bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune profiling and functional analysis of NK and T cells in ataxia telangiectasia
Authors: Graafen Lea , Heinze Annekathrin , Albinger Nawid , Salzmann-Manrique Emilia , Ganß Franziska , Hünecke Sabine , Cappel Claudia , Wölke Sandra , Donath Helena , Trischler Jordis , Theilen Till-Martin , Heller Christine , Königs Christoph , Ehl Stephan , Bader Peter , Klingebiel Thomas , Klusmann Jan-Henning , Zielen Stefan , Schubert Ralf , Ullrich Evelyn
Published: August 2024

Ataxia telangiectasia (AT) is a rare autosomal-recessive disorder characterized by profound neurodegeneration, combined immunodeficiency, and an increased risk for malignant diseases. Treatment options for AT are limited, and the long-term survival prognosis for patients remains grim, primarily due to the emergence of chronic respiratory pathologies, malignancies, and neurological complications. Understanding the dysregulation of the immune system in AT is fundamental for the development of novel treatment strategies. In this context, we performed a retrospective longitudinal immunemonitoring of lymphocyte subset distribution in a cohort of AT patients (n = 65). Furthermore, we performed FACS analyses of peripheral blood mononuclear cells from a subgroup of 12 AT patients to examine NK and T cells for the expression of activating and functional markers. We observed reduced levels of peripheral blood CD3+CD8+ cytotoxic T cells, CD3+CD4+ T helper cells, and CD19+ B cells, whereas the amount of CD3−-CD56+ NK cells and CD3+CD56+ NKT-like cells was similar compared with age-matched controls. Notably, there was no association between the age-dependent kinetic of T-, B-, or NK-cell counts and the occurrence of malignancy in AT patients. Additionally, our results indicate an altered NK- and T-cell response to cytokine stimulation in AT with increased levels of TRAIL, FasL, and CD16 expression in NK cells, as well as an elevated activation level of T cells in AT with notably higher expression levels of IFN-γ, CD107a, TRAIL, and FasL. Together, these findings imply function alterations in AT lymphocytes, specifically in T and NK cells, shedding light on potential pathways for innovative therapies.
Development and validation of a hypoxia- and mitochondrial dysfunction- related prognostic model based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer
Authors: Li Yirong , Cui Yue , Wang Zhen , Wang Liwei , Yu Yi , Xiong Yuyan
Published: August 2024

Introduction

Gastric cancer (GC) remains a major global health threat ranking as the fifth most prevalent cancer. Hypoxia, a characteristic feature of solid tumors, significantly contributes to the malignant progression of GC. Mitochondria are the major target of hypoxic injury that promotes mitochondrial dysfunction during the development of cancers including GC. However, the gene signature and prognostic model based on hypoxia- and mitochondrial dysfunction-related genes (HMDRGs) in the prediction of GC prognosis have not yet been established.

Methods

The gene expression profile datasets of stomach cancer patients were retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Prognostic genes were selected using Least Absolute Shrinkage and Selection Operator Cox (LASSO-Cox) regression analysis to construct a prognostic model. Immune infiltration was evaluated through ESTIMATE, CIBERSORT, and ssGSEA analyses. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to explore implications for immunotherapy. Furthermore, in vitro experiments were conducted to validate the functional roles of HMDRGs in GC cell malignancy.

Results

In this study, five HMDRGs (ZFP36, SERPINE1, DUSP1, CAV1, and AKAP12) were identified for developing a prognostic model in GC. This model stratifies GC patients into high- and low-risk groups based on median risk scores. A nomogram predicting overall survival (OS) was constructed and showed consistent results with observed OS. Immune infiltration analysis indicated that individuals in the high-risk group tend to exhibit increased immune cell infiltration. Additionally, analysis of cancer immunotherapy responses revealed that high-risk group patients exhibit poorer responses to cancer immunotherapy compared to the low-risk group. Immunohistochemistry (IHC) staining indicated that the expression levels of HMDRGs were remarkably correlated with GC, of which, SERPINE1 displayed the most pronounced up-regulation, while ZFP36 exhibited the most notable down-regulation in GC patients. Furthermore, in vitro investigation validated that SERPINE1 and ZFP36 contribute to the malignant processes of GC cells correlated with mitochondrial dysfunction.

