bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population
Authors: Jongkhajornpong Passara , Ueta Mayumi , Lekhanont Kaevalin , Puangsricharern Vilavun , Prabhasawat Pinnita , Chantaren Patchima , Pisuchpen Phattrawan , Kinoshita Shigeru 
Published: November 2020

Background/aimsTo investigate the association of genetic polymorphisms of human leucocyte antigens (HLA) class I and II genes with acetaminophen-related Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) who developed severe ocular complications (SOC) in the Thai population.MethodsA prospective case–control study including 20 unrelated Thai acetaminophen-related SJS/TEN patients with SOC and 60 Thai healthy volunteers, recruited at three university hospitals in Bangkok, Thailand, from September 2014 to August 2019. HLA genes were analysed using PCR amplification followed by hybridisation with sequence-specific oligonucleotide (SSO) probes with bead-based typing kits. The carrier and gene frequencies of individual HLA alleles in patients were compared with those in control volunteers based on dominant assumption using Fisher’s exact test.ResultsAmong HLA class I polymorphisms, HLA-A*33:03, HLA-B*44:03 and HLA-C*07:01 were significantly associated with acetaminophen-related SJS/TEN and SOC with high ORs (95% CI, corrected p value; Pc) in carrier frequency of 5.4 (1.8 to 16.3, Pc=0.0274), 9.0 (95% CI 2.7 to 30.4, Pc=0.0034), and 9.3 (2.8 to 30.2, Pc=0.0022), respectively. There were no significant HLA class II associations with the disease after corrected for a total number of alleles tested.ConclusionHLA-B*44:03 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. In addition, we also found moderate to strong associations with HLA-A*33:03 and HLA-C*07:01 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.
Why women choose abortion through telemedicine outside the formal health sector in Germany: a mixed-methods study
Authors: Killinger Kristina , Günther Sophie , Gomperts Rebecca , Atay Hazal , Endler Margit 
Published: November 2020

IntroductionWomen on Web (WoW) is a global medical abortion telemedicine service operating outside the formal health sector. In April 2019 they opened their helpdesk to Germany. Our aim was to understand the motivations, and perceived barriers to access, for women who choose telemedicine abortion outside the formal health sector in Germany.MethodsWe conducted a parallel convergent mixed-methods study among 1090 women consulting WoW from Germany between 1 January and 31 December 2019. We performed a cross-sectional study of data contained in online consultations and a content analysis of 108 email texts. Analysis was done until saturation; results were merged and triangulation used to validate results.ResultsThe quantitative analysis found that the need for secrecy (n=502, 48%) and the wish for privacy (n=500, 48%) were frequent reasons for choosing telemedicine abortion. Adolescents were more likely to report secrecy, cost, stigma and legal restrictions as reasons for using telemedicine abortion compared with older women. The content analysis developed two main themes and seven subsidiary categories, (1) internal motivations for seeking telemedicine abortion encompassing (i) autonomy, (ii) perception of external threat and (iii) shame and stigma, and (2) external barriers to formal abortion care encompassing (iv) financial stress, (v) logistic barriers to access, (vi) provider attitudes and (vii) vulnerability of foreigners.ConclusionsWomen in Germany who choose telemedicine abortion outside the formal health sector do so both from a place of empowerment and a place of disempowerment. Numerous barriers to abortion access exist in the formal sector which are of special relevance to vulnerable groups such as adolescents and undocumented immigrants.
Gut-focused hypnotherapy for children and adolescents with irritable bowel syndrome
Authors: Vasant Dipesh H , Hasan Syed S , Cruickshanks Pamela , Whorwell Peter J 
Published: November 2020

