bluuebunny/crossref_metadata_2025 huggingface dataset:
WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway
Authors: Zhang Xuyang , Sun Kairui , Gan Ruihuan , Yan Yuxiang , Zhang Chaochao , Zheng Dali , Lu Youguang
Published: May 2024

Background

5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection.

Methods

5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy.

Results

In this study, the WNT/β-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells.

Conclusions

These data underscored the activation of the WNT/β-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.
Correlation of gasdermin B staining patterns with prognosis, progression, and immune response in colorectal cancer
Authors: Sun Liang , Wang Jiahui , Li Yuxuan , Kang Yixin , Jiang Yi , Zhang Jun , Qian Senmi , Xu Fangying
Published: May 2024

Background

Pyroptosis is a type of programmed cell death mediated by the gasdermin family. Gasdermin B (GSDMB), as a member of gasdermin family, can promote the occurrence of cell pyroptosis. However, the correlations of the GSDMB expression in colorectal cancer with clinicopathological predictors, immune microenvironment, and prognosis are unclear.

Methods

Specimens from 267 colorectal cancer cases were analyzed by immunohistochemistry to determine GSDMB expression, CD3+, CD4+, and CD8+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, and S100A8+ immune cells. GSDMB expression in cancer cells was scored in the membrane, cytoplasm, and nucleus respectively. GSDMB+ immune cell density was calculated. Univariate and multivariate survival analyses were performed. The association of GSDMB expression with other clinicopathological variables and immune cells were also analyzed. Double immunofluorescence was used to identify the nature of GSDMB+ immune cells. Cytotoxicity assays and sensitivity assays were performed to detect the sensitivity of cells to 5-fluorouracil.

Results

Multivariate survival analysis showed that cytoplasmic GSDMB expression was an independent favorable prognostic indicator. Patients with positive cytoplasmic or nuclear GSDMB expression would benefit from 5-fluorouracil based chemotherapy. The assays in vitro showed that high GSDMB expression enhanced the sensitivity of colorectal cancer cells to 5-fluorouracil. Patients with positive membranous or nuclear GSDMB expression had more abundant S100A8+ immune cells in the tumor invasive front. Positive nuclear GSDMB expression indicated more CD68+ macrophages in the tumor microenvironment. Moreover, GSDMB+ immune cell density in the stroma was associated with a higher neutrophil percentage but a lower lymphocyte counts and monocyte percentage in peripheral blood. Furthermore, the results of double immunofluorescence showed that GSDMB co-expressed with CD68 or S100A8 in stroma cells.

Conclusion

The GSDMB staining patterns are linked to its role in cancer progression, the immune microenvironment, systemic inflammatory response, chemotherapeutic efficacy, and prognosis. Colorectal cancer cells with high GSDMB expression are more sensitive to 5-fluorouracil. However, GSDMB expression in immune cells has different effects on cancer progression from that in cancer cells.
The contribution and interplay of implicit and explicit processes on physical activity behavior: empirical testing of the physical activity adoption and maintenance (PAAM) model
Authors: Jekauc Darko , Gürdere Ceren , Englert Chris , Strobach Tilo , Bottesi Gioia , Bray Steven , Brown Denver , Fleig Lena , Ghisi Marta , Graham Jeffrey , Martinasek Mary , Tamulevicius Nauris , Pfeffer Ines
Published: May 2024

The adoption and maintenance of physical activity (PA) is an important health behavior. This paper presents the first comprehensive empirical test of the Physical Activity Adoption and Maintenance (PAAM) model, which proposes that a combination of explicit (e.g., intention) and implicit (e.g., habit,, affect) self-regulatory processes is involved in PA adoption and maintenance. Data were collected via online questionnaires in English, German, and Italian at two measurement points four weeks apart. The study included 422 participants (Mage= 25.3, SDage= 10.1; 74.2% women) from Germany, Switzerland, Italy, Canada, and the U.S. The study results largely supported the assumptions of the PAAM model, indicating that intentions and habits significantly mediate the effects of past PA on future PA. In addition, the effect of past PA on future PA was shown to be significant through a mediation chain involving affect and habit. Although the hypothesis that trait self-regulation moderates the intention-behavior relationship was not supported, a significant moderating effect of affect on the same relationship was observed. The results suggest that interventions targeting both explicit and implicit processes may be effective in promoting PA adoption and maintenance.
YTHDF2-Mediated m6A methylation inhibition by miR27a as a protective mechanism against hormonal osteonecrosis in BMSCs
Authors: Yuan Tianyi , Liu Hongjiang , Abudoukadier Maimaitiyibubaji , Yang Zengqiang , Zhou Zhiheng , Cui Yong
Published: May 2024

Background

With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited.

