bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes From Cytotoxic Chemotherapy Following Progression on Immunotherapy in Metastatic Melanoma: An Institutional Case-Series
Authors: Gaughan Elizabeth M. , Horton Bethany J. 
Published: April 2022

IntroductionThe role of chemotherapy in the management of advanced melanoma is limited due to low response rates and short survival. Improved outcomes to chemotherapy administered after immunotherapy for metastatic melanoma and other solid tumors have been reported. We studied the outcomes of subjects treated at the University of Virginia (UVA) with chemotherapy following progression on prior systemic immunotherapy and compared the results with the existing literature.Materials and MethodsSubjects were identified through an institutional database of patients treated with immunotherapy at UVA. Demographic, pathologic and clinical factors were collected, along with dates of therapy, investigator-assessed best response as per Response Evaluation Criteria for Solid Tumors version 1.1 and dates of death or last follow up. Kaplan-Meier survival estimates and log-rank tests were used to perform time to event analysis of progression free survival and overall survival.ResultsForty-five patients were identified who met the inclusion criteria including 24 men and 21 women with a median age of 61 years. All patients had received at least one line of immunotherapy including 64.4% with prior anti-PD1 treatment. The cytotoxic chemotherapy regimens used included carboplatin with paclitaxel (55.6%), temozolomide (31.1%) and nab-paclitaxel (13.3%). The overall response rate for cytotoxic chemotherapy 22.2% and the disease control rate was 35.6%. The median progression-free survival was 1.7 months and median overall survival was 4.7 months. Nineteen (42.2%) patients survived greater than 6 months and seven (15.5%) patients survived over 12 months. Fourteen patients were able to proceed to further therapy.DiscussionOur results reveal that receipt of immunotherapy prior to chemotherapy for metastatic melanoma does not appear to improve the benefit of chemotherapy. The palliation of symptoms, maintenance of performance status and disease control may be valuable for some patients during this time of robust research and discovery for metastatic melanoma.
Chemotherapy Decision-Making and Survival Outcomes in Older Women With Early Triple-Negative Breast Cancer: Evidence From Real-World Practice
Authors: Xiu Meng , Zhang Pin , Li Qing , Yuan Peng , Wang Jiayu , Luo Yang , Ma Fei , Cai Ruigang , Fan Ying , Li Qiao , Xu Binghe 
Published: April 2022

Data regarding chemotherapy options and benefits in older women with early triple-negative breast cancer (TNBC) are limited. Our study aimed to assess the effects of adjuvant chemotherapy on recurrence-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) rates in elderly TNBC patients. Patients aged ≥65 years diagnosed with stage I-III TNBC (except T1aN0) between 2010 and 2016 were retrospectively included. Multivariate Cox regression was performed to minimize bias. A total of 177 patients were included with a median age of 69 years (range, 65-86), almost all had a Charlson Comorbidity Index of 0-2, and 127 (71.8%) received chemotherapy. Patients who received chemotherapy were younger, had more advanced-stage disease and had better ECOG performance status (P&lt;0.05). Among the 127 patients who were administered chemotherapy, 45 (35%) received taxane plus carboplatin, 36 (28%) received anthracycline-and-taxane-based regimens, and 23 (18%) received taxane-based regimens. The regimen options differed based on patient age and tumour stage (P&lt;0.05). Nearly 80% of the patients completed ≥6 cycles of chemotherapy, and half had their dosage decreased. After adjustment for confounding factors, patients who received ≥6 cycles of chemotherapy were found to have improved RFS rates (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.09-0.87; P=0.027), and receipt of chemotherapy (≥1 cycle) was associated with better BCSS (HR, 0.19; 95% CI, 0.04-0.97; P=0.046) and OS (HR, 0.26; 95% CI, 0.08-0.87; P=0.029) rates. These results support the considering the risk for recurrence and performing individualized assessments when determining the appropriate chemotherapy approach for older women with early TNBC.
Meta-Analysis of Efficacy From CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients
Authors: Xu Li , Yan Xin , Ding Weiyue 
Published: April 2022

