bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty acid‐binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4+ γ/δ T cell in a murine model
Authors: Kobayashi Shuhei , Phung Hai The , Kagawa Yoshiteru , Miyazaki Hirofumi , Takahashi Yu , Asao Atsuko , Maruyama Takashi , Yoshimura Akihiko , Ishii Naoto , Owada Yuji 
Published: October 2020

AbstractBackgroundFatty acid‐binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear.MethodsContact hypersensitivity (CHS) induced by 2,4‐dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild‐type and Fabp3−/− mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co‐culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3.ResultsFabp3‐deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL‐17‐producing Vγ4+ γ/δ T cells that critically control skin inflammation. In Fabp3−/− mice, we found a larger proportion of Vγ4+ γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3−/− mice also contained a higher amount of Vγ4+ γ/δ T cells not only in the skin but in the thymus when compared with wild‐type mice. Furthermore, thymic double‐negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4+ γ/δ T cells in the thymus.ConclusionsThese findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4+ γ/δ T‐cell generation in the thymus.
Post‐operative outcomes in the elderly following colorectal cancer surgery
Authors: Park Hyerin , Parys Simon , Tan Jonathan , Entriken Fiona , Hodder Rupert 
Published: October 2020

AbstractBackgroundDespite the prevalence of colorectal cancer in the elderly, there has been a lack of recent studies examining surgical outcomes in these patients. Post‐operative outcomes of colorectal cancer surgeries in those aged 80 and above will be compared to those younger than 80.MethodsA retrospective study was conducted of adults receiving surgical resections at a single tertiary centre for colorectal cancer diagnosed between January 2017 and December 2019. Patient demographics, mode of presentation, tumour demographics, operative data and post‐operative outcomes were investigated.ResultsOf the 326 patients included, 56 were aged 80 and above. Older patients were more likely to be female (P = 0.02), present with surgical emergencies or from other workup rather than through screening (P = 0.002), have more locally advanced cancers (P = 0.009) and receive less neoadjuvant therapy (P = 0.016). Despite this, they had comparable outcomes to those younger than 80 in terms of length of stay (P = 0.21) and rates of complications including mortality (P = 0.67).ConclusionWith appropriate patient selection and management, elderly patients can achieve comparable post‐operative outcomes to their younger counterparts.
Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries
Authors: Shahid Abu Sadat Mohammad Sayeem Bin , Alam Tahmina , Shahrin Lubaba , Shahunja K. M. , Sarmin Monira , Afroze Farzana , Waliur Rahman Muhammad , Faruque A. S. G. , Ahmed Tahmeed , Chisti Mohammod Jobayer 
Published: October 2020

AbstractAimThis study evaluated the factors associated with hypokalaemia and their outcomes, in severely malnourished children under 5 years of age.MethodsWe focused on 407 severely malnourished children under five who were admitted to the Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from April 2011 to June 2012. The cases were 139 with hypokalaemia, and the comparisons were 268 without hypokalaemia.ResultsCases were older than the comparisons, with a poor socio‐economic status and a higher death rate of 12% vs 7%. They were more likely to present with a history of measles, diarrhoea, lethargy, lower pulse rates, hyponatraemia, metabolic acidosis, hypocalcaemia, hypomagnesaemia, higher height or length, severe underweight, severe wasting and leucocytosis on admission. At discharge, cases had lower potassium levels and a higher proportion had persistent hypokalaemia. Cases received longer treatment with ampicillin and micronutrients. After adjusting for confounders, hypokalaemia was independently associated with poor socio‐economic status, diarrhoea, lower pulse rates, hypocalcaemia, metabolic acidosis and leucocytosis.ConclusionIdentifying simple clinical signs, like diarrhoea and lower pulse rates, and laboratory parameters, such as hypocalcaemia and metabolic acidosis, may enable the early management of hypokalaemia in severely malnourished children under 5 years. This could reduce morbidity and mortality.
Sophisticated electoral accountability
Authors: Belmonte Alessandro 
Published: October 2020