Conclusions

This study presents a novel and efficient approach to evaluate GC prognosis and immunotherapy efficacy, and also provides insights into understanding the pathogenesis of GC.
Policy and perspective on outpatient programs for autologous hematopoietic cell transplantation and immune-effector cell therapy administration
Authors: Goldsmith Scott R. , San-Rozano May , Katindoy Justine , Rattanapichetkul Janet , Rosenzweig Michael
Published: August 2024

High-dose chemotherapy with autologous hematopoietic cell transplantation (AutoHCT) has long been an integral treatment modality for multiple myeloma and non-Hodgkin lymphoma. Over the past 25 years, numerous institutions have shifted this practice from requiring hospitalization to one that can be performed in an ambulatory setting, resulting in cost savings and improved quality of life for patients. The recent advent immune-effector cell (IEC) therapies and expansion of their indications is changing the treatment landscape for hematologic and non-hematologic malignancies. However, current financial models and reimbursement structures threaten the viability and sustainability of this treatment modality should it continue to require inpatient administration and management. This threat is leading institutions to develop outpatient IEC programs based off the outpatient AutoHCT templates. Integral to the success of both is a cohesive program with outpatient-specific standard operating protocols, highly-trained providers and staff with expertise specific in these treatment modalities, evidenced-based supportive care and prophylaxis plans, extensive caregiver vetting and education, and the infrastructure to support all individuals involved. In this policy and practice review we provide an overview of the guidelines and published academic experiences, give a perspective-based description of the roles and responsibilities of the individuals involved in this process at our institution, and highlight actionable recommendations that could allow for the dissemination and implementation of outpatient AutoHCT and IEC programs more broadly.
Situational crime analysis of poaching within Territorial Use Rights Fisheries (TURFs)
Authors: Vallejos Tomás , Nahuelhual Laura , Gelcich Stefan , Oyanedel Rodrigo
Published: August 2024

Introduction

Illegal, unreported, and unregulated (IUU) fishing poses a significant threat to marine resource management globally. Environmental criminology plays a vital role in understanding and mitigating IUU activities by focusing on the contextual elements surrounding these crimes. This study examines the dynamics of poaching within areas managed through Territorial User Rights for Fisheries (TURFs), with a specific emphasis on the loco (Concholepas concholepas) fishery in Chile.

Methods

Employing Crime Script Analysis (CSA) as the primary methodological lens, this research meticulously deconstructs the criminal process involved in TURFs poaching operations. CSA is used to identify key elements, providing a comprehensive understanding of poachers modus operandi. Additionally, by integrating CSA with Situational Precipitators of Crime (SPC), the study identifies critical factors such as environmental conditions, socio-economic disparities, and enforcement weaknesses that shape poaching opportunities within TURFs.

Results

The analysis reveals a complex interplay between SPC factors, underscoring their role in shaping poaching dynamics. Key findings highlight the importance of specific environmental conditions, socio-economic disparities, and enforcement weaknesses in facilitating poaching activities. The study identifies various tactics and strategies employed by poachers and the roles of different actors involved in the poaching process.

Discussion

Building upon these findings, the study proposes a comprehensive Situational Crime Prevention (SCP) framework aimed at effectively combating TURFs poaching. The framework emphasizes the importance of striking a careful balance between restrictive and inclusive measures to mitigate potential negative consequences. The study contributes valuable insights into understanding and addressing IUU fishing, particularly within TURFs in Chile.
Case report: A case of widespread soft tissue infection and multiple abscesses secondary to hidradenitis suppurativa inducing septic shock caused by Lawsonella clevelandensis in China
Authors: Lijia Zhi , Jia Chao Qi , Li Li , Shikun Deng , Peiyang Gao
Published: August 2024