Objective

We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs.

Methods

We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed.

Results

miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH.

Conclusion

miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.
Machine learning-empowered sleep staging classification using multi-modality signals
Authors: Satapathy Santosh Kumar , Brahma Biswajit , Panda Baidyanath , Barsocchi Paolo , Bhoi Akash Kumar
Published: May 2024

The goal is to enhance an automated sleep staging system's performance by leveraging the diverse signals captured through multi-modal polysomnography recordings. Three modalities of PSG signals, namely electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG), were considered to obtain the optimal fusions of the PSG signals, where 63 features were extracted. These include frequency-based, time-based, statistical-based, entropy-based, and non-linear-based features. We adopted the ReliefF (ReF) feature selection algorithms to find the suitable parts for each signal and superposition of PSG signals. Twelve top features were selected while correlated with the extracted feature sets' sleep stages. The selected features were fed into the AdaBoost with Random Forest (ADB + RF) classifier to validate the chosen segments and classify the sleep stages. This study's experiments were investigated by obtaining two testing schemes: epoch-wise testing and subject-wise testing. The suggested research was conducted using three publicly available datasets: ISRUC-Sleep subgroup1 (ISRUC-SG1), sleep-EDF(S-EDF), Physio bank CAP sleep database (PB-CAPSDB), and S-EDF-78 respectively. This work demonstrated that the proposed fusion strategy overestimates the common individual usage of PSG signals.
Drivers of district-level differences in outpatient antibiotic prescribing in Germany: a qualitative study with prescribers
Authors: Schüz Benjamin , Scholle Oliver , Haug Ulrike , Tillmann Roland , Jones Christopher
Published: May 2024

Background

Previous studies have identified substantial regional variations in outpatient antibiotic prescribing in Germany, both in the paediatric and adult population. This indicates inappropriate antibiotic prescribing in some regions, which should be avoided to reduce antimicrobial resistance and potential side effects. The reasons for regional variations in outpatient antibiotic prescribing are not yet completely understood; socioeconomic and health care density differences between regions do not fully explain such differences. Here, we apply a behavioural perspective by adapting the Theoretical Domains Framework (TDF) to examine regional factors deemed relevant for outpatient antibiotic prescriptions by paediatricians and general practitioners.

Methods

Qualitative study with guideline-based telephone interviews of 40 prescribers (paediatricians and general practitioners) in outpatient settings from regions with high and low rates of antibiotic prescriptions, stratified by urbanity. TDF domains formed the basis of an interview guide to assess region-level resources and barriers to rational antibiotic prescription behaviour. Interviews lasted 30–61 min (M = 45 min). Thematic analysis was used to identify thematic clusters, and relationships between themes were explored through proximity estimation.

Results

Both paediatricians and general practitioners in low-prescribing regions reported supporting contextual factors (in particular good collegial networks, good collaboration with laboratories) and social factors (collegial support and low patient demand for antibiotics) as important resources. In high-prescribing regions, poor coordination between in-patient and ambulatory health services, lack of region-level information on antimicrobial resistance, few professional development opportunities, and regional variations in patient expectations were identified as barriers to rational prescribing behaviour.

