bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and toxicity of Ipilimumab-Nivolumab combination therapy in elderly metastatic melanoma patients
Authors: Stoff Ronen , Grynberg Shirly , Asher Nethanel , Laks Shachar , Steinberg Yael , Schachter Jacob , Shapira-Frommer Ronnie , Ben-Betzalel Guy 
Published: November 2022

IntroductionImmunotherapy has revolutionized metastatic Melanoma therapy. The most active regimen is combination therapy of Ipilimumab-Nivolumab (Ipi-Nivo) with response rates (RR) of ~60% and median overall survival (OS) of ~6 years. Immune-related adverse events (irAE) are common (~60% develop grade 3-4) and pose a challenge when treating frail patients. We sought to examine whether Ipi-Nivo therapy is feasible in elderly metastatic melanoma patients.MethodsElectronic records of patients treated at the Ella Lemelbaum Institute with Ipi-Nivo between the years 2017-2021 were screened for age. Elderly patients were defined as age 75 and older (group A) and were matched with records of patients age &lt;75 (group B). Records were analyzed for baseline parameters, immunotherapy regimen, RR, toxicity and progression-free survival (PFS).ResultsTwenty-six relevant patients age &gt;75 (median 77) were identified and were matched to 34 younger patients (median age 57). No statistically significant differences were noted in terms of baseline parameters except for BRAF mutation status (group A 15%, group B 47%, p=0.008). Response rate in group A was 38% and is consistent with previously published data. Median PFS was the same for both groups (A = 5.5 months, B= 7.5 months, p=NS). Treatment was similarly tolerated: 35% of group A patients completed 4 cycles of therapy compared to 28% for group B (p=NS). Grade 2-4 irAE were the same (A=58%, B=66%, p=NS) and there was no difference in the need for hospitalization for G3-4 events between the groups. (A=63%, B=69%, p=NS). Further division into 4 age groups (&gt;80 vs 75-79 in group A and 65-74 vs &lt;65 in group B) found no difference in terms of response rate or G3-4 toxicity.ConclusionIpilimumab-Nivolumab combination therapy in elderly metastatic Melanoma patients seems to be well tolerated and efficient in selected elderly patients based on performance status and comorbidities, just as in younger patients. This regimen seems to be a feasible treatment option for this age group.
Feasibility and efficacy of spinal microtubular technique for resection of lumbar dumbbell-shaped tumors
Authors: Wang Rui , Liang Zeyan , Chen Yan , Xu Xiongjie , Chen Chunmei 
Published: November 2022

ObjectiveMinimally invasive surgical resection of lumbar dumbbell-shaped tumors is rarely reported. We retrospectively collected clinical data of lumbar dumbbell-shaped tumors treated with the spinal microtubular technique to evaluate the feasibility, complications and efficacy of the surgical methods.MethodsFrom September 2013 to August 2021, clinical data of patients with lumbar dumbbell-shaped tumors that underwent paravertebral approach and micro-tubular tumorectomy (PAMT) were collected; neurological function was assessed using the pain visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) score.ResultsA total of 46 patients that underwent PAMT were included in this study. In all patients, total resection of the tumor was performed at one stage (100%). The median follow-up period was 27.5 months (P25, P75: 16.5- 57 months). Symptoms such as pain or lower extremity weakness were significantly relieved in 46 patients. The postoperative VAS score and JOA score were significantly higher compared with preoperative scores (p &lt;0.001), and the patients had no tumor recurrence or spinal instability. According to the Eden classification, there were 7 cases of type I, 8 cases of type II, 15 cases of type III, and 16 cases of type IV. In the comparison of the improvement of VAS score at 12 months after PAMT, there were significant differences among different types of tumors (H =15.756, p =0.001); type I was better than type III (Z =2.768, p =0.029) and type IV (Z =2.763, p =0.029), and type II was also better than type III (Z =2.679, p =0.037) and type IV (Z =2.708, p =0.034). With respect to estimated blood loss (Z =-3.041, p =0.013) and postoperative hospital stays (Z =-3.003, p =0.014), type IV was less than type III; and type IV was also less than type II about operation time (Z =-2.653, p =0.040).ConclusionIn small lumbar dumbbell-shaped tumors, PAMT is indicated for Eden types I-IV and different pathological types of tumors, and can achieve complete resection of the tumor (GTR) in one stage with a good prognosis.
Multilevel analysis of individual and community level factors associated with the application of cow dung and oil on the umbilical cord stump in Ethiopia
Authors: Dessie Anteneh Mengist , Geremew Habtamu , Feleke Sefineh Fenta , Anley Denekew Tenaw , Mruts Kalayu Brhane , Yenew Chalachew , Bantie Berihun , Misganaw Natnael Moges , Kerebeh Gashaw , Gebeyehu Asaye Alamneh , Asnakew Desalegn Tesfa , Anteneh Rahel Mulatie 
Published: November 2022

