Nevin Manimala

Genomics. 2023 Oct 20:110733. doi: 10.1016/j.ygeno.2023.110733. Online ahead of print.

ABSTRACT

BACKGROUND: Big data mining and experiments are widely used to mine new prognostic markers.

METHODS: Candidate genes were identified from CROEMINE and FerrDb. Kaplan-Meier survival and Cox regression analysis were applied to assess the association of genes with Overall survival time (OS) and Disease-free survival time (DFS) in two HCC cohorts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry were performed in HCC samples.

RESULTS: 21 and 15 genes that can predict OS and DFS, which had not been reported before, were identified from 719 genes, respectively. Survival analysis showed elevated mRNA expression of GLMP, SLC38A6, and WDR76 were associated with poor prognosis, and three genes combination signature was an independent prognostic factor in HCC. RT-qPCR and Immunohistochemistry confirmed the results.

CONCLUSIONS: We established a novel computational process, which identified the expression levels of GLMP, SLC38A6, and WDR76 as potential ferroptosis-related biomarkers indicating the prognosis of HCC.

PMID:37866659 | DOI:10.1016/j.ygeno.2023.110733

Physiol Behav. 2023 Oct 20:114385. doi: 10.1016/j.physbeh.2023.114385. Online ahead of print.

ABSTRACT

Wild animals are brought to captivity for different reasons, for example to be kept in zoos and rehabilitation centres, but also for basic research. Such animals usually undergo a process of adjustment to captive conditions. While this adjustment occurs on the behavioural and the physiological level, those are usually studied separately. The aim of this study was to assess both the physiological and behavioural responses of wild wood mice, Apodemus sylvaticus, while adjusting to laboratory conditions. Over the course of four weeks, we measured in wild-caught mice brought to the laboratory faecal corticosterone metabolites and body mass as physiological parameters, stereotypic behaviour and nest-quality, as welfare-linked behavioural parameters, and four personality measures as additional behavioural parameters. The results of our study indicate that mice exhibited an adjustment in both behaviour and physiology over time in the laboratory. While the hormonal stress response decreased significantly, body mass and the proportion of stereotypic behaviours showed a tendency to increase over time. The slight increase of stereotypic behaviours, although not statistically significant, suggests the development of repetitive and non-functional behaviours as a response to laboratory conditions. However, we suggest that those behaviours might have been used by animals as a coping strategy to decrease the physiological stress response. Other behavioural parameters measured, such as boldness and nestbuilding behaviour were stable over time. The information obtained in the present study hints at a complex interplay between behavioural and physiological adjustments of wild animals to laboratory conditions, which should be considered when intending to use wild animals in experimental research.

PMID:37866641 | DOI:10.1016/j.physbeh.2023.114385

Sci Total Environ. 2023 Oct 20:167985. doi: 10.1016/j.scitotenv.2023.167985. Online ahead of print.

ABSTRACT

The interactions of aerosol and planetary boundary layer (PBL) play a crucial role in deteriorating the air quality in vast urban agglomeration areas in eastern China. However, there remains a lacking of report regarding their performance in the hazy events in Mongolian Plateau cities in northern China. In this study, half-month (01-16 January 2020) physical and material datasets of the PBL measured by multi instrumentations mounted in downtown Hohhot, a largest Mongolian Plateau city, are statistically analyzed. Results demonstrate that the aerosol-PBL feedback is of particular importance in promoting the hazy outbreak and the statistical relationship follows PBLH = -76.14 × ln(PM_2.5) + 820.61. The non-linear fitting implies that there exists a potential threshold of 76.14 μg m^-3 for PM_2.5, below which the PBLH decrease rapidly along with the increasing of air pollutants, defined as strong aerosol-PBL interaction phase, while beyond which there is minimal decrease for PBLH even when PM reaches to a high value, i.e., the hazy accumulation phase. Using a large-eddy simulation model named as Dutch Atmospheric Large-Eddy Simulation (DALES) initialized with the synergetical observations in a representative hazy process in 11 January 2020, we found that the DALES is effective to capture the diurnal PBLH in this region. The existence of atmospheric aerosols is essential for lowering PBLH by 51.4 % from 1090 m of clean scenario to 530 m of polluted condition, postponing the development time, and advancing the afternoon lapse time. The enhancement of aerosol absorption ability strengthens the aerosol heating rate, thereby weakening the sensible heat flux, and inhibiting the development of PBLH. While opposite elevation on PBLH is found for the scattering aerosols. These findings highlight the importance of aerosol-PBL interaction in motivating the hazy episodes in Mongolian Plateau cities, which provide scientific references for the local policy-making towards pollution reductions in future.