IntroductionImmune checkpoint inhibitors (ICIs) have been approved to prolong overall survival (OS), compared to other treatments. However, the recent studies reported consistent and inconsistent results. Hence, we conducted this meta-analysis to evaluate the efficacy of ICIs.Materials and MethodsThe articles were identified by searching PubMed, Embase, and Google Scholar published up to December 2021. A total of 12,126 participants (6,450 cases and 5,676 controls) were involved in the meta-analysis. Median OS and median progression-free survival (PFS) were selected to evaluate the efficacy of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab or pembrolizumab, and atezolizumab, respectively). Utilizing the random-effect model, hazard ratios (HRs) with 95 confidence intervals (CIs) were calculated by R software.ResultsWe observed a significant association between cancer patients and ICIs in OS (HR = 0.79, CI = 0.74–0.84) and PFS (HR = 0.80, CI = 0.75–0.86).ConclusionsThe meta-analysis suggested that ICIs were associated with obvious improvements in PFS and OS compared with non-ICI therapies.
PC Splice-Site Variant c.1825+5G>A Caused Intron Retention in a Patient With Pyruvate Carboxylase Deficiency: A Case Report
Authors: Tao DongYing , Zhang HuiQin , Yang Jingmin , Niu HuanHong , Zhang JingJing , Zeng Minghua , Cheng ShengQuan 
Published: April 2022

BackgroundPyruvate carboxylase deficiency (PCD; MIM#266150) is a rare autosomal recessive disorder characterized by a wide range of clinical features, including delayed neurodevelopment, elevated pyruvate levels, lactic acidosis, elevated ketone levels, and hyperammonemia. The pyruvate carboxylase (PC) gene was identified to be the disease-causing gene for PCD. A novel homozygous splice variant in the PC gene was identified in a Chinese boy, but the pathogenicity is still unclear. The objective of the present study was to determine the effect of this splice-site variant by reverse transcription analysis.MethodsWe reported the clinical course of a 20-month-old Chinese pediatric patient who was diagnosed with PCD using whole-exome sequencing (WES). The effects of the variant on mRNA splicing were analyzed through the transcript analysis in vivo.ResultsThe results of metabolic blood and urine screening suggested PCD by employing tandem mass spectrometry. WES revealed a novel homozygous splice-site variant (c.1825+5G&gt;A) in the PC gene. in vivo transcript analysis indicated that the splice-site variant caused the retention of 192 bp of the intron.ConclusionThus, c.1825+5G&gt;A was established as a pathogenic variant, thereby enriching the mutational spectrum of the PC gene and providing a basis for the genetic diagnosis of PCD.
Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database
Authors: Zhou Zhi-Xuan , Yin Xue-Dong , Zhang Yu , Shao Qi-Hui , Mao Xin-Yu , Hu Wen-Juan , Shen Yun-Lin , Zhao Bin , Li Zhi-Ling 
Published: April 2022

Aims: We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice.Methods: We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents.Results: A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged &gt;45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36–6.98) &gt; anidulafungin (5.15; 3.69–7.18) &gt; itraconazole (5.06; 4.58–5.60) &gt; voriconazole (4.58; 4.29–4.90) &gt; micafungin (4.53; 3.89–5.27) &gt; posaconazole (3.99; 3.47–4.59) &gt; fluconazole (3.19; 2.93–3.47) &gt; ketoconazole (2.28; 1.96–2.64). The onset time of DILI was significantly different among different antifungal drugs (p &lt; 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%).Conclusion: Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins.
Effect of 32-Weeks High-Intensity Interval Training and Resistance Training on Delaying Sarcopenia: Focus on Endogenous Apoptosis
Authors: Su Hao , Wen Tianhao , Liu Dongsen , Shao Jia , Zhao Lei , Gao Qi 
Published: April 2022

