Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver metastases and the efficacy of the PD-1 or PD-L1 inhibitors in cancer: a meta-analysis of randomized controlled trials

ABSTRACT Objective: To explore the relations between liver metastases (LM) and the efficacy of the treatments with programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. Method: Pubmed, Embase, American Society of Clinical Oncology and the European Society for Medical Oncology were searched to select eligible studies about PD-1 or PD-L1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab, Avelumab, Durvalumab, and Atezolizumab). We included only the original randomized controlled trials (RCTs), including the hazard ratios (HR) of death in both patients with LM and patients without LM. Then the data were extracted for the meta-analysis. Subgroup analyses of cancer types and drug types were also performed. Results: 5293 patients [1246 (24%) patients with LM, and 4047 (76%) patients without LM] from the eight RCTs were included for the final analysis. The pooled hazard ratio (HR) of death in the patients with LM was 0.82 (95% CI, 0.71 to 0.93, P = .003) while the pooled HR in the patients without LM was 0.72 (95% CI, 0.66 to 0.79, P < .001). Additionally, no significant difference was found between the two groups (P = .137). Conclusion: No statistically significant association of liver metastases with the efficacy of treatments with PD-1 or PD-L1 inhibitors in the treatment of advanced or metastatic cancer was found in the stratified analyses. Moreover, future studies about the safety of the PD-1 or PD-L1 inhibitors in patients with or without liver metastases are warranted.
The Semantic Data Dictionary – An Approach for Describing and Annotating Data

It is common practice for data providers to include text descriptions for each column when publishing data sets in the form of data dictionaries. While these documents are useful in helping an end-user properly interpret the meaning of a column in a data set, existing data dictionaries typically are not machine-readable and do not follow a common specification standard. We introduce the Semantic Data Dictionary, a specification that formalizes the assignment of a semantic representation of data, enabling standardization and harmonization across diverse data sets. In this paper, we present our Semantic Data Dictionary work in the context of our work with biomedical data; however, the approach can and has been used in a wide range of domains. The rendition of data in this form helps promote improved discovery, interoperability, reuse, traceability, and reproducibility. We present the associated research and describe how the Semantic Data Dictionary can help address existing limitations in the related literature. We discuss our approach, present an example by annotating portions of the publicly available National Health and Nutrition Examination Survey data set, present modeling challenges, and describe the use of this approach in sponsored research, including our work on a large National Institutes of Health (NIH)-funded exposure and health data portal and in the RPI-IBM collaborative Health Empowerment by Analytics, Learning, and Semantics project. We evaluate this work in comparison with traditional data dictionaries, mapping languages, and data integration tools.
Validation of Motor Outcome Measures in Myotonic Dystrophy Type 2

Introduction: Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients' reported outcomes (PROs). This represents a limit for the monitoring of disease progression and treatment response. Our aim was to identify the most appropriate OMs to be translated in clinical practice and clinical trials on DM2. This study has been registered on clinicaltrials.gov NCT03603171 (https://clinicaltrials.gov/ct2/show/NCT03603171). Methods: Sixty-six patients with genetically confirmed DM2 underwent a baseline and a follow-up visit after 1 year. The tested OMs included: hand opening time, pressure pain threshold (PPT), manual muscle testing (MMT), hand held dynamometry (HHD), scale for the assessment and rating of ataxia (SARA), quantitative motor function test (QMFT), gait stairs Gowers chair (GSGC), 30-s sit to stand test, functional index 2 (FI-2) and 6MWT. The PROs included DM1-Active-C, Rasch-built Pompe-specific activity scale (R-Pact), fatigue and daytime sleepiness (FDSS), brief pain inventory short form (BPI-sf), myotonia behavior scale (MBS), and the McGill pain questionnaire. Results: All patients completed the MBS and the results correlated well with the hand-opening time. The PPT showed a low reliability, no correlation with pain questionnaires, and did not differentiate patients with or without myalgia. Both muscle strength assessments, MMT and HHD, showed good construct validity. The QMFT showed an acceptable ceiling effect (14.5%), good convergent and differential validity and performed overall better than GSGC. The SARA score showed high flooring effect and is not useful in DM2. 6MWT proved a valid outcome measure in DM2. The 30-s sit to stand is a feasible test with good convergent validity, showing a flooring effect of 20% as it cannot be used in more severely affected patients. The FI-2 is time-consuming and has a high ceiling effect. At the 1-year visit the only assessments able to detect a worsening of DM2 were HHD, QMFT, and 6MWT, which are the most sensitive to change, and therefore clinically meaningful OMs in DM2. Conclusion: The clinical meaningful motor outcome measures that best depict the multifaceted phenotype of DM2 and its slow progression are MBS, MMT, or HHD (depending on the clinical setting), QMFT, and the 6MWT.
Joint and Muscle Assessments of the Separate Effects of Botulinum NeuroToxin-A and Lower-Leg Casting in Children With Cerebral Palsy

Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 ± 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon levels were performed using Spearman correlation coefficients (p < 0.05). Increased joint resistance, measured during slow ankle rotations, was not significantly reduced after either treatment. Additional joint resistance assessed during fast rotations only reduced in the BoNT-A group (−37.6%, p = 0.013, effect size = 0.47), accompanied by a reduction in MG stretch reflexes (−70.7%, p = 0.003, effect size = 0.56). BoNT-A increased the muscle length measured at the resting ankle angle (6.9%, p = 0.013, effect size = 0.53). Joint angles shifted toward greater dorsiflexion after casting (32.4%, p = 0.004, effect size = 0.56), accompanied by increases in tendon length (5.7%, p = 0.039, effect size = 0.57; r = 0.40). No associations between the changes in muscle or tendon lengths and the changes in the stretch reflexes were found. We conclude that intramuscular BoNT-A injections reduced stretch reflexes in the MG accompanied by an increase in resting muscle belly length, whereas casting resulted in increased dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle.
Multisystemic Impairments in 93 Chinese Patients With Myotonic Dystrophy Type 1

Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease characterized by muscle weakness and multisystemic impairments, which significantly impact the quality of life. There is currently an increasing consensus on the necessity of a multidisciplinary assessment in patients with DM1, to improve the management of the disease. Methods: To analyze the prevalence and pairwise relationships between various organs involved, we performed a retrospective study by reviewing demographic and clinical information of DM1 patients including age, disease duration, clinical history, muscular impairment rating scale score (MIRS), results of blood biochemistry, electrocardiogram, echocardiography, and ophthalmologic examination. Results: Ninety three DM1 patients (60 males and 33 females), aged 34.7 ± 12.6 (mean ± standard deviation) years were recruited. Of which, two congenital cases were of maternal and paternal inheritance, respectively. In the other 91 patients, cataract was found in 44.1% of patients, followed by hypogonadism (40.8%), frontal balding (40.7%), and cardiac abnormalities (34.5%). Thyroid dysfunction and insulin insensitivity were relatively uncommon. Age (p < 0.001) is independently correlated with cataract, and MIRS correlates positively with cardiac abnormalities (p = 0.005) and frontal balding (p = 0.015). Male patients more frequently had frontal balding (Risk ratio, 3.98; 95% confidence interval, 1.493–10.611) compared with female patients. Male patients with cataract presented more frequent cardiac abnormalities (Risk ratio, 4.40; 95% confidence interval, 1.055–18.358) compared with non-cataract male patients. Hypogonadism in male patients was characterized as decreased testosterone level, accompanied by elevated levels of luteinizing hormone and follicle-stimulating hormone. Conclusions: In Chinese patients with DM1, we conclude that (1) cataract, hypogonadism, frontal balding and cardiac abnormalities are frequently observed; (2) age is an independent indicator to cataract and MIRS is the only predictor for cardiac abnormalities and frontal balding; (3) a positive correlation between ophthalmologic and cardiac impairments in male patients is found; (4) endocrine abnormalities show diverse manifestations and hormone tests are recommended; (5) particular attention should be given to patients with older age and higher MIRS score.
Redirection of Cord Blood T Cells and Natural Killer Cells for Elimination of Autologous HIV-1-Infected Target Cells Using Bispecific DART® Molecules

Mother-to-child transmission of HIV-1 remains a major global health challenge. Currently, HIV-1-infected infants require strict lifelong adherence to antiretroviral therapy to prevent replication of virus from reservoirs of infected cells, and to halt progression of disease. There is a critical need for immune interventions that can be deployed shortly after infection to eliminate HIV-1-infected cells in order to promote long-term remission of viremia, or to potentially cure pediatric HIV-1-infection. Bispecific HIV × CD3 DART® molecules able to co-engage the HIV-1 envelope protein on the surface of infected cells and CD3 on cytolytic T cells have been previously shown to eliminate HIV-1 infected cells in vitro and are candidates for passive immunotherapy to reduce the virus reservoir. However, their potential utility as therapy for infant HIV-1 infection is unclear as the ability of these novel antibody-based molecules to work in concert with cells of the infant immune system had not been assessed. Here, we use human umbilical cord blood as a model of the naïve neonatal immune system to evaluate the ability of HIV x CD3 DART molecules to recruit and redirect neonatal effector cells for elimination of autologous CD4+ T cells infected with HIV-1 encoding an envelope gene sequenced from a mother-to-child transmission event. We found that HIV × CD3 DART molecules can redirect T cells present in cord blood for elimination of HIV-infected CD4+ T cells. However, we observed reduced killing by T cells isolated from cord blood when compared to cells isolated from adult peripheral blood—likely due to the absence of the memory and effector CD8+ T cells that are most cytolytic when redirected by bispecific DART molecules. We also found that newly developed HIV × CD16 DART molecules were able to recruit CD16-expressing natural killer cells from cord blood to eliminate HIV-infected cells, and the activity of cord blood natural killer cells could be substantially increased by priming with IL-15. Our results support continued development of HIV-specific DART molecules using relevant preclinical animal models to optimize strategies for effective use of this immune therapy to reduce HIV-1 infection in pediatric populations.
Current Research on the Impact of Foreign Language Learning Among Healthy Seniors on Their Cognitive Functions From a Positive Psychology Perspective—A Systematic Review

