bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel deep learning-based algorithm combining histopathological features with tissue areas to predict colorectal cancer survival from whole-slide images
Authors: Li Yan-Jun , Chou Hsin-Hung , Lin Peng-Chan , Shen Meng-Ru , Hsieh Sun-Yuan 
Published: October 2023

Abstract
Background
Many methodologies for selecting histopathological images, such as sample image patches or segment histology from regions of interest (ROIs) or whole-slide images (WSIs), have been utilized to develop survival models. With gigapixel WSIs exhibiting diverse histological appearances, obtaining clinically prognostic and explainable features remains challenging. Therefore, we propose a novel deep learning-based algorithm combining tissue areas with histopathological features to predict cancer survival.

Methods
The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset was used in this investigation. A deep convolutional survival model (DeepConvSurv) extracted histopathological information from the image patches of nine different tissue types, including tumors, lymphocytes, stroma, and mucus. The tissue map of the WSIs was segmented using image processing techniques that involved localizing and quantifying the tissue region. Six survival models with the concordance index (C-index) were used as the evaluation metrics.

Results
We extracted 128 histopathological features from four histological types and five tissue area features from WSIs to predict colorectal cancer survival. Our method performed better in six distinct survival models than the Whole Slide Histopathological Images Survival Analysis framework (WSISA), which adaptively sampled patches using K-means from WSIs. The best performance using histopathological features was 0.679 using LASSO-Cox. Compared to histopathological features alone, tissue area features increased the C-index by 2.5%. Based on histopathological features and tissue area features, our approach achieved performance of 0.704 with RIDGE-Cox.

Conclusions
A deep learning-based algorithm combining histopathological features with tissue area proved clinically relevant and effective for predicting cancer survival.
Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study
Authors: Zhang Caihui , Yu Zhongxun , Gao Sihao , Ma Mingsheng , Gou Lijuan , Wang Changyan , Wang Lin , Li Ji , Zhong Linqing , Zhou Yu , Wang Wei , Song Hongmei 
Published: October 2023

Abstract
Background
Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs.

Methods
This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses.

Results
A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions.

Conclusion
The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.
Parental Intervention Program for Preschool children with Rare Diseases – a mixed methods evaluation of parents’ experiences and utility
Authors: Velvin Gry , Johnsen Vigdis , Lidal Ingeborg Beate , Berg Ellen 
Published: October 2023

Abstract
Background
The purpose of this study was twofold: (i) To assess the parents’ experiences and perception of participating in a “Parental Intervention Program for Preschool children with Rare Diseases” (PIPP-RDs). (ii) To evaluate which elements of the PIPP-RDs that the parents emphasized as important for improving their health literacy related to facilitating the transition of their children from kindergarten to school.

Method
A mixed methods evaluation study was conducted ten and eleven months post-intervention, integrating an online quantitative survey combined with individual semi-structured interviews. Twenty-two parents participated in individual interviews, of these 18 also responded to the online questionnaire survey.

Results
All parents that participated in this study reported that the information conveyed at the program was of great value and utility, 88% reported significantly alleviated stress associated to their child`s school-start, 84% indicated had improved the school-home collaboration and 84% reported that it had encouraged them to establish contact with the school prior to school commencement. From the qualitative data five main themes emerged: (i) Competence and Knowledge Acquisition, (ii) Becoming more Prepared and Relaxed, (iii) Achieved Realistic Expectations, (iv) Enhanced Communication Skills, (v) Increased Health Literacy and Self-Efficacy. The evaluative findings suggest that this invention program has notably improved the parents’ aptitude for school interaction, enhanced the adaptions according to children`s needs for accommodations, and has provided reassurance in the school-home collaboration. Parents also described increased self-confidence and self-efficacy in managing the school start for children with RDs.

Conclusion
The highly positive response of participating in PIPP-RDs may not only reflect the merits of the program`s content, but also underscore the significant needs for such support during the transition to school for parents of children with RDs. Comparable initiatives, oriented towards enhancing the health literacy and empowering the parents, are anticipated to yield similarly favourable results. We argue that intervention program amalgamate pertinent information, group discourse, and workshops on school-related issues, alongside opportunities for parents to meet other parents in similar situations.
A systematic review of measures of the personal recovery orientation of mental health services and staff
Authors: Leamy Mary , Foye Una , Hirrich Anne , Bjørgen Dagfin , Silver Josh , Simpson Alan , Ellis Madeline , Johan-Johanson Karl 
Published: October 2023

Abstract
Purpose
This review aimed to update and extend the Williams and colleagues 2012 systematic review of measures of recovery-orientation of mental health services by examining whether any of the specific knowledge gaps identified in this original review had subsequently been addressed.

