bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab Versus Regorafenib in Patients With Hepatocellular Carcinoma After Sorafenib Failure
Authors: Kuo Yuan-Hung , Yen Yi-Hao , Chen Yen-Yang , Kee Kwong-Ming , Hung Chao-Hung , Lu Sheng-Nan , Hu Tsung-Hui , Chen Chien-Hung , Wang Jing-Houng 
Published: May 2021

BackgroundNivolumab and regorafenib are approved second-line therapies for patients with hepatocellular carcinoma (HCC) after sorafenib failure. This study compared the effectiveness of nivolumab and regorafenib following sorafenib.MethodsWe retrospectively enrolled HCC patients who had undergone nivolumab or regorafenib after sorafenib failure. Treatment response, treatment-related adverse events (TRAE) and clinical outcomes of study patients were recorded and analyzed.ResultsA total of 90 patients (male/female: 67/23, mean age: 63 years) were enrolled, including 32 patients in the Nivolumab group and 58 patients in the Regorafenib group. The Nivolumab group had better objective response rates (16% vs 6.4%) and disease control rates (44% vs 31.9%) than the Regorafenib group, but there was no statistical difference. The comparison of time to progression (3.0 months vs 2.6 months, p=0.786) and overall survival (OS) (14 months vs 11 months, p = 0.763) between Nivolumab and Regorafenib groups were also insignificant. Regarding number of TRAE incidences, the Nivolumab group was significantly lower than the Regorafenib group (37.5% vs 68%). After cession of nivolumab/regorafenib, 34 patients (37.8%) (Nivolumab group/Regorafenib group: 11/23) could afford the following therapies. Concerning sequential systemic therapies, 17 patients (18.9%) received third-line therapy, whereas six patients (6.7%) could move to fourth-line therapy. In multivariable analysis, patients who achieved disease control were associated with improved OS (hazard ratio, 0.18; 95% confidence interval, 0.07–0.46; p&lt;0.001) after adjusting Child-Pugh class and post-treatment.ConclusionsAfter sorafenib failure, using nivolumab or regorafenib both illustrated promising treatment outcomes.
Jejunoileal Atresia: A National Cohort Study
Authors: Schmedding Andrea , Hutter Martin , Gfroerer Stefan , Rolle Udo 
Published: May 2021

Purpose: Jejunoileal atresia (JIA) is a rare disease. We aimed to determine the overall incidence of this malformation and associated malformations in a national cohort. Furthermore, we compared the treatment results of this cohort with the current literature.Methods: Data from the major health insurance company, which covers ~30% of the German population, were analyzed. All patients with ICD-10-Code Q41.1-9 (atresia of jejunum, ileum, other parts and not designated parts of the small bowel) who underwent any surgical procedure for small bowel were analyzed in a 10-year period between 2007 and 2016.Results: A total of 435 patients were included in the study. The incidence was 2.1 per 10,000 live births. The male:female ratio was 1:2. Sixty-four percent were premature, 21% had associated cardiac anomalies, 16% had abdominal wall defects, 7% had urogenital malformations, and 7% had cystic fibrosis. Sixty percent of all patients with jejunoileal atresia, 57% of patients with accompanying abdominal wall defects and 72% of patients with associated cystic fibrosis required ostomy as the initial procedure. In 25% of all patients, only one intestinal operation was coded. In 39% of patients, two operations were coded. Twelve percent of all patients required feeding gastrostomy or jejunostomy. Sixteen percent of all patients presented with liver-related complications, i.e., cholestasis or liver insufficiency. Six patients underwent an intestinal lengthening procedure (2 Bianchi, 4 STEP). In five patients, initial lengthening was performed within 1 year after the first intestinal operation. Mortality until 1 year after initial surgery was 5%. Of those who died, 88% were premature, 34% had cardiac anomalies and 16% had abdominal wall defects. None had cystic fibrosis. Patients with ostomy significantly more often needed operative central venous line or operative feeding tube. Short bowel was coded significantly more often in these patients.Conclusion: Patients with JIA present with low mortality. The rate of ostomies is higher than in literature. To give clinical recommendations for the initial surgical approach, further clinical research is needed.
Predictors of Diffusing Capacity in Children With Sickle Cell Disease: A Longitudinal Study
Authors: Mondal Pritish , Midya Vishal , Khokhar Arshjot , Sathianathan Shyama , Forno Erick 
Published: May 2021

