bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of meconium-stained amniotic fluid among laboring mother in Ethiopia, systematic review and meta-analysis
Authors: Gashaw Anteneh , Adamu Yayeh , Sime Yohanes , Destaw Belete
Published: July 2024

Background

Meconium-stained amniotic fluid (MSAF) occurs during childbirth when the amniotic fluid carries traces of meconium, the initial stool passed by a newborn. Often signaling fetal distress, MSAF is linked to heightened risks for both the mother and the newborn. In Ethiopia, there is insufficient attention given to this condition. Despite varied study results indicating a considerable range in MSAF occurrences, there is an absence of a comprehensive national overview. Therefore, this systematic review and meta-analysis aim to evaluate the aggregated prevalence of meconium-stained amniotic fluid among laboring mothers and its influencing factors in Ethiopia, providing a consolidated understanding for healthcare strategies and policies.

Method

Following PRISMA guidelines, a systematic review and meta-analysis were executed. Extensive literature searches were conducted on PubMed, Google Scholar, and African Online Journal databases. The pooled prevalence was estimated using a weighted inverse variance random effect model. Heterogeneity among studies was evaluated through Cochrane Q-test and I2 statistics. To assess publication bias, a funnel plot and Egger's test were performed. The identification of factors associated with meconium-stained amniotic fluid among laboring mothers in Ethiopia was conducted using Stata v 18 software.

Result

In total, 63 articles were initially identified, and ultimately, four articles were deemed suitable for inclusion in this review. The combined prevalence of meconium-stained amniotic fluid among laboring mothers in Ethiopia was determined to be 20% (95% CI: 14%–25%). Upon conducting subgroup analysis, it was revealed that the prevalence of meconium-stained amniotic fluid was highest in the Oromia region and lowest in Addis Ababa. Notably, pregnancies complicated by pregnancy-induced hypertension disorder showed a significant association with the presence of meconium-stained amniotic fluid, with an odds ratio of 6.21 (95% CI: 4.04–8.38).

Conclusion

In conclusion, this review emphasizes the common occurrence of meconium-stained amniotic fluid (MSAF). Notably, it identifies a significant association between pregnancy complicated by hypertension and the presence of MSAF. This underscores the need for targeted interventions to reduce MSAF incidence and mitigate associated adverse outcomes in the Ethiopian.

Systematic Review Registration

http://www.library.ucsf.edu/, (CRD42023491725).
Sodium levels and immunotherapy efficacy in mRCC patients with bone metastases: sub analysis of Meet-Uro 15 study
Authors: Catalano Martina , Rebuzzi Sara Elena , Maruzzo Marco , De Giorgi Ugo , Buti Sebastiano , Galli Luca , Fornarini Giuseppe , Zucali Paolo Andrea , Claps Melanie , Chiellino Silvia , Zampiva Ilaria , Pipitone Stefania , Ricotta Riccardo , Sorarù Mariella , Mollica Veronica , Tudini Marianna , Fratino Lucia , Prati Veronica , Caffo Orazio , Atzori Francesco , Morelli Franco , Prati Giuseppe , Nolè Franco , Vignani Francesca , Cavo Alessia , Di Napoli Marilena , Malgeri Andrea , Naglieri Emanuele , Signori Alessio , Banna Giuseppe Luigi , Rescigno Pasquale , Cerbone Linda , Antonuzzo Lorenzo , Roviello Giandomenico
Published: July 2024

Background

Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy.

Materials and methods

This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed.

Results

Among 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels ≥140 mEq/L were associated with improved PFS (9.6 vs. 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels ≥140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels.

Conclusion

Elevated sodium levels (≥140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings.
A strategy to reconstitute immunity without GVHD via adoptive allogeneic Tscm therapy
Authors: Guan Liping , Sun Yunqin , Si Yanli , Yan Qingya , Han Ziyu , Liu Youxun , Han Tao
Published: July 2024

Introduction

Adoption of allogeneic T cells directly supplements the number of T cells and rapidly induces T-cell immunity, which has good efficacy for treating some tumors and immunodeficiency diseases. However, poor adoptive T-cell engraftment and graft-versus-host disease (GVHD) limit the application of these methods. Alloreactive T-cell clones were eliminated from the donor T-cell repertoire, and the remaining T-cell clones were prepared as Tscm for T-cell adoptive treatment to reconstruct recipient T-cell immunity without GVHD.

