bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive profile and natural history of pediatric patients with spinal muscular atrophy: A large retrospective study from China
Authors: Hu Chaoping , Li Xihua , Shi Yiyun , Zhu Xiaomei , Zhao Lei , Li Wenhui , Zhou Shuizhen , Wang Yi 
Published: December 2022

BackgroundThere is a large population of people with spinal muscular atrophy (SMA) in China, and new disease-modifying therapies have become available recently. However, comprehensive data on the management and profile of treatment-naive SMA patients in China are still lacking.MethodsAs a retrospective study, a large cohort of treatment-naive patients with clinical and genetic diagnoses of 5q SMA were enrolled, ranging from neonatal to 18 years old, from the Neurology Department of Children's Hospital of Fudan University between January 2013 and December 2020. The data regarding their clinical presentations, genetic defects, motor function assessment results, and follow ups were reviewed.ResultsWe enrolled 392 SMA patients (male: female = 189: 203): 1a = 46, 1b = 44, 1c = 31, 2a = 119, 2b = 56, 3a = 52, 3b = 14, from 27 of the 34 administrative districts in China, and 389 patients harbored homozygous deletion of exon 7 in the SMN1 gene (99.2%). The median age of onset was 0.08 (range: 0–0.30), 0.25 (0.06–0.60), 0.42 (0.08–1.50), 0.67 (0.07–5.08), 1.0 (0.40–1.83), 1.5 (1.00–3.00), and 4.04 (1.80–12.00) years old for SMA 1a, 1b, 1c, 2a, 2b, 3a, and 3b patients, while the median age of first assessment was 0.25 (0.08–2.60), 0.42 (0.17–1.90), 0.80 (0.17–4.5), 2.50 (0.5–15.83), 2.92 (1.08–13.42), 4.25 (1.58–17.33), and 7.34 (3.67–14.00) years old, respectively. Patients were followed up with for up to 15.8 years. The median event-free survival time was 7 months, 15 months, and indeterminate in SMA 1a, 1b, and 1c patients (p &lt; 0.0001), with a better survival situation for higher SMN2 copies (p = 0.0171). The median age of sitting loss was 5.75 years and 13.5 years in SMA 2a and 2b (p = 0.0214) and that of ambulation loss was 9.0 years and undefined in SMA 3a and 3b (p = 0.0072). Cox regression analysis showed that higher SMN2 copies indicated better remaining ambulation in SMA 3. The median time to develop orthopedic deformities was 4.5, 5.2, and 10.1 years in SMAs 1c, 2, and 3, respectively (p &lt; 0.0001), with a possible trend of better preservation of joint function for patients under regular rehabilitation (p = 0.8668).ConclusionOur study elucidated insight into the comprehensive management and profile of different types of SMA patients in China, providing a clinical basis for assessing the efficacy of new therapies.
Long-term neurorehabilitation outcomes of pediatric vs. adult onset acquired brain injury
Authors: Johnson Spring Flores , Klonoff Pamela S. , Perumparaichallai Ramaswamy Kavitha 
Published: December 2022

BackgroundFunctional outcomes of intensive neurorehabilitation for pediatric onset acquired brain injury (ABI) are understudied. The extent and pervasiveness of impairments are often uncovered years after an ABI and can worsen over time, leading to a cascade of academic, functional, and psychosocial difficulties.ObjectiveTo examine the long-term outcomes of survivors with pediatric onset vs. adult onset ABI who completed holistic milieu-oriented neurorehabilitation up to 30 years ago.MethodsOne hundred twenty-three survivors of ABI including a pediatric onset group (n = 22) and an adult onset group (n = 101) with heterogeneous neurological etiologies who attended holistic, milieu-oriented neurorehabilitation. Productivity, driving, and functional outcomes were evaluated using the Mayo-Portland Adaptability Inventory-4 (MPAI-4) and a psychosocial outcome questionnaire. Treatment for the pediatric onset group started much later than onset.ResultsA one-way analysis of covariance revealed no significant differences between the two groups on the MPAI-4. At the follow-up survey, there was no significant difference between age at onset of injury and productivity status. The average follow-up time was ~8 years (SD = 6.28) from time of discharge to the time of the survey. Although there was no significant difference between the two groups for driving at the time of admission, the adult onset group was significantly more likely to return to driving after treatment.ConclusionsThis study demonstrates the positive and enduring benefits of holistic, milieu-oriented neurorehabilitation for survivors of pediatric onset ABI regardless of the time between initial injury and engagement in rehabilitative therapies.
Surface electromyography analysis of mirror movements under unilateral movement in stroke patients: A retrospective study
Authors: Dai Jie , Wu Fangchao , Li Jianhua , Yu Mengjie , Liao Chen , Shou Yiqun 
Published: December 2022

