bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study
Authors: Demirci Nebi Serkan , Azizy Abdulmunir , Paksoy Nail , Doğan İzzet , Karabulut Senem , Karahan Latif , Tastekin Didem
Published: March 2024

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87–7.14) and 5.0 months (95% CI, 4.10–5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53–10.47) and 9.0 months (95% CI, 6.87–11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.
Incidence rate and implications of splenic ischemia during sleeve gastrectomy and its related procedure
Authors: Huang Jinrong , Liao Chenglong , Zhou Weiwei , Li Hancheng
Published: March 2024

Splenic ischemia (SI) is a common finding during sleeve gastrectomy (SG) procedures; however, reports are still lacking. In this study, we retrospectively analyzed our SG patients to understand better the incidence rate and implications of SI. Patients’ data from the beginning of the year 2021 until December 2022 that underwent bariatric surgery at our university hospital were retrospectively analyzed. Patient surgery video was reviewed by all the authors to investigate the incidence of SI. Thereafter, the corresponding patient age, height, weight, BMI, and their postoperative day 1 (POD1) temperature and blood routine test results (patients were routinely discharged at POD2) were collected and analyzed. 204 patients were included in this study. The mean age and preoperative BMI were 31.7 ± 7.4 years old and 38.8 ± 5.6 kg/m2, respectively. SI was observed in 18 cases (8.8%). 30-day readmission rate was seen in 3 patients (1.5%, all without SI during the primary surgery). There was no statistical difference with regard to the POD1 temperature and blood test results between the patients with and without SI. The incidence of SI during sleeve gastrectomy-related procedures is a common finding in our study. We did not observe significant differences postoperatively between the patients with and without SI before discharge. Further study is needed to understand the mechanism for the incidence of SI during SG.
Causal effects of gut microbiota on autism spectrum disorder: A two-sample mendelian randomization study
Authors: Chen Yajun , Xue Yan , Jia Lang , Yang Menghan , Huang Gelin , Xie Jiang
Published: March 2024

There is increasing evidence that alterations in gut microbiota (GM) composition are associated with autism spectrum disorder (ASD), but no reliable causal relationship has been established. Therefore, a 2-sample Mendelian randomization (MR) study was conducted to reveal a potential causal relationship between GM and ASD. Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS) and Mendelian randomization studies to estimate their impact on ASD risk in the iPSYCH-PGC GWAS dataset (18,382 ASD cases and 27,969 controls). Inverse variance weighted (IVW) is the primary method for causality analysis, and several sensitivity analyses validate MR results. Among 211 GM taxa, IVW results confirmed that Tenericutes (P value = .0369), Mollicutes (P value = .0369), Negativicutes (P value = .0374), Bifidobacteriales (P value = .0389), Selenomonadales (P value = .0374), Bifidobacteriaceae (P value = .0389), Family XIII (P value = .0149), Prevotella7 (P value = .0215), Ruminococcaceae NK4A214 group (P value = .0205) were potential protective factors for ASD. Eisenbergiella (P value = .0159) was a possible risk factor for ASD. No evidence of heterogeneous, pleiotropic, or outlier single-nucleotide polymorphism was detected. Additionally, further sensitivity analysis verified the robustness of the above results. We confirm a potential causal relationship between certain gut microbes and ASD, providing new insights into how gut microbes mediate ASD. The association between them needs to be further explored and will provide new ideas for the prevention and treatment of ASD.
Mapping trends and hotspots regarding the use of telenursing for elderly individuals with chronic diseases: A bibliometric analysis
Authors: Yuan Yuan , Wang Sican , Tao Chunhua , Gu Zhie , Kitayama Akio , Yanagihara Kiyoko , Liang Jingyan
Published: March 2024

Background:

Telenursing is receiving extensive attention from scholars and medical staff. However, there are few studies on the knowledge structure of telenursing for elderly individuals with chronic diseases. This study aims to demonstrate current research status and development trend of telenursing for elderly individuals with chronic diseases through a visual analysis of CiteSpace, so as to provide a more comprehensive perspective for future researches.

Methods:

Literature about telenursing for elderly patients with chronic diseases from 2002 to 2022 was retrieved from the Web of Science Core Collection using CiteSpace 6.1.R3.

