Results were adjusted for demographic characteristics and medical and psychiatric comorbidities. Most users were classified into the long-term user analysis group. Long-term users were 9% less likely to have a higher severity score (CI: 0.89–0.93, p-value < 0.001) than non-users. SSRI antidepressant users, both long-term (OR: 1.09; CI: 1.06–1.12) and short-term (OR: 1.17; CI: 1.07–1.27) were significantly more likely to have a lower severity score. However, the results varied across long-term and short-term users for all medication classes. Results of the current study suggest that psychopharmacological agents are associated with reduced COVID-19 severity levels and that antidepressant medications may have a protective role against COVID-19.

Analysis of critical 3D imaging data of surrounding cervical nerves and bone markers in spinal endoscopic surgery

Preoperative antihypertensives and hypotension during bladder tumor resection with oral 5-aminolevulinic acid administration

5-Aminolevulinic acid hydrochloride (5-ALA), a photodynamic diagnostic agent, visualizes bladder cancer. Previous research has indicated that preoperative intake of 5-ALA leads to a higher incidence of hypotension. Particularly in patients with hypertension, suggestions include discontinuing antihypertensive medications on the morning of surgery to prevent hypotension. However, the effects of antihypertensive drugs on hypotension in patients taking 5-ALA before surgery remains unexamined. We conducted a single-center observational study that included patients aged 20 and above who were regularly taking antihypertensives and underwent transurethral resection of bladder tumors (TURBT) after taking 5-ALA. Patients who took antihypertensives on the morning of surgery were defined as the continued group, whereas those who did not were defined as the discontinued group. Hypotension was defined as a mean blood pressure (MBP) of less than 65 mmHg for 20 min or longer. To adjust for confounding factors, we used propensity scores for inverse probability weighting and performed modified Poisson regression analysis to calculate risk ratios (RRs) and 95% confidence intervals (CIs). We analyzed 132 cases. The crude incidence of hypotension was higher in the continued group compared to the discontinued group (33/51 [64.7%] vs 38/81 [46.9%]; RR 1.38, 95% CI 1.01–1.88; p =  0.041). However, no significant difference was observed between groups after adjustment (RR 1.05, 95% CI 0.66–1.68). In conclusion, the adjusted results suggested no significant association between the continuation of antihypertensive medication and the incidence of intraoperative hypotension. No substantial justification was provided for routinely discontinuing antihypertensive medications.