bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study
Authors: Sun Dongren , Wang Rui , Du Qin , Zhang Ying , Chen Hongxi , Shi Ziyan , Wang Xiaofei , Zhou Hongyu 
Published: January 2024

Abstract
Background
Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent.

Objective
We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure.

Methods
MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis.

Results
After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p = .0154, beta (se) = − 9.0301 (3.7281)), cuneus THw (p = .0418, beta (se) =  − 0.0020 (0.0010)), lateral orbitofrontal THw (p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology.

Conclusion
Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.
The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment
Authors: Yin Qinan , Ma Haodi , Dong Yirui , Zhang Shunshun , Wang Junxiang , Liang Jing , Mao Longfei , Zeng Li , Xiong Xin , Chen Xingang , Wang Jingjing , Zheng Xuewei 
Published: January 2024

Abstract
Background
The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches.

Methods
Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated.

Results
A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3.

Conclusions
PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.
Brain computer interface training with motor imagery and functional electrical stimulation for patients with severe upper limb paresis after stroke: a randomized controlled pilot trial
Authors: Brunner Iris , Lundquist Camilla Biering , Pedersen Asger Roer , Spaich Erika G. , Dosen Strahinja , Savic Andrej 
Published: January 2024

Abstract
Background
Restorative Brain–Computer Interfaces (BCI) that combine motor imagery with visual feedback and functional electrical stimulation (FES) may offer much-needed treatment alternatives for patients with severely impaired upper limb (UL) function after a stroke.

Objectives
This study aimed to examine if BCI-based training, combining motor imagery with FES targeting finger/wrist extensors, is more effective in improving severely impaired UL motor function than conventional therapy in the subacute phase after stroke, and if patients with preserved cortical-spinal tract (CST) integrity benefit more from BCI training.

Methods
Forty patients with severe UL paresis (< 13 on Action Research Arm Test (ARAT) were randomized to either a 12-session BCI training as part of their rehabilitation or conventional UL rehabilitation. BCI sessions were conducted 3–4 times weekly for 3–4 weeks. At baseline, Transcranial Magnetic Stimulation (TMS) was performed to examine CST integrity. The main endpoint was the ARAT at 3 months post-stroke. A binominal logistic regression was conducted to examine the effect of treatment group and CST integrity on achieving meaningful improvement. In the BCI group, electroencephalographic (EEG) data were analyzed to investigate changes in event-related desynchronization (ERD) during the course of therapy.

Results
Data from 35 patients (15 in the BCI group and 20 in the control group) were analyzed at 3-month follow-up. Few patients (10/35) improved above the minimally clinically important difference of 6 points on ARAT, 5/15 in the BCI group, 5/20 in control. An independent-samples Mann–Whitney U test revealed no differences between the two groups, p = 0.382. In the logistic regression only CST integrity was a significant predictor for improving UL motor function, p = 0.007. The EEG analysis showed significant changes in ERD of the affected hemisphere and its lateralization only during unaffected UL motor imagery at the end of the therapy.

Conclusion
This is the first RCT examining BCI training in the subacute phase where only patients with severe UL paresis were included. Though more patients in the BCI group improved relative to the group size, the difference between the groups was not significant. In the present study, preserved CTS integrity was much more vital for UL improvement than which type of intervention the patients received. Larger studies including only patients with some preserved CST integrity should be attempted.
The quest for Homer’s moly: exploring the potential of an early ethnobotanical complex
Authors: Molina-Venegas Rafael , Verano Rodrigo 
Published: January 2024

AbstractThe Homeric plantmolyis a mysterious herb mentioned in Book 10 of theOdyssey. In the early 1980s, a pharmacological thesis to identify the plant was put forward for the first time, regarding the snowdrop (Galanthus nivalisL.) as candidate species. The proposal was inspired by the snowdrop’s acetylcholinesterase (AChE)-inhibiting properties and its alleged morphological reminiscence to other plants calledmolyby ancient Greek herbalists. Here, we draw from a compilation of literature from various disciplines, together with an understanding of the Homeric epic as a repository of information based on oral traditions, to (i) show that the assimilation of Homer’smolytoGalanthus nivalisis, at the very least, questionable and (ii) frame and support a new synthesis of the pharmacological thesis. We suggest that the uncertainty that revolves around the identity of Homer’smolycan be tied to an unnamed phylogenetic clade of closely related Mediterranean native species with AChE-inhibiting properties. Further, we speculate that Homer’smolymight represent an early record of an ethnobotanical complex, a sort of cultural taxon resulting from the cognitive crossbreeding of closely related taxonomic species that could have been interchangeably used due to their rough resemblance and common AChE-inhibiting properties. Such cultural taxon would have referred to the phytonymmolyby the centuries-old oral traditions that ultimately crystallized in the poem. We also venture that sea daffodils (Pancratiumspp.) could have greatly contributed to shaping the botanical archetype in the myth as we know it today.
Trans-apical catheter ablation of ventricular tachycardia in a patient with metallic aortic and mitral valves
Authors: Bozorgi Ali , Sadeghian Saeed , Mehrabi Nasab Entezar 
Published: January 2024