Results:

A total of 375 records were obtained. Annual publication and citation frequency gradually increased over the investigated period, reaching a peak in 2022. Journal of Telemedicine and Telecare was the most prolific and the most cited journal. The United States was the most productive country, the University of Melbourne was the most productive institution, and the author CHEN C ranked the highest in the number of publications. The most popular keywords were “care,” “telemedicine,” “management,” “older adult,” “chronic disease,” “health,” and “heart failure,” which had a high frequency and centrality. The keywords “telehealth,” “randomized controlled trail,” “chronic obstructive pulmonary disease,” “implementation” and “time” showed the strongest citation burst. The keywords were clustered to form 10 labels. The article published in 2010 by Chaudhry SI was cited the most. The top 3 cited journals were all special journal of telemedicine.

Conclusion:

This study revealed current research status and development trend of telenursing for elderly individuals with chronic diseases. The bibliometric analysis of telenursing expands the knowledge field of telemedicine and provides new insights into the management of elderly patients with chronic diseases.
Impact of a clinical care pathway developed through the action research method on the psychological well-being and quality of life in male patients with urethral stricture
Authors: Yan Yanhong , Wu Yue , Li Anqi , Yang Aiying , Tao Jun , Wang Xuejing
Published: March 2024

Background:

The objective of this study is to examine the development of a clinical care pathway utilizing an action research methodology for male patients with urethral stricture, and to assess the psychological and quality of life outcomes following the implementation of this pathway.

Methods:

Ninety patients diagnosed with urethral stricture, admitted to our hospital between May 2021 and May 2022, were selected as the study cohort. Employing a random number method, these patients were allocated into an observation group and a control group, each comprising 45 individuals. The control cohort employs standard care protocols for individuals with urethral stenosis, while the experimental group employs an action research methodology to develop a clinical care pathway specific to the management of patients with urethral stenosis, with an intervention cycle of 3 months. The investigation evaluated the impact of the intervention by scrutinizing pre- and post-intervention data through the utilization of the WHO Quality of Life Scale (WHOQOL-BREF), in addition to the Anxiety Rating Scale and the Depression Rating Scale.

Results:

Prior to the intervention, no significant differences were observed in WHOQOL-BREF scores across dimensions, as well as anxiety and depression scores between the 2 groups (P > .05). Subsequent to the intervention, the patients in the observation group exhibited significantly higher scores across all WHOQOL-BREF dimensions and total scores compared to the control group, with statistical significance (P < .05). Moreover, anxiety and depression scores in the observation group were markedly lower than those in the control group, demonstrating statistical significance (P < .05).

Conclusion:

The implementation of a clinical nursing pathway rooted in action research methodology proves to be an effective strategy for enhancing clinical nursing practices, elevating patient quality of life, and diminishing the prevalence of anxiety and depression.
Integrated analysis identifies cuproptosis-related gene DLAT and its competing endogenous RNAs network to predict the prognosis of pancreatic adenocarcinoma patients
Authors: Zhou Congya , Jin Long , Yu Jiao , Gao Zhengchao
Published: March 2024

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with poor prognosis. However, the relationship between cuproptosis-related genes (CRGs) and its competing endogenous RNA (ceRNA) network with the prognosis of PAAD patients remains unclear. To investigate this relationship, we calculated the difference in CRGs between PAAD tissues and normal tissues using the ‘limma’ R package. Additionally, we employed least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a prognostic signature for CRGs. Survival analysis of patients with PAAD was performed using Kaplan–Meier analysis. Furthermore, we used bioinformatics tools to screen for CRGs-related MicroRNA (miRNA) and lncRNAs. To validate these findings, we conducted real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, colony formation, and Transwell assays to assess the effect of DLAT in vitro. Our results revealed a cuproptosis-related prognostic signature consisting of 3 prognostic genes (DLAT, LIAS, and LIPT1). Notably, patients with a high-risk score for the CRGs signature exhibited poor prognosis in terms of overall survival (OS) (P < .05). The receiver operating characteristic (ROC) curve was used to evaluate the prognostic signature of CRGs. The results showed that the 1-year, 3-year, and 5-year area under the curve values for predicting OS were 0.62, 0.66, and 0.79, respectively. Additionally, the CRGs-related ceRNA network revealed the regulatory axis of LINC00857/has-miR-1179/DLAT in PAAD. In vitro experiments demonstrated that knockdown of LINC00857 and DLAT inhibited the growth and invasion of PAAD cells. This study identified a CRG-related prognostic signature consisting of 3 biomarkers (DLAT, LIAS, and LIPT1) for PAAD. Furthermore, ceRNA network analysis suggested the involvement of the LINC00857/has-miR-1179/DLAT axis in the development of PAAD. Overall, this study provides theoretical support for the investigation of diagnostic and prognostic biomarkers as well as potential therapeutic targets in PAAD.
Comparison of the problem-solving performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Korean emergency medicine board examination question bank
Authors: Lee Go Un , Hong Dae Young , Kim Sin Young , Kim Jong Won , Lee Young Hwan , Park Sang O , Lee Kyeong Ryong
Published: March 2024

