bluuebunny/crossref_metadata_2025_split huggingface dataset:
LAT4 drives Temozolomide induced radiotherapy resistance in glioblastoma by enhancing mTOR pathway activation
Authors: Zang Wenrui , Liu Yangwu , Zheng Jiajun , Chen Lei , Li Chiyang , Zhao Jiakun , Zhou Qiang , Wang Zhenyuan , Cao Yongfu , Zhang Wanling , Li Junjie , Lu Yuntao 
Published: October 2024

Abstract

Background
As the strong adaptive radio-chemoresistance, GBM represents the worst prognosis form of primary malignant tumor within the central nervous system. Previous researches indistinctly focused on the mechanisms of resistance to X-ray or chemo regimen in isolation, however, it is still unknown if there exists the synergistic or interact effect between the above two kinds of resistances.
Methods
We established TMZ-resistant GBM cell lines (TMZ-R) by chronically exposing U87MG cell lines to TMZ, and DMSO was used as placebo control. In vivo and in vitro experiments verified the synergistic resistance of TMZ-R cells to radiotherapy. Cell proliferation and clonogenesis assay were used to detect cell tolerance to chemo- or ratio-treatment, immunofluorescence and comet assay to detect cell damage, and in vivo imaging to measure tumor size. By transcriptomics and series validation tests, LAT4 was identified to be associated with such TMZ induced radiotherapy resistance. The relationship between LAT4 and mTOR pathway activity was also analyzed. Finally, the effect of BCH, LAT inhibitor, combined with radiotherapy on GBM prognosis was verified in vivo.
Results
We have first confirmed that TMZ not only induces resistance to chemotherapy in GBM cells but also enhances their resistance to radiotherapy,which is a surprising discovery during the establishment of TMZ-resistant U87MG GBM cell lines. Comprehensive transcriptomic analysis identified amino acid metabolism as a potential key factor in radiotherapy resistance. It has been validated that the upregulation of LAT4, a member of leucine metabolism, subsequent to chemotherapy modulates the mechanistic target of mTOR pathway and leads to radiotherapy resistance both in vitro and in vivo. Importantly, the application of inhibitors targeting leucine metabolism has been demonstrated to restore the sensitivity of these cells to radiotherapy, highlighting a potential therapeutic strategy for overcoming resistance in GBM.
Conclusions
Our study first discover the synergistic effect between tumor resistance to chemotherapy and radiotherapy. Our study highlights the critical role of LAT4 in activating the mTOR pathway and such resistance interaction. Targeting LAT4 and mTOR pathway will improve treatment sensitivity of GBM, especially in recurrent tumors.
The effect of virtual reality glasses and therapeutic touch on pain, anxiety and satisfaction during intrauterine insemination: a randomized controlled trial
Authors: BAL Sümeyye , KARAKAYA Neşe , KOÇ Emine , GÜVEN Davut 
Published: October 2024

Abstract

Background: Intrauterine insemination (IUI) also found that this experience was associated with anxiety. Therefore, measures must be taken to reduce or eliminate the pain and anxiety associated with it. Objectives: This study investigated the effect of virtual reality glasses (VRG) and therapeutic touch on pain, anxiety and satisfaction during intrauterine insemination. Methods: A randomized controlled trial design was used. Patients were randomized into three groups [32 virtual reality group(VRG), 32 therapeutic touch group (TT), 32 control group(CG)]. The study was conducted between January and June 2022 in the obstetric outpatient clinics of a public hospital in northern Türkiye. Anxiety was evaluated using the State Anxiety Inventory. Pain, and satisfaction were evaluated using the Visual Analogue Scale [VAS]. Results: There was a significant difference in the pain level of the VRG group during IUI was lower than those of CG and TT (p=0.01). Women were most satisfied with the TT application in the IUI procedure (p=0.000). Anxiety levels after IUI were lower in the TT and SG groups than in CG (p = 0.000). Conclusion: VRG application was effective in reducing pain associated with IUI procedure in women. Although the use of VRG with music reduced the pain associated with IUI more than the TT application, the women left the TT application satisfied Trial registration: The study was registered at the Clinical Trials.gov website under the code NCT05192330. The first trial registration date was (12/01/2022).
Colistin sulfate is effective and safe in the treatment of severe pneumonia patients with CRE resistance: a retrospective cohort study
Authors: Li Shiying , Zhang An , Tong Jin , Zong Kaican , Fu Xiao , Zhou Zhaogang , Zhang Lu , Zhang Yan , Hu Peng 
Published: October 2024