BackgroundHygienic umbilical cord care is one of the essential interventions advocated to reduce neonatal mortality. However, traditional cord care measures-applying cow dung and oil-that have harmful health consequences are commonly practiced in Ethiopia. Hence, in this study, it was planned to analyze individual and community-level factors associated with the application of cow dung and oil on the umbilical cord stump in Ethiopia.MethodsData from the 2016 Ethiopian demographic and health survey were used to identify individual and community level factors associated with women's practice of applying cow dung and oil on the umbilical cord stump of their neonate. Taking into account for the hierarchical structure of the data; multilevel binary logistic regression analysis has been employed to a nationally representative weighted sample of 7,168 women.ResultsIn Ethiopia, 780 (10.88%) with 95% CI (10.18–11.62) women apply oil and/or cow dung on the neonate's umbilical cord stump. Age increase by one year [AOR = 0.97; 95% CI (0.94–0.99)] and giving birth in a health facility [AOR = 0.61; 95% CI (0.42–0.89)] were individual-level factors that reduced women's practice of applying cow dung and oil on the umbilical cord stump of their neonate. Whereas, rural residence [AOR = 2.54; 95% CI (1.28–5.06)] was the predictor at the community level that raised the practice of applying cow dung and oil on the neonate's umbilical cord stump.ConclusionThis nationwide study revealed that a significant number of mothers in Ethiopia still apply cow dung and/or oil on the umbilical cord stump of their neonates. Both the individual and community level characteristics: maternal age, place of delivery, and residence were found to have significant inﬂuence on the practice of applying cow dung and/or oil on the umbilical cord stump in Ethiopia. Thus, to reduce neonatal mortality due to avoidable umbilical cord infections, clean cord care practice strategies should be designed by considering these factors.
Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family
Authors: Wang Yu , Song Zhen , Zhang Lihua , Li Na , Zhao Jie , Yang Ruifang , Ji Shuhua , Sun Ping 
Published: November 2022

BackgroundDystrophic epidermolysis bullosa (DEB) is an incurable and inherited skin disorder mainly caused by mutations in the gene encoding type VII collagen (COL7A1). The purpose of this study was to identify the causative genetic variants and further perform genetic diagnosis in a Chinese family affected by DEB.MethodsHigh-throughput sequencing was performed to analyze the genetic skin disorder-related genes of parents of the proband, and the variants were further confirmed in the other members by Sanger sequencing. Sanger sequencing, karyotype analysis, and chromosomal microarray analysis (CMA) were used together for prenatal diagnosis after the second pregnancy. The phenotype of the fetus was tracked after the diagnosis and induction of labor. Moreover, skin and muscle pathological examination and whole-exome sequencing (WES) of the skin and muscle tissue of the induced fetus were performed.ResultsHere, we determined two heterozygous variants of the COL7A1 gene that contributed to the autosomal recessive DEB (RDEB) in the family, i.e., a novel pathogenic variant (c.8335G &gt; T, p.E2779*) and a likely pathogenic variant (c.7957G &gt; A, p.G2653R). Sanger sequencing of amniotic fluid cells showed that the fetus carried the above two compound heterozygous variants, and the karyotype analysis and CMA results showed no abnormality. The clinical phenotype and pathological results of the induced fetus were consistent with the characteristics of DEB. Further, WES analysis also confirmed a novel compound heterozygous variation in COL7A1, consisting of two variants, namely, c.8335G &gt; T and c.7957G &gt; A in the fetus.ConclusionThis study expands the spectrum of disease-causing variants of COL7A1 and provides a theoretical basis for diagnosis, genetic counseling, and prognosis of families affected by RDEB
Clustering patterns of metabolic syndrome: A cross-sectional study in children and adolescents in Kyiv
Authors: Aliusef Maiia H. , Gnyloskurenko Ganna V. , Churylina Alina V. , Mityuryayeva Inga O. 
Published: November 2022