Large language models (LLMs) have been deployed in diverse fields, and the potential for their application in medicine has been explored through numerous studies. This study aimed to evaluate and compare the performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Emergency Medicine Board Examination question bank in the Korean language. Of the 2353 questions in the question bank, 150 questions were randomly selected, and 27 containing figures were excluded. Questions that required abilities such as analysis, creative thinking, evaluation, and synthesis were classified as higher-order questions, and those that required only recall, memory, and factual information in response were classified as lower-order questions. The answers and explanations obtained by inputting the 123 questions into the LLMs were analyzed and compared. ChatGPT-4 (75.6%) and Bing Chat (70.7%) showed higher correct response rates than ChatGPT-3.5 (56.9%) and Bard (51.2%). ChatGPT-4 showed the highest correct response rate for the higher-order questions at 76.5%, and Bard and Bing Chat showed the highest rate for the lower-order questions at 71.4%. The appropriateness of the explanation for the answer was significantly higher for ChatGPT-4 and Bing Chat than for ChatGPT-3.5 and Bard (75.6%, 68.3%, 52.8%, and 50.4%, respectively). ChatGPT-4 and Bing Chat outperformed ChatGPT-3.5 and Bard in answering a random selection of Emergency Medicine Board Examination questions in the Korean language.
Effect of acupuncture on Hashimoto thyroiditis: A systematic review and meta-analysis
Authors: Wang Xiaohui , Li Yu , Xie Hai , Dai Zhicheng , Ma Limin , Zhu Xinying , Zhan Tongxia
Published: March 2024

Background:

Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients’ quality of life.

Methods:

We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs).

Results:

A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = −63.18, 95%CI = −91.73 to −34.62, P < .00001), TGAb content (MD = −68.56, 95%CI = −101.55 to −35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = −2.16, 95%CI = −3.14 to −1.19, P < .00001) had a significant effect.

Conclusion:

Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH.
CNP model intervention effect on acute urticaria patients’ psychological status, compliance, and life quality
Authors: Yang Min , Ma Lei , Wei Yihua , Li Na , Aggari Michael I. , De Ala Minerva B. , Yang Shuang
Published: March 2024

This study aimed to evaluate the impact of the clinical nursing pathway (CNP) on the psychological state, treatment adherence, and quality of life in patients with acute urticaria. A total of 240 patients diagnosed with acute urticaria at a tertiary hospital in Shandong Province were retrospectively assigned to either a control group, receiving standard care, or an intervention group, receiving care according to the CNP model. The primary outcomes assessed were levels of anxiety, depression, quality of life, and patient compliance. Statistical analyses were employed to evaluate the outcomes. Following the intervention, significant differences were observed in the anxiety and depression scores (P < .001), with the intervention group demonstrating lower levels of both. The control group’s psychological state exhibited significant variance pre- and post-intervention (P < .001), alongside notably reduced overall compliance (P < .01). Post-intervention, patients in the intervention group showed enhanced treatment compliance, with a rapid increase within the first hour and a stable ascent over the following 10 hours, albeit with a marginally greater increase in the CNP group. Beyond 10 hours, the CNP group’s compliance gradually declined, with a slight uptick in noncompliance rates. By 14 hours, the control group’s overall compliance began to wane, with a sharp decline in full compliance and a rapid rise in noncompliance rates observed after 19 hours. At the 20-hour mark, the control group’s noncompliance rate surpassed both the partial and full compliance rates. Conversely, post-20 hours, the CNP group maintained higher rates of full and partial compliance, with a lower noncompliance rate. No significant changes were noted in the control group’s physiological or mental state, except in the domains of self-care and social ability, where notable differences were absent pre- and post-intervention. In contrast, the CNP group showed significant improvements in physiological and mental states, self-care, and social abilities post-intervention (P < .001), with noticeable differences in these domains evident 6 hours into the treatment (P < .01), leading to an enhanced quality of life. The CNP-based clinical nursing model intervention significantly benefits patients with acute urticaria by alleviating anxiety and depression, enhancing treatment adherence, and improving overall quality of life.
Oxidative stress’s impact on red blood cells: Unveiling implications for health and disease
Authors: Obeagu Emmanuel Ifeanyi , Igwe Matthew Chibunna , Obeagu Getrude Uzoma
Published: March 2024