Conclusions

Interventions targeting professional development, better collaboration structures with laboratories and clearer and user-friendly guidelines could potentially support rational antibiotic prescribing behaviour. In addition, better networking and social support among physicians could support lower prescription rates.
An integrated cofactor and co-substrate recycling pathway for the biosynthesis of 1,5-pentanediol
Authors: Hua Wenfeng , Liang Bo , Zhou Suhui , Zhang Qiushui , Xu Shuang , Chen Kequan , Wang Xin
Published: May 2024

Background

1,5-pentanediol (1,5-PDO) is a linear diol with an odd number of methylene groups, which is an important raw material for polyurethane production. In recent years, the chemical methods have been predominantly employed for synthesizing 1,5-PDO. However, with the increasing emphasis on environmentally friendly production, it has been a growing interest in the biosynthesis of 1,5-PDO. Due to the limited availability of only three reported feasible biosynthesis pathways, we developed a new biosynthetic pathway to form a cell factory in Escherichia coli to produce 1,5-PDO.

Results

In this study, we reported an artificial pathway for the synthesis of 1,5-PDO from lysine with an integrated cofactor and co-substrate recycling and also evaluated its feasibility in E.coli. To get through the pathway, we first screened aminotransferases originated from different organisms to identify the enzyme that could successfully transfer two amines from cadaverine, and thus GabT from E. coli was characterized. It was then cascaded with lysine decarboxylase and alcohol dehydrogenase from E. coli to achieve the whole-cell production of 1,5-PDO from lysine. To improve the whole-cell activity for 1,5-PDO production, we employed a protein scaffold of EutM for GabT assembly and glutamate dehydrogenase was also validated for the recycling of NADPH and α-ketoglutaric acid (α-KG). After optimizing the cultivation and bioconversion conditions, the titer of 1,5-PDO reached 4.03 mM.

Conclusion

We established a novel pathway for 1,5-PDO production through two consecutive transamination reaction from cadaverine, and also integrated cofactor and co-substrate recycling system, which provided an alternative option for the biosynthesis of 1,5-PDO.
Real-world effectiveness of a new powered stapling system with gripping surface technology on the intraoperative clinical and economic outcomes of gastrectomy for gastric cancer
Authors: Guo Honghai , Zheng Tao , Lin Yecheng , Tang Tiange , Zhang Zhidong , Wang Dong , Zhao Xuefeng , Liu Yu , Tan Bibo , Yang Peigang , Tian Yuan , Li Yong , Zhao Qun
Published: May 2024

Background

Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer.

Method

The data were extracted from the Fourth Hospital of Hebei Medical University’s (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann–Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables.

Results

Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241).

Conclusion

The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.
Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis
Authors: Li Junqiu , Pan Jielu , Xiao Dinghong , Shen Nan , Wang Ruiqing , Miao Hongyv , Pu Peimin , Zhang Haiyan , Yv Xiao , Xing Lianjun
Published: May 2024

Background

Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer.

Methods

Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software.

Results

This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20–5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60–2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77–2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17–2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21–3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33–77% higher risk of developing cancer compared to diagnosing CAG through serological methods.

Conclusion

This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.
Physically demanding occupations among females and sex-related differences to develop osteoarthritis of the hip: a systematic review and meta-analysis
Authors: Unverzagt Susanne , Bergmann Annekatrin , Denny Kathleen , Frese Thomas , Hirpa Selamawit , Weyer Johannes
Published: May 2024

Background

Hip osteoarthritis (HOA) is a leading cause of disability increasing with age and is more prevalent in women and in various physically demanding occupations. This systematic review identifies and summarises occupational exposures for women in physically demanding occupations and discusses sex differences and consequences.

Methods

In this systematic review, we searched various electronic databases for reports published between date of database inception and October 2022. We included cohort studies and case-control studies that assessed the association between exposure to physically demanding occupations and the development of HOA. We then assessed the methodological quality of selected studies, extracted relative effects, compared the risk for women and men and meta-analytically reviewed the effects of physically demanding occupations. All steps were based on a study protocol published in PROSPERO (CRD42015016894).

Results

We included six cohort studies and two case-control studies in this systematic review. These studies showed a considerably increased risk of developing HOA in both sexes. Women working in traditionally female-dominated occupations such as cleaning, sales, catering, childcare and hairdressing that are physically demanding, have a higher risk of developing HOA than men in similarly physically demanding occupations. Conversely, in traditionally male-dominated occupations with a high heterogeneity of work activities, such as agriculture, crafts, construction, as well as in low-skilled occupations, the risk was higher for men. One exception are health occupations, which are grouped together with a wide range of other technical occupations, making it difficult to draw conclusions.