PMID:37866603 | DOI:10.1016/j.scitotenv.2023.167985

Sci Total Environ. 2023 Oct 20:167909. doi: 10.1016/j.scitotenv.2023.167909. Online ahead of print.

ABSTRACT

Particulate matter (PM_2.5) and its components have been studied widely around the world and are associated with many adverse health events (e.g. cardiovascular diseases and death). Flow-mediated dilation (FMD) is a non-invasive assessment that is able to detect endothelial damage at an early stage, therefore, improving the prognosis of atherosclerotic cardiovascular disease. The current study used data from Shanghai to explore the relationship between PM_2.5 and its components and FMD using multiple statistical models. The results of the analysis of 812 patients’ data (age ≥ 65) suggested that as PM_2.5 level rises, endothelial function reduces. Among the five PM_2.5 components included in this study, black carbon was shown by both models to be the dominating factor three days post-exposure (lag3). However, results from lag4 and lag5 were inconclusive in the two models with some evidence proposing the significance of sulphate, organic matter, and ammonium. Our results are in concordance with previous literature and further prove the significance of black carbon as an individual pollutant in the atmosphere. More research is needed to confirm the role of sulphate, organic matter, and ammonium as independent pollutants in relation to health.

PMID:37866598 | DOI:10.1016/j.scitotenv.2023.167909

J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.

ABSTRACT

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.

OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.

METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I² statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.

RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I² = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I² = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I² = 0%). The overall risk of fatal ICH was not different between anticoagulants.

DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

J ISAKOS. 2023 Oct 20:S2059-7754(23)00582-5. doi: 10.1016/j.jisako.2023.10.007. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effects of liposomal bupivacaine use for interscalene blocks on postoperative analgesia in total shoulder arthroplasty patients.

METHODS: De-identified total or reverse total shoulder arthroplasty patients between 2018 and 2021 were analyzed. Patients were grouped into single shot interscalene block with Liposomal Bupivacaine (LB) with plain bupivacaine, Other Block (OB) with other local anesthetics (mepivacaine, ropivacaine, or plain bupivacaine), or No Block (NB). The primary outcome was the proportion of patients with clinically tolerable pain scores (mean VAS <4) from 0 – 24 hours in each group. Secondary outcomes included averaged visual analog pain scores (VAS) and opioid consumption measured in morphine milligram equivalents (MMEs) from 0 – 24 hours. We also analyzed the proportion of patients with clinically tolerable pain, mean VAS, and opioid consumption from 0 – 72 hours in those patients with at least a 3-day hospital length of stay.

RESULTS: A total of 491 de-identified total shoulder arthroplasty patients, 285 liposomal bupivacaine group (LB), 178 other block group (OB), and 28 no block group (NB), were analyzed. The primary outcome showed a statistically significant different proportion of patients with clinically tolerable pain from 0 – 24 hours in the LB group (69%) vs. OB group (39%) vs. NB group (11%) (<0.001). Secondary outcomes included statistically significant differences in VAS (LB median = 3.35, OB median = 4.38, NB median = 5.25 (p <0.001, <0.001)) and total MME opioid consumption (LB median= 40, OB median=60, NB median=88 (p < 0.001, 0.001)) between groups from 0 – 24 hours. For patients who had hospital stays of at least 3 days, a significant association was found with having achieved clinically tolerable pain 0-72 hours and the LB group (51%) vs. OB group (21%) vs. NB group (11%) (P= 0.006). However, there was no statistical difference in mean VAS or opioid consumption between these groups.

CONCLUSION: A greater proportion of total shoulder arthroplasty patients that received liposomal bupivacaine in interscalene block have clinically tolerable pain scores from 0 to 24 hours, lower VAS, and lower MME consumption in patients following total shoulder arthroplasty.

LEVEL OF EVIDENCE: Level III – Clinical Study.

PMID:37866512 | DOI:10.1016/j.jisako.2023.10.007

Chem Biol Interact. 2023 Oct 20:110774. doi: 10.1016/j.cbi.2023.110774. Online ahead of print.