Methods

The subjects in this study included three different strains of mice. Lymphocytes from mice (C57BL/6) were used as the donor T-cell repertoire, from which the Tscm allo-reactive T cell clone was depleted (ATD-Tscm). This was confirmed by showing that the Tscm was not responsive to the alloantigen of the recipient (BALB/c). To prepare ATD-Tscm cells, we used recipient lymphocytes as a simulator, and coculture of mouse and recipient lymphocytes was carried out for 7 days. Sorting of non-proliferative cells ensured that the prepared Tscm cells were nonresponsive. The sorted lymphocytes underwent further expansion by treatment with TWS119 and cytokines for an additional 10 days, after which the number of ATD-Tscm cells increased. The prepared Tscm cells were transferred into recipient mice to observe immune reconstitution and GVHD incidence.

Results

Our protocol began with the use of 1×107 donor lymphocytes and resulted in 1 ×107 ATD-Tscm cells after 17 days of preparation. The prepared ATD-Tscm cells exhibited a nonresponse upon restimulation of the recipient lymphocytes. Importantly, the prepared ATD-Tscm cells were able to bind long and reconstitute other T-cell subsets in vivo, effectively recognizing and answering the “foreign” antigen without causing GVHD after they were transferred into the recipients.

Discussion

Our strategy was succeeded to prepare ATD-Tscm cells from the donor T-cell repertoire. The prepared ATD-Tscm cells were able to reconstitute the immune system and prevent GVHD after transferred to the recipients. This study provides a good reference for generating ATD-Tscm for T-cell adoptive immunotherapy.
Novel vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma
Authors: Azzi Lorenzo , Celesti Fabrizio , Chiaravalli Anna Maria , Shaik Amruth Kaleem Basha , Shallak Mariam , Gatta Andrea , Battaglia Paolo , La Rosa Stefano , Tagliabue Angelo , Accolla Roberto Sergio , Forlani Greta
Published: July 2024

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%. Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA). Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells. Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4+ and CD8+ T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor.
Microglia targeting by adeno-associated viral vectors
Authors: Stamataki Maria , Rissiek Björn , Magnus Tim , Körbelin Jakob
Published: July 2024

Microglia play a crucial role in maintaining homeostasis of the central nervous system and they are actively involved in shaping the brain’s inflammatory response to stress. Among the multitude of involved molecules, purinergic receptors and enzymes are of special importance due to their ability to regulate microglia activation. By investigating the mechanisms underlying microglial responses and dysregulation, researchers can develop more precise interventions to modulate microglial behavior and alleviate neuroinflammatory processes. Studying gene function selectively in microglia, however, remains technically challenging. This review article provides an overview of adeno-associated virus (AAV)-based microglia targeting approaches, discussing potential prospects for refining these approaches to improve both specificity and effectiveness and encouraging future investigations aimed at connecting the potential of AAV-mediated microglial targeting for therapeutic benefit in neurological disorders.
A Ménage à trois: NLRC5, immunity, and metabolism
Authors: Brunschwiler Fabienne , Nakka Surender , Guerra Jessica , Guarda Greta
Published: July 2024

The nucleotide-binding and oligomerization domain-like receptors (NLRs) NLR family CARD domain-containing protein 5 (NLRC5) and Class II Major Histocompatibility Complex Transactivator (CIITA) are transcriptional regulators of major histocompatibility complex (MHC) class I and class II genes, respectively. MHC molecules are central players in our immune system, allowing the detection of hazardous ‘non-self’ antigens and, thus, the recognition and elimination of infected or transformed cells from the organism. Recently, CIITA and NLRC5 have emerged as regulators of selected genes of the butyrophilin (BTN) family that interestingly are located in the extended MHC locus. BTNs are transmembrane proteins exhibiting structural similarities to B7 family co-modulatory molecules. The family member BTN2A2, which indeed contributes to the control of T cell activation, was found to be transcriptionally regulated by CIITA. NLRC5 emerged instead as an important regulator of the BTN3A1, BTN3A2, and BTN3A3 genes. Together with BTN2A1, BTN3As regulate non-conventional Vγ9Vδ2 T cell responses triggered by selected metabolites of microbial origin or accumulating in hematologic cancer cells. Even if endogenous metabolites conform to the canonical definition of ‘self’, metabolically abnormal cells can represent a danger for the organism and should be recognized and controlled by immune system cells. Collectively, new data on the role of NLRC5 in the expression of BTN3As link the mechanisms regulating canonical ‘non-self’ presentation and those marking cells with abnormal metabolic configurations for immune recognition, an evolutionary parallel that we discuss in this perspective review.
Implications of MHC-restricted immunopeptidome in transplantation
Authors: Zhanzak Zhuldyz , Cina Davide , Johnson Aileen C. , Larsen Christian P.
Published: July 2024