The purpose of this review study is to explore the existing research focusing on the impact of foreign language learning among healthy seniors on their cognitive functions from the positive psychology perspective. The methods are based on a literature review of available sources found on the research topic in two acknowledged databases: Web of Science and Scopus. The search period was not limited by any time period since there are not many studies on this topic. Altogether seven original studies were detected. The findings of this review study thus reveal that foreign language learning (FLL) has a positive impact on the maintenance and/or enhancement of cognitive abilities irrespective of age. In addition, the FLL courses seem to offer new opportunities for healthy seniors in the area of socializing and integration into society, which consequently may positively affect their overall well-being. Furthermore, the research shows that it is partly through the stimulation of social well-being that the cognitive effects of FLL might be observed. Cognitive aspects of older age are to be further investigated, including the importance of learning a foreign language, as basically all research conducted proves at least some maintenance or even improvement of cognitive functions of older people when starting intensive language training.
Modulation on Glutamic Pathway of Frontal-Striatum-Thalamus by rs11146020 and rs3813296 Gene Polymorphism in First-Episode Negative Schizophrenia

Objectives The frontal-striatum-thalamus pathway is important in the glutamic neural circuit. The hypofunction of GRIN1 and GRIA2 subunits from glutamic receptors has been hypothesized as the primary process in the etiology of schizophrenia. Identified gene polymorphism involved in the pathogenesis of schizophrenia may uncover relevant mechanism pathways. Methods We selected two loci of rs11146020 and rs3813296 distributed in GRIN1 and GRIA2 genes and tested their main and interaction effects on causality connections and structural characteristics in the frontal-striatum-thalamus pathway in 55 Han Chinese first-episode negative schizophrenia patients. Results We found that: (1) rs11146020 has a significant main effect on the causality connections between the bilateral dorsolateral prefrontal cortex, and rs3813296 mainly influences those of the descending pathway from the prefrontal cortex to the striatum; (2) interaction effect of rs11146020 and rs3813296 on causality connections are located in the ascending pathway from the pallidum to the dorsolateral prefrontal cortex; and (3) the two loci have effects on the volumes of several regions of this pathway. Conclusion Our results suggested there is modulation on glutamic frontal-striatum-thalamus pathway by rs11146020 and rs3813296 gene polymorphism. Patients with different genotypes have different neuroimaging characteristics, which indirectly reminded clinicians those patients should receive different clinical interventions.
Online Tourism Information and Tourist Behavior: A Structural Equation Modeling Analysis Based on a Self-Administered Survey

This study presents the interacting phenomena of perceptions of tourist destination online content (TDOC) and tourists’ behavioral intentions with a mediating role of tourists’ satisfaction, which is as yet under-explored in hospitality and tourism research. A model based on three main constructs, namely TDOC (with sub-constructs of online information quality and user-friendly accessibility), satisfaction, and tourists’ behavioral intentions [with sub-constructs of intentions to visit a tourist destination and electronic word-of-mouth (eWOM)], is presented to determine the growth of tourism business with the internet. Data were collected via a questionnaire-based survey from 413 tourists staying at hotels in Lahore city in Pakistan. Partial least square structural equation modeling was used to statistically analyze the gathered data. The findings indicate that tourists’ perceptions of TDOC directly influence their behavioral intentions, while tourists’ satisfaction exerts a mediating influence between tourists’ perceptions of TDOC and their behavioral intentions. Taking advantage of an economical and widespread online environment, destination marketing organizations could attract more tourists by fostering confidence in TDOC and positive eWOM to remain competitive in the long run. Important theoretical and practical implications are discussed.
Study Protocol for a Prospective Longitudinal Cohort Study to Identify Proteomic Predictors of Pluripotent Risk for Mental Illness: The Seoul Pluripotent Risk for Mental Illness Study