ObjectiveThe aim: to identify subgroups by cluster analysis according parameters: original homeostatic model of insulin resistance (HOMA-1 IR), updated computer model of insulin resistance (HOMA-2 IR), β-cell function (%B) and insulin sensitivity (%S) for the prognosis of different variants of metabolic syndrome in children for more individualized treatment selection.Patients and methodsThe observational cross-sectional study on 75 children aged from 10 to 17 with metabolic syndrome according to the International Diabetes Federation criteria was conducted at the Cardiology Department of Children's Clinical Hospital No.6 in Kyiv. HOMA-1 IR was calculated as follows: fasting insulin (µIU/ml) × fasting glucose (mmol/L)/22.5. HOMA-2 IR with %B and %S were calculated according to the computer model in [http://www.dtu.ox.ac.uk]. All biochemical analysis were carried out using Cobas 6000 analyzer and Roche Diagnostics (Switzerland). The statistical analysis was performed using STATISTICA 7.0 and Easy R. The hierarchical method Ward was used for cluster analysis according the parameters: HOMA-1 IR, HOMA-2 IR, %B and %S.ResultsFour clusters were identified from the dendrogram, which could predict four variants in the course of metabolic syndrome such that children in cluster 1 would have the worst values of the studied parameters and those in cluster 4 – the best. It was found that HOMA-1 IR was much higher in cluster 1 (6.32 ± 0.66) than in cluster 4 (2.19 ± 0.13). HOMA-2 IR was also much higher in cluster 1 (3.80 ± 0.34) than in cluster 4 (1.31 ± 0.06). By the analysis of variance using Scheffe's multiple comparison method, a statistically significant difference was obtained between the laboratory parameters among the subgroups: HOMA-1 IR (p &lt; 0,001), glucose (p &lt; 0.001), insulin (p &lt; 0,001), HOMA-2 IR (p &lt; 0.001), %B (p &lt; 0.001), %S (p &lt; 0.001), TG (p = 0.005) and VLDL-C (p = 0.002).ConclusionsA cluster analysis revealed that the first two subgroups of children had the worst insulin resistance and lipid profile parameters. It was found positive correlation between HOMA-1 IR, HOMA-2 IR, %B and %S with lipid metabolism parameters TG and VLDL-C and negative correlation between %B and HDL-C in children with metabolic syndrome (MetS).The risk of getting a high TG result in the blood analysis in children with MetS was significantly dependent with the HOMA-2 IR &gt;2.26.
Seroprevalence of SARS CoV-2 among children after the second surge (June 2021) in a rural district of South India: Findings and lessons from a population-based survey
Authors: George Carolin Elizabeth , Inbaraj Leeberk Raja , Rajukutty Shon , Joan Roshni Florina , Muthuraj Sangeetha , Chandrasingh Sindhulina 
Published: November 2022