The peptide presentation by donor and recipient major histocompatibility complex (MHC) molecules is the major driver of T-cell responses in transplantation. In this review, we address an emerging area of interest, the application of immunopeptidome in transplantation, and describe the potential opportunities that exist to use peptides for targeting alloreactive T cells. The immunopeptidome, the set of peptides presented on an individual’s MHC, plays a key role in immune surveillance. In transplantation, the immunopeptidome is heavily influenced by MHC-derived peptides, delineating a key subset of the diverse peptide repertoire implicated in alloreactivity. A better understanding of the immunopeptidome in transplantation has the potential to open up new approaches to identify, characterize, longitudinally quantify, and therapeutically target donor-specific T cells and ultimately support more personalized immunotherapies to prevent rejection and promote allograft tolerance.
Deep learning-enabled classification of kidney allograft rejection on whole slide histopathologic images
Authors: Ye Yongrong , Xia Liubing , Yang Shicong , Luo You , Tang Zuofu , Li Yuanqing , Han Lanqing , Xie Hanbin , Ren Yong , Na Ning
Published: July 2024

Background

Diagnosis of kidney transplant rejection currently relies on manual histopathological assessment, which is subjective and susceptible to inter-observer variability, leading to limited reproducibility. We aim to develop a deep learning system for automated assessment of whole-slide images (WSIs) from kidney allograft biopsies to enable detection and subtyping of rejection and to predict the prognosis of rejection.

Method

We collected H&E-stained WSIs of kidney allograft biopsies at 400x magnification from January 2015 to September 2023 at two hospitals. These biopsy specimens were classified as T cell-mediated rejection, antibody-mediated rejection, and other lesions based on the consensus reached by two experienced transplant pathologists. To achieve feature extraction, feature aggregation, and global classification, we employed multi-instance learning and common convolution neural networks (CNNs). The performance of the developed models was evaluated using various metrics, including confusion matrix, receiver operating characteristic curves, the area under the curve (AUC), classification map, heat map, and pathologist-machine confrontations.

Results

In total, 906 WSIs from 302 kidney allograft biopsies were included for analysis. The model based on multi-instance learning enables detection and subtyping of rejection, named renal rejection artificial intelligence model (RRAIM), with the overall 3-category AUC of 0.798 in the independent test set, which is superior to that of three transplant pathologists under nearly routine assessment conditions. Moreover, the prognosis models accurately predicted graft loss within 1 year following rejection and treatment response for rejection, achieving AUC of 0.936 and 0.756, respectively.

Conclusion

We first developed deep-learning models utilizing multi-instance learning for the detection and subtyping of rejection and prediction of rejection prognosis in kidney allograft biopsies. These models performed well and may be useful in assisting the pathological diagnosis.
Droughts and deluges: changes in river discharge and the carbonate chemistry of an urbanized temperate estuary
Authors: Barrett Lauren J. , Vlahos Penny , McGuinness Mary A. , Whitney Michael M. , Vaudrey Jamie M.P.
Published: July 2024

Long Island Sound (LIS) is a highly urbanized estuary that receives high inputs of nitrogen pollution leading to summertime hypoxia in the bottom waters of its western region. Though LIS hypoxia has been well-studied for decades, there is a paucity of information regarding eutrophication-induced acidification due to the challenges of obtaining high-precision observations of the marine carbonate system. In this work, we established a time-series of carbon dioxide (CO2) system observations in LIS through measurements of dissolved inorganic carbon (DIC) and total alkalinity (TA) during thirteen sampling events between March 2020 and August 2022. This time span captured both seasonal and interannual variation, including the contrast between two historic drought years (2020 and 2022) and one high-freshwater flow year with significant tropical storm activity (2021). Observations revealed reduced acidification in western LIS (WLIS) (minimum aragonite saturation state, Ωar > 1.5) during the high-river discharge summer of 2021, corresponding to a decrease in the DIC/TA ratio of the Housatonic River. By contrast, LIS bottom water DIC and DIC/TA were higher during the drought summers of 2020 and 2022 (bottom DIC/TA = 0.9-1.0 and 0.85-0.9 in 2020 and 2021, respectively), leading to more acidified conditions and persistent aragonite undersaturation (minimum Ωar <1.0 and 1.1 in 2020 and 2022, respectively). Increased river discharge mitigated respiration-induced acidification in WLIS, likely due to a combination of decreased estuarine residence time and reduced riverine DIC/TA. These results motivate future studies of the carbonate chemistry of LIS and its freshwater endmembers in relation to hypoxia dynamics, with consideration of climate related shifts in physical and biological dynamics of the estuary with time.
A longitudinal behavioral analysis of aquarium whale sharks (Rhincodon typus): insights into anticipatory cues, individual variation, and social interaction
Authors: Gallimore Connor G. , Walton Celeste , Nugent Richard , Fradkin Maury , Poppell Laurie , Schreiber Christian , Coco Christopher , Grober Matthew , Carlson Bruce , Dove Alistair D. M. , Black Michael P.
Published: July 2024