ObjectiveSevere irritable bowel syndrome (IBS) in school children and adolescents often leads to stigmatisation, social withdrawal, disrupted education and psychological distress. While there are few effective treatment options for IBS in this age group, gut-focused hypnotherapy (GFH) has shown promise in several trials. Unfortunately, GFH is not widely available, and clinical data outside of trials are scarce. Here, we evaluated outcomes from GFH in patients with IBS, aged ≤18 years, from a tertiary referral centre.Design/MethodConsecutive patients aged ≤18 years with severe IBS received 12 sessions of GFH, at weekly intervals, using the Manchester Protocol. Clinical outcomes data, including IBS Symptom Severity Score (IBS-SSS), Hospital Anxiety and Depression Scale (HADS), Non-colonic Symptom Score and Quality-of-Life (QoL) score, were collected prospectively, and compared pre-GFH and post-GFH. Clinical response was defined as ≥50 point reduction in IBS-SSS.Results32 young patients fulfilling Rome III diagnostic criteria for IBS (median age 16 (range 8–18) years, n=23/32 (72%) female individuals) completed GFH. At baseline, the mean duration of IBS was 5.9±0.9 years, and the mean IBS-SSS was 313±14. After GFH, 28/32 (88%) responded, with a mean overall reduction in IBS-SSS −159±16 (p<0.0001), and 24/32 (75%) achieved ≥30% reduction in abdominal pain scores. GFH also improved: non-colonic symptoms (p<0.0001), HADS-anxiety (p<0.0001), HADS-depression (p=0.0002) and QoL Scores (p<0.0001).ConclusionGFH is highly effective in children and adolescents with IBS. Early intervention with GFH in childhood IBS may reduce the subsequent burden of this problem in adults.
Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy
Authors: Abed Afaf , Calapre Leslie , Lo Johnny , Correia Suzana , Bowyer Samantha , Chopra Abha , Watson Mark , Khattak Muhammad Adnan , Millward Michael , Gray Elin Solomonovna 
Published: November 2020

BackgroundWe aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors.MethodsWe collected blood from 170 patients with advanced lung cancer treated with immunotherapy at two major oncology centers in Western Australia. Genomic DNA was extracted from white blood cells and used for HLA-I/II high-resolution typing. HLA-I/II homozygosity was tested for association with survival outcomes. Univariable and multivariable Cox regression models were constructed to determine whether HLA homozygosity was an independent prognostic factor affecting Overall Survival (OS) and Progression Free Survival (PFS). We also investigated the association between individual HLA-A and -B supertypes with OS.ResultsHomozygosity at HLA-I loci, but not HLA-II, was significantly associated with shorter OS (HR=2.17, 95% CI 1.13 to 4.17, p=0.02) in both univariable and multivariable analysis. The effect of HLA-I homozygosity in OS was particularly relevant for patients with tumors expressing PDL1 ≥50% (HR=3.93, 95% CI 1.30 to 11.85, p<0.001). The adverse effect of HLA-I homozygosity on PFS was only apparent after controlling for interactions between PDL1 status and HLA-I genotype (HR=2.21, 95% CI 1.04 to 4.70, p=0.038). The presence of HLA-A02 supertype was the only HLA-I supertype to be associated with improved OS (HR=0.56, 95% CI 0.34 to 0.93, p=0.023).ConclusionOur results suggest that homozygosity at ≥1 HLA-I loci is associated with short OS and PFS in patients with advanced non-small cell lung cancer with PDL1 ≥50% treated with single-agent immunotherapy. Carriers of HLA-A02 supertype reported better survival outcomes in this cohort of patients.
Metabolic brain changes across different levels of cognitive impairment in ALS: a18F-FDG-PET study
Authors: Canosa Antonio , Moglia Cristina , Manera Umberto , Vasta Rosario , Torrieri Maria Claudia , Arena Vincenzo , D'Ovidio Fabrizio , Palumbo Francesca , Zucchetti Jean Pierre , Iazzolino Barbara , Peotta Laura , Calvo Andrea , Pagani Marco , Chiò Adriano 
Published: November 2020

ObjectiveTo identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) imaging.Methods274 ALS patients underwent neuropsychological assessment and brain18F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with frontotemporal dementia (ALS–FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex and ALS Functional Rating Scale-Revised as covariates.ResultsWe identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS–FTD. ALS–FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared with ALS-Cn.ConclusionsThese data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared with patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterisation.
Correlation between intracranial vertebral artery stenosis diameter measured by digital subtraction angiography and cross-sectional area measured by optical coherence tomography
Authors: Feng Yao , Wu Tingxia , Wang Tao , Li Yingying , Li Mengyue , Li Long , Yang Bin , Bai Xuesong , Zhang Xiao , Wang Yabing , Gao Peng , Chen Yanfei , Ma Yan , Jiao Liqun 
Published: November 2020