Oxidative stress, a condition characterized by an imbalance between reactive oxygen species (ROS) production and the body’s ability to detoxify them, has emerged as a pivotal factor in the pathophysiology of various diseases. Red blood cells (RBCs), essential components of the circulatory system, are particularly susceptible to oxidative damage due to their high oxygen-carrying capacity and the abundance of vulnerable biomolecules. This review comprehensively explores the intricate mechanisms underlying oxidative stress-induced damage to red blood cells and the subsequent implications for overall health and disease. We delve into the sources of ROS generation within RBCs, including metabolic processes and external factors, shedding light on the delicate redox balance that governs cellular homeostasis. The impact of oxidative stress on red blood cells extends beyond the confines of their primary physiological role, as these cells actively participate in immune responses, inflammation modulation, and nitric oxide metabolism. Consequently, understanding the implications of oxidative stress on RBCs provides valuable insights into the broader landscape of health and disease. In conclusion, this review underscores the critical role of oxidative stress in influencing red blood cell physiology and its far-reaching implications for human health. Elucidating the molecular intricacies of this relationship not only enhances our understanding of fundamental biological processes but also paves the way for the development of targeted therapeutic interventions to mitigate the adverse effects of oxidative stress on red blood cells and, by extension, on overall health.
Mechanism exploration of SanShi ShengXin Ointment in the treatment of pressure ulcers based on network pharmacology and molecular docking
Authors: Yang Kai , Fei Chenchen , Gao Xiang
Published: March 2024

Background:

To explore the active ingredients, prospective targets, and action mechanisms of SanShi ShengXin Ointment in the treatment of pressure ulcers (PU) based on the network pharmacology technique and molecular docking technology.

Methods:

The active ingredients and action targets of Sanshishengxin Ointment were searched through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform. The PU-related targets were retrieved from the GeneCards and DisGeNET databases. The intersection target genes of disease and drugs were obtained. The “disease-drug-active ingredient-target” was constructed using Cytoscape software. The intersection target genes were imported into the String database to construct a protein–protein interaction network for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The Auto Dock software was used for relevant molecular docking.

Results:

A total of 78 active ingredients of SanShi ShengXin Ointment were obtained, corresponding to 539 target genes. There were 5896 PU-related target genes, and 373 intersection target genes of disease and drugs were obtained, such as STAT3, TP53, JUN, MAPK3, CTNNB1, involving PI3K-Akt, TNF, MAPK, and other related signaling pathways.

Conclusion:

Based on network pharmacology and molecular docking analyses, this study demonstrates that SanShi ShengXin Ointment can treat PU through multicomponent, multitarget, and multipathway. .
Effect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis
Authors: Zhang Hongxia , Wu Huijun , Qi Xiaoyuan , Wu Fan , Zhang Danxue
Published: March 2024

To explore the efficacy and safety of butylphthalide combined with idebenone in the treatment of vascular dementia. The clinical data of 126 patients with vascular dementia who were admitted to our hospital between March 2021 and February 2023 were retrospectively reviewed. Among them, 62 patients received butylphthalide alone (single group) and 64 patients received butylphthalide combined with idebenone (combined group). Cognitive function scores, serum inflammatory factor levels, oxidative stress index levels, and incidence of adverse reactions were compared between the 2 groups before and after treatment. After treatment, the Hasegawa Dementia Scale, Mini Mental State Examination Scale, and activities of daily living scores in both groups were higher than before treatment, and the scores in the combined group were higher than before treatment (P < .05). After treatment, the levels of serum C-reactive protein, tumor necrosis factor-α, and interleukin 6 in both groups were lower than those before treatment, and those in the combined group were lower than those in the simple group (P < .05). After treatment, the levels of serum glutathione peroxidase and superoxide dismutase in the 2 groups were higher than those before treatment, and the level of malondialdehyde was lower than that before treatment. The levels of serum glutathione peroxidase and superoxide dismutase in the combined group were higher than those in the simple group, and the level of malondialdehyde was lower than that in the simple group (P < .05). There was no significant difference in the incidence of adverse reactions between the combined group (6.25%) and the simple group (3.23%) (P > .05). Compared with butylphthalide alone, intervention of butylphthalide combined with idebenone on vascular dementia can effectively reduce the degree of inflammatory and oxidative stress reactions, improve cognitive function, and promote the ability to perform activities of daily living in a safe manner.
Intracellular lipase and regulation of the lipid droplet
Authors: Cabodevilla Ainara G. , Son Ni , Goldberg Ira J.
Published: March 2024

Purpose of review

Lipid droplets are increasingly recognized as distinct intracellular organelles that have functions exclusive to the storage of energetic lipids. Lipid droplets modulate macrophage inflammatory phenotype, control the availability of energy for muscle function, store excess lipid, sequester toxic lipids, modulate mitochondrial activity, and allow transfer of fatty acids between tissues.