Lawsonella clevelandensis is rare to associated with human infection, which may cause abscesses in abdominal cavity, liver, breast, and spine. Lawsonella clevelandensis is very difficult to be cultivated in regular manner; detection of 16S rRNA sequence is the main evidence for L. clevelandensis infection. The clinical manifestations of L. clevelandensis infection resemble other agents of Nocardia, Tuberculosis and non-tuberculous Mycobacterium (NTM) due to their morphologic similarities. Hidradenitis suppurativa (HS) is a chronic inflammatory disorder, which affects the intertriginous skin and is associated with numerous systemic comorbidities. HS eventually leads to severe pain, multiple abscesses, pus discharge, and irreversible tissue destruction. Lawsonella clevelandensis has not been reported to cause HS and systemic comorbidities. We presented the case of a 33-year-old male with widespread soft tissue infection and multiple abscesses secondary to HS (Hurley stage III) inducing septic shock caused by L. clevelandensis in China. He was diagnosed as HS and treated with intravenous antibiotic empirically. He developed multiple abscesses including lung and scrota. Bacterial and fungal cultures on blood and secretions from multiple skin lesions were all negative. Due to the misdiagnosis and progression of disease, the patient was transferred to intensive care unit, and he underwent drainage of the chest and right hemothorax removal under thoracoscopic. During the hospitalization, the patient developed septic shock and received mechanical ventilation. Computerized tomography (CT) scans revealed mediastinal emphysema, multiple subcutaneous emphysema, and severe pneumonia. Gene analysis of samples of incision and drainage of pus at the skin showed the rare infection of L. clevelandensis. Finally, the patients with recurrent soft tissue infections and multiple abscesses with negative microbiological culture results recovered after effective abscess drainage and antibiotic therapy. We suggested that NGS is a crucial supplementary diagnostic tool in individuals with recurrent skin infections and multiple abscesses, especially when conventional diagnostic methods are inconclusive.
Physical activity levels during COVID-19 pandemic and its associated factors in patients with Chagas disease
Authors: Xavier Isis Gabrielli Gomes , Andrade Patrícia Mello , Vitor Rodrigo de Lima , Barros Tayná Cruz , Portela Luciana Fernandes , de Holanda Marcelo Teixeira , Sangenis Luiz Henrique Conde , Sperandio da Silva Gilberto Marcelo , Mazzoli-Rocha Flavia , Mendes Fernanda de Souza Nogueira Sardinha , da Costa Andréa Rodrigues , Quintana Marcel de Souza Borges , Hasslocher-Moreno Alejandro Marcel , Araujo Itauá Leston , Junqueira Angela Cristina Verissimo , Pinheiro Roberta Olmo , Georg Ingebourg , Paravidino Vitor Barreto , Gonçalves Tatiana Rehder , Saraiva Roberto Magalhães , Mediano Mauro Felippe Felix
Published: August 2024

Background

A better understanding of the consequences of the Coronavirus Disease 2019 (COVID-19) pandemic on lifestyle of patients with Chagas disease (ChD) is of paramount importance to facilitate the implementation of intervention strategies tailored to this specific population.

Objective

The present study aimed to evaluate the level of physical activity (PA) in Chagas disease (ChD) patients during the Coronavirus Disease 2019 (COVID-19) pandemic and its main associated factors.

Methods

This is a cross-sectional study with 187 patients of both sexes, aged ≥18 years, followed in a national infectious disease center (Rio de Janeiro, Brazil). The level of PA was determined by the International Physical Activity Questionnaire short version and expressed in terms of total volume of physical activity (PA) (MET-minutes per week). Individuals were classified as physically active following the 2020 World Health Organization PA guideline. The exposure variables were age, sex, race, marital status, schooling, income per capita, number of rooms per domicile, number of residents per domicile, body mass index, clinical form of ChD, COVID-19 antibodies, comorbidities, self-reported anxiety, self-reported depression, self-reported fear, and self-reported sadness. The association between the exposure variables with total PA (as a continuous variable) was determined using univariate and multivariate linear regression models.

Results

Mean age was 61.1 ± 11.6 years. Most (62%) were women and self-declared their race as mixed (50.8%). The percentage of physically active individuals according to was 52%. The variables independently associated with total PA levels were non-white race (Exp β = 1.39; 95% CI 1.02 to 1.90), dyslipidemia (Exp β = 0.73; 95% CI 0.56 to 0.95) and self-reported depression during quarantine (Exp β = 0.71; 95% CI 0.52 to 0.96).

Conclusion

Non-white race was positively associated with total levels of PA, while dyslipidemia, and self-reported depression during quarantine were negatively associated with total levels of PA. The identification of associated factors can facilitate the development of tailored strategies to increase PA levels ChD patients.
Soybean oil-based HFD induces gut dysbiosis that leads to steatosis, hepatic inflammation and insulin resistance in mice
Authors: Jacob Texy , Sindhu Sardar , Hasan Amal , Malik Md. Zubbair , Arefanian Hossein , Al-Rashed Fatema , Nizam Rasheeba , Kochumon Shihab , Thomas Reeby , Bahman Fatemah , Shenouda Steve , Wilson Ajit , Akther Nadeem , Al-Roub Areej , Abukhalaf Nermeen , Albeloushi Shaima , Abu-Farha Mohamed , Al Madhoun Ashraf , Alzaid Fawaz , Thanaraj Thangavel Alphonse , Koistinen Heikki A. , Tuomilehto Jaakko , Al-Mulla Fahd , Ahmad Rasheed
Published: August 2024

