bluuebunny/crossref_metadata_2025_split huggingface dataset:
A landscape analysis of clinical trials and infant clinical trials in Kenya, Ethiopia, and Nigeria
Authors: Amboka Patrick , Kurui Daniel , Wamukoya Marylene , Sindi Julius Kirimi , Vicente-Crespo Marta 
Published: August 2024

IntroductionGlobal inequality in clinical research capacity and service delivery can be indicated simply by the proportion of clinical trials that a country or region has registered in clinical trial registry databases. The proportion of clinical trials registered in Africa is very low at 0.02%, even though the region accounts for approximately 15% of the world's population. Despite the economic challenges in most African countries, they have shown potential for growth and change in recent years.MethodsWe conducted desk reviews on the interventional clinical trials done in Kenya, Ethiopia, and Nigeria between 2015 to May 2023. The search was done in clinical trials repositories, and journal repositories. The search focused on intervention clinical trials. Data was extracted by screening through the publications and clinical trial platforms. The data extracted from the publications included the type of clinical trial, clinical trial phase, diseases, etc. The data extracted from the reports included: challenges in conducting clinical trials, capacity-building efforts, and the impact of the clinical trial.ResultsThe number of clinical trial studies identified in Kenya was 113 (28 were on infant clinical trials). The study identified 97 clinical trials in Nigeria, of which 11 studies were on infant clinical trials. In Ethiopia, there were 28 clinical trials and only five were on infant clinical trials. The landscape review also expanded to capacity and gaps in clinical trials in the three countries. The largest proportion of clinical trials carried out in Kenya was on injury, occupational disease, and poisoning, 30.5% (n = 18) and the smallest proportion was on kidney disease, neonatal disease, obstetrics, and gynecology. Most Infant clinical trials were carried out in the area of infections and infestations 33.3% (n = 7). Most of the challenges faced by clinical trials in the three countries include a lack of infrastructure, a lack of human resources, and a lack of financial resources.ImplicationsThere is a need to map clinical trials done by African researchers based in Africa to exclude the trials done by non-African researchers based in Africa. Opportunities for clinical trials should be supported and challenges addressed.
Association between lactate to hematocrit ratio and 30-day all-cause mortality in patients with sepsis: a retrospective analysis of the Medical Information Mart for Intensive Care IV database
Authors: Duan Wentao , Yang Feng , Ling Hua , Li Qiong , Dai Xingui 
Published: August 2024

BackgroundThe lactate to hematocrit ratio (LHR) has not been assessed for predicting all-cause death in sepsis patients. This study aims to evaluate the relationship between LHR and 30-day all-cause mortality in sepsis patients.MethodsThis retrospective study used the data from Medical information mart for intensive care IV (MIMIC-IV, version 2.0). Our study focused on adult sepsis patients who were initially hospitalized in the Intensive care unit (ICU). The prognostic significance of admission LHR for 30-day all-cause mortality was evaluated using a multivariate Cox regression model, ROC curve analysis, Kaplan–Meier curves, and subgroup analyses.ResultsA total of 3,829 sepsis patients participated in this study. Among the cohort, 8.5% of individuals died within of 30 days (p &lt; 0.001). The area under the curve (AUC) for LHR was 74.50% (95% CI: 71.6–77.50%), higher than arterial blood lactate (AUC = 71.30%), hematocrit (AUC = 64.80%), and shows no significant disadvantage compared to qSOFA, SOFA, and SAPS II. We further evaluated combining LHR with qSOFA score to predict mortality in sepsis patients, which shows more clinical significance. ROC curve analysis showed that 6.538 was the optimal cutoff value for survival and non-survival groups. With LHR ≥6.538 vs. LHR &lt;6.538 (p &lt; 0.001). Subgroup analysis showed significant interactions between LHR, age, sex, and simultaneous acute respiratory failure (p = 0.001–0.005).ConclusionLHR is an independent predictor of all-cause mortality in sepsis patients after admission, with superior predictive ability compared to blood lactate or hematocrit alone.
Investigating the causal relationship between gut microbiota and gastroenteropancreatic neuroendocrine neoplasms: a bidirectional Mendelian randomization study
Authors: Zhang Chun-yu , Jiang Shi-jing , Cao Jing-jing , Xu Yan , Wang Xiao-yu , Li Rui , Miao Zhi-wei 
Published: August 2024