Recent findings

There have been several major advances in our understanding of the formation, dissolution, and function of this organelle during the past two years. These include new information on movement and partition of amphipathic proteins between the cytosol and lipid droplet surface, molecular determinants of lipid droplet formation, and pathways leading to lipid droplet hydrophobic lipid formation. Rapid advances in mitochondrial biology have also begun to define differences in their function and partnering with lipid droplets to modulate lipid storage versus oxidation.

This relationship of lipid droplets biology and cellular function provides new understanding of an important cellular organelle that influences muscle function, adipose lipid storage, and diseases of lipotoxicity.
Investigating the Impact of Tumor Biology and Social Determinants on Time to Diagnosis and Stage at Presentation of Wilms Tumor
Authors: Collins Adele , Molina Kuna Elizabeth , Anderson-Mellies Amy , Cost Carrye , Green Adam L.
Published: March 2024

Delays in diagnosis and time to diagnosis generally are used interchangeably in cancer disparity research, but these terms may have important differences. Although these terms are related, we hypothesize that time to diagnosis is determined by the aggressiveness of the tumor based on intrinsic factors such as tumor biology, whereas delays in diagnosis are caused by extrinsic factors such as socioeconomic status, leading to presentation at higher stage of disease due to barriers of care. We conducted a retrospective study of 306 patients diagnosed with Wilms tumor at Children’s Hospital Colorado between 1971 and 2016 identifying patient barriers as extrinsic markers and using unfavorable histology and loss of heterozygosity as markers of aggressive tumor biology. Multivariable logistic regression was performed. Patients with Medicaid were more likely to present greater than 4 days after initial symptoms compared to those with private insurance, and those with housing concerns were more likely to be diagnosed greater than 9 days from initial symptoms. Tumor biology was noted to be associated with higher stage at diagnosis, but patient barriers were not. These findings suggest the interplay between tumor biology, patient barriers, diagnostic timing, and stage at diagnosis is more complex, multifactorial, and in need of further study.
Use of Home-Based Self-Collected Dried Blood Spots to Test for Syphilis, Human Immunodeficiency Virus, Hepatitis C and B Virus Infections and Measuring Creatinine Concentration
Authors: Nieuwenburg S.A. , Bruisten S.M. , Heijman T. , Vermeulen W. , van Dam A.P , Schim van der Loeff M.F. , de Vries H.J.C
Published: March 2024

Introduction

Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration.

Methods

We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing.

Results

In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 μmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3–5).

Discussion

Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low.
High Heart Rate Variability Buffers the Effect of Attachment Insecurity on Sleep Quality
Authors: Paoletti-Hatcher Jensine , Argueta Daniel L. , Wu-Chung E. Lydia , Chen Michelle A. , Brown Ryan L. , LeRoy Angie S. , Murdock Kyle W. , Thayer Julian F. , Fagundes Christopher P.
Published: March 2024

Objective

Sleep quality is an important health-protective factor. Psychosocial factors, including attachment orientation, may be valuable for understanding who is at risk of poor sleep quality and associated adverse health outcomes. High attachment anxiety is reliably associated with adverse health outcomes, whereas high attachment avoidance is associated with adverse health outcomes when co-occurring with poor self-regulatory capacity, indexed by heart rate variability (HRV). We examined the associations between attachment anxiety, attachment avoidance, HRV, and sleep quality.

Methods

Using longitudinal data from a sample of 171 older adults measured four times over 1 year (M = 66.18 years old; 67.83% women), we separated the between-person variance (which we call “trait”) and within-person variance (which we call “state”) for attachment anxiety, attachment avoidance, and HRV (via the root mean square of successive differences). Sleep quality was measured with the Pittsburgh Sleep Quality Index.

Results

Higher trait attachment anxiety was associated with poorer global sleep quality (B = 0.22, p = .005). Higher state attachment avoidance was associated with poorer sleep quality (B = −0.13, p = .01), except for those with higher trait HRV. Higher state attachment anxiety was associated with poorer sleep quality (B = −0.15, p = .002), except for those with higher or mean trait HRV. Higher trait attachment anxiety was associated with poorer sleep quality (B = −0.31, p = .02), except for those with higher trait HRV.