Rhincodon typus, or the whale shark, is the largest extant fish in the world and is classified as endangered on the IUCN’s Red List. Due to their enormous size and conservation status, whale sharks are rarely housed in aquaria. Here we present a behavioral analysis culminating from a large effort by 89 observers from 2008–2012 to study four R. typus (ID codes: AL, TA, TR, YU) longitudinally in an aquarium setting. We found that relatively simple behavioral metrics such as swim speed, depth occupation, swimming direction, and lead-follow interactions demonstrated R. typus individual variation and responses to habitat changes. All sharks displayed increased swim speeds 30-minutes before regimented feed times, when there was scent of food being fed to other animals in the habitat. Consistently in the habitat, one male shark (YU) was recorded swimming more at depth, faster, almost exclusively clockwise, and engaged in fewer close proximity interactions with others than expected by chance. In contrast, a larger female shark (AL) was observed swimming the slowest, at the surface more than others, led other sharks more than she followed, and had strong lead-follow interactions with another shark of the opposite sex (TA). TA and TR did not differ from each other in depth profiles or speed, but did differ in their proclivity to lead or follow. Depth preferences and lead-follow interactions suggest some partitioning of the habitat and the possibility of social hierarchy in this species. These results represent the first longitudinal behavioral analysis of aquarium R. typus, offering meaningful similarities and contrasts to field observations.
Kinetic isotope effect of decomposing fatty acids in the continental shelf sediment of the northern South China Sea
Authors: Wang Tengteng , Lin Chuhan , Zhang Han , Li Jiying , Wang Lifang , Luo Yaohua , Liu Jie , Shen Jiaheng , Tang Tiantian
Published: July 2024

As a response of the coastal oceans to more severe anthropogenic disturbance, increasing coastal primary production has been more frequently observed in recent years. This raises the question of how this progressive change reshapes the long-term carbon sequestration in the coastal oceans. With this question in mind, we investigated the sediment organic matter (OM) preserved on the shelf of the northern South China Sea (NSCS) where high primary production has been observed. Across this sediment core, relatively low total organic carbon content of around 0.60% was observed. Fatty acids with less carbon numbers exhibit exponential decreases downward with degradation rate constants ranging from 0.10 to 0.17 y-1, no matter they were from single sources (14:0 presumably from marine OM and ai-15:0, i-15:0, 15:0 from bacterial OM) or mixed sources (16:0). Meanwhile fatty acids with more carbon numbers, either 18:0 and 24:0 from mixed sources, or 26:0 and 28:0 presumably from terrestrial input, were less varied in concentrations with depth. This demonstrates a preferential decomposition of labile fatty acids during the early diagenesis of coastal sediment organic matter. A decrease of labile fatty acids δ13C values was observed with the decomposition, from which kinetic isotope fractionations were predicted ranging from 0.7 to 1.5‰. This provides an isotopic constraint of the mixing model to quantify labile organic matter from terrestrial input and local phytoplankton production, from which declined contribution of local phytoplankton production to labile fatty acids was identified in more recent sediment. This finding together with the low organic carbon content and rapid removal of fatty acids in the top sediment, demonstrates the poor preservation of labile organic matter on the shelf of NSCS, implying that the increasing primary production has not enhanced the coastal carbon sequestration yet, but rather leads to more intensified respiration with a potential risk to increase the CO2 outgassing from the coastal oceans.
Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
Authors: Hernandez-Morfa Mirelys , Reinoso-Vizcaino Nicolas M. , Zappia Victoria E. , Olivero Nadia B. , Cortes Paulo R. , Stempin Cinthia C. , Perez Daniel R. , Echenique Jose
Published: July 2024

Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.
Occlusion dysfunction and Alzheimer’s disease: Mendelian randomization study
Authors: Wang Qing , Zhen Wenyu , Hu Rui , Wang Zifei , Sun Yuqiang , Sun Wansu , Huang Chunxia , Xu Jianguang , Zhang Hengguo
Published: July 2024

Aim

Occlusion dysfunction (OD) is increasingly linked to Alzheimer’s disease (AD). This study aimed to elucidate the causal relationship between OD and AD using Mendelian randomization (MR) analysis.

Materials and methods

Genome-wide association study (GWAS) meta-analysis data obtained from FinnGen, IEU Open GWAS, and UK Biobank (UKBB) was represented as instrumental variables. We validated the causal relationship between periodontal disease (PD), loose teeth (PD & occlusion dysfunction), dentures restoration (occlusion recovery), and AD.