AbstractHow does voter sophistication affect electoral accountability and policy‐making? This paper studies this question in a political‐economic model where a politician in office, with career concerns, can conceal relevant information for policy‐making. Voters have a different level of electoral sophistication, yet all care about the provision of a public good. Sophistication helps voters to formulate correct electoral and economic decisions and can be developed by investing in education. Where this ability is low, voters misjudge the behavior of the politician in office who cheats the electorate, misappropriates public funds, and, nonetheless, obtains re‐election. I discuss the implications of this equilibrium. First, political deception deters aware, sophisticated voters from investing in education, which restricts future political expertise and electoral accountability. Second, fully revealed information deters cheating and can help less sophisticated societies embark on economic enhancing trajectories. In an infinite‐horizon extension of the model, I underline a potential complementarity between accountability and sophistication that can be used to explain divergent equilibria in the long‐run.
Toxicological analysis of azide and cyanide for azide intoxications using gas chromatography
Authors: Bruin Maaike A. C. , Dekker Douwe , Venekamp Nikkie , Tibben Matthijs , Rosing Hilde , de Lange Dylan W. , Beijnen Jos H. , Huitema Alwin D. R. 
Published: October 2020

AbstractAzide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0‐100 µg/mL for both analytes, and azide was stable in human plasma at −20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.
Lipid antigens in bile from patients with chronic liver diseases activate natural killer T cells
Authors: Valestrand L , Berntsen N L , Zheng F , Schrumpf E , Hansen S H , Karlsen T H , Blumberg R S , Hov J R , Jiang X , Melum E 
Published: October 2020

SummaryNatural killer T (NKT) cells are an abundant subset of liver lymphocytes activated by lipid antigens presented on CD1d molecules that are expressed by cholangiocytes. We aimed to determine if bile from patients with chronic liver diseases contains antigenic lipids that can activate NKT cells. Using murine invariant (24.7, 24.8 and DN32.D3) and non-invariant (14S.6, 14S.7 and 14S.10) NKT hybridomas we investigated the presence of lipid antigens in bile collected from the gallbladder of patients undergoing liver transplantation due to end-stage liver disease. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing. We found that the patient bile samples contain antigens that activate both invariant and non-invariant NKT hybridomas (24.7, 24.8, DN32.D3, 14S.6, 14S.7 and 14S.10), as demonstrated by activation of at least one hybridoma by eight of 10 bile samples. Activation at high dilutions suggests that some antigens are highly potent. We used the non-invariant NKT hybridoma 14S.6 to screen 21 additional patient bile samples for NKT-reactivity and demonstrated that 12 of 21 bile samples resulted in activation, three of which gave a strong activation. Four of 12 activating bile samples contained microbial DNA. Our results reveal an immunological pathway that could be of critical importance in biliary immunology.
Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD)
Authors: Pouw J N , Leijten E F A , van Laar J M , Boes M 
Published: October 2020

Summary
Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti-citrullinated protein antibodies. Autoantibody-based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness. Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization. In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification. We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage. We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative.
Older age does not influence the success of weight loss through the implementation of lifestyle modification
Authors: Leyden Eimear , Hanson Petra , Halder Louise , Rout Lucy , Cherry Ishbel , Shuttlewood Emma , Poole Donna , Loveder Mark , Abraham Jenny , Kyrou Ioannis , Randeva Harpal S. , Lam FT , Menon Vinod , Barber Thomas M. 
Published: October 2020

AbstractObjectiveAge is sometimes a barrier for acceptance of patients into a hospital‐based obesity service. Our aim was to explore the effect of age on the ability to lose weight through lifestyle interventions, implemented within a hospital‐based obesity service.DesignRetrospective study.PatientsWe included a cohort of randomly selected patients with morbid obesity (n = 242), who attended our hospital‐based obesity service during 2005‐2016 and received only lifestyle weight loss interventions.MeasurementsPrimary outcome measures were percentage weight loss (%WL) and percentage reduction in body mass index (%rBMI) following implemented lifestyle interventions. Data were stratified according to patient age at referral: group 1 (age < 60 years, n = 167) and group 2 (age ≥ 60 years, n = 75). Weight loss was compared between groups, and correlations with age at referral were explored.ResultsThe duration of hospital‐based weight loss interventions ranged between 1 and 143 months (mean: 38.9 months; SD: 32.3). Baseline BMI at referral differed significantly between groups 1 and 2 (49.7 kgm−2 [SD: 8.7] vs 46.9 kgm−2 [SD: 6.1], respectively; P < .05). Following implemented lifestyle interventions, between groups 1 and 2 there were no differences in %WL (6.9% [SD: 16.7] vs 7.3% [SD: 11.60], respectively; P = NS) or %rBMI (8.1% [SD: 14.9] vs 7.8% [SD: 11.7], respectively; p = NS). Overall, there was no significant correlation between patient age at referral and %WL (r = −.13, p = NS).ConclusionsOlder age does not influence the success of weight loss through the implementation of lifestyle modification within a hospital‐based obesity service. Therefore, age per se should not influence clinical decisions regarding acceptance of patients to hospital‐based obesity services.
Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non‐syndromic inherited retinal dystrophies
Authors: Liu Xiaozhen , Tao Tianchang , Zhao Lin , Li Genlin , Yang Liping 
Published: October 2020