Conclusions

High trait HRV mitigated the adverse effects of attachment insecurity on sleep quality. Our results suggest that people with high trait HRV had greater self-regulation capacity, which may enable them to enact emotion regulation strategies effectively.
Impact of Collaborative Nursing Care Delivery on Patient Safety Events in an Emergency Intensive Care Unit: A Retrospective Observational Study
Authors: Obayashi Masato , Shimoyama Keiichiro , Ono Koji
Published: March 2024

Objectives

Patient safety events (PSEs) have detrimental consequences for patients and healthcare staff, highlighting the importance of prevention. Although evidence shows that nurse staffing affects PSEs, the role of an appropriate nursing care delivery system remains unclear. The current study aimed to investigate whether nursing care delivery systems could prevent PSEs.

Methods

This retrospective study was conducted in Japan. The study examined the collaborative 4:2 nursing care delivery system in which 2 nurses are assigned to care for 4 patients, collaborating to perform tasks, and provide care. The cohort receiving care from a collaborative 4:2 nursing care delivery system was labeled the postintervention, whereas the cohort receiving care from a conventional individualized system, in which one nurse provides care for 2 patients, was labeled the preintervention. The primary outcome was the occurrence of PSEs.

Results

The preintervention and postintervention comprised 561 and 401 patients, respectively, with the latter consisting of a younger and more critically ill population. The number of PSEs per 1000 patient-days was not significantly different between the 2 groups (10.3 [95% confidence interval, 7.1–13.5] versus 6.0 [95% confidence interval, 3.2–8.9], P = 0.058). Multiple logistic regression analysis showed that the collaborative 4:2 nursing care delivery system was significantly associated with PSEs (adjusted odds ratio, 0.53; 95% confidence interval, 0.29–0.95; P = 0.037).

Conclusions

These findings suggest that in an emergency intensive care unit, a collaborative nursing care delivery system was associated with a decrease in PSEs.
Seminal root angle is associated with root system architecture in durum wheat
Authors: Kang Yichen , Rambla Charlotte , Haeften Shanice V. , Fu Brendan , Akinlade Oluwaseun , Potgieter Andries B. , Borrell Andrew K. , Mace Emma , Jordan David R. , Alahmad Samir , Hickey Lee T.
Published: March 2024

Optimal root system architecture (RSA) is critical for efficient resource capture in soils, hence being an interest in crop breeding. Seminal root angle (SRA) at the seedling stage in durum wheat has been suggested to be a good indicator of RSA. However, research on correlating such lab-based seedling root phenotyping to RSA at later phases of plant growth is limited, resulting in the importance of root trait variation seen in seedlings often being overstated. To explore the role of SRA in modifying RSA at later phases of plant growth, we assessed 11 genotypes contrasting in SRA (wide and narrow), grown in a rhizobox designed for phenotyping root systems of plants during late-tillering. Above-ground traits and root dry mass in different soil depths and across the entire soil volume were measured manually, while root architectural traits were extracted using image analysis and summarised by multiple factor analysis to describe RSA. When comparing the wide and narrow genotypes, no differences were detected for above-ground traits and total root dry mass. However, differences were observed in the allocation of root dry mass at different depths. The wide and narrow genotypes showed distinct RSAs, particularly in the upper soil (0 ‒ 30 cm). The wide genotypes exhibited a ‘spread-out’ root system with dense and thin roots, whereas the narrow genotypes had a compact root system with fewer but thicker roots. Our study demonstrated a clear difference in RSA between the wide and narrow genotypes, highlighting the association between SRA on the direction and distribution of root growth in plants at later growth stages.
Staphylococcus aureus lipid factors modulate melanoma clustering and invasion in zebrafish
Authors: Giese Morgan , Ramakrishnan Gayathri , Steenberge Laura , Dovan Jerome , Sauer JD , Huttenlocher Anna
Published: March 2024