Results

According to the MR analysis, PD and AD have no direct causal relationship (P = 0.395, IVW). However, loose teeth significantly increased the risk of AD progression (P = 0.017, IVW, OR = 187.3567, 95%CI = 2.54E+00−1.38E+04). These findings were further supported by the negative causal relationship between dentures restoration and AD (P = 0.015, IVW, OR = 0.0234, 95%CI = 1.13E-03−0.485).

Conclusion

The occlusion dysfunction can ultimately induce Alzheimer’s disease. Occlusion function was a potentially protective factor for maintaining neurological health.
Prevalence of wasting and associated factors among children aged 6–59 months in Habro district, Eastern Ethiopia: a cross-sectional study
Authors: Tilahun Sileshi , Roba Kedir Teji , Roba Hirbo Shore , Nure Jemal Ahmed , Sosengo Teshome , Ayele Behailu Hawulte , Maruta Melat B. , Debella Adera , Eyeberu Addis , Mussa Ibsa
Published: July 2024

Background

Globally, five million children under the age of five died in 2021. Asia and African countries contributed to 69% and 27.2% of wasting, respectively. In Ethiopia, out of 901 (10.1%) under-five children, 632 (8.1%) were found to be moderately wasted, and 269 (3.0%) were severely wasted. The purpose of this study was to assess the prevalence of wasting and its associated factors among children between the ages of 6 and 59 months in Habro Woreda, Oromia, Eastern Ethiopia.

Methods

A community-based cross-sectional study was conducted in Habro Woreda from 25 August to 20 September 2020. In total, 306 participants were included in this study through a systematic sampling technique. Data were collected using a pretested structured questionnaire through a face-to-face interview, entered into EpiData version 3.1, and analyzed using SPSS version 25. Predictors were assessed using a multivariate logistic regression analysis model and reported using an adjusted odds ratio (AOR) with a 95% confidence interval (CI). Statistical significance was set at p < 0.05.

Results

Overall, the prevalence of wasting among children aged 6–59 months in the Habro district was 28%, with a 95% confidence interval [26.5, 32.2%]. Factors such as mothers illiterate [AOR = 3.4; 95% CI: 1.14–10.47], households without latrines [AOR = 2.91; 95% CI: 1.33–6.37], food-insecure households [AOR = 4.11; 95% CI: 1.87–9], households that did not receive home visits [AOR = 4.2; 95% CI: 1.92–9.15], did not eat a variety of food [AOR = 7.44; 95% CI: 2.58–21.45], sick children after discharge from the program [AOR = 6.55; 95% CI: 2.85–15.02], readmitted children [AOR = 3.98; 95% CI: 1.43–15.07], and wasting 3.42 [AOR = 3.42; 95% CI: 1.24–9.45] were factors statistically associated with outcome variables.

Conclusion

This study noted that the prevalence of wasting among children aged 6–59 months following discharge from the Outpatient Therapeutic Program remains high. Educational status of the mother, availability of a latrine, separate kitchen in the household, household food insecurity, household dietary diversity, home visit, and admission type were significantly associated with wasting of children after discharge from the outpatient therapeutic program. Therefore, efforts that target these factors should be maximized to reduce the occurrence of wasting among children aged 6–59 months after discharge from the outpatient therapeutic program.
Assessing the predictive value of the controlling nutritional status score on all-cause mortality during hospitalization in patients with acute decompensated heart failure: a retrospective cohort study from Jiangxi, China
Authors: Huang Xin , Qiu Jiajun , Kuang Maobin , Wang Chao , He Shiming , Yu Changhui , Xie Guobo , Sheng Guotai , Zou Yang
Published: July 2024

Objective

Nutritional status is closely associated with the prognosis of heart failure. This study aims to assess the relationship between the Controlling Nutritional Status (CONUT) score and in-hospital mortality among patients with acute decompensated heart failure (ADHF) in Jiangxi, China.

Methods

A retrospective cohort study was conducted. Multivariable Cox regression models and restricted cubic spline regression were employed to evaluate the relationship between the CONUT score and in-hospital mortality in ADHF patients from Jiangxi, China. The predictive value of the CONUT score for in-hospital mortality in ADHF patients was analyzed using receiver operating characteristic curves. Subgroup analyses were performed to identify risk dependencies of the CONUT score in specific populations.

Results

The study included 1,230 ADHF patients, among whom 44 (3.58%) mortality events were recorded. After adjusting for confounding factors, a positive correlation was found between the CONUT score and the risk of in-hospital mortality in ADHF patients. Restricted cubic spline regression analysis indicated a non-linear relationship between the CONUT score and the risk of in-hospital mortality in ADHF patients, estimating a rapid increase in mortality risk when the CONUT score exceeded 5. Receiver operating characteristic analysis demonstrated a good predictive value of the CONUT score for all-cause mortality events in ADHF patients [area under the curve = 0.7625, optimal threshold = 5.5]. Additionally, a relatively higher risk associated with the CONUT score was observed in male patients and those with concomitant cerebral infarction.