Conclusions

Existing studies indicate an association between various occupations with a high physical workload and an increased risk of developing HOA. Occupational prevention and individual health promotion strategies should focus on reducing the effects of heavy physical workloads at work. The aforementioned as well as early detection should be specifically offered to women in female-dominated occupations and to people working in elementary occupations.
Comparison of the forearm rotation restriction capacities of four upper-extremity immobilization methods: there is no difference between single and double sugar tong splinting
Authors: Dastan Ali Engin , Vahabi Arman , Coskunol Erhan , Aktuglu Kemal
Published: May 2024

Background

The aim of this study was to compare the effects of four different immobilization methods [single sugar tong splint (SSTS), double sugar tong splint (DSTS), short arm cast (SAC), and long arm cast (LAC)] commonly used for restricting forearm rotation in the upper extremity.

Methods

Forty healthy volunteers were included in the study. Dominant extremities were used for measurements. Basal pronation and supination of the forearm were measured with a custom-made goniometer, and the total rotation arc was calculated without any immobilization. Next, the measurements were repeated with the SAC, LAC, SSTS and DSTS. Each measurement was compared to the baseline value, and the percentage of rotation restriction was calculated.

Results

The most superior restriction rates were observed for the LAC (p = 0.00). No statistically significant difference was detected between the SSTS and DSTS in terms of the restriction of supination, pronation or the rotation arc (p values, 1.00, 0.18, and 0.50, respectively). Statistically significant differences were not detected between the SAC and the SSTS in any of the three parameters (p values, 0.25; 1.00; 1.00, respectively). When the SAC and DSTS were compared, while there was no significant difference between the two methods in pronation (p = 0.50), a statistically significant difference was detected in supination (p = 0.01) and in the total rotation arc (p = 0.03).

Conclusion

The LAC provides superior results in restricting forearm rotation. The SAC and SSTS had similar effects on forearm rotation. The DSTS, which contains, in addition to the SSTS, a sugar tong portion above the elbow, does not provide additional rotational stability.
Genome-wide distribution of 5-hydroxymethyluracil and chromatin accessibility in the Breviolum minutum genome
Authors: Marinov Georgi K. , Chen Xinyi , Swaffer Matthew P. , Xiang Tingting , Grossman Arthur R. , Greenleaf William J.
Published: May 2024

Background

In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties are originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools.

Results

In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays.

Conclusions

Our results provide the first window into the 5-hmU and chromatin accessibility landscapes in dinoflagellates.
Hidden blood loss and the influential factors after minimally invasive treatment of posterior pelvic ring injury with sacroiliac screw
Authors: Xu Ding , Liu Min , Lou Weigang , Li Ming , Xiao Jingwei , Wu Hongbao , Zhuang Yunqiang , Chen Jianming
Published: May 2024

Background

To analyze the perioperative bleeding and hidden blood loss (HBL) of sacroiliac screw minimally invasive treatment of pelvic posterior ring injury and explore the influential factors of HBL after operation for providing reference for clinical treatment.

Method

A retrospective analysis was conducted on data from 369 patients with posterior pelvic ring injuries treated with sacroiliac screws internal fixation at our hospital from January 2015 to January 2022. The research was registered in the Chinese Clinical Trial Registry in July 2022 (ChiCTR2200061866). The total blood loss (TBL) and HBL of patients were counted, and the factors such as gender, age, and surgical duration were statistically analyzed. The influential factors of HBL were analyzed by multiple linear regression.

Results

The TBL was 417.96 ± 98.05 ml, of which the visible blood loss (VBL) was 37.00 ± 9.0 ml and the HBL was 380.96 ± 68.8 ml. The HBL accounted for 91.14 ± 7.36% of the TBL. Gender, surgical duration, fixed position, and fixed depth had significant effects on the HBL (P < 0.05).