AbstractWe present a patient with a history of heart failure and metallic aortic and mitral valves surgeries, who required ablation for a drug-refractory left ventricular tachycardia. But the metallic valves prohibited the insertion of catheters via retrograde or via trans-septal approaches. Therefore, we decided to perform catheter ablation by direct left ventricle puncture through a minithoracotomy. The arrhythmia was successfully ablated via of trans-apical approach and did not recur at six months follow-up.
Rapid expansion of a left atrial myxoma caused by acute multiple internal hemorrhages: a case report and literature review
Authors: Kato Takayoshi , Umeda Etsuji , Suzui Natsuko , Fujii Ryo , Ogura Hiroki , Sakai Osamu , Shimabukuro Katsuya , Doi Kiyoshi 
Published: January 2024

Abstract
Background
Left atrial myxoma is the most common benign tumor, with the growth rate remaining unknown because specific symptoms do not present until the tumor grows to a certain size. Early surgical management is performed in most cases once it is detected by physicians. Despite cardiac myxomas commonly being perceived as slow-growing tumors, rapid enlargement of myxomas has been reported.

Case presentation
A 64-year-old woman was referred to our hospital with a diagnosis of a left atrial tumor. The pointed tumor changed morphologically in a few hours, and her respiratory condition, which had been normal at admission, suddenly deteriorated. Emergent surgery was performed, and the diagnosis was myxoma with multiple intratumor massive hematomas. The patient recovered uneventfully and was discharged on postoperative day 12 without any complications.

Conclusions
We report an extremely rare case of left atrial myxoma rapidly expanded due to acute multiple hemorrhages within itself. Massive internal hemorrhage alters the size, shape, and fragility of the tumor. We should recognize the potential risk of internal hemorrhage that may lead to acute deterioration of the so-called “slow-growing benign” tumors, such as myxomas.
Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review
Authors: Arhip Loredana , Brox-Torrecilla Noemi , Romero Inmaculada , Motilla Marta , Serrano-Moreno Clara , Miguélez María , Cuerda Cristina 
Published: January 2024

Abstract
Introduction
Combined methylmalonic acidemia and homocystinuria, cblC type is an inborn error of intracellular cobalamin metabolism and the most common one. The age of onset ranges from prenatal to adult. The disease is characterised by an elevation of methylmalonic acid (MMA) and homocysteine and a decreased production of methionine. The aim is to review existing scientific literature of all late onset cblC patients in terms of clinical symptoms, diagnosis, and outcome.

Methods
A bibliographic database search was undertaken in PubMed (MEDLINE) complemented by a reference list search. We combined search terms regarding cblC disease and late onset. Two review authors performed the study selection, data extraction and quality assessment.

Results
Of the sixty-five articles included in this systematic review, we collected a total of 199 patients. The most frequent clinical symptoms were neuropathy/myelopathy, encephalopathy, psychiatric symptoms, thrombotic microangiopathy, seizures, kidney disease, mild to severe pulmonary hypertension with heart failure and thrombotic phenomena. There were different forms of supplementation used in the different studies collected and, within these studies, some patients received several treatments sequentially and/or concomitantly. The general outcome was: 64 patients recovered, 78 patients improved, 4 patients did not improve, or the disease progressed, and 12 patients died.

Conclusions
Most scientific literature regarding the late onset cblC disease comes from case reports and case series. In most cases treatment initiation led to an improvement and even recovery of some patients. The lack of complete recovery underlines the necessity for increased vigilance in unclear clinical symptoms for cblC disease.
Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
Authors: Hu Yamei , Dong Zigang , Liu Kangdong 
Published: January 2024

AbstractSignal transducer and activator of transcription 3 (STAT3) is a transcriptional factor involved in almost all cancer hallmark features including tumor proliferation, metastasis, angiogenesis, immunosuppression, tumor inflammation, metabolism reprogramming, drug resistance, cancer stemness. Therefore, STAT3 has become a promising therapeutic target in a wide range of cancers. This review focuses on the up-to-date knowledge of STAT3 signaling in cancer. We summarize both the positive and negative modulators of STAT3 together with the cancer hallmarks involving activities regulated by STAT3 and highlight its extremely sophisticated regulation on immunosuppression in tumor microenvironment and metabolic reprogramming. Direct and indirect inhibitors of STAT3 in preclinical and clinical studies also have been summarized and discussed. Additionally, we highlight and propose new strategies of targeting STAT3 and STAT3-based combinations with established chemotherapy, targeted therapy, immunotherapy and combination therapy. These efforts may provide new perspectives for STAT3-based target therapy in cancer.
Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial
Authors: Chen Yizhe , Liu Zirui , Wang Qiuhui , Gao Fei , Xu Hongyang , Ke Lu , Lee Zheng-Yii , Stoppe Christian , Heyland Daren K. , Liang Fengming , Lin Jiajia ,   for the Chinese Critical Care Nutrition Trials Group (CCCNTG)
Published: January 2024

Abstract
Background and aims
Exclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.