Conclusion

This study reveals a positive correlation between the CONUT score and the risk of in-hospital mortality in ADHF patients. Based on the findings of this study, we recommend maintaining a CONUT score below 5 for patients with ADHF in Jiangxi, China, as it may significantly contribute to reducing the risk of in-hospital all-cause mortality.
A novel bioaccessibility-based probabilistic risks assessment of potentially toxic elements (PTEs) in earthworm
Authors: Zuo Tian-Tian , Liu Jia-Lin , Jin Hong-Yu , Chang Yan , Wei Feng , Wei Sheng , Kang Shuai , Ma Shuang-Cheng
Published: July 2024

Graphical Abstract

Probabilistic risk assessment strategy of potentially toxic elements in earthworms based on bioaccessibility and MCS technique.
Inhibition of NNMT enhances drug sensitivity in lung cancer cells through mediation of autophagy
Authors: Wang Jian , Zhang Ming , You Xin , Xu Yang , Zhang Congcong , Li Ying , Yang Chunhui , Wang Qi
Published: July 2024

Introduction

This study aimed to investigate the role of Nicotinamide N-methyltransferase (NNMT) in the drug sensitivity of non-small cell lung cancer (NSCLC) cells, with a focus on its impact on autophagy and resistance to the chemotherapeutic agent osimertinib. The study hypothesized that NNMT knockdown would enhance drug sensitivity by modifying autophagic processes, providing a potential new therapeutic target for overcoming chemoresistance in lung cancer.

Methods

Proteomic analysis was utilized to identify changes in protein expression following NNMT knockdown in H1975 and H1975 osimertinib resistance (H1975OR) lung cancer cell lines. Gene expression patterns and their correlation with NNMT expression in lung cancer patients were analyzed using The Cancer Genome Atlas (TCGA) dataset. Additionally, a predictive model for lung cancer survival was developed via lasso regression analysis based on NNMT-associated gene expression. Drug sensitivity was assessed using the IC50 values and apoptosis ratio, and autophagy was evaluated through Western blot and flow cytometric analysis.

Results

Significant variations in the expression of 1,182 proteins were observed following NNMT knockdown, with a significant association with autophagy-related genes. Analysis of gene expression patterns unveiled a significant correlation between NNMT expression and specific changes in gene expression in lung cancer. The predictive model successfully forecasted lung cancer patient survival outcomes, highlighting the potential of NNMT-associated genes in predicting patient survival. Knockdown of NNMT reversed osimertinib resistance in H1975 cells, as evidenced by altered IC50 values and apoptosis ratio, and changes were observed in autophagy markers.

Discussion

Knockdown of NNMT in lung cancer cells enhances drug sensitivity by modulating autophagy, providing a promising therapeutic target to overcome chemoresistance in NSCLC. The study underscores the importance of NNMT in lung cancer pathology and underscores its potential as a predictive marker for clinical outcomes. Additionally, the developed predictive model further supports the clinical relevance of NNMT-associated gene expression in improving the prognosis of lung cancer patients.
PTGES2 and RNASET2 identified as novel potential biomarkers and therapeutic targets for basal cell carcinoma: insights from proteome-wide mendelian randomization, colocalization, and MR-PheWAS analyses
Authors: Han Qiu-Ju , Zhu Yi-Pan , Sun Jing , Ding Xin-Yu , Wang Xiuyu , Zhang Qiang-Zhe
Published: July 2024

Introduction

Basal cell carcinoma (BCC) is the most common skin cancer, lacking reliable biomarkers or therapeutic targets for effective treatment. Genome-wide association studies (GWAS) can aid in identifying drug targets, repurposing existing drugs, predicting clinical trial side effects, and reclassifying patients in clinical utility. Hence, the present study investigates the association between plasma proteins and skin cancer to identify effective biomarkers and therapeutic targets for BCC.

Methods

Proteome-wide mendelian randomization was performed using inverse-variance-weight and Wald Ratio methods, leveraging 1 Mb cis protein quantitative trait loci (cis-pQTLs) in the UK Biobank Pharma Proteomics Project (UKB-PPP) and the deCODE Health Study, to determine the causal relationship between plasma proteins and skin cancer and its subtypes in the FinnGen R10 study and the SAIGE database of Lee lab. Significant association with skin cancer and its subtypes was defined as a false discovery rate (FDR) < 0.05. pQTL to GWAS colocalization analysis was executed using a Bayesian model to evaluate five exclusive hypotheses. Strong colocalization evidence was defined as a posterior probability for shared causal variants (PP.H4) of ≥0.85. Mendelian randomization-Phenome-wide association studies (MR-PheWAS) were used to evaluate potential biomarkers and therapeutic targets for skin cancer and its subtypes within a phenome-wide human disease category.