BackgroundThe interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis.MethodsTwo-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran’s Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs.ResultsWe identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora.ConclusionThe present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.
Impact of repetitive negative thinking on subjective cognitive decline: insights into cognition and brain structure
Authors: Mulet-Pons Lídia , Solé-Padullés Cristina , Cabello-Toscano María , Abellaneda-Pérez Kilian , Perellón-Alfonso Ruben , Cattaneo Gabriele , Solana Sánchez Javier , Alviarez-Schulze Vanessa , Bargalló Nuria , Tormos-Muñoz Josep M. , Pascual-Leone Alvaro , Bartrés-Faz David , Vaqué-Alcázar Lídia 
Published: August 2024

IntroductionIndividuals with subjective cognitive decline (SCD) express concern about self-perceived cognitive decline despite no objective impairment and are at higher risk of developing Alzheimer’s disease. Despite documented links between SCD and repetitive negative thinking (RNT), the specific impact of RNT on brain integrity and cognition in exacerbating the SCD condition remains unclear. We aimed to investigate the influence of RNT on global cognition and brain integrity, and their interrelationships among healthy middle-aged and older adults experiencing SCD.MethodsOut of 616 individuals with neuroimaging and neuropsychological data available, 89 (mean age = 56.18 years; 68.54% females) met SCD criteria. Eighty-nine non-SCD individuals matched by age, sex, and education were also selected and represented the control group (mean age = 56.09 years; 68.54% females). Global cognition was measured using the preclinical Alzheimer’s cognitive composite (PACC5), which includes dementia screening, episodic memory, processing speed, and category fluency tests. RNT was calculated through three questionnaires assessing intrusive thoughts, persistent worry, and rumination. We generated cortical thickness (CTh) maps and quantified the volume of white matter lesions (WML) in the whole brain, as grey and white matter integrity measures, respectively.ResultsSCD individuals exhibited higher RNT scores, and thinner right temporal cortex compared to controls. No differences were observed in PACC5 and WML burden between groups. Only the SCD group demonstrated positive associations in the CTh-PACC5, CTh-RNT, and WML-RNT relationships.DiscussionIn this cross-sectional study, RNT was exclusively associated with brain integrity in SCD. Even though our findings align with the broader importance of investigating treatable psychological factors in SCD, further research may reveal a modulatory effect of RNT on the relationship between cognition and brain integrity in SCD.
Transplantation of neural stem cells improves recovery of stroke-affected mice and induces cell-specific changes in GSDMD and MLKL expression
Authors: Lisjak Damir , Alić Ivan , Šimunić Iva , Mitrečić Dinko 
Published: August 2024