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFD-group. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SF-Soy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis.
Variation on gut microbiota diversity of endangered red pandas (Ailurus fulgens) living in captivity acrosss geographical latitudes
Authors: Chen Wenqi , Chen Xiaobing , Zhang Yushuo , Wu Hong , Zhao Dapeng
Published: August 2024

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas (Ailurus fulgens) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__norank_o__Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, the main functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity.
Synergistic combination of baicalein and rifampicin against Staphylococcus aureus biofilms
Authors: Muniyasamy Rajeshwari , Manjubala I.
Published: August 2024

Staphylococcus aureus, a Gram-positive bacterium, is a predominant pathogen associated with various infections. The rapid emergence of antibiotic resistance has intensified the challenge of managing fracture-related infections in severe osteoporotic patients. Rifampicin, a potent antimicrobial agent employed against fracture and implant-related infections, necessitates combination therapies due to its susceptibility to antibiotic resistance. In this study, we explored the potential of baicalein, a bioactive flavonoid from Oroxylum indicum and Scutellaria baicalensis, in combination with rifampicin against S. aureus biofilms invitro. The minimum inhibitory concentration of baicalein and rifampicin were determined as 500 μg/mL and 12.5 ng/mL respectively. The synergistic activity of baicalein and rifampicin was determined by the fractional inhibitory concentration index (FICI) using checkerboard assay. The results showed the FICI of baicalein and rifampicin was lesser than 0.5, demonstrating synergistic effect. Furthermore, the efficacy of baicalein and rifampicin, both individually and in combination, was evaluated for biofilm inhibition and eradication. Scanning electron microscopy and confocal laser microscopy also confirmed that the synergistic combinations effectively removed most of the biofilms and partially killed pre-formed biofilms. In conclusion, the findings demonstrate that baicalein is as effective as rifampicin in inhibiting and eradicating S. aureus biofilms. Their combination exhibits synergistic effect, enhancing their bactericidal effect in completely eradicating S. aureus biofilms. The findings of this research underscore the research potential of combining baicalein and rifampicin as a novel therapeutic strategy against S. aureus biofilms, offering a promising direction for future research in the treatment of fracture-related S. aureus infections.
From haystack to high precision: advanced sequencing methods to unraveling circulating tumor DNA mutations
Authors: Silva Tamires Ferreira da , Azevedo Juscelino Carvalho de , Teixeira Eliel Barbosa , Casseb Samir Mansour Moraes , Moreira Fabiano Cordeiro , Assumpção Paulo Pimentel de , Santos Sidney Emanuel Batista dos , Calcagno Danielle Queiroz
Published: August 2024

Identifying mutations in cancer-associated genes to guide patient treatments is essential for precision medicine. Circulating tumor DNA (ctDNA) offers valuable insights for early cancer detection, treatment assessment, and surveillance. However, a key issue in ctDNA analysis from the bloodstream is the choice of a technique with adequate sensitivity to identify low frequent molecular changes. Next-generation sequencing (NGS) technology, evolving from parallel to long-read capabilities, enhances ctDNA mutation analysis. In the present review, we describe different NGS approaches for identifying ctDNA mutation, discussing challenges to standardized methodologies, cost, specificity, clinical context, and bioinformatics expertise for optimal NGS application.
Multiscale modeling of neuronal dynamics in hippocampus CA1
Authors: Tesler Federico , Lorenzi Roberta Maria , Ponzi Adam , Casellato Claudia , Palesi Fulvia , Gandolfi Daniela , Gandini Wheeler Kingshott Claudia A. M. , Mapelli Jonathan , D'Angelo Egidio , Migliore Michele , Destexhe Alain
Published: August 2024