ObjectiveMirror movements (MMs) are common abnormal motor performance in patients with poststroke hemiparesis. The study aimed to utilize the Electromyography (EMG) characterization of MMs in stroke patients and explore the relationship between MMs and the motor function of affected limbs.MethodsSixty patients with stroke who had used to undergo clinical assessment and surface Electromyography (sEMG) were selected in this study. We investigated the standardized net excitation (SNE) and overflow percentage (OF) as a measure of mirror activities on bilateral muscles of stroke patients.ResultsIn stroke patients, mirror activities occurred in both affected and unaffected muscles during maximal contractions. We found that OF at unilateral contraction on the affected side (UCA) was significantly greater than that at unilateral contraction on the unaffected side (UCU). Additionally, a negative correlation between OF at UCA and Brunnstrom stages on admission and discharge. However, there were no significant correlations between OF and disease duration, Barthel Index, or the degree of improvement in all clinical evaluations. We still found a positive correlation between SNE at UCA and the improvement of the Brunnstrom stage of the hand. But we could not find any significant correlation between SNE and other clinical evaluation scores.ConclusionIn conclusion, the study found mirror activities in both affected and unaffected muscles, confirming an asymmetry between them. Although the mechanisms are still unclear, we confirmed a significant correlation between MMs at UCA and the motor function of the affected upper extremity, which might provide further evidences for understanding MMs in stroke patients and a new research direction on evaluation for motor function and outcomes of stroke patients.
Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer
Authors: Abulikemu Nuerbiyemu , Gao Xin , Wang Wei , He Qingyuan , Wang Gang , Jiang Tao , Wang Xiaodong , Cheng Yumeng , Chen Min , Li Yanran , Liu Lulu , Zhao Jingjing , Li Jin , Jiang Chunhui , Wang Yunling , Han Hongbin , Wang Jian 
Published: December 2022

PurposeThis study aimed to investigate the changes in extracellular space (ECS) in cryptococcal brain granuloma and its pathological mechanism.Materials and methodsThe animal model of cryptococcal brain granuloma was established by injecting 1 × 106 CFU/ml of Cryptococcus neoformans type A suspension into the caudate nucleus of Sprague–Dawley rats with stereotactic technology. The infection in the brain was observed by conventional MRI scanning on days 14, 21, and 28 of modeling. The tracer-based MRI with a gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a magnetic tracer was performed on the rats with cryptococcal granuloma and the rats in the control group. The parameters of ECS in each area of cryptococcal brain granuloma were measured. The parameters of ECS in the two groups were compared by independent sample t-test, and the changes in ECS and its mechanism were analyzed.ResultsUp to 28 days of modeling, the success rate of establishing the brain cryptococcal granuloma model with 1 × 106 CFU/ml Cryptococcus neoformans suspension was 60%. In the internal area of cryptococcal granuloma, the effective diffusion coefficient D* was significantly higher than that of the control group (t = 2.76, P &lt; 0.05), and the same trend showed in the volume ratio α (t = 3.71, P &lt; 0.05), the clearance rate constant k (t = 3.137, P &lt; 0.05), and the tracer half-life T1/2 (t = 3.837, P &lt; 0.05). The tortuosity λ decreased compared with the control group (t = −2.70, P &lt; 0.05). At the edge of the cryptococcal granuloma, the D* and α decreased, while the λ increased compared with the control group (D*:t = −6.05, P &lt; 0.05; α: t = −4.988, P &lt; 0.05; λ: t = 6.222, P &lt; 0.05).ConclusionThe internal area of the lesion demonstrated a quicker, broader, and more extended distribution of the tracer, while the edge of the lesion exhibited a slower and narrower distribution. MRI tracer method can monitor morphological and functional changes of ECS in pathological conditions and provide a theoretical basis for the treatment via ECS.
Enhanced sweet taste perception in obesity: Joint analysis of gustatory data from multiple studies
Authors: Ribeiro Gabriela , Torres Sandra , Fernandes Ana B. , Camacho Marta , Branco Teresa L. , Martins Sandra S. , Raimundo Armando , Oliveira-Maia Albino J. ,   Food Reward in Bariatric Surgery Portuguese Study Group
Published: December 2022