BackgroundIntracranial vertebral artery (V4 segment) stenosis quantification traditionally uses the narrowest stenosis diameter. However, the stenotic V4 lumen is commonly irregularly shaped. Optical coherence tomography (OCT) allows a more precise calculation of V4 geometry. We compared the narrowest diameter stenosis (DS), measured by digital subtraction angiography (DSA), with the area stenosis (AS), measured by OCT. We hypothesized that DS is the gold standard for measuring the degree of stenosis.MethodsFive neuroradiologists evaluated 49 stenosed V4 segments in a blinded protocol. V4 stenosis was measured in millimeters on DSA at its narrowest diameter. OCT was used to estimate the cross-sectional luminal area. We also used automated software to measure DS. Three different angles (anterior, lateral, and oblique views) were used for calculations, and the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) methods were used in all measurements. Spearman’s R values were calculated. Non-linear regression analysis was performed between the DS and AS, with statistically different correlations.ResultsA high correlation was observed between the WASID and NASCET methods to measure DS with observer measurement and automated software. A good correlation was found between DS measured by observers and AS measured by OCT. Non-linear regression analysis showed that only observer measurement using the oblique view and the WASID method could attain statistically significant differences, but it was weak (r=0.389).ConclusionMeasurement of the narrowest diameter was not a reliable predictor of the cross-sectional area of V4 stenosis. Larger studies are therefore needed to develop a new evaluation system based on V4 stenosis.
Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial
Authors: Patnaik Amita , Yap Timothy A. , Chung Hyun Cheol , de Miguel Maria J. , Bang Yung-Jue , Lin Chia-Chi , Su Wu-Chou , Italiano Antoine , Chow Kay Hoong , Szpurka Anna M. , Yu Danni , Zhao Yumin , Carlsen Michelle , Schmidt Shelly , Vangerow Burkhard , Gandhi Leena , Xu Xiaojian , Bendell Johanna 
Published: November 2020

Abstract

Purpose:
This phase Ia/Ib PACT study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of a new programmed cell death ligand 1 (PD-L1) inhibitor, LY3300054, as monotherapy or in combination with ramucirumab, abemaciclib, or merestinib (a type II MET kinase inhibitor) in patients with advanced, refractory solid tumors (NCT02791334).

Patients and Methods:
Patients were enrolled into cohorts of escalating LY3300054 dose (phase Ia) as monotherapy (N = 15) or combined with ramucirumab (N = 10), abemaciclib (N = 24), or merestinib (N = 12). The phase Ib dose expansion enrolled 8 patients with melanoma in the monotherapy arm and 12 patients with pancreatic cancer in the merestinib combination arm. Combination treatments were administered concurrently from day 1 of each cycle. A 14-day lead-in abemaciclib arm was also explored. Primary endpoints were dose-limiting toxicity (DLT) and safety.

Results:
Treatment-related adverse events included fatigue and nausea in the monotherapy arm (13% for each), hypothyroidism (30%) in the ramucirumab arm, diarrhea (54%) in the abemaciclib arm, and nausea (25%) in the merestinib arm. DLTs associated with hepatoxicity were observed in 3 of 4 patients in the abemaciclib lead-in cohorts. No DLTs or grade 3 or 4 hepatoxicity were reported in the concurrent abemaciclib arm. Pharmacokinetic characteristics were comparable with other PD-L1 inhibitors. One patient in each arm experienced a partial response per RECIST v1.1 lasting ≥7 months.