The development of biologically realistic models of brain microcircuits and regions constitutes currently a very relevant topic in computational neuroscience. One of the main challenges of such models is the passage between different scales, going from the microscale (cellular) to the meso (microcircuit) and macroscale (region or whole-brain level), while keeping at the same time a constraint on the demand of computational resources. In this paper we introduce a multiscale modeling framework for the hippocampal CA1, a region of the brain that plays a key role in functions such as learning, memory consolidation and navigation. Our modeling framework goes from the single cell level to the macroscale and makes use of a novel mean-field model of CA1, introduced in this paper, to bridge the gap between the micro and macro scales. We test and validate the model by analyzing the response of the system to the main brain rhythms observed in the hippocampus and comparing our results with the ones of the corresponding spiking network model of CA1. Then, we analyze the implementation of synaptic plasticity within our framework, a key aspect to study the role of hippocampus in learning and memory consolidation, and we demonstrate the capability of our framework to incorporate the variations at synaptic level. Finally, we present an example of the implementation of our model to study a stimulus propagation at the macro-scale level, and we show that the results of our framework can capture the dynamics obtained in the corresponding spiking network model of the whole CA1 area.
Relationship between enteral nutrition timing and 28-day mortality in critically ill stroke patients in the MIMIC-IV database
Authors: Wang Xiaoliang , Xie Xiuling , Xu Xin , Tan Lan
Published: August 2024

Background

The ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database.

Methods

This study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups.

Results

A total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88–1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9–1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06–1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1–1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses.

Conclusions

Early commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.
Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies
Authors: Khodavirdi Ani C. , Multani Jasjit K. , Oh Sam S. , Vuvu Fiston , Bensink Mark E. , Stockl Karen M. , Hawkins Kevin , Chiang Chia-Chun , Green A. Laine , Tepper Stewart J.
Published: August 2024

Introduction

Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients’ disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients.

Methods

These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database. Patients were required to have ≥ 12 months of continuous enrollment in medical and pharmacy benefits prior to index (baseline) and after index (follow-up). Patients were stratified into chronic migraine (CM) and non-chronic migraine (non-CM) by diagnosis codes. Based on acute migraine-specific medication dispensing data in the follow-up period, non-CM patients were divided into 3 cohorts: highest, middle, and lowest tertile of total units of dispensed acute migraine-specific medication (gepants, ditans, ergot derivatives, and triptans). Migraine medication use was captured in the baseline and follow-up periods.

Results

A total of 22,584 CM and 216,807 non-CM patients (72,269 patients in each tertile) were identified and included in the study. Over the follow-up, CM patients had a mean of 70 units of acute migraine-specific medications dispensed, while the highest, middle, and lowest tertile of non-CM patients had a mean of 92, 29, and 10 units, respectively. Anti-calcitonin gene-related peptide pathway mAbs were dispensed for 28.9% of CM patients, and for 6.9%, 4.1%, and 2.9% of non-CM patients in the highest, middle, and lowest tertiles, respectively.

Conclusion

A lower proportion of non-CM patients had use of anti-calcitonin gene-related peptide pathway mAbs compared to CM patients, confirming the unmet need with appropriate preventive medication. There appears to be a persistent gap in management of patients without a diagnosis of CM who are dispensed high quantities of acute migraine-specific medications.
Enteral tube feeding practices and associated factors among nurses working in South Wollo Zone Specialized and General Hospitals, Wollo, Ethiopia, 2022
Authors: Ahmed Ali , Anteneh Samuel , Hussien Adem , Seid Anwar , Semanew Yaregal
Published: August 2024

Background

Enteral tube feeding is recommended as a route for nutrient delivery in critically ill patients. The practice of enteral tube feeding by nurses significantly influences patient treatment outcomes. Therefore, this study aimed to identify the practices of enteral tube feeding and the associated factors among nurses working in South Wollo Zone Specialized and General Hospitals, Wollo, Ethiopia, 2022.

Methods

A hospital-based cross-sectional study design was conducted on 420 nurses from 1st August to 1st September 2022. Simple random sampling methods were used to select study participants. Data were collected using self-administered questionnaires and an observational checklist. The data were entered into Epi Data version 4.6 and analyzed using SPSS version 26. Variables with a p-value <0.05, a 95% confidence interval, and an adjusted odd ratio were considered to be significantly associated with enteral tube feeding practice.

Result

A total of 400 nurses participated in the study, yielding a 95.2% response rate. The overall good practice of enteral tube feeding among nurses was 114 (28.5%) with a 95% CI of 23.8–33. Enteral tube feeding practice was significantly associated with a lack of adequate resources (AOR = 0.359, 95% CI: 0.192–0.673), unfamiliarity with current guidelines (AOR = 0.346, 95% CI: 0.203–0.586), lack of awareness (AOR = 0.511, 95% CI: 0.306–0.673) and the thermal effect of food (AOR = 0.56, 95% CI: 0.348–0.889).