Background: Gas exchange abnormalities in Sickle Cell Disease (SCD) may represent cardiopulmonary deterioration. Identifying predictors of these abnormalities in children with SCD (C-SCD) may help us understand disease progression and develop informed management decisions.Objectives: To identify pulmonary function tests (PFT) estimates and biomarkers of disease severity that are associated with and predict abnormal diffusing capacity (DLCO) in C-SCD.Methods: We obtained PFT data from 51 C-SCD (median age:12.4 years, male: female = 29:22) (115 observations) and 22 controls (median age:11.1 years, male: female = 8:14), formulated a rank list of DLCO predictors based on machine learning algorithms (XGBoost) or linear mixed-effect models, and compared estimated DLCO to the measured values. Finally, we evaluated the association between measured or estimated DLCO and clinical outcomes, including SCD crises, pulmonary hypertension, and nocturnal desaturation.Results: Hemoglobin-adjusted DLCO (%) and several PFT indices were diminished in C-SCD compared to controls. Both statistical approaches ranked FVC (%), neutrophils (%), and FEF25−75 (%) as the top three predictors of DLCO. XGBoost had superior performance compared to the linear model. Both measured and estimated DLCO demonstrated a significant association with SCD severity: higher DLCO, estimated by XGBoost, was associated with fewer SCD crises [beta = −0.084 (95%CI: −0.13, −0.033)] and lower TRJV [beta = −0.009 (−0.017, −0.001)], but not with nocturnal desaturation (p = 0.12).Conclusions: In this cohort of C-CSD, DLCO was associated with PFT estimates representing restrictive lung disease (FVC, TLC), airflow obstruction (FEF25−75, FEV1/FVC, R5), and inflammation (neutrophilia). We used these indices to estimate DLCO, and show association with disease outcomes, underscoring the prediction models' clinical relevance.
Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment
Authors: Sun Weipeng , Li Minying , Xie Lei , Mai Zhexing , Zhang Yan , Luo Lieliang , Yan Zijian , Li Zige , Dong Hang , Huang Feng , Shen Zhen , Jiang Ziwei 
Published: May 2021

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.
Switching Between Second-Generation Antipsychotics in Patients with Schizophrenia and Schizoaffective Disorder: 10-Year Cohort Study in Brazil
Authors: Fulone Izabela , Silva Marcus Tolentino , Lopes Luciane Cruz 
Published: May 2021

Objective: Switching between second-generation antipsychotics (SGAs) is a common clinical practice in the treatment of schizophrenia and schizoaffective disorders due to differences in the drugs’ tolerability and safety profiles as well as the challenge of obtaining an ideal response. However, the factors associated with SGA switching remain uncertain and related real-world data are scarce. The main objective was to identify the factors associated with the switching of SGAs in patients with schizophrenia or schizoaffective disorder.Methods: We conducted a retrospective cohort study of outpatients with schizophrenia or schizoaffective disorder, who were aged ≥18 years and received a SGA (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a Brazilian pharmaceutical assistance program for at least 3 months. We identified SGA users from 2008 to 2017 by using a national administrative database (Ambulatory Information System-SIA/SUS). The factors associated with the switches were evaluated by Cox proportional hazards regression and adjusted for sex and age; the confidence interval was set at 95% (95% CI).Results: In total, 563,765 patients were included. Female sex, advanced age of ≥70 years, residence in the Brazilian northeast region, and the type of antipsychotic used were associated with an increased risk of switching (p &lt; 0.001). The incidence of switching ranged from 37.6/100 person-years for clozapine users to 58.2/100 person-years for risperidone users. Compared to the adjusted hazard ratio, for clozapine users, the corresponding ratios for risperidone, ziprasidone, quetiapine and olanzapine were 1.59 (95% CI, 1.57–1.61), 1.41 (95% CI, 1.39–1.44), 1.25 (95% CI, 1.23–1.26) and 1.11 (95% CI, 1.10–1.12) respectively.Conclusion: The groups most susceptible to SGA switching in real-life setting were older individuals, women, and those living in the Brazilian northeast region. Risperidone was associated with the highest risk of switching and as expected, clozapine was associated with the lowest risk of switching than that associated with the other SGAs.
Protective Effects of Sacubitril/Valsartan on Cardiac Fibrosis and Function in Rats With Experimental Myocardial Infarction Involves Inhibition of Collagen Synthesis by Myocardial Fibroblasts Through Downregulating TGF-β1/Smads Pathway
Authors: Wu Meifang , Guo Yanguang , Wu Ying , Xu Kaizu , Lin Liming 
Published: May 2021

Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts.Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107–10–5 M) or Sac/Val (107–105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry.Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively.Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.
Acoustic Measures of Brazilian Transgender Women's Voices: A Case–Control Study
Authors: Villas-Bôas Anna Paula , Schwarz Karine , Fontanari Anna Martha Vaitses , Costa Angelo Brandelli , Cardoso da Silva Dhiordan , Schneider Maiko Abel , Cielo Carla Aparecida , Spritzer Poli Mara , Rodrigues Lobato Maria Inês 
Published: May 2021

Objective: This study aims to compare the acoustic vocal analysis results of a group of transgender women relative to those of cisgender women.Methods: Thirty transgender women between the ages of 19 and 52 years old participated in the study. The control group was composed of 31 cisgender women between the ages of 20 and 48 years old. A standardized questionnaire was administered to collect general patient data to better characterize the participants. The vowel /a/ sounds of all participants were collected and analyzed by the Multi-Dimensional Voice Program advanced system.Results: Statistically significant differences between cisgender and transgender women were found on 14 measures: fundamental frequency, maximum fundamental frequency, minimum fundamental frequency, standard deviation of fundamental frequency, absolute jitter, percentage or relative jitter, fundamental frequency relative average perturbation, fundamental frequency perturbation quotient, smoothed fundamental frequency perturbation quotient, fundamental frequency variation, absolute shimmer, relative shimmer, voice turbulence index (lower values in the cases), and soft phonation index (higher values in the cases). The mean fundamental frequency value was 159.046 Hz for the cases and 192.435 Hz for the controls.Conclusion: Through glottal adaptations, the group of transgender women managed to feminize their voices, presenting voices that were less aperiodic and softer than those of cisgender women.
A Comparison in Physical Fitness Attributes, Physical Activity Behaviors, Nutritional Habits, and Nutritional Knowledge Between Elite Male and Female Youth Basketball Players
Authors: Sánchez-Díaz Silvia , Yanci Javier , Raya-González Javier , Scanlan Aaron T. , Castillo Daniel 
Published: May 2021

Background: Limited evidence exists comprehensively assessing physical fitness attributes, physical activity behaviors, nutritional habits, and nutritional knowledge according to sex in basketball players during early adolescence. Insight of this nature could be used to optimize the training process and lifestyles in young basketball players.Objective: To compare physical fitness attributes, physical activity levels, nutritional habits, and nutritional knowledge between elite male and female basketball players under 14 years of age (U-14).Methods: Twenty-three U-14 basketball players (male, n = 13 and female, n = 10) from the same elite basketball academy (Spanish Asociación de Clubes de Baloncesto [ACB] League) participated in this study. Physical fitness attributes were assessed using a basketball-specific test battery (countermovement jump, drop jump, linear sprint, Lane Agility Drill, 505 change-of-direction, and repeated-change-of-direction tests), while physical activity levels (Physical Activity Questionnaire for Adolescents, PAQ-A), nutritional habits (Turconi questionnaire), and nutritional knowledge (Turconi questionnaire) were assessed using questionnaires.Results: Male players exhibited better physical fitness in all tests (p &lt;0.001 to 0.036, effect size = −0.44 to −0.76, intermediate to strong) compared to female players. Male players also performed more physical activity in their leisure time (p = 0.036) than females. No significant differences in nutritional habits and nutritional knowledge were evident between sexes (p &gt; 0.05). Of note, a high proportion of players declared never or only sometimes eating fruit (males: 23%; females: 40%) and vegetables (males: 46%; females: 70%). In addition, relatively poor nutritional knowledge was evident in all players with the group correctly answering &lt;50% of nutritional questions overall (4.57 ± 1.88 out of 11 points, 42%) and according to sex (males: 4.07 ± 2.10, 37%; females: 5.20 ± 1.40, 47%).Conclusion: These findings emphasize the necessity to perform individualized prescription of training stimuli across sexes to optimize the physical preparedness and development of youth basketball players. Additionally, strategies such as nutrition-focused education interventions may be necessary in this population given the low consumption of fruits and vegetables, as well as the poor nutritional knowledge observed in players.
Post-hospitalization Daycare Treatment for Adolescents With Eating Disorders
Authors: Litmanovich-Cohen Liron , Yaroslavsky Amit , Halevy-Yosef Liron Roni , Shilton Tal , Enoch-Levy Adi , Stein Daniel 
Published: May 2021