Conclusions:
LY3300054 was well tolerated without unexpected safety concerns when administered alone or concurrently with ramucirumab, abemaciclib, or merestinib. Lead-in abemaciclib before combining with LY3300054 was not feasible due to hepatotoxicity. Durable clinical benefits were seen in all regimens.
Combined Inhibition of Gαq and MEK Enhances Therapeutic Efficacy in Uveal Melanoma
Authors: Hitchman Tyler D. , Bayshtok Gabriella , Ceraudo Emilie , Moore Amanda R. , Lee Cindy , Jia Ruobing , Wang Naitao , Pachai Mohini R. , Shoushtari Alexander N. , Francis Jasmine H. , Guan Youxin , Chen Juliet , Chang Matthew T. , Taylor Barry S. , Sakmar Thomas P. , Huber Thomas , Chi Ping , Chen Yu 
Published: November 2020

Abstract

Purpose:
All uveal melanoma and a fraction of other melanoma subtypes are driven by activation of the G-protein alpha-q (Gαq) pathway. Targeting these melanomas has proven difficult despite advances in the molecular understanding of key driver signaling pathways in the disease pathogenesis. Inhibitors of Gαq have shown promising preclinical results, but their therapeutic activity in distinct Gαq mutational contexts and in vivo have remained elusive.

Experimental Design:
We used an isogenic melanocytic cellular system to systematically examine hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (L129Q) found in human uveal melanoma. This cellular system and human uveal melanoma cell lines were used in vitro and in in vivo xenograft studies to assess the efficacy of Gαq inhibition as a single agent and in combination with MEK inhibition.

Results:
We demonstrate that the Gαq inhibitor YM-254890 inhibited downstream signaling and in vitro growth in all mutants. In vivo, YM-254890 slowed tumor growth but did not cause regression in human uveal melanoma xenografts. Through comprehensive transcriptome analysis, we observed that YM-254890 caused inhibition of the MAPK signaling with evidence of rebound by 24 hours and combination treatment of YM-254890 and a MEK inhibitor led to sustained MAPK inhibition. We further demonstrated that the combination caused synergistic growth inhibition in vitro and tumor shrinkage in vivo.

Conclusions:
These data suggest that the combination of Gαq and MEK inhibition provides a promising therapeutic strategy and improved therapeutic window of broadly targeting Gαq in uveal melanoma.
See related commentary by Neelature Sriramareddy and Smalley, p. 1217
Magnetic Resonance Imaging in Stable Mild Cognitive Impairment, Prodromal Alzheimer’s Disease, and Prodromal Dementia with Lewy Bodies
Authors: Siddiqui Tahreem Ghazal , Whitfield Timothy , Praharaju Sudhakar Janaki , Sadiq Dilman , Kazmi Hiba , Ben-Joseph Aaron , Walker Zuzana 
Published: November 2020

<b><i>Introduction:</i></b> Fifteen percent of people with mild cognitive impairment (MCI) will progress to dementia within 2 years. There is increasing focus on the evaluation of biomarkers which point towards the underlying pathology. This enables better prediction of clinical outcomes. Early diagnosis of the dementia subtype is crucial for appropriate management and accurate prognosis. The aim of this study was to compare MRI measures in stable mild cognitive impairment patients (stable-MCI), prodromal Alzheimer’s disease (pro-AD), and prodromal dementia with Lewy bodies (pro-DLB). <b><i>Methods:</i></b> Out of 1,814 patients assessed in Essex memory clinic between 2002 and 2017, 424 had MCI at baseline with follow-up data. All patients underwent comprehensive clinical and cognitive assessment at each assessment. MRI scans were acquired at patients’ baseline assessment, corresponding to the time of initial MCI clinical diagnosis. Patients were grouped according to their diagnosis at the end of follow-up. All baseline scans were visually rated according to established rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA), and white matter lesions (WMLs). <b><i>Results:</i></b> MRI scans were available for 28 pro-DLB patients and were matched against 27 pro-AD and 28 stable-MCI patients for age, sex, and education. The mean follow-up duration was 34 months for the pro-AD group, 27 months for the pro-DLB group, and 21 months for the stable-MCI group. MTA scores were significantly greater in pro-AD patients compared to pro-DLB (<i>p</i> = 0.047) and stable-MCI patients (<i>p</i> = 0.012). There was no difference on GCA or WMLs between pro-AD, pro-DLB, and stable-MCI. <b><i>Conclusions:</i></b> This study indicates that a simple visual rating of MTA at the stage of MCI already differs at a group level between patients that progress to AD, DLB, or continue to be stable-MCI. This could aid clinicians to differentiate between MCI patients who are likely to develop AD, versus those who might progress to DLB or remain stable.
Contamination rate of commonly consumed fresh vegetables and fruits with parasites of medically importance in Wolkite and Butajira Towns of Gurage Zone, Southern Ethiopia
Authors: Bekele Fitsum , Shumbej Teha , Dendir Andamlak , Mesfin Dereje , Solomon Absra 
Published: November 2020