Conclusion

The enteral tube feeding practice among nurses was found to be 28.5%. Significant determinants of enteral tube feeding practice included a lack of awareness, inadequate resources in the institution, and unfamiliarity with the current guidelines for enteral feeding. To improve enteral feeding practices, it is recommended that sufficient resources be provided, guidelines be made readily available, and training programs be conducted for the nursing staff.
Vitamin A supplementation status and associated factors among children aged 6–59 months in Tanzania: a multi-level analysis
Authors: Gebrekidan Amanuel Yosef , Asgedom Yordanos Sisay , Woldegeorgis Beshada Zerfu , Kassie Gizachew Ambaw , Haile Kirubel Eshetu , Damtew Solomon Abrha , Teklay Ashenafi , Ayele Amare Demsie
Published: August 2024

Background

Vitamin A supplementation every 4–6 months is an economical, rapid, and effective strategy to enhance vitamin A status and minimize child morbidity and mortality due to vitamin A deficiency in the long run. Therefore, this study was aimed at investigating the level as well as the factors influencing VAS status among children aged 6–59 months in Tanzania.

Methods

This analysis relied on data from the 2022 Tanzania Demographic and Health Survey (TDHS). The study used a weighted sample of 9,382 children aged 6–59 months. Given the effect of clustering and the binary character of the outcome variable, we employed a multilevel binary logistic regression model. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to determine statistical significance, considering the model with the lowest deviation that best fits the data.

Results

In this study, vitamin A supplementation among children aged 6–59 months was found to be 53.18% [95% CI: 52.17, 54.19]. Mother’s/caregiver’s working status; Working [AOR = 1.59, 95% CI: 1.34, 1.89], ANC follow-up [AOR = 1.71, 95%CI: 1.34, 2.2], and health facility delivery [AOR = 1.55, 95%CI: 1.25, 1.91] were individual-level factors associated with vitamin A supplementation. Whereas administrative zones of Western [AOR = 2.02, 95% CI: 1.16, 3.52], Southern highlands [AOR = 3.83, 95% CI: 2.02, 7.24], Southern administrative zone [AOR = 2.69, 95% CI: 1.37, 5.3], and South West highlands [AOR = 0.56, 95% CI: 0.33, 0.95] were community-level factors associated with vitamin A supplementation.

Conclusion

The proportion of VAS among children in Tanzania is low compared to UNICEF’s target of 80. Mother’s/caregiver’s working status, antenatal care, place of delivery, community-level media exposure, and administrative zones were significantly associated factors with vitamin A supplementation. Therefore, interventions should be designed to improve the uptake of VAS. Provision and promotion of ANC and institutional delivery and strengthening of routine supplementation are recommended to increase coverage of childhood vitamin A supplementation. Moreover, special focus should be given to regions in the south-western highlands.
Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group
Authors: Mattavelli Davide , Wichmann Gunnar , Smussi Davide , Paderno Alberto , Plana Maria Serrahima , Mesia Ricard Nin , Compagnoni Micaela , Medda Alessandro , Chiocca Susanna , Calza Stefano , Zhan Yinxiu , Rognoni Carla , Tarricone Rosanna , Stucchi Erika , Lorini Luigi , Gurizzan Cristina , Khelik Ksenia , Hovig Eivind , Dietz Andreas , Piazza Cesare , Bossi Paolo
Published: August 2024

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.
Long-term survival of a patient with gastric cancer with bone marrow metastasis receiving S-1 plus oxaliplatin beyond three years: a case report and literature review
Authors: Suto Hirotaka , Inui Yumiko , Okamura Atsuo
Published: August 2024

Background

Bone marrow metastasis (BMM) of gastric cancer (GC), which is the most common cause of disseminated intravascular coagulation (DIC) among solid tumors, has a poor prognosis. Studies on prognostic improvement beyond one year in patients with GC with BMM are limited. This is the first report of a patient who survived over three years after 30 months of S-1 plus oxaliplatin (SOX) therapy for GC with BMM.