Abstract

Objective
Severe pneumonia is difficult to treat and with a high mortality. The increasing drug resistance problem increased the difficulties to treat, so we estimated whether colistin sulfate reduces the mortality of severe pneumonia patients with suspicious CRO infection.
Method
A retrospective cohort study was conducted on the patients consecutively admitted for pneumonia to the Second Affiliated Hospital of Chongqing Medical University from Jan 2022 to Feb 2023. Data were recorded.
Results
We found that the 28-day mortality after discharge of severe pneumonia patients with suspected MDR bacterial infections in our cohort study is also high (42/84, 50%). The 28-day mortality of discharge in tigecycline (TC) group is a bit lower than that of colistin combined with other antibiotics (OC) group (18/46, 39.1% vs. 24/38, 63.2%, P = 0.048). Further multivariate analysis revealed that positive sputum culture was significantly associated with the 28-day discharge mortality rate with different treatment regimens (OR 0.073, 95% CI 0.006–0.882, P = 0.040). And no significant differences were founded before and after the use of colistin sulfate for the white blood count (WBC), platelet count, level of CRP, PCT, ALT, and creatinine.
Conclusion
Colistin sulfate is effective and safe in the treatment of severe pneumonia patients with CRE resistance.
Evaluation of the implementation of the Kangaroo Mother Care after the DIB project in three health facilities in the central Cameroon region
Authors: Mandeng Marcelle Nina Ehouzou , Ndjabo Monique Amor , Bilo'o Lydienne Leslie , Kalla Ginette Claude Mireille , Omolomo Etienne Kimessoukié , Sap Suzanne Ngo Um 
Published: October 2024

Abstract

Background
Neonatal mortality remains high in Cameroon and stagnant since 2014 at 28‰ according to DHS 2018. In the strategy to reduce this mortality, the project named “Development Impact Bond” (DIB) was set up in ten health facilities in Cameroon. Our objective was to determine the level of implementation of KMC as well as its effect on neonatal mortality in three health facilities in the central region.
Methods
We carried out a cross-sectional study using a mixed (quantitative and qualitative) approach with simultaneous triangulation and retrospective data collection. To assess the level of KMC implementation, we chose the progress monitoring model proposed by Bergh et al in 2005. Qualitatively, we used an observation grid and a semi-structured interview guide to collect their verbatims according to the different phases of KMC implementation.
Results
After the DIB project, our evaluation showed a level of achievement in the institutionalization stage and progress towards sustainable KMC practice, with scores of 24.5, 25 and 27.5 out of 30 points respectively for YGOPH, YUTH and BDH. During the project, there was a 1.6-fold, 2-fold and 4-fold reduction in mortality for YGOPH, YUTH and BDH respectively, followed by a trend towards increased mortality in 2 first-rate facilities, notably YUTH and YGOPH. The causes of this post-project performance appear to be difficulties in involving administrators, in communicating with mothers and in reducing the motivation of caregiver’s staff.
Conclusion
The level of implementation of the KMC after the DIB project was high, notwithstanding a rebound in mortality that may be explained by continuing managerial, social and technical difficulties.
Microaggressions in Medicine: A Pilot Study on Differences and Determinants Among Doctors and Nurses
Authors: Lv TAO , Yan Wenjie , Li longlong , Jiang Shuai , Zhang Min , Du Yasong 
Published: October 2024