Sarcopenia caused by aging is an important factor leading to a decline in the quality of life of older people. Apoptosis in muscle atrophy accelerates the process of muscle loss in older populations. The present study aimed to investigate the effects of 32 weeks of high-intensity interval training (HIIT) and resistance training (RT) on the skeletal muscle-related indices and provide a theoretical basis for regulating the mitochondrial-mediated pathway to delay sarcopenia. We randomly selected 10 from eight-month-old male SD rats (N = 130) as the baseline group; after 1 week of adaptive feeding, the rats were sacrificed. The remaining rats were randomly assigned to one of three groups: control group (C, N = 40, natural aging for 32 weeks), HIIT group (H, N = 40, performed six loops of 3 min at 90% and 3 min at 50% VO2 max speed treadmill running, with 5 min at 70% VO2 max speed at the beginning and the end of the training, 3 times a week for 32 weeks), and resistance group (R, n = 40, 46 min per day, 3 days per week, with a 30% maximum load on a treadmill with a slope of 35°, 15 m/min). The soleus muscles were collected for analysis at baseline and every 8 weeks. Aging resulted in decreased soleus muscle mass and Bcl-2 levels in the mitochondria, while the levels of reactive oxygen species (ROS) and Bax did not change. HIIT reversed the age-associated activation of pro-apoptotic processes, but RT did not. In addition, when rats were aged from 8 to 16 months, the level of Cyt-C did not change, the Caspase-9 levels and Caspase-3 levels decreased gradually in the soleus muscles, the rats of both the HIIT and RT groups had these indices decreased at 32 weeks. The results suggest that the age-associated loss of muscle mass was reversed by training, and the effect of RT was better than that of HIIT. Both the HIIT and RT rats showed a decrease in the apoptosis of skeletal muscle cells after 32 weeks of intervention. HIIT performed better for long-term intervention regarding the pro-apoptotic factors. This study warranted further research to delineate the underlying mechanism of effects of different exercise methods on the changes of aging skeletal muscle at in vivo level.
Dietary Energy and Protein Levels During the Prelay Period on Production Performance, Egg Quality, Expression of Genes in Hypothalamus-Pituitary-Ovary Axis, and Bone Parameters in Aged Laying Hens
Authors: Xin Qian , Ma Ning , Jiao Hongchao , Wang Xiaojuan , Li Haifang , Zhou Yunlei , Zhao Jingpeng , Lin Hai 
Published: April 2022

Nutrition during the pre-lay period takes effect on the production performance in the laying flock. This study evaluated the effects of dietary energy and protein levels in pre-lay diet on performance during the whole laying period and the egg quality, bone quality, and mRNA expression of hypothalamus-pituitary-gonadal (HPG) axis-related genes of hens at the end of the laying cycle. A total of 1,856 15-wk old Hy-Line brown pullets were randomly assigned to one of the four dietary treatments: using a 2 × 2 factorial arrangement with 2 energy levels (2,700 and 2,800 kcal/kg ME, respectively) and 2 protein levels (15 and 16.5% CP, respectively). Pullets were fed ad libitum from 15 to 20 wk and from 20 wk onward, fed with a similar laying diet till 72 wk of age. At 72 wk, the expression of genes in the hypothalamus, pituitary, ovarian, and follicles and bone quality was evaluated. At 72wk, there were no differences in production performance, BW, organ index, and ovarian parameters among the dietary treatments. High-CP diet increased the egg shape index and eggshell thickness (p &lt; 0.05), but the eggshell breaking strength, Haugh unit, and albumen height did not differ among the treatments. Neither dietary energy nor protein level took an effect of bone quality. Low-energy diet increased the mRNA expression of gonadotropin-releasing hormone-1 (GnRH-1) in the hypothalamus (p &lt; 0.05). The mRNA expression level of estrogen receptor-1 (ESR-1) in the hypothalamus and ovary was elevated by the 2,700 ME-15%CP diet (p &lt; 0.05). The expression of cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) in the large white follicle (LWF), small yellow follicles (SYF) and dominant follicle (DF) was decreased by the 2,800 kcal/kg diet (p &lt; 0.05). These results indicate that the prelay diet had no influence on the production performance but had minimal effect on the eggshell characteristics and bone parameters. These results suggest that the energy and protein level of the prelay diet changes the expression of HPG axis-related genes of hens around the end of the laying cycle without changing the circulating sex hormone profile. The effect of prelay diet on the endocrinal adjustment at the end of the laying cycle needs to be investigated further.
Relationships Between Health-Related Quality of Life and Speech Perception in Bimodal and Bilateral Cochlear Implant Users
Authors: Brumer Nadav , Elkins Elizabeth , Hillyer Jake , Hazlewood Chantel , Parbery-Clark Alexandra 
Published: April 2022