Results

PTGES2, RNASET2, SF3B4, STX8, ENO2, and HS3ST3B1 (besides RNASET2, five other plasma proteins were previously unknown in expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL)) were significantly associated with BCC after FDR correction in the UKB-PPP and deCODE studies. Reverse MR showed no association between BCC and these proteins. PTGES2 and RNASET2 exhibited strong evidence of colocalization with BCC based on a posterior probability PP.H4 >0.92. Furthermore, MR-PheWAS analysis showed that BCC was the most significant phenotype associated with PTGES2 and RNASET2 among 2,408 phenotypes in the FinnGen R10 study. Therefore, PTGES2 and RNASET2 are highlighted as effective biomarkers and therapeutic targets for BCC within the phenome-wide human disease category.

Conclusion

The study identifies PTGES2 and RNASET2 plasma proteins as novel, reliable biomarkers and therapeutic targets for BCC, suggesting more effective clinical application strategies for patients.
The impact of school closures during the COVID-19 pandemic on reading fluency among second grade students: socioeconomic and gender perspectives
Authors: Shaul Shelley , Lipka Orly , Tal-Cohen Dana , Bufman Adi , Dotan Shahar
Published: July 2024

Introduction

The acquisition of reading skills is a crucial milestone in early education, with formal instruction and practice playing pivotal roles. The outbreak of COVID-19 led to widespread school closures and a shift to remote learning.

Methods

This study aimed to investigate the effects of school closures on reading acquisition and fluency among a large sample of second-grade children, considering socioeconomic status (SES) and gender differences. In 2019, a cohort of 2228 second-grade students from 34 schools was assessed for word reading fluency and comprehension. In 2020, during the pandemic, 765 students from a subsample of 20 original schools were re-evaluated using the same measures. The study also collected school-related data.

Results

The findings from the entire sample indicated no significant differences in fluency and comprehension scores between children in the second grade in 2019 and 2020. However, a significant interaction emerged when analyzing low SES versus high SES children. Children from low SES backgrounds exhibited notably lower reading scores after a year of remote learning due to the COVID-19 outbreak. Moreover, the disparity in reading scores between low SES and high SES children nearly doubled in 2020. Gender differences were also detected.

Discussion

These results underscore the impact of remote learning during the COVID-19 crisis on exacerbating gaps in reading fluency and comprehension between children from high and low SES backgrounds. The implications of these findings highlight the critical role of in-person schooling and targeted support for disadvantaged students, especially during pivotal stages of reading development.
Development and validation of the self-consciousness type scale
Authors: Lee Jiye , Baek Hyemi , Oh Eunjee , Kim Jin-young , Ko Young-gun
Published: July 2024

Introduction

Previous research has highlighted the duality of self-consciousness, which simultaneously plays adaptive and maladaptive roles. This study aims to develop a measure that categorically distinguishes between different types of self-consciousness styles based on the Regulatory Focus Theory (RFT) and examines their relationship with mental health-related indicators.

Methods

Data were gathered through an online mental health survey conducted at a University Student Counseling Center in Seoul. The study involved exploratory factor analysis, confirmatory factor analysis, and reliability and validity analysis, which resulted in the development of a 14-question Self-Consciousness Type Scale (SCTS).

Results

Both exploratory and confirmatory factor analyses validated the two-factor structure of the SCTS. The fit indices of the final model indicated a good fit, with high internal consistency for both sub-factors. Convergent and discriminant validity were confirmed through correlations between the sub-scales. Cluster analysis identified four distinct subtypes of self-consciousness styles: Growth-oriented, Defensive, Ambivalent, and Low-focus self-consciousness. Group difference analysis revealed significant differences in mental health-related variables among the subtypes, supporting the 2 × 2 model of prevention-focused and promotion-focused self-consciousness.

Discussion

The findings support the SCTS as a valid measurement tool capable of distinguishing four distinct types of self-consciousness, aligning with the multidimensional model of self-consciousness. The study’s limitations and implications were discussed based on the results, emphasizing the potential applications of the SCTS in mental health research and practice.
The relationship between family-school socioeconomic status match and adolescent aggressive behavior
Authors: Lu Furong , Wang Yuyu , Wu Xinru
Published: July 2024