Case Report

The patient was a 72-year-old woman who presented with anemia and high levels of alkaline phosphatase (ALP) and carbohydrate antigen 19-9 (CA19-9). Detailed examination led to the diagnosis with BMM of GC uncomplicated by DIC and the SOX regimen was initiated in November 2018. After six cycles, she was switched to S-1 monotherapy, and both ALP and CA19-9 levels reached normal by November 2019. However, computed tomography in April 2021 showed multiple bone metastases. Therefore, she was switched to paclitaxel-based therapy. In November 2021, the patient was further switched to nivolumab monotherapy, but she succumbed due to DIC in March 2022.

Conclusion

GCs with BMM are prone to DIC, and the SOX regimen, which includes S-1 with efficacy against micrometastases, may constitute a safe and effective treatment modality.
YAP activation in Müller cells protects against NMDA-induced retinal ganglion cell injury by regulating Bcl-xL expression
Authors: Kashihara Toshihide , Morita Yui , Hatta Misaki , Inoue Sae , Suzuki Yume , Morita Akane , Nakahara Tsutomu
Published: August 2024

Retinal neurodegeneration, characterized by retinal ganglion cell (RGC) death, is a leading cause of vision impairment and loss in blind diseases, such as glaucoma. Müller cells play crucial roles in maintaining retinal homeostasis. Thus, dysfunction of Müller cells has been implicated as one of the causes of retinal diseases. Yes-associated protein 1 (YAP), a nuclear effector of the Hippo pathway, regulates mammalian cell survival. In this study, we investigated the role of YAP in Müller cells during N-methyl-D-aspartic acid (NMDA)-induced excitotoxic RGC injury in rats. We found that YAP expression increased and was activated in Müller cells after NMDA-induced RGC injury. This YAP response was partly due to an increase in Yap mRNA levels, although it may be independent of the Hippo pathway and β-TrCP-mediated YAP degradation. Morphological analysis revealed that verteporfin, a selective YAP inhibitor, exacerbated NMDA-induced RGC degeneration, suggesting that YAP activation in Müller cells contributes to RGC survival in NMDA-treated retinas. Studies in the rat Müller cell line (rMC-1) demonstrated that overexpression of YAP increased the levels of Bcl-xL, while verteporfin decreased the levels of Bcl-xL and cell viability and increased the levels of cytochrome c released from mitochondria and cleaved caspase-3. Finally, we found that Bcl-xL expression increased slightly in NMDA-treated retinas, whereas intravitreal injection of verteporfin suppressed this increase. Our findings suggest that activated YAP in Müller cells protects against NMDA-induced RGC injury by upregulating Bcl-xL expression.
State-of-the-art analysis of quantum cryptography: applications and future prospects
Authors: Sahu Swastik Kumar , Mazumdar Kaushik
Published: August 2024

Quantum computing provides a revolution in computational competences, leveraging the principles of quantum mechanics to process data in fundamentally novel ways. This paper explores the profound implications of quantum computing on cryptography, focusing on the vulnerabilities it introduces to classical encryption methods such as RSA and ECC, and the emergence of quantum-resistant algorithms. We review the core principles of quantum mechanics, including superposition and entanglement, which underpin quantum computing and cryptography. Additionally, we examine quantum encryption algorithms, particularly Quantum Key Distribution (QKD) protocols and post-quantum cryptographic methods, highlighting their potential to secure communications in the quantum era. This analysis emphasizes the urgent need for developing robust quantum-resistant cryptographic solutions to safeguard sensitive information against the imminent threats posed by advancing quantum technologies.
Impact on the scape of Farfugium japonicum var. japonicum (Asteraceae) under strong wind conditions based on morphological and mechanical analyses
Authors: Shiba Masayuki , Arihara Shuma , Harada Shiori , Fukuda Tatsuya
Published: August 2024

Adaptation of Farfugium japonicum (L.) Kitam. var. japonicum (Asteraceae) to the strong wind environment of coastal areas has been shown to reduce lamina size and shorten petioles; however, their effects on other traits of this species remain unknown. Our morphological analyses showed that shortening of the scape of this species is correlated with shortening of the petiole in coastal areas. The results suggested that when the height of the scapes became higher than that of the petioles, the wind stress on the scapes became stronger and their growth was suppressed. Therefore, the populations in coastal areas with strong winds had significantly shorter scapes than inland populations, and the height of petioles and scapes in the coastal populations were correlated. Further mechanical analysis by three-point bending tests revealed that the scapes had higher strength than the petioles. This species is evergreen and can produce new leaves regardless of the season, even if it loses its leaves by strong winds; however, because scapes only develop above ground for a limited period of the year, the loss of the scapes by strong winds has a significant impact on reproduction in that year. Therefore, even though the scapes were stronger than the petiole, shortening the scapes plays an important role in reducing strong wind stress in coastal areas.
The curvilinear responses of biomass accumulation and root morphology to a soil salt-nitrogen environment reflect the phytodesalination capability of the euhalophyte Suaeda salsa L.
Authors: Wang Yanyan , Guo Tongkai , Tian Changyan , Zhao Zhenyong , Zhang Ke , Mai Wenxuan
Published: August 2024