ObjectiveTo determine the seroprevalence of SARS COV 2 among children in the Bangalore Rural district.MethodsWe conducted a cross-sectional study after the second surge of COVID-19 from 14 June to 13 July 2021 and recruited 412 children through house to house visits from four villages in a rural district. We administered a questionnaire to collect demographics and details of COVID-19 infection and used the ABCHEK Antibody Card test (NuLifecare,India) which is an ICMR approved test for detecting antibodies (IgG &amp; IgM) by immunochromatography using the finger prick method. We used Statistical Package for the Social Sciences version 20.0 for analysis.ResultsOur participants had an age group ranging from 11 months to 18 years. There was an almost equal distribution of boys (48.3%) and girls (51.7%). We estimated seroprevalence of 45.9% (95% CI: 41–50.8) among children. Seroprevalence was significantly associated with a history of symptoms suggestive of COVID-19 in the past, the seropositive status of the parents, and any other family members being tested positive. Age and gender of the child, education and occupation of the parents were not associated with the seropositivity status of the child.ConclusionSeroprevalence of COVID-19 among children corresponds to adult seroprevalence during the same time interval. This knowledge can be of practical application where adult prevalence is documented. Unvaccinated children in low-resource settings need special attention with respect to monitoring for new mutations as well as managing endemic needs.
(+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate
Authors: Chen Hanze , Xu Xinxin , Tang Qiwen , Ni Linhui , Cao Shuxia , Hao Yonggang , Wang Li , Hu Xingyue 
Published: November 2022

Background and purpose: Neutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis.Methods: Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis in vitro. Neutrophils treated with (+)-borneol at three different time points (−30 min, 0, and 30 min) associated with PMA stimulation were used to examine the effect of (+)-borneol on the formation of NETs. The ROS generation of neutrophils was also measured to explore the potential mechanism of the inhibitory effect of (+)-borneol on NETosis.Results: (+)-Borneol pretreatment inhibited NETosis induced by PMA. Immunofluorescence staining visualized and confirmed the inhibitory effect. (+)-Borneol inhibited the burst of ROS in neutrophils caused by PMA. Suppressing NADPH oxidase or protein kinase C (PKC) eliminated the effect of (+)-borneol on NETosis. Moreover, inhibiting Toll-like receptor 2 (TLR2) led to increased NETosis which can be inhibited by (+)-borneol.Conclusion: (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation in vitro. (+)-Borneol therapy may be effective in some NET-dependent conditions.
Comparison of seven cyclosporine A formulations for dry eye disease: A systematic review and network meta-analysis
Authors: Gao Dongyang , Da Zhuoli , Yang Kan , Shi Yuanyuan 
Published: November 2022

Background: Dry eye disease is a common ocular surface disease affecting tens of millions of people worldwide. It is characterized by an unstable tear film and increasing prevalence. Different commercial formulations of cyclosporine A for dry eye have been approved, however, it is still unclear whether the differences in formulations of these products will make a difference in clinical efficacy and safety.Methods: Randomized controlled trials of commercial cyclosporine A formulation for dry eye disease were searched in Pubmed, EMBASE, Scopus, and Cochrane controlled trials registries and Web of Science from inception till 1 December 2021. Independent literature screening, data extraction, quality evaluation, and the study in line with quality standards were analyzed by using Stata16.0 software. The study is registered with PROSPERO under the number CRD42022301423. Code and data for this study is publicly available (https://github.com/DongYangGao/Dongyang.github.io.git).Results: 21 randomized clinical trials with a total of 4,107 participants were included in this study. Restasis® (OR-4.82, 95% CI-6.18 to 3.45, SUCRA 77.2%) was the most effective commercial formulation for reducing OSDI, Zirun® (SUCRA 73.9%) performed better in improving Schirmer’s test. TJ Cyporin® (SUCRA 65.3%) ranked first in terms of improving tear film break-up time. For treatment-emergent adverse events incidence, Clacier® was close to placebo. The risk of reporting bias is considered low.Conclusion: In the comparison of outcomes included in this study, the optimal order of various commercial cyclosporine A formulations is different, so it is difficult to select the optimal formula. Appropriate commercial formulations should be selected according to patients’ conditions in clinical practice.
Explore the interaction between root metabolism and rhizosphere microbiota during the growth of Angelica sinensis
Authors: Chen Jing-Mei , Feng Wei-Meng  , Yan Hui , Liu Pei , Zhou Gui-Sheng , Guo Sheng , Yu Guang  , Duan Jin-Ao 
Published: November 2022