The objective of the present study was to analyze the effect of the match between family and school socioeconomic status (SES) on adolescents’ aggressive behaviors. Additionally, the moderating roles of gender and the parent–child relationship were examined. A total of 2,823 adolescents completed the Aggressive Behavior Scale, the Parent–Child Relationship Scale, and the Family SES Scale. School SES was measured by the average family SES of all students in the school. SES was categorized as high or low based on one standard deviation above or below the mean. The results showed that when there was a match between family and school SES, adolescents with “Low Family-Low School” SES exhibited more aggressive behaviors compared to those with “High Family-High School” SES. When there was a mismatch between family and school SES, adolescents with “High Family-Low School” SES exhibited higher levels of aggressive behaviors than those with “Low Family-High School” SES. Gender did not moderate these effects. Furthermore, when the parent–child relationship was poor, adolescents exhibited higher levels of aggressive behaviors when family SES exceeded school SES. Conversely, the effects of family and school SES on aggressive behavior were not significant when the parent–child relationship was strong. The present study highlights that the match and mismatch between family and school SES significantly influence adolescents’ aggressive behaviors and that a strong parent–child relationship has a protective effect.
PROD-ALERT 2: replicating and extending psychiatric restraint open data analysis using logarithmic estimates of reporting trends
Authors: Reid Keith S. , Price Owen
Published: July 2024

Care, management, and statute each mandate restraint-reporting in psychiatric settings in England. PROD-ALERT in this journal (“PA1”) correlated log incidence of restraint, log institutional size, and log detention. The period was September 2020 to August 2021. It showed a clear trend among reporters. Restraint correlated with institutional size and use of legal detention. Some large detaining providers reported no restraints per month despite that trend. Inference from size suggested that non-complete reporters restrained 1,774 people per month. This paper “PA2” develops analysis repeating it for September 2021 to August 2022. PA2 shows how to count L-information, i.e., questionable information, added by null reports, by applying an L-test to data sets. PA2 uses illustrative vignettes about human height to ground L-information scores from English restraint reporting. In PA2, reported restraint again correlates with size and detention as in PA1. PA2 shows evolving data. Providers still follow a trend in restraint by size and detention. Providers which newly report restraint are on trend. Inference suggests that non-complete reporters restrained 1,305 people per month (536–3233), 95% CI, a large but reduced number since PA1. English restraint data have an L-test L-information score of increase in information by a factor of L = 145. This is as surprising as claiming that an average English man of 1.72 m is 2.64 m tall. Persons restrained per month is a robust measure continuing to log-correlate with size and legal compulsion. Providers over a certain size who report null restraint probably have some. Restraint remains underreported in England. Imputation of incomplete reporters shows a large shrinking cohort of patients detained by incomplete reporters. Knowledge of this may promote reporting. Improved reporting, and the infrastructure and integrity it demands, may help providers measure and reduce restraint. PA1 remains unrefuted. L-test can measure L-information in intuitively representable ways. The informational effect of nulls on the reliable data set is similar to a claim that an average-heighted man is as tall as people with clinical gigantism.
Evaluating the safety and efficacy of zuranolone in the management of major depressive disorder and postpartum depression, with or without concurrent insomnia: a rigorous systematic review and meta-analysis
Authors: Raja Adarsh , Ahmed Saboor , Basit Ali Siddiqui Muhammad , Lamiya Mir Syeda , Kumar Rakesh , Ahmed Muhammad , Raja Sandesh , Bin Amin Shafin , Alim Ur Rahman Hafsah , Deepak Fnu , Asghar Muhammad Sohaib
Published: July 2024

Introduction

Major depressive disorder (MDD), postpartum depression (PPD), and insomnia are neuropsychological conditions in which zuranolone is used to improve symptoms and prognosis of the disorder. This meta-analysis aimed to determine the efficacy of zuranolone in comparison to other drugs used for treating these conditions.

Methods

This meta-analysis included patients aged between 18 and 75 years who were diagnosed with major depressive disorder and postpartum depression with or without insomnia and were administered zuranolone for treatment. Only randomized controlled trials (RCTs) were included, and animal studies were excluded. The databases used were PubMed, Scopus, Cochrane, and Clinicaltrials.gov, with MeSH terms and relevant keywords for (Zuranolone) and (Depression). The Cochrane risk of bias tool was used for quality assessment.

Results

The meta-analysis included eight RCTs that analyzed data from 2031 patients. The meta-analysis revealed statistically significant changes in the Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and treatment-emergent adverse effects (TEAE) scores in the PPD subgroup. HAM-D and TEAEs scores were also significant in the MDD subgroup, but the changes in the MADRS, HAM-A, and Bech-6 scores were insignificant. Serious adverse events were insignificant in all subgroups.

Conclusion

Meta-analysis found a significant improvement in depressive symptoms with zuranolone treatment, especially on day 15. This suggests that zuranolone is a promising therapeutic option for patients with MDD and PPD with or without insomnia.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459554, identifier CRD42023459554.