IntroductionWhile sweet taste perception is a potential determinant of feeding behavior in obesity, the supporting evidence is inconsistent and is typically associated with methodological limitations. Notably, possible associations between sweet taste perception and measures of food reward remain undetermined.Materials and methodsWe conducted a cross-sectional analysis comparing 246 individuals with severe obesity and 174 healthy volunteers using a validated method for taste perception assessment. We included gustatory variables, namely intensity and pleasantness ratings of sour, salt, sweet, and bitter tastants, and taste thresholds assessed by electrogustometry. Reward-related feeding behavior, including hedonic hunger, food addiction, feeding behavior traits, and acceptance of foods and alcohol, was evaluated using self-rated scales for comparison with gustatory measures.ResultIn logistic regressions adjusted for age, gender, educational level, and research center, we found that a greater likelihood of belonging to the obesity group was associated with higher sweet intensity ratings (OR = 1.4, P = 0.01), hedonic hunger, food addiction symptoms, restrained and emotional eating (1.7 &lt; OR ≤ 4.6, all P ≤ 0.001), and lower alcohol acceptance (OR = 0.6, P = 0.0002). Using principal component analysis, we found that while hedonic hunger, food addiction, and emotional eating were strongly interrelated, they were not associated with sweet intensity perception that, in turn, had a closer relationship with alcohol acceptance and restrained eating.ConclusionWe found that individuals with obesity report higher sweet taste intensity ratings than healthy controls. Furthermore, while psychological measures of reward-related feeding behavior assess a common construct, sweet intensity perception may represent a different obesity-related dimension.
The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma
Authors: Aly Nesreen Amer Ramadan , Rizk Samia , Aboul Enein Azza , El Desoukey Nermeen , Zawam Hamdy , Ahmed Manzoor , El Shikh Mohey Eldin , Pitzalis Costantino 
Published: December 2022

BackgroundDespite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals.ObjectiveWe reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role.MethodsThere were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs).ResultsSPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs.ConclusionFDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients.
Survival analysis of women breast cancer patients in Northwest Amhara, Ethiopia
Authors: Feleke Bereket , Tesfaw Lijalem Melie , Mitku Aweke A. 
Published: December 2022

IntroductionBreast cancer, the most common cause of cancer death and the most frequently diagnosed cancer among women worldwide, ranks as the second cause of death next to lung cancer. Thus, the main objective was to assess the factors that affect the survival time of breast cancer patients using the shared frailty model.MethodsA retrospective study design was used to collect relevant data on the survival time of breast cancer patients from the medical charts of 322 breast cancer patients under follow-up at the Felege Hiwot Comprehensive Specialized Hospital (FHCSH). The data were explored using the Cox proportional hazard model, the accelerated failure time model, and shared frailty models. The model comparison was done using AIC and BIC. As a result, the Weibull gamma shared frailty model had a minimum AIC and BIC value.ResultFrom a total of 322 patients, about 95 (29.5%) died and 227 (70.5%) were censored. The overall mean and median estimated survival times of breast cancer patients under study were 43.7 and 45 months, respectively. The unobserved heterogeneity in the population of clusters (residence) as estimated by the Weibull-gamma shared frailty model was 0.002 (p-value = 0.000), indicating the presence of residential variation in the survival time of breast cancer patients. The estimated hazard rate of patients who had not had recurrent breast cancer was 0.724 (95% CI: 0.571, 0.917) times the estimated hazard rate of patients who had had recurrent breast cancer.ConclusionThe prevalence of breast cancer was considerably high. Under this investigation, older patients, patients in stages III and IV, anemic and diabetes patients, patients who took only chemotherapy treatment, metastasized patients, patients with an AB blood type, patients with a positive breast cancer family history, and patients whose cancer was recurrent had high death rates. Patient characteristics such as age, stage, complications, treatment, metastasis, blood type, family history, and recurrence were significant factors associated with the survival time of women with breast cancer.
Stem-cell therapy via gastroscopy improves the outcome of esophageal anastomotic leakage
Authors: Hu Yannan , Chu Heng , Xue Xiang , Yan Yan , Chen Wenbang , Lang Xilong , Zhang Hao 
Published: December 2022

BackgroundEsophageal anastomotic leakage (EAL) is a severe complication usually occurring after esophagectomy. Although there are various therapeutic methods for EAL treatment, they have not achieved satisfactory results. A previous study showed that the combination of mesenchymal stem cells (MSCs) and fibrin scaffold (FS) can treat EAL. This study aimed to evaluate the efficacy of the injection of MSCs and FS through a new engraftment gastroscope for EAL treatment.MethodsTwelve adult pigs were randomly divided into the MSCs group (n = 6) and control group (n = 6). A stomach tube was then inserted through the leakage to construct the EAL model, which was removed after one week. The combination of MSCs and FS was autografted at the EAL site for pigs in the MSCs group using the tailor-made gastroscope while only FS was autografted for the pigs in the control group. Local status of EAL was evaluated using gastroscopy. Histological analyses and western blot (WB) were used to assess the gross specimens of esophagi around EALs.ResultsGastroscopy showed a higher closure rate and a lower infection rate in the MSCs group than in the control group. However, the mortality was not significantly different between the two groups. HE staining showed a severe inflammatory response with dispersive infiltration of inflammatory cells and unhealed leakage in the control group. However, the infiltration of inflammatory cells was not altered in the MSCs group, and the leakage was completely healed. WB analyses showed that Myogenin and α-SMA expressions were significantly higher in the MSCs group than in the control group.ConclusionA porcine model of EAL was successfully developed by accessing the transplantation site through the esophagus. Further data revealed that the implantation of MSCs in FS via the novel engraftment gastroscope can promote the repair and occlusion of EAL. Therefore, the proposed method is a promising strategy for EAL treatment.
Translational analysis and final efficacy of the AVETUX trial – Avelumab, cetuximab and FOLFOX in metastatic colorectal cancer
Authors: Tintelnot Joseph , Ristow Inka , Sauer Markus , Simnica Donjete , Schultheiß Christoph , Scholz Rebekka , Goekkurt Eray , von Wenserski Lisa , Willscher Edith , Paschold Lisa , Lorenzen Sylvie , Riera-Knorrenschild Jorge , Depenbusch Reinhard , Ettrich Thomas J. , Dörfel Steffen , Al-Batran Salah-Eddin , Karthaus Meinolf , Pelzer Uwe , Hinke Axel , Bauer Marcus , Massa Chiara , Seliger Barbara , Wickenhauser Claudia , Bokemeyer Carsten , Hegewisch-Becker Susanna , Binder Mascha , Stein Alexander 
Published: December 2022