The microbiome can influence cancer development and progression. However, less is known about the role of the skin microbiota in melanoma. Here, we take advantage of a zebrafish melanoma model to probe the effects of Staphylococcus aureus on melanoma invasion. We find that S. aureus produces factors that enhance melanoma invasion and dissemination in zebrafish larvae. We used a published in vitro 3D cluster formation assay which correlates increased clustering with tumor invasion. S. aureus supernatant increased clustering of melanoma cells which was abrogated by use of a Rho-Kinase inhibitor, implicating a role for Rho-GTPases. The melanoma clustering response was specific to S. aureus and not other staphylococcal species, including S. epidermidis. Our findings suggest that S. aureus may promote melanoma clustering and invasion via lipids generated by the lipase SAL2 (gehB). Taken together, these findings suggest that specific bacterial products mediate melanoma invasive migration in zebrafish.
Aberrant cytoplasmic localization of MLH1 characterizes a sub-clonal breast cancer cell population that seeds recurrence
Authors: Mazumder A , DeWitt JT , Oropeza E , Punturi N , Lozano D , Raghunathan M , Piscitelli JM , Sajjadi E , Guerini-Rocco E , Venetis K , Ivanova M , Mane E , Fusco N , Bainbridge MN , Manhart CM , Haricharan S
Published: March 2024

Estrogen receptor positive (ER+) breast cancer is one of the most common causes of cancer-related death in women. Mortality is largely driven by recurrence of treatment-resistant disease after many years of apparent response, making the molecular events that cause recurrence a critical area of investigation. Loss of expression ofMLH1, a tumor suppressor best studied in its role in mismatch repair, induces resistance of ER+ breast cancer cells to standard estrogen-targeting therapies. It does so by delinking cell cycle progression from estrogen regulation, a role distinct from its function in mismatch repair. MLH1 loss, as currently clinically diagnosed by detecting genomic instability or by immunohistochemistry for absence of protein, occurs in 12-15% of all cancers. Here, we demonstrate that sub-clonal, patient-derived mutations inMLH1, which neither impact protein abundance nor contribute sufficiently to genomic instability to be detected diagnostically, seed endocrine treatment resistance by enabling estrogen-independent growthin vitro,ex vivoin patient-derived organoids (p=0.005) andin vivo(p=0.0001). The mechanism underlying this endocrine treatment resistance is aberrant localization of MLH1 to the cytoplasmin vitroandin vivo(p=0.04), which precludes cell cycle arrest in response to endocrine therapy while simultaneously rendering cells acutely dependent on CDK4/6 activity. Consequently, administration of CDK4/6 inhibitors causes extreme regression in cells with cytoplasmic MLH1 compared to control cell populations with nuclear localization of MLH1in vitro(p=0.00000009),ex vivo(p=0.01) andin vivo(p=0.01). As aberrant cytoplasmic localization occurs in an additional ∼12% of ER+ breast cancer patients, it constitutes a new, major contributor to MLH1 dysregulation. The potential applicability of cytoplasmic MLH1 as a predictor of responsiveness to existing targeted therapies in a hard-to-treat breast cancer subtype posits an update of current clinical diagnostic criteria and therapeutic strategies. This is particularly important in the adjuvant setting where identification of biomarkers predicting responsiveness to CDK4/6 inhibitors remains an urgent, unmet clinical need.
Promoting Longevity in Aged Liver through NLRP3 Inflammasome Inhibition Using Tauroursodeoxycholic Acid (TUDCA) and SCD Probiotics
Authors: Baba Burcu , Ceylani Taha , Acikgoz Eda , Gurbanov Rafig , Keskin Seda , Samgane Gizem , Tombuloglu Huseyin , Teker Hikmet Taner
Published: March 2024

This study investigates the combined impact of SCD Probiotics and tauroursodeoxycholic acid (TUDCA) on the biomolecular makeup, histological changes and levels of inflammasome in the liver tissue of 24-month-old male Sprague-Dawley rats. By administering TUDCA (300 mg/kg, intravenously) and SCD Probiotics (3 mL (1 x 108 CFU), orally) daily for a week, the researchers employed ATR-FTIR spectroscopy along with machine learning approaches such as Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) to analyze the biomolecular profiles. In addition, the study measured the expression levels of inflammasome markers NLRP3, ASC, Caspase-1, IL18, and IL1β using RT-qPCR and examined liver sections for histopathological changes and NLRP3 inflammasome activation. The results revealed significant differences in the levels of lipids, proteins, and nucleic acids, with TUDCA having a noteworthy impact on enhancing lipid bands and reducing cholesterol ester bands, while SCD Probiotics showed the opposite effects. Furthermore, TUDCA was found to decrease the acyl chain length of fatty acids and improve protein conformation, whereas SCD Probiotics increased both the acyl chain length and protein phosphorylation ratio, suggesting a decrease in lipid and protein dynamics from both treatments. The histological assessments showed significant reductions in cellular degeneration, lymphatic infiltration, hepatic fibrosis, and the immunoreactivity of NLRP3 and ASC in the treated groups. SCD Probiotics exhibited a marked reduction in inflammasome-related gene expressions, and the lowest gene expression levels were observed in the group receiving both treatments. Despite an increase in serum AST and LDH levels across all groups, only the SCD Probiotics group showed an increase in albumin levels. The findings suggest that SCD Probiotics, TUDCA, and their combined administration may provide a promising avenue for therapeutic interventions in age-associated liver conditions and may mitigate age-related liver fibrosis while enhancing liver functionality.
Macroscale brain states support the control of semantic cognition
Authors: Wang Xiuyi , Krieger-Redwood Katya , Cui Yanni , Smallwood Jonathan , Du Yi , Jefferies Elizabeth
Published: March 2024