IntroductionStroke, the second leading cause of death and disability in Europe, is primarily caused by interrupted blood supply, leading to ischemia–reperfusion (IR) injury and subsequent neuronal death. Current treatment options are limited, highlighting the need for novel therapies. Neural stem cells (NSCs) have shown promise in treating various neurological disorders, including stroke. However, the underlying mechanisms of NSC-mediated recovery remain unclear.MethodsEighty C57Bl/6–Tyrc-Brd mice underwent ischemic stroke induction and were divided into four groups: sham, stroke-affected, stroke-affected with basal cell medium injection, and stroke-affected with NSCs transplantation. NSCs, isolated from mouse embryos, were stereotaxically transplanted into the stroke-affected brains. Magnetic resonance imaging (MRI) and neurological scoring were used to assess recovery. Immunohistochemical analysis and gene expression assays were performed to evaluate pyroptosis and necroptosis markers.ResultsNSC transplantation significantly improved neurological recovery compared to control groups. In addition, although not statistically significant, NSCs reduced stroke volume. Immunohistochemical analysis revealed upregulation of Gasdermin D (GSDMD) expression post-stroke, predominantly in microglia and astrocytes. However, NSC transplantation led to a reduction in GSDMD signal intensity in astrocytes, suggesting an effect of NSCs on GSDMD activity. Furthermore, NSCs downregulated Mixed Lineage Kinase Domain-Like Protein (Mlkl) expression, indicating a reduction in necroptosis. Immunohistochemistry demonstrated decreased phosphorylated MLKL (pMLKL) signal intensity in neurons while stayed the same in astrocytes following NSC transplantation, along with increased distribution in microglia.DiscussionNSC transplantation holds therapeutic potential in stroke recovery by targeting pyroptosis and necroptosis pathways. These findings shed light on the mechanisms underlying NSC-mediated neuroprotection and support their further exploration as a promising therapy for stroke patients.
Food security intervention mechanisms in the drought-prone rural areas of Tigray
Authors: Gebre Tewelde , Abraha Zenebe , Zenebe Amanuel , Zeweld Woldegebrial 
Published: August 2024

IntroductionTigray is one of the food-insecure regions with many people living under the condition of chronic hunger. Proper intervention mechanisms are vital for addressing food insecurity. Yet, food security intervention mechanisms of various levels are not researched well. Besides, previous studies have rarely addressed the objectives of food security intervention mechanisms in relation to the four pillars of food security: availability, access, utilization, and stability. Thus, this study aims to investigate the food security intervention mechanisms in the drought-prone rural areas of Tigray in relation with the major components of food security.MethodologyThis study has employed a cross-sectional study design based on a mixed research approach with primary and secondary data. For this, 363 households from three selected drought-prone rural districts, i.e., Atsbi-wenberta, Irob, and Hintalo- wejerat were studied. Primary data were collected using questionnaires and key-informant interviews. And, secondary data were collected from relevant archives and policy documents. The obtained data were analyzed descriptively and content-wise.ResultsFindings show that there were several international interventions intended to halt food insecurity sustainably through financial aid, but many of the interventions were found to be responding to humanitarian crises mainly the food shortages. Ethiopia's Food and Nutrition Policy, Food Security Program, Food Security Strategy, and Food Security Pack program were the food security intervention mechanisms at the national level. These interventions were found to be inconsistent with each other in their intended goals. Regionally, no food security strategy or program was found intervening to the prevailing food insecurity in Tigray. More notably, the region has no food security bureau or office that deals with food security issues of the region. At a community level, food aid, and PSNP transfers have been the usual food security intervention mechanisms. 35.6% (77,010) of the population in the study rural districts were found to be rural PSNP beneficiaries. The food aid and PSNP transfers were outrageously insufficient for the recipients to cope with food insecurity.ConclusionIntervention mechanisms should focus on enhancing vulnerable households' coping and adaptive capacities to deal with food security problems. In this regard, all the food security intervention mechanisms of various levels should be integrated into the common goal of achieving food security.
Anlotinib inhibits cervical cancer cell proliferation and invasion by suppressing cytokine secretion in activated cancer-associated fibroblasts
Authors: Xiong Yaozu , Xu Xiaoting , Zhou Xilei , Tong Yusuo , Yu Changhua 
Published: August 2024

