bluuebunny/crossref_metadata_2025_split huggingface dataset:
The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Capillary Malformations
Authors: Baselga Eulalia , Andersen Rune , Barea Maria , Bejarano Serrano Miguel , Berger Sigurd , Bisdorff-Bresson Annouk , Boccara Olivia , Bom-Sucesso Maria , Boon Laurence M. , Borgards Petra , Diociaiuti Andrea , Dompmartin Anne , Dvorakova Veronika , El Hachem May , Frisk Sofia , Gasparella Paolo , Ghaffarpour Nader , Haxhija Emir , Hjuler Thomas , Holm Annegret , Kaltoft Mikkel , Kapp Friedrich G. , Kyrklund Kristiina , Irvine Alan D. , Madureira Miguel , Palionis Darius , Rößler Jochen , Salminen Päivi , Tolonen Jukka , Vaisnyte Birute , Van Den Bosch Caroline , van der Vleuten Carine , Schultze Kool Leo , Vikkula Miikka 
Published: February 2025

Objective:
VASCERN (https://vascern.eu/) is the European Reference Network for Rare Multisystemic Vascular Diseases. VASCERN-VASCA is the working group within VASCERN that focuses on the study of vascular anomalies. One of the objectives of this group is to establish patient pathways to guide physicians toward efficient diagnostic and management measures. The patient pathway presented here is focused on capillary malformations (CMs).

Methods:
The Nominal Group Technique, a structured variation of small group discussion was used. Two facilitators were identified: one to propose initial discussion points and draw the pathway and another to chair the discussion. A dermatologist (E. Baselga) was chosen as the first facilitator due to her specific clinical and research expertise. The draft was subsequently discussed within VASCERN-VASCA monthly virtual meetings and biannual face-to-face meetings.

Results:
The pathway starts from the clinical recognition of a vascular red stain, describing clinical characteristics and location. Depending on the clinical features, a subsequent workup for associated manifestations or complications is suggested. These steps should enable the establishment of 6 subtypes of CMs: (1) nevus simplex; (2) isolated CM, syndromic or nonsyndromic; (3) CM of microcephaly CM syndrome; (4) CM of CM–arteriovenous malformation syndromes; (5) “pseudo” CM of arteriovenous malformation; (6) cutis marmorata telangiectatica congenita. Management according to the recognized phenotype is detailed in subsequent pages of the pathway. A color code is used to differentiate (1) clinical evaluations, (2) investigations, (3) associated genes, and (4) treatments. Actions relevant to all types are marked in separate boxes, for example, when to perform specific imaging.

Conclusion:
The collaborative efforts of VASCERN-VASCA, a European network of the 14 Expert Centers for Vascular Anomalies, have led to a consensus pathway for CMs. This pathway may help clinicians to guide in the diagnosis and management of CMs, as well as to emphasize the crucial role of multidisciplinary expert centers in the management of these patients. This pathway is available on the VASCERN website (http://vascern.eu/).
Effects of foot intrinsic muscle dynamic stretching on balance, gait parameters, and dynamic gait index in patients with chronic stroke: A randomized controlled study (CONSORT)
Authors: Kwag Younghwan , Park Donghwan 
Published: February 2025

Background:
Foot intrinsic muscle dynamic stretching intervention can correct balance ability and induce a change in spatiotemporal parameters gait ability. Our objective was to compare the effects of a 4-week program of foot intrinsic muscle dynamic stretching with those of lunge exercise on static balance, dynamic balance, gait parameters (velocity, cadence, step length, and stride length), and the dynamic gait index (DGI) in chronic stroke patients.

Methods:
The participants were randomized to either the foot intrinsic muscle dynamic stretching (n = 10) or standard lunge exercise (n = 10) groups. Both groups performed 3 sets of lunge exercises 5 times per week for 4 weeks. Each set comprised 10 repetitions. Static and dynamic balance, gait parameters, and the DGI were measured after 4 weeks of training.

Results:
After 4 weeks of training, the foot intrinsic muscle dynamic stretching group showed significant improvement in all outcome measures compared with the baseline (P < .05). Furthermore, timed up and go, velocity, step length, stride length, and DGI showed greater improvement in the foot intrinsic muscle dynamic stretching group than in the standard lunge exercise group (P < .05).