Understanding how the human brain adapts to varying cognitive demands is crucial in neuroscience. Here, we examined how networks involved in controlled semantic retrieval reconfigure themselves to generate neurocognitive states appropriate to different task contexts. We parametrically varied the demands of two semantic tasks - global association and feature matching judgments - and contrasted these effects of cognitive control with those of non-semantic tasks. We then characterized these effects on the cortical surface and within a whole-brain state space, anchored by the top three dimensions of intrinsic connectivity. Our results revealed that demanding semantic association tasks elicited more activation in the anterior regions of the prefrontal and temporal cortex. In contrast, difficult semantic feature matching tasks produced more posterior activation, aligning closely with regions engaged during multiple demanding non-semantic tasks. In both semantic feature matching and non-semantic contexts, the difficulty effects were situated towards the controlled end of a dimension capturing functional separation between cognitive control and default mode regions. Conversely, in semantic association tasks, the difficulty effects elicited similar responses across both cognitive control and default mode networks. Furthermore, controlled association and non-semantic control were located towards the heteromodal end of a heteromodal-unimodal dimension, while semantic feature matching involved a brain state that was more visual and unimodal. These findings demonstrate that a variety of brain states underpin controlled cognition. Specifically, cognitive control regions interact with heteromodal semantic knowledge system to identify contextually relevant conceptual overlaps (e.g., associating 'DOG' with 'BEACH'), and separate from heteromodal memory regions for modality-specific conceptual overlaps (e.g., connecting 'DALMATIAN' with 'BLACK AND WHITE').
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic
Authors: Bach Emil , Ghanizada Mustafa , Kirkby Nikolaj , Buus Søren , Østerbye Thomas
Published: March 2024

Background

Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition.

Methods

Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent “high-fidelity regions” (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering.

Results

We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density the order would be reversed.

Conclusion

We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.
NEK1 haploinsufficiency impairs ciliogenesis in human iPSC-derived motoneurons and brain organoids
Authors: Nice Sorce Marta , Sabrina Invernizzi , Valeria Casiraghi , Serena Santangelo , Chiara Lattuada , Paola Podini , Alberto Brusati , Alessio Silva , Silvia Peverelli , Angelo Quattrini , Vincenzo Silani , Patrizia Bossolasco , Antonia Ratti
Published: March 2024

Primary cilia are microtubule-based organelles acting as specialized signalling antennae that respond to specific stimuli to maintain cellular integrity and homeostasis. Recent studies indicate defective primary cilia in post-mortem human brains and animal models of neurodegenerative conditions, including Amyotrophic Lateral Sclerosis (ALS). Heterozygous loss-of-function mutations (LOF) inNEK1gene are present in about 1% of familial and sporadic ALS cases. The protein kinase NEK1 regulates various cellular processes, including ciliogenesis, but a clear link betweenNEK1LOF mutation in ALS and primary cilia is unknown. In this study we generated a human iPSC line carrying aNEK1LOF mutation by gene editing, leading to NEK1 protein haploinsufficiency. In differentiated iPSC-motoneurons (MNs) we observed that primary cilia were significantly shorter inNEK1-LOF iPSC-MNs compared to wild-type (WT) iPSC-MNs and that also the percentage of ciliated iPSC-MNs was significantly decreased inNEK1-LOF cells. We also investigated ciliogenesis inNEK1-LOF iPSC-brain organoids confirming that primary cilia were thinner with no apparent alteration in the ultrastructure by transmission electron microscopy.

Our data suggest that NEK1 protein plays a role in regulating ciliogenesis in both 2D and 3D human iPSC-derived neuronal models and thatNEK1LOF mutations associated to ALS, leading toNEK1haploinsufficiency and likely to reduced kinase activity, impair primary cilium formation. The involvement of ciliogenesis dysfunction in ALS deserves further investigation providing novel therapeutic targets and strategies to be addressed for this incurable disease.