IntroductionIn metastatic colorectal cancer (mCRC), the efficacy of immune checkpoint blockade (ICB) has so far been limited to patients with microsatellite instability high tumors (MSI-H). Unfortunately, most mCRC patients suffer from non-immunogenic microsatellite stable (MSS) tumors. Therefore, new combinatorial strategies are urgently needed to enhance the immunogenicity of MSS tumors to finally increase the number of patients benefiting from ICB.MethodsThe AVETUX trial aimed to combine the PD-L1 antibody avelumab with the standard of care chemotherapy combination FOLFOX and the anti-EGFR antibody cetuximab. Furthermore, we performed a central radiological review of the pre- and on-treatment computed tomography scans to better define the individual response to treatment.Results and DiscussionIn total, 43 patients were treated of which 39 patients were confirmed as RAS/BRAF wildtype in central tissue review and finally response evaluated. A final progression-free survival (PFS) of 11.1 (range: 0.8 to 22.3 months) and a herein updated final overall survival (OS) of 32.9 months (range: 0.8 to 47.1 months) was reached. We observed a strong median depth of response of 67.5% tumor shrinkage and deepness of response correlated significantly with survival. On the other hand, early tumor shrinkage was not an indicator of better outcome at a cut-off of 20% (median values). In a next step, we correlated the individual best radiological response with potential ICB response biomarkers and found that the clonality and diversity, but not frequency of tumor infiltrating lymphocytes (TiLs) and peripheral blood mononuclear cells (PBMCs), strongly correlated with response. In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC by performing a central radiological review.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03174405).
Body movement as a biomarker for use in chronic pain rehabilitation: An embedded analysis of an RCT of a virtual reality solution for adults with chronic pain
Authors: Liikkanen Sammeli , Mäkinen Mika , Huttunen Teppo , Sarapohja Toni , Stenfors Carina , Eccleston Christopher 
Published: December 2022

IntroductionChronic low back pain (CLBP) is a major public health problem. Reliably measuring the effects of chronic pain on movement and activity, and any changes due to treatment, is a healthcare challenge. A recently published paper demonstrated that a novel digital therapeutic (DTxP) was efficacious in reducing fear of movement and increasing the quality of life of adult patients with moderate to severe CLBP. In this paper, we report a study of how data from wearable devices collected in this study could be used as a digital measure for use in studies of chronic low back pain.MethodsMovement, electrodermal recording, general activity and clinical assessment data were collected in a clinical trial of a novel digital therapeutic intervention (DTxP) by using the sensors in commercial Garmin Vivosmart 4, Empatica Embrace2 and Oculus Quest wearables. Wearable data were collected during and between the study interventions (frequent treatment sessions of DTxP). Data were analyzed using exploratory statistical analysis.ResultsA pattern of increased longitudinal velocity in the movement data collected with right-hand, left-hand, and head sensors was observed in the study population. Correlations were observed with the changes in clinical scales (Tampa Scale of Kinesiophobia, EQ5D Overall health VAS, and EQ5D QoL score). The strongest correlation was observed with the increased velocity of head and right-hand sensors (Spearman correlation with increasing head sensor velocity and Tampa Scale of Kinesiophobia −0.45, Overall health VAS +0.67 and EQ5D QoL score −0.66). The sample size limited interpretation of electrodermal and general activity data.Discussion/ConclusionWe found a novel digital signal for use in monitoring the efficacy of a digital therapeutics (DTxP) in adults with CLBP. We discuss the potential use of such movement based digital markers as surrogate or additional endpoints in studies of chronic musculoskeletal pain.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04225884?cond=NCT04225884&amp;draw=2&amp;rank=1, identifier: NCT04225884.