Methods
A systematic review using CINAHL, ASSIA, Embase, PsycINFO, Medline and other sources, searched from 2012 until 2021. The conceptualisation of recovery and recovery-orientation of services was explored. Psychometric properties of measures were evaluated using quality criteria and according to ease of use.

Results
Fourteen measures assessing aspects of the recovery orientation of services and staff were identified, of which ten met the eligibility. Psychometric properties were evaluated, and conceptualisations of recovery and recovery-orientation of services investigated.

Conclusion
After over a decade of research in the field of recovery outcome measurement, there remains a lack of a single gold-standard measure of recovery-orientation of mental health services. There is a need for researchers to develop a new gold standard measure of recovery-orientation of services that is psychometrically valid and reliable, demonstrates sensitivity to change and is easy to use. It needs to show a good fit to an underpinning conceptual model/ framework of both personal recovery and recovery-oriented services and/or systems, with different versions for stakeholders at each level of an organisation or system.
Self-regulation facets differentially predict internalizing symptom trajectories from middle childhood to early adolescence: a longitudinal multimethod study
Authors: Klinge Johanna L. , Warschburger Petra , Busching Robert , Klein Annette M. 
Published: October 2023

Abstract
Background
Internalizing symptoms are among the most common psychological symptoms in childhood and adolescence, are highly stable and can cause severe impairment. Current research discusses lower capacities of self-regulation (SR) as risk factors for the development of internalizing symptoms. The present study identifies trajectories of internalizing symptoms in the transition phase from middle childhood to adolescence and examines multiple SR facets as predictors of potentially unfavorable trajectories, also in the presence of other established risk factors.

Methods
The study utilized a community sample of N = 1453 (52.2% female) German children, who provided data at up to three measurement points (t1: 6–11 years, t2: 7–11 years, t3: 9–13 years). Trajectories of internalizing symptoms were based on parents’ ratings of the emotional problems scale of the Strengths and Difficulties Questionnaire. SR facets were assessed using multiple methods and informants. Two multinomial regression analyses were conducted to predict class membership by (1) SR facets and gender and (2) SR facets, gender, and other established risk factors (education status, family adversity, peer problems).

Results
Using growth mixture modelling, we identified three trajectory classes with stable low (n = 1200), increasing (n = 124), and early high decreasing internalizing symptoms (n = 129). In the regression analysis controlling for risk factors, membership in the increasing trajectory was significantly predicted by higher emotional reactivity (OR = 2.65, p < .001), higher cognitive flexibility/set-shifting (OR = 1.48, p = .032), and higher family adversity (OR = 1.38, p = .046). Membership in the early high decreasing trajectory was significantly predicted by higher emotional reactivity (OR = 4.15, p < .001), higher inhibitory control (OR = 1.47, p = .045), lower working-memory updating (OR = 0.69, p = .016), lower delay of gratification (OR = 0.75, p = .028), and higher family adversity (OR = 1.63, p = .001).

Conclusions
SR facets incrementally and differentially predict potentially unfavorable trajectories of internalizing symptoms from age 6 to 13, surpassing the predictive value of gender or education status. Higher emotional reactivity emerged as the most influential factor, which could therefore be addressed in future prevention and intervention efforts.
AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo
Authors: Kook Yeon Hee , Lee Hyoin , Lee Jinsu , Jeong Yeonji , Rho Jaerang , Heo Won Do , Lee Sangkyu 
Published: October 2023

AbstractCalcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitter release, and gene expression. In our previous work, we developed ‘monster OptoSTIM1’ (monSTIM1), an improved OptoSTIM1 that selectively activates Ca2+-release–activated Ca2+ (CRAC) channels in the plasma membrane through blue light, allowing precise control over intracellular Ca2+ signaling and specific brain functions. However, the large size of the coding sequence of monSTIM1 poses a limitation for its widespread use, as it exceeds the packaging capacity of adeno-associated virus (AAV). To address this constraint, we have introduced monSTIM1 variants with reduced coding sequence sizes and established AAV-based systems for expressing them in neurons and glial cells in the mouse brain. Upon expression by AAVs, these monSTIM1 variants significantly increased the expression levels of cFos in neurons and astrocytes in the hippocampal CA1 region following non-invasive light illumination. The use of monSTIM1 variants offers a promising avenue for investigating the spatiotemporal roles of Ca2+-mediated cellular activities in various brain functions. Furthermore, this toolkit holds potential as a therapeutic strategy for addressing brain disorders associated with aberrant Ca2+ signaling.
Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1
Authors: Mur Pilar , Viana-Errasti Julen , García-Mulero Sandra , Magraner-Pardo Lorena , Muñoz Inés G. , Pons Tirso , Capellá Gabriel , Pineda Marta , Feliubadaló Lidia , Valle Laura 
Published: October 2023

Abstract
Background
Germline variants affecting the proofreading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a specific mutational spectrum. In addition to the implementation of multiple pieces of evidence for the classification of gene variants, POLE and POLD1 variant classification is particularly challenging given that non-disruptive variants affecting the proofreading activity of the corresponding polymerase are the ones associated with cancer. In response to an evident need in the field, we have developed gene-specific variant classification recommendations, based on the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) criteria, for the assessment of non-disruptive variants located in the sequence coding for the exonuclease domain of the polymerases.

Methods
A training set of 23 variants considered pathogenic or benign was used to define the usability and strength of the ACMG/AMP criteria. Population frequencies, computational predictions, co-segregation data, phenotypic and tumor data, and functional results, among other features, were considered.

Results
Gene-specific variant classification recommendations for non-disruptive variants located in the exonuclease domain of POLE and POLD1 were defined. The resulting recommendations were applied to 128 exonuclease domain variants reported in the literature and/or public databases. A total of 17 variants were classified as pathogenic or likely pathogenic, and 17 as benign or likely benign.

Conclusions
Our recommendations, with room for improvement in the coming years as more information become available on carrier families, tumor molecular characteristics and functional assays, are intended to serve the clinical and scientific communities and help improve diagnostic performance, avoiding variant misclassifications.
miR-125a-5p regulates the sialyltransferase ST3GAL1 in murine model of human intestinal campylobacteriosis
Authors: Kraski Angelina , Mousavi Soraya , Heimesaat Markus M. , Bereswill Stefan , Einspanier Ralf , Alter Thomas , Gölz Greta , Sharbati Soroush 
Published: October 2023

Abstract
Background
Zoonotic microorganisms are increasingly impacting human health worldwide. Due to the development of the global population, humans and animals live in shared and progressively crowded ecosystems, which enhances the risk of zoonoses. Although Campylobacter species are among the most important bacterial zoonotic agents worldwide, the molecular mechanisms of many host and pathogen factors involved in colonisation and infection are poorly understood. Campylobacter jejuni colonises the crypts of the human colon and causes acute inflammatory processes. The mucus and associated proteins play a central host-protective role in this process. The aim of this study was to explore the regulation of specific glycosyltransferase genes relevant to differential mucin-type O-glycosylation that could influence host colonisation and infection by C. jejuni.

Results
Since microRNAs are known to be important regulators of the mammalian host cell response to bacterial infections, we focussed on the role of miR-125a-5p in C. jejuni infection. Combining in vitro and in vivo approaches, we show that miR-125a-5p regulates the expression of the sialyltransferase ST3GAL1 in an infection-dependent manner. The protein ST3GAL1 shows markedly increased intestinal levels in infected mice, with enhanced distribution in the mucosal epithelial layer in contrast to naïve mice.