Background: There are several possible facilities for the treatment of eating disorders (EDs). Specifically, there is the issue of the use of specialized daycare and ambulatory services over inpatient settings and the place of daycare programs following inpatient treatment.Aim: We sought to examine the contribution of post-hospitalization daycare program to the treatment of adolescents hospitalized with an ED.Methods: We assessed 61 female adolescents hospitalized with an ED. All but three were diagnosed with clinical or subthreshold anorexia nervosa (AN). Three were diagnosed with bulimia nervosa. Thirty-seven patients continued with a post-hospitalization daycare program for at least 5 months, whereas 24 did not enter or were enrolled in the program for &lt;5 months. Patients completed on admission to, and discharge from, inpatient treatment self-rating questionnaires assessing ED-related symptoms, body-related attitudes and behaviors, and depression and anxiety. Social functioning was assessed 1 year from discharge using open-ended questions. One-year ED outcome was evaluated according to the patients' body mass index (BMI) and according to composite remission criteria, assessed with a standardized semistructured interview. To be remitted from an ED, patients were required to maintain a stable weight, to have regular menstrual cycles, and not to engage in binging, purging, and restricting behaviors for at least eight consecutive weeks before their assessment.Results: BMI was within normal range at follow-up, whether completing or not completing daycare treatment, and around 75% of the patients had menstrual cycles. By contrast, when using comprehensive composite remission criteria, less than a quarter of former inpatients not entering/not completing daycare program achieved remission vs. almost a half of the completers. In addition, a greater percentage of completers continued with psychotherapy following discharge. Fifty percent of both groups showed good post-discharge social functioning. No between-group differences were found in the BMI and the scores of the self-rating questionnaires at admission to, and discharge from, inpatient treatment.Conclusion: Adolescent females with EDs can maintain a normal-range BMI from discharge to 1-year follow-up, even if not completing daycare treatment. By contrast, completion of a post-hospitalization daycare program may improve the 1-year follow-up ED-related outcome of former ED inpatients.
Multimorbid Patient Experiences With Primary Care at Community Health Centers in Shanghai, China
Authors: Jin Hua , Wang Zhaoxin , Shi Leiyu , Chen Chen , Huo Yongyan , Huang Wuquan , Zhang Yi , Lu Yuan , Ge Xuhua , Shi Jianwei , Yu Dehua 
Published: May 2021

Objective: Primary care in China is facing mounting challenges with multimorbidity as the aging population grows. Knowing how patients experience primary care may highlight the deficiencies of the care system and guide health system reform. The purpose of this study was to compare the quality of primary care experienced by patients with and without multimorbidity at community health centers (CHCs) in Shanghai, China and to examine the factors influencing these experiences.Methods: A cross-sectional survey was conducted from August to December 2019 using the validated Chinese Primary Care Assessment Tool-Adult Edition (PCAT-AE). ANOVA was performed to compare the overall and domain-specific quality of primary care for patients with and without multimorbidity. Multivariate linear regressions were used to assess the factors associated with primary care quality while controlling for patients' sociodemographic and healthcare characteristics.Results: From 2,404 completed questionnaires, patients with multimorbidity reported higher PCAT scores in the domains of first contact-utilization (3.54 ± 0.55 vs. 3.48 ± 0.56, P &lt; 0.01), accessibility (2.93 ± 0.49 vs. 2.86 ± 0.47, P &lt; 0.001), and ongoing care (3.20 ± 0.39 vs. 3.14 ± 0.43, P &lt; 0.001), while reporting lower scores in coordination (information system) (2.72 ± 0.41 vs. 2.79 ± 0.35, P &lt; 0.001) and family-centeredness (3.23 ± 0.63 vs. 3.30 ± 0.64, P &lt; 0.01). Multimorbidity (ß = 0.355, P &lt; 0.01), education level (ß = 0.826, P &lt; 0.01), district (suburb: ß = 1.475, P &lt; 0.001), and self-perceived good health status (ß = 0.337, P &lt; 0.05) were associated with better patient experiences in primary care. Patients between the age 61 and 70 (ß = −0.623, P &lt; 0.001; &gt;70 years: ß = −0.573, P &lt; 0.01), with a monthly household income ≥6,000 RMB (ß = −1.385, P &lt; 0.001) and with more than 20 outpatient visits the previous year (ß = −1.883, P &lt; 0.001) reported lower total PCAT scores.Conclusion: The findings of our study suggest that CHCs in China have contributed to better primary care experiences for patients with multimorbidity in certain quality domains, including first contact-utilization, accessibility, and ongoing care. However, there is still room for improvement in care coordination and family-centeredness.