Abstract

Introduction
"Microaggression", encapsulates the notion that subtle and commonplace instances of discrimination and bias, can result in psychological and emotional distress, further entrenching inequality and cultivating a hostile social atmosphere for marginalized individuals or collectives. Studies endeavors to shed light on illuminating the impact of microaggressions on healthcare workers have found that they have consistently underscored their pervasive detrimental effects. This study aims to investigate the current status of microaggression encounters among healthcare workers, alongside an examination of the contributing risk factors associated with the occurrence of such microaggressions.
Methods
A total of 190 aged 18–60 years clinical healthcare practitioners were recruited from March to April 2023. Questionnaires including the Everyday Discrimination Scale-9 items (EDS).
Results
A total of 83 nurses [82(98.8%) female] and 107 doctors [54(50.5%) female] participated. Among the participants, 40(37.4%) doctors and 50(60.2%) nurses reported encountering microaggressions. Notably, the prevalence of microaggressions among nurses was significantly higher than that among doctors (P = 0.002). Binary logistic regression analysis provided insights into the independent factors influencing the experience of microaggressions. For doctors, the department emerged as a significant influencer (reference level = internal; ORauxiliary=6.138, Pauxiliary=0.016), for nurses, age (reference level = 18 ~ 35y; OR36 ~ 60=3.497, P36 ~ 60=0.037), department (reference level = internal; ORauxiliary=0.072, Pauxiliary=0.007), and family structure (reference level = nuclear family; ORbig family=0.242, Pbig family=0.012) demonstrated significant influence of experience of microaggressions.
Conclusions
Healthcare professionals have encountered a significant prevalence of microaggressions, with a distinct impact observed among nurses. The encounters with microaggressions within the healthcare workforce have exhibited a robust connection with symptoms of anxiety and depression. Specifically, doctors employed in auxiliary departments have been identified as being at a heightened risk of encountering microaggressions in comparison to their peers in internal medicine. Conversely, nurses stationed in auxiliary departments face an elevated risk in contrast to their counterparts in internal medicine. Moreover, among nurses, an advanced age and living in a nuclear family (as opposed to big family) have been identified as factors contributing to an increased vulnerability to microaggressions.
Effect of caloric restriction with protein supplementation on weight, adipose mass, and muscle mass in professional male soccer players: a controlled randomized trial
Authors: García Gloria , Díaz Gustavo , Niño Alexander , Belalcázar-Monsalve María Paula , Ballesteros-Arbeláez Felipe , Cruz Angélica , Del-Campo Juan , Tejero-González Carlos 
Published: October 2024

Abstract

Background
Achieving optimal body composition can be advantageous for athletes in terms of competitive performance. To date, there is no research examining the effects of caloric restriction (CR) on body composition in male professional soccer players.
Purpose
This study aims to investigate the impact of 6 weeks of CR with protein supplementation on body composition and the maintenance of changes after stopping CR for the next 6 weeks.
Methods
The study was a controlled, randomized, parallel-group, experiment involving 28 participants. The experimental group received a CR diet (2650 kcal/d) and the control group received a normal caloric (NC) diet (3500 kcal/d). The intervention lasted for 6 weeks, followed by 6 weeks without intervention and provision of ad libitum diet in both groups. Body composition was assessed using anthropometric measurements.
Results
The study participants were aged 27.6 ± 4.4 years on average. After 6 weeks, the CR group showed a significant reduction in body weight compared with the NC group (− 0.33 kg for CR vs. −0.08 kg for NC; p < 0.05). Both groups experienced a reduction in adipose mass after 6 weeks (p > 0.05), but only the CR group continued to decrease body fat after stopping CR (p < 0.05). Throughout the study, there was an increase in muscle mass, and no significant difference was observed between the two groups (p > 0.05).
Conclusions
CR with protein supplementation improves body composition in male professional soccer players by reducing weight, promoting fat loss, and enhancing muscle mass.
Comparative Effectiveness of Liraglutide versus Dulaglutide in Asian Patients with Type 2 Diabetes: A Retrospective Study
Authors: Dai Jhih-Wei , Lin Yuan , Li Xiu-Wei , Tseng Chin-Ju , Tsai Ming-Lung , Yang Ning-I , Hung Ming-Jui , Chen Tien-Hsing 
Published: October 2024