ObjectiveThe aim of this study was to investigate whether anlotinib could exert an inhibitory effect on the proliferation and invasion of cervical cancer cells by inhibiting cytokines secreted by activated cancer-associated fibroblasts (CAFs).MethodsCAFs were isolated from cervical cancer tissues and experimentally studied in vivo and in vitro. Molecular biology experimental methods were used to verify whether anlotinib could inhibit the pro-carcinogenic effects of CAFs derived from cervical cancer tissues.ResultsCAFs promote the proliferation and invasion of cervical cancer cells. Anlotinib inhibited the activation of CAFs and suppressed the promotion of cervical cancer cells by CAFs. Anlotinib inhibited the expression of multiple cytokines within CAFs and suppressed the release of interleukin (IL)-6 (IL-6) and IL-8. In vivo studies have shown that anlotinib diminished the growth of xenografted cervical cancer cells, and treatment in combination with docetaxel had an even more significant tumor growth inhibitory effect.ConclusionAnlotinib inhibits the pro-cancer effects of CAFs by suppressing the activation of CAFs and the secretion of pro-cancer cytokines. Our findings suggest that the combination of anlotinib and docetaxel may be a potential strategy for the treatment of refractory cervical cancer.
Expanding treatment options for patients with HER2+ metastatic breast cancer with margetuximab plus chemotherapy: a case report series
Authors: Mahtani Reshma , Harpalani Natasha , Yan Fengting , Phiel Kristen , Kovalenko Iuliia 
Published: August 2024

BackgroundHuman epidermal growth factor receptor 2 protein (HER2)-positive (+) metastatic breast cancer (MBC) is an aggressive disease and patients often undergo multiple lines of therapy following HER2 targeted therapies. The most recent National Comprehensive Cancer Network (NCCN) guidelines recommend margetuximab plus chemotherapy as fourth-line or later therapy for HER2+/hormone receptor (HR) + or negative (–) MBC. The aim of this case series is to provide information regarding margetuximab utilization in clinical practice as later-line therapy in women with HER2+ MBC.Case summariesMargetuximab plus chemotherapy was used as fourth- or later-line treatment in patients who had received multiple HER2-targeted agents, including trastuzumab, pertuzumab, ado-trastuzumab emtansine, trastuzumab deruxtecan, tucatinib, and neratinib. Patients responded to margetuximab plus chemotherapy with real-world progression-free survival (PFS) of 3, 4, and 7 months.ConclusionClinical outcomes from three heavily pretreated patients with metastatic HER2+/HR+ MBC demonstrated that margetuximab plus chemotherapy resulted in real-world PFS comparable to that reported in the controlled pivotal clinical trial and support use of this targeted therapy option in appropriately identified patients.
Case report: intracranial lesions in a patient with anxiety and depression: tumor recurrence or radiation encephalopathy?
Authors: You Haiping , He Lin , Ouyang Zhibo , Yang Yao , Xie Shu , Zhou Jiwei , Zhang Yun , Shi Jian 
Published: August 2024

PurposeRadiation encephalopathy (REP) is one of the most common complications of radiotherapy for malignant tumors of the head and neck. Symptoms usually appear months to years following radiotherapy, with headache, insomnia, and memory loss as the main clinical features. We report a patient who was admitted to the hospital with anxiety and depressive disorder and was eventually diagnosed with REP.Patients and methodsA 48-year-old patient who had undergone over 2 years of radiotherapy for nasopharyngeal carcinoma was admitted to the Department of Psychosomatic Medicine of our hospital because of recurrent fear, low mood, and waking up from dreams. Magnetic resonance imaging (MRI) revealed a mass in the left temporal lobe with a large peripheral edema. After multidisciplinary consultation, the possibility of tumor recurrence could not be excluded.ResultsResection of the lesioned brain tissue to obtain pathological tissue showed glial cell proliferation and small focal areas of degeneration and necrosis, which indicated that the lesions were inflammatory. Postoperative MRI showed no abnormal signal, and the patient’s condition improved.ConclusionNasopharyngeal carcinoma patients with a history of radiotherapy and symptoms of increased intracranial pressure and neurological damage should be examined for REP. Furthermore, patients may experience anxiety and depressive disorders as a result of temporal lobe damage caused by REP.
Applying enhanced recovery after surgery protocols in a patient with a giant spleen: a case report
Authors: Fang Dan , Gan Biling , Li Mei , Xiong Dailan 
Published: August 2024