Under the sufficient nitrogen supply, it is of great significance to investigate the law of biomass allocation, root morphological traits, and the salt absorption capacity of euhalophytes to evaluate their biological desalination in saline soil. Although the curvilinear responses of biomass accumulation and root morphology in response to soil salinity have been recognized, these perceptions are still confined to the descriptions of inter-treatment population changes and lack details on biomass allocation in organs at an individual level. In this study, Suaeda salsa was grown in root boxes across a range of soil salt levels. The study showed that their growth and development were significantly affected by soil soluble salts. The law of biomass allocation was described as follows: increased soil soluble salts significantly increased the leaf mass ratio and decreased the stem mass ratio, and slightly increased the root mass ratio among treatments. For individuals at each treatment, leaf mass ratio > stem mass ratio > root mass ratio, except in the control treatment at the flower bud and fruit stages. Biomass responses of the control treatment indicated that salt was not rigorously required for Suaeda salsa in the presence of an adequate nitrogen supply, as verified by the correlation between biomass, nitrogen, and soil soluble salt. Salt could significantly inhibit the growth of Suaeda salsa (P<0.01), whereas nitrogen could significantly promote its growth (P<0.01). Root morphology in response to soil soluble salts showed that salt acquisition by the root was highest at a salt level of 0.70%, which corresponds to light saline soil. Consequently, we conclude that phytodesalination by Suaeda salsa was optimal in the light saline soil, followed by moderate saline soil.
Transcriptomic and physiological responses of Quercus acutissima and Quercus palustris to drought stress and rewatering
Authors: Kim Tae-Lim , Oh Changyoung , Denison Michael Immanuel Jesse , Natarajan Sathishkumar , Lee Kyungmi , Lim Hyemin
Published: August 2024

Establishment of oak seedlings, which is an important factor in forest restoration, is affected by drought that hampers the survival, growth, and development of seedlings. Therefore, it is necessary to understand how seedlings respond to and recover from water-shortage stress. We subjected seedlings of two oak species, Quercus acutissima and Quercus palustris, to drought stress for one month and then rewatered them for six days to observe physiological and genetic expression changes. Phenotypically, the growth of Q. acutissima was reduced and severe wilting and recovery failure were observed in Q. palustris after an increase in plant temperature. The two species differed in several physiological parameters during drought stress and recovery. Although the photosynthesis-related indicators did not change in Q. acutissima, they were decreased in Q. palustris. Moreover, during drought, content of soluble sugars was significantly increased in both species, but it recovered to original levels only in Q. acutissima. Malondialdehyde content increased in both the species during drought, but it did not recover in Q. palustris after rewatering. Among the antioxidant enzymes, only superoxide dismutase activity increased in Q. acutissima during drought, whereas activities of ascorbate peroxidase, catalase, and glutathione reductase increased in Q. palustris. Abscisic acid levels were increased and then maintained in Q. acutissima, but recovered to previous levels after rewatering in Q. palustris. RNA samples from the control, drought, recovery day 1, and recovery day 6 treatment groups were compared using transcriptome analysis. Q. acutissima exhibited 832 and 1076 differentially expressed genes (DEGs) related to drought response and recovery, respectively, whereas Q. palustris exhibited 3947 and 1587 DEGs, respectively under these conditions. Gene ontology enrichment of DEGs revealed “response to water,” “apoplast,” and “Protein self-association” to be common to both the species. However, in the heatmap analysis of genes related to sucrose and starch synthesis, glycolysis, antioxidants, and hormones, the two species exhibited very different transcriptome responses. Nevertheless, the levels of most DEGs returned to their pre-drought levels after rewatering. These results provide a basic foundation for understanding the physiological and genetic expression responses of oak seedlings to drought stress and recovery.