Abstract

Background & Aims: Given the limited head-to-head comparison of effectiveness between liraglutide and dulaglutide, our study aimed to investigate the clinical effectiveness of dulaglutide versus liraglutide in a real-world setting.
Method: In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis.
Results: A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85–1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.05, 95% CI 0.97–1.13).
Conclusion: Liraglutide and dulaglutide demonstrated comparable clinical effectiveness in composite cardiovascular and composite renal outcomes in a real-world setting
Between-and within-socioeconomic groups temporal inequality in the uptake of malaria prevention strategies among pregnant women and under-five children in Ghana
Authors: Okova Denis , Lukwa Akim Tafadzwa , Edusei Marian , Bodzo Paidamoyo , Atta-Obeng Christian , Chiwire Plaxcedes , Hongoro Charles 
Published: October 2024

Abstract

Background
Malaria is one of the leading causes of mortality among pregnant women and children in Africa. Despite efforts to distribute insecticide-treated nets (ITNs) and provide intermittent preventive treatment in pregnancy (IPTp) in Ghana, significant socioeconomic inequalities persist. This study investigates the temporal trends in socioeconomic inequalities related to ITN and IPTp coverage among children and pregnant women in Ghana.
Methods
We utilized data from the Ghana Demographic and Health Surveys (DHS) for 2003, 2008, 2014, and 2022. We assessed ITN use by pregnant women and children under five, and IPTp coverage, employing the Erreygers normalized concentration index (ENCI) and Theil index to measure and decompose inequalities by socioeconomic status (SES) and residence.
Results
ITN use among children under five increased from 58.11% in 2003 to 62.86% in 2022, while ITN use among pregnant women showed fluctuations, dropping in 2008 and 2014 but rising to 60% in 2022. IPTp coverage increased steadily from 0.85% in 2003 to 60% in 2022. Overall socioeconomic inequalities in ITN use and IPTp coverage were predominantly driven by within-group rather than between-group inequalities. ITN use was higher among the poorest households, while IPTp coverage showed a pro-rich distribution in recent years.
Conclusion
Despite improvements in malaria prevention uptake, significant inequalities persist in Ghana. Addressing these disparities requires a multipronged approach, including strengthening supply chains, tailoring interventions to specific population needs, and reducing healthcare access barriers. Policies must focus on localized factors and specific barriers faced by disadvantaged groups to achieve equitable health outcomes in malaria prevention.
Clinicopathological characteristics of complicated colorectal cancers: a retrospective analysis over 10 years in two tertiary centers in Egypt
Authors: Torky Radwan A. , RM Farghaly , Hussein Ahmed M. , Abdeltawab Asmaa A. 
Published: October 2024

Abstract

Background
The prognosis for emergency surgery for colorectal cancers (CRCs) and metastatic tumors was reported to be extremely poor. Our objective is to ascertain the clinical characteristics of patients who have been diagnosed with complications and metastases at two tertiary centers in Egypt.
Methods
a comparative retrospective study between complicated and non-complicated CRCs conducted in two tertiary centers in Egypt in 10 years.
Results
a total of 320 patients underwent surgery for CRC, of which 25% underwent emergency surgery (80 cases) and 240 (75%) patients underwent an elective one. There was a higher rate of complicated colon and non-complicated rectal cancer (P = 0.009). There was a significantly higher rate of positive L.Ns, positive LVI and PNI (P = 0.001), (P < 0.001) and (P < 0.001) respectively. In multivariate analysis, only the tumor site (right colon P = 0.010, left colon P = 0.022) as well as the LVI (P = 0.038) remained the most important predicting factors for complication. There was a significantly higher rate of OS in patients with T1 and T2 (P = 0.002), in patients with grade I and II (P = 0.005), node-negative and non-metastatic disease with (P = < 0.001) and (P = < 0.001) respectively.
Conclusion
Right and left colon cancers, along with positive lymphovascular invasion (LVI), are regarded as risk factors for surgical complications and metastases in cases of advanced stages, unfavorable grades, and node-positive tumors, leading to a poor prognosis.
Bedside Endoscopic Ultrasound Guided Gallbladder Drainage in the Intensive Care Unit in Critically Ill Patients
Authors: Thomas Raj Jessica , Chatterjee Arjun , Abdallah Mohamed , Garg Rajat , Singh Amandeep , Chahal Prabhleen 
Published: October 2024