Although splenomegaly is a common finding in several diseases, massive splenomegaly is rare. Patients with massive splenomegaly often present with a complex clinical picture. This case report describes a 72-year-old female with a complex medical history. Fifteen years ago, she was diagnosed with primary myelofibrosis, which subsequently led to progressive abdominal enlargement and bloating over the past 5 years. Recently, she developed edema in her limbs, accompanied by dizziness, shortness of breath, and fatigue. A massive splenomegaly was discovered during her hospitalization. Additionally, the patient has a history of Crohn’s disease, gout, renal insufficiency, and hypertension. Laboratory results reveal severe anemia and thrombocytopenia. Abdominal CT scans confirm the enlarged spleen and show ascites. She was treated by a multidisciplinary team comprising several departments. Even after a period of comprehensive treatment, the symptoms of massive splenomegaly did not significantly improve. Thus, the patient underwent an open surgical excision of the giant spleen. The weight of the giant spleen was 5.0 kg. During the perioperative period, Enhanced Recovery After Surgery (ERAS) protocols were applied to facilitate recovery. Her recovery was uneventful, and she was able to resume her regular daily routine shortly after the procedure. This report presented a complex and rare case of massive splenomegaly, and underscored that a proper medical and nursing care is the key to better recovery.
Lingguizhugan oral solution alleviates MASLD by regulating bile acids metabolism and the gut microbiota through activating FXR/TGR5 signaling pathways
Authors: Wang Jiahua , Zang Juan , Yu Yang , Liu Yang , Cao Huimin , Guo Ruibo , Zhang Lu , Liu Mo , Zhang Zixu , Li Xuetao , Kong Liang 
Published: August 2024

BackgroundThe preservation of the Lingguizhugan (LGZG) decoction and patient compliance issue often limit the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Hence, herein, an LGZG oral solution was developed for alleviating MASLD. Additionally, the potential mechanisms underlying LGZG-mediated MASLD mitigation were explored.MethodsA MASLD mouse model was constructed using oleic and palmitic acid-induced LO2 cells and a high-fat diet. The apoptosis, lipid deposition, and mouse liver function were analyzed to assess the therapeutic effects of the LGZG oral solution on MASLD. Serum untargeted metabolomics, gut microbiota, bile acid (BA) metabolism, immunohistochemistry, and Western blotting analyses were performed to investigate the potential mechanism of action of LGZG oral solution on MASLD.ResultsThe LGZG oral solution ameliorated lipid deposition, oxidative stress, inflammation, and pathological damage. Serum untargeted metabolomics results revealed the LGZG-mediated regulation of the primary BA biosynthetic pathway. The 16S ribosomal RNA sequencing of the fecal microbiota showed that LGZG oral solution increased the relative abundance of the BA metabolism-associated Bacteroides, Akkermansia, and decreased that of Lactobacillus. Additionally, the BA metabolism analysis results revealed a decrease in the total taurine-α/β-muricholic acid levels, whereas those of deoxycholic acid were increased, which activated specific receptors in the liver and ileum, including farnesoid X receptor (FXR) and takeda G protein-coupled receptor 5 (TGR5). Activation of FXR resulted in an increase in short heterodimer partner and subsequent inhibition of cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, and activation of FXR also results in the upregulation of fibroblast growth factor 15/19 expression, and consequently inhibition of cholesterol 7α-hydroxylase, which correlated with hepatic BA synthesis and lipogenesis, ultimately attenuating lipid deposition and bile acid stasis, thereby improving MASLD.ConclusionAltogether, the findings of this study suggest that modulating microbiota–BA–FXR/TGR5 signaling pathway may be a potential mechanism of action of LGZG oral solution for the treatment of MASLD.