Conclusions

The HBL was the main cause of anemia after minimally invasive treatment of posterior pelvic ring injury with a sacroiliac screw. Gender, surgical duration, fixed position, and fixed depth were closely related to the occurrence of HBL. In clinical treatment, we should consider these influential factors and take effective measures to reduce the impact of HBL on patients.
Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model
Authors: Henningfield Caden M. , Soni Neelakshi , Lee Ryan W. , Sharma Rishi , Cleland Jeffrey L. , Green Kim N.
Published: May 2024

Background

In Alzheimer’s disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue.

Methods

Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113).

Results

Treatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice.

Conclusions

This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.
Influence of elevated liver enzyme level on 30-day mortality rates in patients undergoing nonemergency orthopedic surgery
Authors: Liao Tzu-Ruei , Lee Yuan-Wen , Chang Chuen-Chau , Liao Alan Hsi-Wen , Lai Yen-Chun , Liu Chih-Chung
Published: May 2024

Background

The effect of elevated preoperative liver enzyme levels on postoperative outcomes is a topic of concern to clinicians. This study explored the association between elevated preoperative liver enzyme levels and surgical outcomes in patients undergoing orthopedic surgery.

Methods

Using the American College of Surgeons National Surgical Quality Improvement Program database, we obtained data on adult patients who received nonemergency orthopedic surgery under general anesthesia between 2011 and 2021.

Results

We evaluated the data of 477,524 patients, of whom 6.1% (24 197 patients) had elevated preoperative serum glutamic oxaloacetic transaminase (SGOT) levels. An elevated SGOT level was significantly associated with 30-day postoperative mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.39 to 1.90). We determined that the mortality rate rose with SGOT levels. The results remained unchanged after propensity score matching.

Conclusion

Elevated preoperative SGOT levels constitute an independent risk factor for 30-day postoperative mortality and are proportionately associated with the risk of 30-day postoperative mortality.
Forecasting the fate of vertically propagating dikes from geodetic data
Authors: Aoki Yosuke
Published: May 2024

Magmas, especially mafic ones, usually intrude into the upper crust as dikes. The intruded dike is often arrested before reaching the surface to make an eruption. Many geophysical observations, including geodetic measurements, have documented dike intrusions and arrests. Also, many theoretical considerations and analog experiments explored the mechanics of dike propagation and arrest. However, insights gained from theoretical considerations, analog experiments, and geophysical observations have yet to be well reconciled. This study attempts to reconcile geodetic measurements with insights gained from theoretical considerations and analog experiments to investigate how to forecast whether an intruded dike results in an eruption or not. This study considers four causes of dike arrests: (1) solidification of the intruded magma, (2) insufficient volume of dike intrusion, (3) negative buoyancy acting on the intruded magma, and (4) stress perturbation near the dike tip by a large earthquake. Then, this study investigates the cause of dike arrests associated with the 1997 and 1998 seismic swarm off the Izu Peninsula, Japan, and the 2015 failed eruption of Sakurajima volcano, Japan, as an example. This study suggests that the dike intrusions associated with the 1997 and 1998 seismic swarm off the Izu Peninsula are caused by insufficient volume of the dike, the loss of buoyancy, or both. The failed eruption of the 2015 Sakurajima eruption is most likely by insufficient volume. To investigate the contribution of geodetic data in understanding the cause of dike arrests, it is essential to consider the characteristics of geodetic data. They are: (1) geodetic data constrain the intruded volume and the location relatively well, (2) geodetic data cannot constrain the geometry of the intruded dike very well, (3) an assumption of the host rock as homogeneous halfspace underestimates the volume of the intruded dike and estimates the depth of the dike shallower than the true value. These limitations indicate that we cannot fully understand the cause of dike arrests solely from geodetic data. Independent information gained from, for example, the location of dike-induced earthquakes, seismic structures, or density structure from gravity anomalies or muon radiography helps better understand the cause of dike arrests.