Background The Seoul Pluripotent Risk for Mental Illness (SPRIM) study was designed to identify predictors leading to mental illness in help-seeking individuals by securing sufficient statistical power through transdiagnostic approaches. The SPRIM study aims to examine the clinical characteristics of high-risk individuals for mental illness and to identify proteomic biomarkers that can predict the onset of mental illness. Methods This paper describes the study protocol of the SPRIM study. We aim to recruit 150 participants who meet the criteria for high risk for major mental illness, 150 patients with major psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder), and 50 matched healthy control subjects for 2 years. Clinical evaluations, self-report measures, and proteomic analyses will be implemented. The assessment points are at baseline, 6, 12, 18, and 24 months. Conclusions In the present study, we introduced the study protocol of the SPRIM study, which is the first prospective cohort study of transdiagnostic high-risk concepts using proteomic biomarkers. This study has a paradigm that encompasses various diseases without aiming at predicting and preventing the development of a specific mental illness in help-seeking individuals. The transdiagnostic high-risk concept could be extended to provide a perspective for people with various psychopathological tendencies below a threshold, such that they do not meet the existing diagnostic criteria of mental illnesses, to determine what may lead them to a specific disease and help identify appropriate preventative interventions.
Different Shades of Beauty: Adolescents’ Perspectives on Drawing From Observation

Background Drawing from observation (DFO) is an art therapy method that entails drawing an object, along with guided reflections on process and outcome. In this qualitative study, we explored adolescents’ perspectives on their DFO experience, and how they perceive it as having influenced their emotional well-being. Methods We interviewed 10 adolescents who participated in a DFO group, regarding their perspectives on DFO. Participants were asked to refer to their experience, as well as to provide examples of their drawings. Through a thematic analysis we integrated data from interviews and drawings. Results Adolescents experienced three lines of tension in DFO: Between self-acceptance and self-judgment, between merging and separation, and between similarities and differences. Processing these tensions has the potential to increase their emotional well-being. Conclusion DFO could make a meaningful contribution to adolescents’ emotional well-being. The unique intersection between object, observation, and drawing in art-therapy addresses adolescents’ emotional-developmental challenges.
New Insights Into the Complex Mutational Landscape of Sézary Syndrome

Sézary syndrome (SS) is a genetically and clinically distinct entity among cutaneous T-cell lymphomas (CTCL). SS is characterized by more aggressive disease compared to the most common indolent type of CTCL, mycosis fungoides. However, there are limited available genomic data regarding SS. To characterize and expand current mappings of the genomic landscape of CTCL, whole exome sequencing (WES) was performed on peripheral blood samples from seven patients with SS. We detected 21,784 variants, of which 21,140 were novel and 644 were previously described. Filtering revealed 551 nonsynonymous variants among 525 mutated genes−25 recurrent mutations and 1 recurrent variant. Several recurrently mutated genes crucial to pathogenesis pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT), peroxisome proliferator-activated receptors (PPAR), PI3K-serine/threonine protein kinases (AKT), and fibroblast growth factor receptors (FGFR), were identified. Furthermore, genetic mutations spanned both known and novel genes, supporting the idea of a long-tail distribution of mutations in lymphoma. Acknowledging these genetic variants and their affected pathways may inspire future targeted therapies. WES of a limited number of SS patients revealed both novel findings and corroborated complexities of the “long-tail” distribution of previously reported mutations.
Motor Cortex Reorganization in Limb Amputation: A Systematic Review of TMS Motor Mapping Studies

Purpose: The purpose of this systematic review is to evaluate motor cortex reorganization in amputees as indexed by transcranial magnetic stimulation (TMS) cortical mapping and its relationship with phantom limb pain (PLP). Methods: Pubmed database were systematically searched. Three independent researchers screened the relevant articles, and the data of motor output maps, including the number of effective stimulation sites, center of gravity (CoG) shift, and their clinical correlations were extracted. We calculated a pooled CoG shift for motor cortex TMS mapping. Results: The search yielded 468 articles, 11 were included. Three studies performed correlation between the cortical changes and PLP intensity, and only one study compared cortical mapping changes between amputees with pain and without pain. Results showed (i) enlarged excitable area and a shift of CoG of neighboring areas toward the deafferented limb area; (ii) no correlation between motor cortex reorganization and level of pain and (iii) greater cortical reorganization in patients with PLP compared to amputation without pain. Conclusion: Our review supports the evidence for cortical reorganization in the affected hemisphere following an amputation. The motor cortex reorganization could be a potential clinical target for prevention and treatment response of PLP.