PurposePrevious studies examining the relationship between health-related quality of life (HRQoL) and speech perception ability in cochlear implant (CI) users have yielded variable results, due to a range of factors, such as a variety of different HRQoL questionnaires and CI speech testing materials in addition to CI configuration. In order to decrease inherent variability and better understand the relationship between these measures in CI users, we administered a commonly used clinical CI speech testing battery as well as two popular HRQoL questionnaires in bimodal and bilateral CI users.MethodsThe Glasgow Benefit Inventory (GBI), a modified five-factor version of the GBI (GBI-5F), and the Nijmegen Cochlear Implant Questionnaire (NCIQ) were administered to 25 CI users (17 bimodal and 8 bilateral). Speech perception abilities were measured with the AzBio sentence test in several conditions (e.g., quiet and noise, binaural, and first-ear CI only).ResultsHigher performance scores on the GBI general subscore were related to greater binaural speech perception ability in noise. There were no other relationships between the GBI or NCIQ and speech perception ability under any condition. Scores on many of the GBI-5F factors were substantially skewed and asymmetrical; therefore, correlational analyses could not be applied. Across all participants, binaural speech perception scores were greater than first-ear CI only scores.ConclusionThe GBI general subscore was related to binaural speech perception, which is considered the everyday listening condition of bimodal and bilateral CI users, in noise; while the more CI-specific NCIQ did not relate to speech perception ability in any listening condition. Future research exploring the relationships between the GBI, GBI-5F, and NCIQ considering bimodal and bilateral CI configurations separately is warranted.
Autism Diagnostic Assessments With Children, Adolescents, and Adults Prior to and During the COVID-19 Pandemic: A Cross-Sectional Survey of Professionals
Authors: Spain Debbie , Stewart Gavin R. , Mason David , Robinson Janine , Capp Simone J. , Gillan Nicola , Ensum Ian , Happé Francesca 
Published: April 2022

BackgroundAccess to timely high quality autism diagnostic assessments has traditionally been patchy; many individuals wait months, if not years, for an appointment. The onset of the COVID-19 pandemic has likely impacted autism diagnostic services. This study investigated professionals' experiences of, and thoughts about: (1) how autism diagnostic assessments were conducted before the pandemic; (2) adaptations to service provision because of the pandemic; and (3) challenges, risks, advantages and opportunities associated with autism assessments conducted via online platforms (telehealth).MethodFifty-two professionals, based in different autism diagnostic services and working with children, adolescents and/or adults, completed an online cross-sectional survey in August and September 2020. This comprised demographic questions (about professionals' roles and experiences), and closed and open questions about service provision and telehealth autism assessments.ResultsThere was substantial variation in how autism assessments were conducted prior to and during the pandemic; for example, in relation to the number of professionals involved in the assessment and types of structured, semi-structured and unstructured measures used to conduct this. Fifty-two percent of participants (n = 27) reported some service disruption (e.g., full closure, substantial reduction in provision, and/or pausing of in person appointments). Waiting times for assessment had become longer for 58% of services (n = 30), due to pandemic-related disruption. Six themes emerged from thematic analysis of open responses: (1) the autism diagnostic pathway, pre-pandemic; (2) initial impact of the pandemic on service delivery; (3) conducting autism assessments during the pandemic; (4) working remotely; (5) improving service design and delivery; and (6) post-diagnostic support. Views about the accessibility, validity, and reliability of conducting telehealth autism assessments were polarized. Some participants considered this efficient, flexible, and adequate; others viewed this as unethical and inappropriate. What constitutes good practice in telehealth autism assessments remains unclear, but there is a general openness to using this method (potentially in a hybrid telehealth—in person model), provided rigor and standardization are enhanced.ConclusionsThe pandemic has potentially compounded existing bottlenecks to the autism diagnostic pathway. Future research should seek to improve timeliness, standardization, accessibility and robustness of this pathway, and the validity and reliability of telehealth autism assessments.
The Unique Contribution of Past Bullying Experiences to the Presence of Psychosis-Like Experiences in University Students
Authors: Zhao Jie , Lu Xiao-Hua , Liu Yuan , Wang Nan , Chen Dong-Yang , Lin Iun-An , Li Xiao-Hong , Zhou Fu-Chun , Wang Chuan-Yue 
Published: April 2022