Abstract

Cholecystectomy remains the treatment of choice in average surgical-risk patients with acute cholecystitis. In patients with high perioperative risk, percutaneous transhepatic gallbladder drainage (PT-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) become the next avenues of treatment. However, PT-GBD is contraindicated in large hepatic masses, large-volume ascites, and coagulopathy. Furthermore, some critically ill patients may not be amenable to transportation to the interventional radiology suite for PT-GBD or the endoscopy suite for EUS-GBD. In this case series, we demonstrated that performing EUS-GBD at the bedside in the intensive care unit is both technically feasible and safe for critically ill patients at high risk for other interventions.
Potential drug targets for asthma identified through Mendelian randomization analysis
Authors: Chen Xingxuan , Shang Yu , Shen Danting , Shi Si , wen Zhe , Li Lijuan , Chen Hong 
Published: October 2024

Abstract

Background
The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).
Methods
We utilized GWAS data from the UK Biobank (comprising 56,167 patients and 352,255 control subjects) and the FinnGen cohort (including 23,834 patients and 228,085 control subjects). Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid proteins were derived from recently published GWAS. Bidirectional Mendelian randomization analysis, Steiger filtering, colocalization, and phenotype scanning were employed for reverse causal inference detection, further substantiating the Mendelian randomization results. A protein-protein interaction network was also constructed to reveal potential associations between proteins and asthma medications.
Results
Under Bonferroni significance conditions, Mendelian randomization analysis revealed causal relationships between seven proteins and asthma. In plasma, we observed that an increase of one standard deviation in IL1R1[1.30 (95% CI, 1.20–1.42)], IL7R[1.07 (95% CI, 1.04–1.11)], ECM1[1.03 (95% CI, 1.02–1.05)], and CD200R1[1.18 (95% CI, 1.09–1.27)] were associated with an increased risk of asthma, while an increase in ADAM19 [0.87 (95% CI, 0.82–0.92)] was found to be protective. In the brain, each 10-fold increase in IL-6 sRa [1.29 (95% CI, 1.15–1.45)] was associated with an increased risk of asthma, while an increase in Layilin [0.61 (95% CI, 0.51–0.73)] was found to be protective. None of the seven proteins exhibited a reverse causal relationship. Colocalization analysis indicated that ECM1 (coloc.abf-PPH4 = 0.953), IL-6 sRa (coloc.abf-PPH4 = 0.966), and layilin (coloc.abf-PPH4 = 0.975) shared the same genetic variation as in asthma.
Conclusion
A causal relationship exists between genetically determined protein levels of IL1R1, IL7R, ECM1, CD200R1, ADAM19, IL-6 sRa, and Layilin (LAYN) and asthma. Moreover, the identified proteins may serve as attractive drug targets for asthma, especially ECM1 and Layilin (LAYN). However, further research is required to comprehensively understand the roles of these proteins in the occurrence and progression of asthma.
Prevalence of degenerative disease of the temporomandibular joint in anterior open bite patients with different molar relationships: a retrospective observational study
Authors: Wang Chenxu , Guo Feng , Hu Hengyu , Liu Chenghuan , Lei Lang 
Published: October 2024

Abstract

Objectives: To assess the prevalence of degenerative disease of the temporomandibular joint in anterior open bite patients with different molar relationships.
Methods: 246 anterior open bite adult orthodontic patients were divided into Class I group (n=65), Class II group (n=116) and Class III group (n=65) based on their sagittal molar relationships, meanwhile, 70 normal subjects were selected as control group. The occurrence of degenerative joint disease was detected by cone beam computed tomography, and the prevalence of degenerative joint disease among groups was compared. Mandibular plane angle and the vertical distance between the upper and lower incisors were also measured.
Results: The overall prevalence of degenerative joint disease in anterior open bite patients and control group was 30.28% and 5.00%, respectively. Class II group showed the significantly highest prevalence of degenerative joint disease (50.43%, P＜0.001), highest frequency of bilateral degenerative joint disease (43.95%，P＜0.001) and highest mandibular plane angle. Among the anterior open bite groups, Class III group exhibited the highest vertical distance between the upper and lower incisors (3.35 ±1.86mm, P＜0.05) but the lowest prevalence of degenerative joint disease(10.77%).
Conclusions: For Class II anterior open bite patients, condylar resorption in degenerative diseases of TMJ may be an important cause of malocclusion.