Conclusion
From our previous studies and the data presented here, we conclude that miR-125a-5p and the previously reported miR-615-3p are involved in regulating the glycosylation patterns of relevant host cell response proteins during C. jejuni infection. The miRNA-dependent modulation of mucin-type O-glycosylation could be part of the mucosal immune response, but also a pathogen-driven modification that allows colonisation and infection of the mammalian host.
Plants acquired mitochondrial linear plasmids horizontally from fungi likely during the conquest of land
Authors: Wei Yutong , Gong Zhen , Han Guan-Zhu 
Published: October 2023

AbstractMitochondrial linear plasmids have been sporadically reported in fungi and plants. Yet, much remains obscure about the diversity, distribution, and evolution of mitochondrial linear plasmids. Here, through phylogenomic analyses across 7,163 cellular organisms (including 991 plants), we find that mitochondrial linear plasmids are widely present in land plants and fungi. Phylogenetic analyses indicate that plants are likely to have acquired mitochondrial linear plasmids horizontally from fungi before or during the conquest of terrestrial environments by plants. Gene content analyses show that mitochondrial linear plasmids harbor a highly dynamic and promiscuous repertoire of genes. Our study refines the understanding of the origin and evolution of mitochondrial linear plasmids.
Gradual loaded exercise of knee extension muscles using an orthosis after wide resection of a femoral sarcoma and quadriceps muscle: a case report
Authors: Kitade Ippei , Oki Hisashi , Sakamoto Takumi , Matsumine Akihiko 
Published: October 2023

Abstract
Background
Details of improved gait ability after wide resection of soft tissue sarcomas that necessitate removal of portions of the quadricep muscle have not yet been reported. We describe a patient with improved gait ability following a rehabilitation program after wide resection of a soft tissue sarcoma that included four components of the quadricep muscle.

Case presentation
An 85-year-old Japanese man underwent wide resection of an undifferentiated pleomorphic sarcoma that included portions of the quadriceps femoris muscle. The rectus femoris, vastus medialis, sartorius, and vastus intermedius were separated in the maximally bulging region of the tumour. Three weeks postoperatively, gait exercise was initiated using a rigid knee orthosis with a dual-adjustable lock knee. The contraction loading of the knee extension muscle was controlled by adjusting the hinge motion range of the orthosis as follows: fully extended, fixed knee 0°–30°, and free range. Under this regimen, he could walk independently without a rigid orthosis within 5 weeks postoperatively but could not sit on his heels during daily living activities. At six months, there was no clinical evidence of recurrent tumours or complications.

Conclusions
Postoperative gait ability might be affected by not only the number of resected muscles but also by the function of the separated muscles and the cross-sectional area of the remaining muscle. Gradually loaded exercise of the knee extension muscles using an orthosis could result in an improved gait motion for patients who undergo wide resection of a sarcoma that includes four components of the quadriceps femoris.
Association of triglyceride–glucose index with coronary severity and mortality in patients on dialysis with coronary artery disease
Authors: Xie Enmin , Ye Zixiang , Wu Yaxin , Zhao Xuecheng , Li Yike , Shen Nan , Guo Xiaochun , Gao Yanxiang , Zheng Jingang 
Published: October 2023

Abstract
Background
The triglyceride–glucose (TyG) index is validated as a reliable biomarker of insulin resistance and an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients on dialysis with coronary artery disease (CAD) remained unexplored. This study aimed to determine the association between the TyG index and CAD severity and mortality in these patients.

Methods
A total of 1061 dialysis patients with CAD were enrolled in this multi-center cohort study from January 2015 to June 2021. The extent and severity of CAD were evaluated using the multivessel disease and Gensini score (GS). Patients were followed up for all-cause death and cardiovascular death.

Results
The multivariable logistic regression model indicated that the TyG index was significantly associated with multivessel disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.18–1.94, P = 0.001), and high GS (OR 1.33, 95% CI 1.10–1.61, P = 0.003). After adjusting for baseline risk factors, the hazards of all-cause death and cardiovascular death were 1.23 (95% CI 1.06–1.43, P = 0.007), and 1.33 (95% CI 1.11–1.59, P = 0.002), independent of CAD severity. Restricted cubic spline analysis identified a dose–response association between the TyG index and both CAD severity and mortality (all P for nonlinearity > 0.05). When modeling the TyG index as a categorical variable, these independent associations remained. Subgroup analyses did not substantially modify the results. Furthermore, incorporating the TyG index into the existing risk prediction model improved the predictive accuracy for all-cause death and cardiovascular death, as evaluated by C-statistic, continuous net reclassification improvement, and integrated discrimination improvement.

Conclusions
In patients on dialysis with CAD, the TyG index was significantly associated with more severe CAD as well as mortality. These results highlight the clinical importance of the TyG index for assessing CAD severity and risk stratification in patients on dialysis with CAD.