Conclusions:
This study demonstrated that foot intrinsic muscle dynamic stretching training improved dynamic balance, velocity, step lengths, stride length, and DGI in patients with chronic stroke.
Transarterial chemoembolization in hepatocellular carcinoma: exploring its role in vascular invasion and extrahepatic metastasis: A systematic review
Authors: Usman Younas Muhammad , Saeed Abdullah , Ramzan Muhammad , Junaid Tahir Muhammad , Abbasher Hussien Mohamed Ahmed Khabab , Ahmed Ali 
Published: February 2025

Background and aims:
Transarterial chemoembolization (TACE) is a significant intervention in hepatocellular carcinoma (HCC) management, but controversies persist regarding its application in advanced cases with vascular invasion or extrahepatic metastasis. This systematic review aims to explore TACE’s efficacy and safety in these cases.

Methods:
A literature search was conducted on TACE in HCC patients with vascular invasion or extrahepatic metastasis. The study compared TACE with surgical resection/chemotherapeutic drugs or with no group as well. Safety was assessed for adverse outcomes and efficacy, including overall survival, mean survival, and progression-free survival (PFS). Data extraction included study characteristics, patient demographics, intervention details, outcomes, and adverse events.

Results:
A study of 28 studies involving 3740 patients found that TACE showed diverse safety and efficacy outcomes. Safety evaluations focused on liver function tests, while patient-reported symptoms included fever, pain, vomiting, and gastrointestinal issues. Overall survival was under 10 months in 9 studies, with PFS lower in the TACE group compared to conservative treatments. Survival rates ranged from 93.4% at 3 months to 13% at 24 months across studies. The study identified potential subsets where TACE exhibited efficacy, especially in cases with favorable liver function or specific tumor classifications.

Conclusion:
Our findings suggest a potential role for TACE in certain subsets of advanced HCC patients. Tailored treatment algorithms, informed by rigorous clinical trials and considering various prognostic factors, hold the potential to enhance the management and outcomes for this complex patient population.
Are more exercise components in combined cognitive and physical training better for older adults?: A systematic review and network meta-analysis of randomized controlled trials
Authors: Han Conglin , Zhang Dan , Sun Weishuang , Liu Jiawei , Sun Ruifeng , Gong Weijun 
Published: February 2025

Background:
Age-related cognitive problems are becoming increasingly prevalent in older adults; thus, maintaining normal cognitive abilities and delaying cognitive decline are essential for promoting healthy aging.

Methods:
This systematic review and network meta-analysis examined the effects of combining cognitive and physical training by including various exercise components to improve memory and executive function in older adults. The Cochrane Risk Assessment Tool was used to assess the risk of bias in the included literature. Pairwise meta-analysis was conducted using RevMan 5.3, while network meta-analysis was performed with Stata 15.1, and interventions were ranked based on the results.

Results:
A total of 8180 articles were screened, and 16 randomized controlled trials were included. Pairwise meta-analysis showed that cognitive-physical interventions with 2 (SMD = 0.26, 95% CI: 0.07–0.44, P = .007) and 3 or more exercise components (SMD = 0.43, 95% CI: 0.13–0.73, P = .004) significantly improved memory compared to controls. For executive function, both interventions with 2 (SMD = 0.40, 95% CI: 0.15–0.65, P = .002) and 3 or more exercise components (SMD = 0.55, 95% CI: 0.16–0.93, P = .005) outperformed the control group. Network meta-analysis confirmed that interventions with 2 (SMD = 0.24, 95% CI: 0.06–0.42) and 3 or more components (SMD = 0.43, 95% CI: 0.13–0.73) improved memory, while a single exercise component was most effective for executive function (SMD = 1.27, 95% CI: 0.05–2.49). Overall, we demonstrated that combined cognitive-physical intervention training with multiple exercise components significantly improved memory and executive function compared to controls. The effects of combined training with 3 or more exercise components were likely the most effective in improving memory.

Conclusion:
Cognitive-physical combined interventions are increasingly applied in clinical research on age-related cognitive decline. Our meta-analysis indicates that interventions incorporating multiple exercise components are more effective than those with a single exercise component. These findings provide a basis for future cognitive and physical interventions for older adults and can inform the design of effective intervention programs.
Analgesic therapy failure in a COMT HPS/HPS diplotype carrier heterozygous for the CYP2D6 *4 allele with fibromyalgia—a case report
Authors: Bollinger Anna , Gianora Julia , Schüpbach Tanja , Allemann Samuel S. , Stäuble Céline K. , Meyer zu Schwabedissen Henriette E. 
Published: February 2025

Abstract

Introduction:
The cytochrome P450 enzyme 2D6 (CYP2D6) and the catechol-O-methyltransferase (COMT) enzyme are involved in catecholamine metabolism, potentially influencing pain modulation. Catechol-O-methyltransferase has 3 major haplotypes related to pain sensitivity: low (LPS), average (APS), and high (HPS). However, the reliability of these haplotypes in predicting clinical outcomes is not well investigated. We present a 40-year-old female patient with fibromyalgia. Despite extensive pharmacotherapy with 120 mg/d duloxetine, 150 mg/d pregabalin, 80 mg/d oxycodone, 2 g/d paracetamol, and 1.6 g/d ibuprofen, she suffered from severe pain.