ObjectivesBoth bullying and psychosis-like experiences (PLEs) have gained much attention in recent years, but their interactions are not fully unraveled. The aim of the current study was to validate the Chinese version of Bullying Scale for Adults (C-BSA), and to investigate whether past bullying experiences independently predict the presence of PLEs in university students.MethodsThe validity and reliability of the C-BSA were determined in two independent samples. A battery of psychological inventories was also administered to assess the presence of PLEs, maltreatment history in the family, and current depression and anxiety, including the 15-item positive subscale of the community assessment of psychic experiences (CAPE-p15), the Chinese version of the Childhood Trauma Questionnaire (CTQ), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS).ResultsIn the construction sample (N = 629), a Cronbach's α of 0.921 indicated a good internal consistency of C-BSA. The exploratory factor analysis (EFA) yielded a four-factor model and a three-factor model, and both were verified by using the confirmatory factorial analysis (CFA) in the validation sample (N = 629). The total scores of C-BSA were significantly correlated with that of CTQ, CAPE-p15, SDS, and SAS. Multivariate logistic regression revealed that bullying was associated with 2.0 or 3.7 times of risk for the presence of PLEs (numbers of bullying types &lt; = 3 or &gt; 3, respectively) after controlling for CTQ, SDS, and SAS scores.ConclusionsC-BSA has shown good psychometric properties in college students. The contribution of past bullying experiences to the present PLEs seems to be independent of other childhood trauma, current depression, and anxiety.
Parents' Hesitancy to Vaccinate Their Children Against COVID-19, a Country-Wide Survey
Authors: Alhazza Sultan F. , Altalhi Ali M. , Alamri Khaled M. , Alenazi Saleh S. , Alqarni Bader A. , Almohaya Abdulellah M. 
Published: April 2022

ObjectiveParents' hesitancy (PH) toward childhood vaccination, including the vaccine of coronavirus disease (COVID-19), is one of the top public health threats. We aim to assess the PH toward children COVID-19 vaccination as compared to PH toward children routine vaccination among the residents of Saudi Arabia.MethodBefore the official approval of children's COVID-19 vaccination in the country, a cross-sectional study using an electronically distributed survey was performed. Responses from parents of children younger than 18 years of age were accepted. The Oxford COVID-19 vaccine hesitancy scale (OC19-VHS) and the routine vaccination hesitancy scale (R-VHS) were used. Parents were classified as hesitant, non-hesitant, and unsure.ResultsBetween June 18th−30th, 2021, we included 1,052 parents. More than half of the parents were positive toward the childhood COVID-19 vaccination (63%) while 10% were unsure. Higher parental hesitancy toward children COVID-19 vaccination among mothers, parents younger than 40 years, did not receive COVID-19 nor influenza vaccines, had higher educational levels, and parents who recovered from COVID-19 infection. Hesitancy was mainly driven by the novelty of the vaccines and the fear of serious adverse effects. Compared to the routine vaccination, parents were more hesitant toward COVID-19 vaccination (6 vs. 27%).ConclusionGenerally, parents in Saudi Arabia were positive toward children's COVID-19 vaccination. Focused education to reassure hesitant parents on the safety of the vaccine is essential to achieve larger vaccination coverage.