Graphical Abstract
Integrating multi-platform assembly to recover MAGs from hot spring biofilms: insights into microbial diversity, biofilm formation, and carbohydrate degradation
Authors: Liew Kok Jun , Shahar Saleha , Shamsir Mohd Shahir , Shaharuddin Nawal Binti , Liang Chee Hung , Chan Kok-Gan , Pointing Stephen Brian , Sani Rajesh Kumar , Goh Kian Mau
Published: May 2024

Background

Hot spring biofilms provide a window into the survival strategies of microbial communities in extreme environments and offer potential for biotechnological applications. This study focused on green and brown biofilms thriving on submerged plant litter within the Sungai Klah hot spring in Malaysia, characterised by temperatures of 58–74 °C. Using Illumina shotgun metagenomics and Nanopore ligation sequencing, we investigated the microbial diversity and functional potential of metagenome-assembled genomes (MAGs) with specific focus on biofilm formation, heat stress response, and carbohydrate catabolism.

Results

Leveraging the power of both Illumina short-reads and Nanopore long-reads, we employed an Illumina-Nanopore hybrid assembly approach to construct MAGs with enhanced quality. The dereplication process, facilitated by the dRep tool, validated the efficiency of the hybrid assembly, yielding MAGs that reflected the intricate microbial diversity of these extreme ecosystems. The comprehensive analysis of these MAGs uncovered intriguing insights into the survival strategies of thermophilic taxa in the hot spring biofilms. Moreover, we examined the plant litter degradation potential within the biofilms, shedding light on the participation of diverse microbial taxa in the breakdown of starch, cellulose, and hemicellulose. We highlight that Chloroflexota and Armatimonadota MAGs exhibited a wide array of glycosyl hydrolases targeting various carbohydrate substrates, underscoring their metabolic versatility in utilisation of carbohydrates at elevated temperatures.

Conclusions

This study advances understanding of microbial ecology on plant litter under elevated temperature by revealing the functional adaptation of MAGs from hot spring biofilms. In addition, our findings highlight potential for biotechnology application through identification of thermophilic lignocellulose-degrading enzymes. By demonstrating the efficiency of hybrid assembly utilising Illumina-Nanopore reads, we highlight the value of combining multiple sequencing methods for a more thorough exploration of complex microbial communities.
Genome-wide somatic mutation analysis of sinonasal adenocarcinoma with and without wood dust exposure
Authors: Sipilä Lauri J. , Katainen Riku , Aavikko Mervi , Ravantti Janne , Donner Iikki , Lehtonen Rainer , Leivo Ilmo , Wolff Henrik , Holmila Reetta , Husgafvel-Pursiainen Kirsti , Aaltonen Lauri A.
Published: May 2024

Background

Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown.

Methods

We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized.

Results

Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype.

Conclusions

Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.
Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality
Authors: Jieru Peng , Zhang Shanshan , Cai Lin , Long Wencheng , Wang Yueshan , Zhang Lu , Dong Yao , Zhang Wenqi , Liao Juan , Yang Chunxia
Published: May 2024

Background

Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S.

Methods

This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations.

Results

In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60–0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk.

Conclusion

Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.
Trends in the implementation of biopesticides in the Euro-Mediterranean region: a narrative literary review
Authors: Fusar Poli Elena , Fontefrancesco Michele Filippo
Published: May 2024

This article explores the global commitment to achieving sustainable solutions for addressing hunger, emphasizing the urgent need to transform the agricultural sector in the face of escalating global population growth and threats to the food system. Despite commitments to reduce conventional pesticide use, the global market for these products is expanding. Biopesticides are a sustainable alternative with targeted action and ecological benefits. While the biopesticide market is growing, it remains a small segment within the overall expanding pesticide market. The study focuses on the Mediterranean region, specifically Spain, Tunisia, and Turkey, to investigate the structural challenges hindering the adoption of biopesticides. Technical issues, coupled with broader market dynamics involving producers, farmers, regulators, and consumers, contribute to the limited market presence of biopesticides in the region. Challenges such as knowledge gaps, market constraints, limited manufacturing plants, and registration complexities further impede biopesticide development, confining them to niche markets. Overcoming these challenges requires addressing issues of availability, affordability, and efficacy, alongside legislative barriers. The paper suggests potential roles for farmers, producers, and regulators as agents of change, acknowledging the complexity of devising concrete strategies to navigate the current impasse. The research proposes directions for facilitating change.
Epiglottis calcification: forgotten cause of dysphagia in elderly population
Authors: Seth Namdev , Varshney Dushyant , Verma Saumya
Published: May 2024

Background

Dysphagia is a relatively common clinical issue in elderly population with numerous causes, which are divided into oropharyngeal and substernal categories. Most of the causes of dysphagia can be diagnosed easily with clinical and radiological examinations. However, we encountered a rare cause of dysphagia in an elderly patient, which can be missed easily during diagnostic workup, that entity is epiglottis calcification.