Objectives:
We aim to investigate the patient’s susceptibility to analgesic therapy failure (TF) and pain sensitivity with pharmacogenotyping.

Methods:
PGx panel testing, including CYP2D6 and COMT rs4680, was conducted by a commercial provider. Additional genotyping of COMT rs6269, rs4633 and rs4818 was performed applying PCR, restriction fragment length polymorphism assay and sanger sequencing.

Results:
The patient was identified as COMT HPS/HPS diplotype carrier and CYP2D6 intermediate metabolizer. CYP2D6 is mainly responsible for the bioactivation of oxycodone into oxymorphone. Reduced CYP2D6 activity may result in a lower oxycodone activation. Considering the coadministration of duloxetine (a moderate CYP2D6 inhibitor), the TF of oxycodone could also be the result of a drug–drug–gene interaction. No other medications were affected by her genetic profile.

Conclusion:
We hypothesize that the broad TF of pain medications and associated high pain sensitivity could be related to the patient’s genetic predisposition in CYP2D6 and COMT, warranting further investigation in a larger patient sample.
One-Stop 68Ga-FAPI/18F-FDG Total-Body PET/CT Scan
Authors: Gao Huaping , Tang Han , Zheng Zhe , Yu Haojun , Mao Wujian , Lin Yu , Zheng Jiefu , Al-Ibraheem Akram , He Yibo , Tang Wenxin , Yang Runjun , Xie Yunze , Tan Lijie , Shi Hongcheng 
Published: February 2025

Purpose:
This prospective study aims to assess the feasibility of a one-stop imaging protocol using 68Ga-FAPI-04/18F-FDG dual-radiotracer with dual-low-activity for tumor imaging.

Patients and Methods:
Forty patients underwent one-stop 68Ga-FAPI-04 PET (PETFAPI) and dual-radiotracer PET (PETDUAL) using a total-body PET/CT scanner with a 194-cm axial field of view. After a half-dose (0.925 MBq/kg) 68Ga-FAPI-04 PET/CT, an additional half-dose (1.85 MBq/kg) of 18F-FDG was administered for a 60-minute dynamic acquisition. PETDUAL was reconstructed at 10-minute intervals (PETD0–10, PETD10–20, PETD20–30, PETD30–40, PETD40–50, and PETD50–60). Data of lesion detectability, target-to-background ratios, tumor staging, and total radiation dose were analyzed. A target-to-liver ratio (TLR) ≥ 3 on PETFAPI was considered indicative of sufficient fibroblast activation protein expression.

Results:
PETD50–60 and PETFAPI showed similar performance in detecting primary tumors (42 vs 41, P > 0.999). However, significantly more metastatic lesions were identified on PETD50–60 compared with PETFAPI (102 vs 60, P < 0.001). PETFAPI demonstrated significantly higher TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio than PETDUAL (P < 0.05). Lesion detectability was similar across PETD10–20, PETD20–30, PETD30–40, PETD40–50, and PETD50–60 (all P’s > 0.05). Notably, PETD30–40 and PETD40–50 detected all lesions identified by PETD50–60. PETD40–50 showed no significant differences in TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio compared with PETD50–60 (P > 0.05). Up to 94.9% of malignant primary lesions exhibited a TLR ≥ 3 on PETFAPI. The average effective dose was 9.85 ± 2.19 mSv, similar to that of a whole-body 18F-FDG PET/CT.

Conclusions:
This one-stop, dual-radiotracer, dual-low-activity imaging protocol combines the strengths of 68Ga-FAPI-04 and 18F-FDG, offering a shorter imaging duration and reduced radiation exposure.
Original Study: Association of High-Deductible Health Plans and Complicated Appendicitis among Children
Authors: Rook Jordan M. , Kelley-Quon Lorraine I. , Jen Howard C. , Gidwani Risha 
Published: February 2025

Objective:
To determine whether high-deductible health plans (HDHPs) are associated with complicated disease and hospitalization costs for children with appendicitis.

Background:
Nearly 60% of families with non-governmental employer-sponsored insurance are enrolled in high-deductible health plans (HDHPs). It is unknown how these plans affect children who require surgical care.