Angelica sinensis is a medicinal plant widely used to treat multiple diseases in Asia and Europe, which contains numerous active components with therapeutic value. The interaction between root and rhizosphere microorganisms is crucial for the growth and quality formation of medicinal plants. But the micro-plant-metabolite regulation patterns for A. sinensis remain largely undetermined. Here, we collected roots and rhizosphere soils from A. sinensis in seedling stage (M) and picking stage (G), respectively cultivated for one year and two years, generated metabolite for roots, microbiota data for rhizospheres, and conducted a comprehensive analysis. Changes in metabolic and microbial communities of A.sinensis over growth were distinct. The composition of rhizosphere microbes in G was dominated by proteobacteria, which had a strong correlation with the synthesis of organic acids, while in M was dominated by Actinobacteria, which had a strong correlation with the synthesis of phthalide and other organoheterocyclic compounds, flavonoids, amines, and fatty acid. Additionally, co-occurrence network analysis identified that Arthrobacter was found to be strongly correlated with the accumulation of senkyunolide A and n-butylidenephthalide. JGI 0001001.H03 was found to be strongly correlated with the accumulation of chlorogenic acid. Based on rhizosphere microorganisms, this study investigated the correlation between root metabolism and rhizosphere microbiota of A. sinensis at different growth stages in traditional geoherb region, which could provide references for exploring the quality formation mechanism of A. sinensis in the future.
Development and delivery cost of digital health technologies for mental health: Application to the Narrative Experiences Online Intervention
Authors: Paterson Luke , Rennick-Egglestone Stefan , Gavan Sean P. , Slade Mike , Ng Fiona , Llewellyn-Beardsley Joy , Bond Carmel , Grundy Andrew , Nicholson Joe , Quadri Dania , Bailey Sylvia , Elliott Rachel A. 
Published: November 2022

BackgroundThe increasing development and use of digital health interventions requires good quality costing information to inform development and commissioning choices about resource allocation decisions. The Narrative Experiences Online (NEON) Intervention is a web-application that delivers recorded mental health recovery narratives to its users. Two randomized controlled trials are testing the NEON Intervention in people with experience of psychosis (NEON) and people experiencing non-psychosis mental health problems (NEON-O).AimThis study describes and estimates the cost components and total cost of developing and delivering the NEON Intervention.Materials and methodsTotal costs for the NEON Trial (739 participants) and NEON-O Trial (1,024 participants) were estimated by: identifying resource use categories involved in intervention development and delivery; accurate measurement or estimation of resource use; and a valuation of resource use to generate overall costs, using relevant unit costs. Resource use categories were identified through consultation with literature, costing reporting standards and iterative consultation with health researchers involved in NEON Intervention development and delivery. Sensitivity analysis was used to test assumptions made.ResultsThe total cost of developing the NEON Intervention was £182,851. The largest cost components were software development (27%); Lived Experience Advisory Panel workshops (23%); coding the narratives (9%); and researchers' time to source narratives (9%). The total cost of NEON Intervention delivery during the NEON Trial was £118,663 (£349 per NEON Intervention user). In the NEON-O Trial, the total delivery cost of the NEON Intervention was £123,444 (£241 per NEON Intervention user). The largest cost components include updating the narrative collection (50%); advertising (19%); administration (14%); and software maintenance (11%). Uncertainty in the cost of administration had the largest effect on delivery cost estimates.ConclusionOur work shows that developing and delivering a digital health intervention requires expertise and time commitment from a range of personnel. Teams developing digital narrative interventions need to allocate substantial resources to curating narrative collections.Implications for practiceThis study identifies the development and delivery resource use categories of a digital health intervention to promote the consistent reporting of costs and informs future decision-making about the costs of delivering the NEON Intervention at scale.Trial registrationNEON Trial: ISRCTN11152837, registered 13 August 2018, http://www.isrctn.com/ISRCTN11152837. NEON-O Trial: ISRCTN63197153, registered 9 January 2020, http://www.isrctn.com/ISRCTN63197153.