ABSTRACT

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B-two active ingredients derived from both EF and PF-are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2, Cd74, Banp, Oas3, Oas2, Gbp8, Slfn8, Gbp2b, Serpina3g, Zbtb40, H2-Ab1, Osgin1, Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury.

PMID:37866487 | DOI:10.1016/j.cbi.2023.110774

J Am Acad Child Adolesc Psychiatry. 2023 Oct 18:S0890-8567(23)02136-6. doi: 10.1016/j.jaac.2023.10.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Adolescence is a key developmental window that may determine long-term mental health. As schools may influence students’ mental health, we examined the association of school-level characteristics with students’ mental health over time.

METHOD: We analysed longitudinal data from a cluster randomised controlled trial on 8,376 students (55% female; aged 11-14 years at baseline) across 84 schools in the United Kingdom. Data collection started in the academic years 2016/2017 (Cohort 1) and 2017/2018 (Cohort 2), with follow-up at 1, 1.5, and 2 years. We explored students’ mental health (risk for depression (Center for Epidemiologic Studies-Depression Scale), social-emotional-behavioural difficulties (Strength and Difficulties Questionnaire)) and well-being (Warwick-Edinburgh Mental Well-Being Scale), and their relationship with student- and school-level characteristics, using multilevel regression models.

RESULTS: Mental health difficulties and poorer well-being increased over time, particularly in girls. Differences among schools represented a small but statistically significant proportion of variation (95% CI) in students’ mental health at each timepoint: depression: 1.7% (0.9%-2.5%) to 2.5% (1.6%-3.4%), social-emotional-behavioural difficulties: 1.9% (1.1%-2.7%) to 2.8% (2.1%-3.5%), and well-being: 1.8% (0.9%-2.7%) to 2.2% (1.4%-3.0%). Better student-rated school climate analysed as time-varying at the student- and school-level was associated with lower risk of depression (regression coefficient (95%CI) student-level: -4.25 (-4.48,-4.01), school-level: -4.28 (-5.81,-2.75)), fewer social-emotional-behavioural difficulties (student-level: -2.46 (-2.57,-2.35), school-level: -2.36 (-3.08,-1.63)), and higher well-being (student-level: 3.88 (3.70,4.05); school-level: 4.28 (3.17,5.38)), which was a stable relationship.

CONCLUSION: Student-rated school climate predicted mental health in early adolescence. Policy and system interventions that focus on school climate may promote students’ mental health.

PMID:37866473 | DOI:10.1016/j.jaac.2023.10.004

J Heart Lung Transplant. 2023 Oct 20:S1053-2498(23)02078-8. doi: 10.1016/j.healun.2023.10.014. Online ahead of print.

ABSTRACT

OBJECTIVE: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and mid-term outcomes of lung transplant recipients of HCV NAT+ donor allografts.

METHODS: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity-score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by one year, early (30-day and in-hospital) mortality and both 1- and 3-year survival were compared between matched groups.

RESULTS: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%), and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, P<0.001), more often female (44% vs 39%, P<0.01) and more commonly died due to drug intoxication (56% vs 15%, P<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, P=0.69) and female gender (43% vs 39%, P=0.15) but had lower lung allocation scores (38 vs 41, P<0.001) compared to others. Rates of acute rejection (13% vs 17%, P=0.09), early mortality (30-day: 2% vs 1%, P=0.59, in-hospital: 3% vs 4%, P=0.38) as well as 1- (90% vs 92%, P=0.29) and 3-year survival (69% vs 75%, P=0.13) were not significantly different between matched groups.

CONCLUSIONS: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

PMID:37866469 | DOI:10.1016/j.healun.2023.10.014

J Am Acad Dermatol. 2023 Oct 20:S0190-9622(23)03029-3. doi: 10.1016/j.jaad.2023.10.026. Online ahead of print.

ABSTRACT

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor.

OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD).

METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included percentage change in the Eczema Area and Severity Index (EASI) from baseline; EASI improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline.

RESULTS: TEAEs were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in EASI vs. placebo (-65% vs. -27%, P=0.014). Other key secondary physician- and patient-reported end points were met.

LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients.

CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements vs. placebo.

PMID:37866456 | DOI:10.1016/j.jaad.2023.10.026