Methods:
This retrospective cohort study used the 2016-2020 MarketScan dataset. We included children aged 17 years and younger with non-governmental employer-sponsored insurance who were treated for acute appendicitis. The exposure was a binary variable indicating family enrollment in a HDHP. We assessed the outcomes of complicated appendicitis and hospitalization costs. We used machine learning-based propensity score weights and multivariable regression to assess the association between HDHP enrollment and outcomes. Covariates included age, gender, geographic region, comorbidities, prior healthcare utilization, and month and year treated.

Results:
Of 18,291 children treated for appendicitis, 40.6% (n=7,434) were enrolled in HDHPs. Groups exhibited covariate balance after propensity score weighting. HDHP enrollment was associated with a 2.6 percentage point (95%CI, 1.2-3.9; P<0.001) increase in the likelihood of presenting with complicated appendicitis (33.2% versus 30.6%); a $2,491 (95%CI, $2,428-$2,555; P<0.001) increase in out-of-pocket costs ($4,341 versus $1,850); and a $703 (95%CI, $185-$1,222; P=0.008) increase in total costs ($24,556 versus $23,852).

Conclusions:
Children in HDHPs more often present with complicated appendicitis and require more costly hospitalizations. High levels of cost sharing, a dominant component of most private insurance plans, may not serve the needs of children with acute illnesses and can increase costs to patients and society.
Computational Platform for streamlining the success of sequential antibiotic therapy
Authors: Anderson Alejandro , Kinahan Matt , Blanco-Rodríguez Rodolfo , Gonzalez Alejandro H. , Udekwu Klas , Hernandez-Vargas Esteban A. 
Published: February 2025

AbstractThe scarcity of antibiotics and the need for swift decision-making present significant challenges for healthcare practitioners. When confronted with such circumstances, practitioners must prioritize their approach based on several key factors. By leveraging the recent biological discovery of collateral sensitivity, we have devised an open-source computational platform. This platform utilizes the drug resistance profile of an evolved strain and initial population conditions to potentially predict the failure of cycling therapy in eradicating or restraining a multi-drug resistant bacterial population. We demonstrate how this framework can anticipate potential failures for a range of antibiotics in chronicpseudomonas aeruginosainfections. This innovative methodology lays the foundation for evolutionary therapies that can facilitate the selection of appropriate treatments, thereby reducing antibiotic resistance.
MYBPC3(c.194C>T) mutation-mediated RyR2 dysfunction contributes to pathogenic phenotypes of dilated cardiomyopathy revealed by hiPSC modeling
Authors: Xie Manting , Xie Bingbing , Chen Ying , Lai Xingqiang , Gong Jixing , Cao Nan , Xiang Andy Peng , Xiang Qiuling 
Published: February 2025

AbstractDilated cardiomyopathy (DCM) is a leading cause of heart failure and the primary indication for heart transplantation. The intricate and poorly elucidated pathogenesis of genetic DCM, coupled with the paucity of effective therapeutic options, imposes a substantial burden on both patients and their families. In this study, we identified a novelMYBPC3mutation (c.194C>T) in a patient diagnosed with DCM and established a patient-specific human induced pluripotent stem cell (hiPSC) model. Cardiomyocytes derived from these patient-specific hiPSCs (hiPSC-CMs) exhibited hallmark features of DCM, including hypertrophic cell size, aberrant distribution of sarcomeric α-actinin, and dysregulated calcium ion homeostasis, as compared to control hiPSC-CMs derived from a healthy individual. RNA sequencing analysis revealed a significant upregulation ofCASQ2, which encodes calsequestrin, a protein that binds to Ryanodine receptor 2 (RyR2). Notably, treatment with the RyR2 inhibitor ryanodine effectively restored the abnormal calcium transients observed in DCM-hiPSC-CMs. In summary, our findings provide compelling evidence that the c.194C>T mutation ofMYBPC3plays a definitive pathogenic role in DCM, and that modulation of the RyR2 receptor may alleviate calcium dysregulation in affected cardiomyocytes. These insights enhance our understanding of the molecular mechanisms underlying DCM and offer a promising therapeutic strategy for patients with calcium ion dysregulation associated with this condition.Graphical AbstractHighlightsCardiomyocytes differentiated from patient-specific induced pluripotent stem cells (hiPSCs) reproduces morphology of cardiac hypertrophy and sarcomeric disorders.novelc.194C>Tmutation inMYBPC3results in abnormal calcium transients in hiPSC-derived cardiomyocytes.c.194C>Tmutation ofMYBPC3leads to a significant increase in the expression of calsequestrin that binds to the ryanodine receptor 2 (RyR2).with RyR2 inhibitor markedly improves the ability of calcium handling in DCM-hiPSC-cardiomyocytes.
Clinical audit on laboratory diagnosis of malaria parasites at Jimma University Medical Center laboratory, Southwest Ethiopia
Authors: Girma Dechasa , Hailu Adane , Abebe Chalachew , Said Hawa , Mohamoud Hamda , Asaye Sintayehu 
Published: February 2025