Intestinal parasitic infections are among the most common on causes of disease in humans, responsible for considerable morbidity and mortality. Commonly consumed raw vegetables and fruits are among the ways through which humans become infected with parasites of medical importance. A prospective cross-sectional study with an aim of describing the parasite contamination rate of raw fresh vegetables and fruits sold at the central open-aired market of Butajira and Wolkite towns, in southern Ethiopia was conducted on a total of 270 fresh vegetable and fruits samples. Standardized parasitological techniques were employed to detect diagnostic stages of parasites.98 out of the 270 (36.3%) samples were found positive for intestinal parasites. Remarkably, twenty eight out of the forty five cabbage samples analyzed, 62.2%, were found to be contaminated with parasites of medical importance, registering the highest level of contamination. On the contrary Avocado was found to be the least contaminated produce with contamination rate of 17.7% (8/45). Significant association was observed between the kind of vegetables analyzed and existence of parasites (p=0.002). This study identified high rate of contamination in commonly consumed vegetables and fruits. The authors believe that the role fruits and vegetables paly in the transmission of intestinal parasitic infections to humans is un questionable. Substantial attention is needed from all relevant bodies to tackle this problem.
Nutritional status of under-five children in rural Bangladesh
Authors: Sen Liton Chandra , Ahmed Md. Sabbir , Touhiduzzaman Abu Shoeb Md. , Mandal Soumitra , Ahmed AH Towfique , Das Sanjit Kumar , Saha Rama 
Published: November 2020

A cross-sectional study was carried out in Dumki Upazila of Patuakhali district in Bangladesh to assess the prevalence of stunting, wasting and underweight among the under-five children. Anthropometric measurements were taken from all children, aged 0-59 months in the studied area using wooden height board and digital weight machine. We used WHO Anthro software for analyzing the z scores of the children. A total of 4409 (2296 boys and 2113 girls) under five children were counted for anthropometric analysis. Regarding the Height-for-age Z-score (HAZ), the study revealed that the prevalence of stunting was 27.10% (95% CI: 25.8-28.5) of the children while 7.80% (95% CI: 7-8.6) were severe stunting. By assessing the Weight-for-height Z-score (WHZ), the study showed that 11.20% (95% CI: 10.3-12.1) were wasting whereas 3% (95% CI 2.5-3.5) were severe wasting. According to Weight-for-age Z-score (WAZ), about 18.20% (95% CI: 17-19.3) were underweight and 4.1% (95% CI: 3.5-4.7) were underweight. The findings of the study show that prevalence of stunting is very high. Focusing on childhood stunting is a high priority, and there should be comprehensive efforts to increase the overall nutritional status of the under-five children in this area.
Implementation of PWM AC chopper controller for capacitor run induction motor drive via bacterial foraging optimization algorithm
Authors: Sivasubramanian Gobi Mohan , Narayanamurthy Murali 
Published: November 2020

<p>This paper focuses on design of closed-loop control for pulse width modulated AC chopper controlled capacitor run induction motor drive engaging enriched optimization algorithm based on foraging of bacteria. Capacitor run induction motor is a non-linear device and its parameter varies under different functional point of the system. A linearized increment model for PWM AC chopper is illustrated for a particular functional point of the drive. The conventional method does not provide acceptable performance under different load conditions. Bacteria foraging optimization technique categorizes accurate control parameters for the superlative dynamic response under unit step load variations. Field Programmable Gate Array is implemented practically for a particular functional point of the drive to exhibit accurate performance. Experimental and simulated results are obtained to authenticate the effectiveness of the optimized controller.</p><p> </p>