Methods
This is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.

Results
Overall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3–19.6) kcal/kg and 0.6 (0.4–0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768–0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770–0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674–0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672–0.962) for protein delivery, respectively), but not in those > 2 mmol/L.

Conclusions
During the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.
Trial registration: ISRCTN12233792, registered on November 24, 2017.
Increasing transcultural competence in clinical psychologists through a web-based training: study protocol for a randomized controlled trial
Authors: Studer Selina , Kleinstäuber Maria , von Lersner Ulrike , Weise Cornelia 
Published: January 2024

Abstract
Background
In mental health care, the number of patients with diverse cultural backgrounds is growing. Nevertheless, evaluated training programs for transcultural competence are missing. Barriers for engaging in transcultural therapy can be identified in patients as well as in therapists. Besides language barriers, clinical psychologists report insecurities, for example, fear of additional expenses when involving a language mediator, ethical concerns such as power imbalances, or fear of lack of knowledge or incorrect handling when working with patients from other cultures. Divergent values and concepts of disease, prejudices, and stereotyping are also among the issues discussed as barriers to optimal psychotherapy care. The planned study aims to empower clinical psychologists to handle both their own as well as patients’ barriers through a web-based training on transcultural competence.

Methods
The training includes 6 modules, which are unlocked weekly. A total of N = 174 clinical psychologists are randomly assigned to two groups: the training group (TG) works through the complete training over 6 weeks, which includes a variety of practical exercises and self-reflections. In addition, participants receive weekly written feedback from a trained psychologist. The waitlist control group (WL) completes the training after the end of the waiting period (2 months after the end of the TG’s training). The primary outcome is transcultural competence. Secondary outcomes consist of experiences in treating people from other cultures (number of patients, satisfaction and experience of competence in treatment, etc.). Data will be collected before and after the training as well as 2 and 6 months after the end of the training.

Discussion
This randomized controlled trial tests the efficacy of and satisfaction with a web-based training on transcultural competence for German-speaking clinical psychologists. If validated successfully, the training can represent a time- and place-flexible training opportunity that could be integrated into the continuing education of clinical psychologists in the long term.

Trial registration
DRKS00031105. Registered on 21 February 2023.
Effectiveness of an 11-week exercise intervention for patients with hip or knee osteoarthritis: results of a quasi-experimental pragmatic trial
Authors: Krauss Inga , Roesel Inka , Martus Peter , Giurgiu Marco , Mueller Gerhard 
Published: January 2024

Abstract
Objective
To assess the effectiveness of exercise and education in addition to standard care (SC) compared to SC alone in patients with hip or knee osteoarthritis (OA) during 24 months follow-up.

Design
We conducted a quasi-experimental pragmatic clinical trial in care centers of a health insurance company. Overall, 1,030 subjects with hip and/or knee OA were included. The intervention group was recruited from clients participating in a hip/knee training (HKT, n = 515) in addition to SC. The control group (CO, n = 515) receiving SC only was recruited from the insurance database. HKT comprised 8 group sessions (1/week) of exercise and education, complemented by a 11-week structured home-exercise program (2/week). Primary endpoints were change of joint-related pain and function (WOMAC Index, score 0–10) after 3 months. Secondary endpoints related to follow-ups at 6, 12 and 24 months. All patient reported outcome measures were analyzed using linear mixed models (LMMs) investigating a time x treatment effect. A multivariable cox proportional hazards regression model was used to identify differences of joint replacement during follow-up between groups.

Results
LMMs revealed statistically significant differences in favor of HKT for the primary outcomes WOMAC pain = 0.47 (CI 0.27–0.66; Effect Size (ES) = 0.22, p < 0.001) and WOMAC function = 0.27 (CI 0.11–0.44; ES = 0.13, p < 0.001). HKT was superior to CO for 6, 12, and 24 months as well (ES < 0.2, p ≤ 0.006). HKT was inferior regarding the first incidence of hip or knee AJR during follow-up in comparison to CO (adjusted hazard ratio, HR = 1.57; CI 1.08—2.30; p = 0.020).

Conclusions
This trial demonstrated short-, mid- and long-term superiority of exercise versus control. However, differences were smaller than those reported in previous efficacy trials, raising questions regarding clinical importance. Responder analysis will follow to identify possible predictors for patient responsiveness on an individual level. Further studies should investigate the frequency and reasons for joint replacement following exercise therapy.

Trial registration
German Clinical Trial Register (DRKS00009251). Registered 10 September 2015.