Case presentation

A 91-year-old male presented with complaints of recurrent aspirations and difficulty in swallowing. Physical examination revealed no abnormalities in the oral cavity, pharynx and nose. Flexible fiberoptic laryngoscopic examination was performed, which mildly swollen and posteriorly moved epiglottis with limited mobility during swallowing. Computed tomography scan of the larynx revealed significant asymmetric amorphous calcification of the free edge of the aryepiglottic, pharyngoepiglottic, and epiglottis folds.

Conclusions

Although dysphagia is a common problem in elderly, it has serious complications such as recurrent aspirations, pneumonia and nutritional deficiency. One of the rare causes of dysphagia in elderly is epiglottic calcifications, which impairs its flexibility and the functionality, and may predispose to difficulty in swallowing and recurrent aspirations.
Oral microbiome dysbiosis and gastrointestinal diseases: a narrative review
Authors: Elghannam Maged Tharwat , Hassanien Moataz Hassan , Ameen Yosry Abdelrahman , Turky Emad Abdelwahab , ELattar Gamal Mohammed , ELRay Ahmed Aly , ELTalkawy Mohammed Darwish
Published: May 2024

Mouth is the gateway to the total body wellness. Accordingly, oral microbiome influences overall health of an individual. Oral microbiome plays a key role in shaping up the host’s health profile. Obvious differences have been reported between patients with gastrointestinal diseases and healthy controls. The oral and gut microbiome profiles are well-segregated due to the oral–gut barrier. However, the oral microbiota can translocate to the intestinal mucosa in conditions of the oral–gut barrier dysfunction. Oral bacteria can disseminate to the distal gut via enteral or hematogenous routes. The translocation of oral microbes to the gut may give rise to a variety of gastrointestinal diseases including Helicobacter-induced diseases, irritable bowel syndrome, inflammatory bowel disease, celiac disease, and colorectal cancer. Understanding the role of the oral-to-gut microbial translocation in the pathogenesis will contribute to precise diagnosis and effective treatment. In this review, we aim to highlight the role of oral microbiota dysfunction in various gastrointestinal disorders.
Process simulation, optimization, and cost analysis of a proposed sulfur recovery unit by applying modified Claus technology
Authors: Medhat Ahmed , Shehata Walaa , Gad Fatma , Bhran Ahmed
Published: May 2024

Removing sour gas from any suitable gas sweetening technology in a cost-effective and environmentally responsible manner is a major challenge. This paper discusses how to safely and economically dispose of small amounts of acid gases resulting from the amine sweetening process. A two-stage Claus desulfurization unit was studied and simulated to treat acid gases resulting from natural gas sweetening operations in Ras Gharib oil fields (Egypt). These acid gases are used as feedstock for the proposed plant to produce a valuable product, such as elemental sulfur, which is used as a raw material in many industries. Although many sulfur recovery techniques are available for various conditions and applications, the Claus process is a critical and widely used method for recovering elemental sulfur from gaseous hydrogen sulfide. This work represents the potential benefits of treating acid gases with high hydrogen sulfide content. In addition, operational variables that could affect sulfur production and sulfur recovery efficiency of the studied Claus unit were studied and optimized. Aspen HYSYS simulation software (version 9) was used to evaluate the economic aspects and optimize the operational parameters of the unit for producing sulfur from acid background gases. The results showed that the maximum sulfur production was achieved at a catalytic converter reactor temperature of 270 °C and 210 °C for the first and second catalytic reactor, respectively, with an air flow rate of 933.3 kg mol/h. The economic study of the proposed desulfurization unit showed that the Claus unit would be economically acceptable with an expected return on investment of approximately 10% and an average payback period of 10 years. Moreover, the introduced plant has a positive impact on the environment by reducing the concentration of hydrogen sulfide in the gas from 69.58 to 0.16%.