1.AbstractBackgroundMicroscopic diagnosis using stained blood films is usually regarded as the gold standard and most acceptable method of diagnosis. There is no clinical audit performed at the Clinical Laboratory of Jimma University Medical Center, which aims to audit malaria diagnosis; therefore, this audit assesses the pre-analytic, analytic, and post-analytic processes that can affect the accuracy and quality of malaria diagnosis in this laboratory against the established acceptable standards of malaria diagnosis.MethodWe conducted a clinical audit at the Jimma University Medical Center Laboratory from January 2-20, 2025, using direct observation of the procedure that laboratory staff follow in blood collection, fixation, blood smear preparation, microscopic examination, reporting, and documentation of malaria diagnosis results, and also by re-examining the diagnosed slides to assess the skill of laboratory staff by maintaining confidentiality of the data.ResultsA total of 26 quality standards were used. It is known that 56.3 percent of the samples are collected from capillaries and 43.7 from veins. Approximately 78 percent of the samples were collected from properly rubbed fingers and 22% from fingers that were not rubbed adequately. All the blood samples collected with an anticoagulant were mixed properly before smearing (n=35), 78.8 % of the slides were preliminarily visualized using a high-power (100x) objective of the microscope, and only 17.5 % of the slides were visualized using a 10x objective.ConclusionProper Disinfection, mixing the anti-coagulated blood well, and fixing thin blood films for the recommended length of time were areas of good practice. On the other hand, failure to report parasitic load and proper and sequential use of types of objectives to examine blood films and prepare smears of good quality were some of the highly violated standards that need consideration.
Adaptations of gram-negative and gram-positive probiotic bacteria in engineered living materials
Authors: Tadimarri Varun Sai , Tyagi Tanya Amit , Duong Cao Nguyen , Rasheed Sari , Müller Rolf , Sankaran Shrikrishnan 
Published: February 2025

AbstractEncapsulation of microbes in natural or synthetic matrices is a key aspect of engineered living materials, although the influence of such confinement on microbial behavior is poorly understood. A few recent studies have shown that spatial confinement and mechanical properties of the encapsulating material significantly influence microbial behavior, including growth, metabolism, and gene expression. While such effects have been shown to elicit various responses in a few micro-organisms likeE. coli, yeast, and cyanobacteria, systematic comparative studies between different organisms in the same confinement conditions are missing. Thus, in this study, we report the adaptive responses exhibited by rod-shaped gram-negative and gram-positive probiotic bacteria that are of great interest for developing therapeutic engineered living materials. Accordingly, gram-negativeE. coliNissle 1917 and gram-positiveL. plantarumWCFS1 were encapsulated in hydrogel matrices and their growth, metabolic activity, and recombinant gene expression were investigated. By varying the polymer concentration and degree of chemical cross-linking in the hydrogels, it was possible to modulate their stiffness and study how the bacteria adapted to these different confinement conditions. In accordance with previous reports, both bacteria grow from single cells into confined colonies but more interestingly, inE. coligels, mechanical properties influenced colony growth, size, and morphology, whereas this did not occur inL. plantarumgels. However, with both bacteria, increased matrix stiffness led to higher levels of recombinant protein production within the colonies. By measuring metabolic heat generated in the bacterial gels using a novel isothermal microcalorimetry technique, it was inferred thatE. coliadapts to the mechanical restrictions through multiple metabolic transitions and is significantly affected by the different hydrogel properties. Contrastingly, both these aspects were not observed withL. plantarum. These results revealed that despite both these bacteria being gut-adapted probiotics with similar geometries, mechanical confinement affects them considerably differently. The weaker influence of matrix stiffness onL. plantarumis attributed to its slower growth and thicker cell wall possibly enabling the generation of higher turgor pressures to overcome restrictive forces under confinement. By providing fundamental insights into the interplay between mechanical forces and bacterial physiology, this work advances our understanding of how matrix properties shape bacterial behavior. The implications of these findings will aid the design of engineered living materials for therapeutic applications.