AbstractImportanceInherited retinal dystrophies (IRDs) are a group of monogenic diseases, one of the leading causes of blindness.BackgroundIntroducing a comprehensive genetic testing strategy by combining single gene Sanger sequencing, next‐generation sequencing (NGS) including whole exome sequencing (WES), and a specific hereditary eye disease enrichment panel (HEDEP) sequencing, to identify the disease‐causing variants of 800 Chinese probands affected with non‐syndromic IRDs.DesignRetrospective analysis.ParticipantsEight hundred Chinese non‐syndromic IRDs probands and their families.MethodsA total of 149 patients were subjected to Sanger sequencing. Of the 651 patients subjected to NGS, 86 patients underwent WES and 565 underwent HEDEP. Patients that likely carried copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation‐dependent probe amplification (MLPA) or quantitative fluorescence PCR (QF‐PCR).Main Outcome MeasuresThe diagnostic rate.Results(Likely) pathogenic variants were determined in 481 cases (60.13% detection rate). The detection rates of single gene Sanger sequencing, WES and HEDEP were 86.58%, 31.40% and 56.99%, respectively. Approximately 11.64% of 481 cases carried autosomal dominant variants, 72.97% carried AR variants and 15.39% were found to be X‐linked. CNVs were confirmed by MLPA or QF‐PCR in 17 families. Fourteen genes that each caused disease in 1% or more of the cohort were detected, and these genes were collectively responsible for disease in almost one half (46.38%) of the families.Conclusions and RelevanceSanger sequencing is ideal to detect pathogenic variants of clinical homogeneous diseases, whereas NGS is more appropriate for patients without an explicit clinical diagnosis.
Myeloperoxidase andCYBAgenetic variants in polycystic ovary syndrome
Authors: Ma Wandi , Li Suiyan , Liu Hongwei , Bai Huai , Liu Qingqing , Hu Kaifeng , Guan Linbo , Fan Ping 
Published: October 2020

AbstractBackgroundOxidative stress plays a pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in myeloperoxidase (MPO;G‐463A) and NADPH oxidase p22phox subunit (CYBA;C242T) cause inter‐individual variability in enzyme activities. Here, we investigated the associations between MPO activity and theMPO G‐463AandCYBA C242Tpolymorphisms in Chinese women with PCOS.MethodsThis case‐control study included 1003 patients with PCOS and 810 controls. TheG‐463AandC242Tpolymorphisms were detected by polymerase chain reaction and restriction analysis, and clinical, hormonal, metabolic and oxidative stress parameters and MPO activity were analysed.ResultsThe frequencies of theGA + AAgenotype andAallele frequency of theMPO G‐463Apolymorphism were significantly higher in the PCOS group than in the control group. Logistic regression analysis showed that theMPO‐463Aallele is a risk factor for PCOS (OR = 1.261, 95% CI: 1.042‐1.526,P = .017). Patients with theAAgenotype tended to have higher plasma MPO activity than those with theGGgenotype. No statistical significance was found in the genotype and allele frequencies of theCYBA C242Tpolymorphism between the PCOS and control groups. However, we demonstrated that the coexistence of theMPO Aallele (GA + AAgenotypes) and theCYBA CCgenotype was associated with an increased risk of PCOS when compared with the wild‐typeGG/CCgenotypes (OR = 1.302, 95% CI: 1.030‐1.646,P = .027).ConclusionTheMPO G‐463Avariant, but notCYBA C242Tvariant, is associated with a risk of PCOS in Chinese women.
A novel somatic PLCG2 variant associated with resistance to BTK and SYK inhibition in chronic lymphocytic leukemia
Authors: Raghunathan Vikram , Fan Guang , Kittai Adam S. , Okada Craig , Danilov Alexey V. , Spurgeon Stephen E. 
Published: October 2020

AbstractThe treatment of chronic lymphocytic leukemia (CLL) has been transformed by the use of targeted small molecules inhibiting components of the B cell receptor (BCR) signaling pathway (Haematologica, 103, 2018 and e204; Curr Hematol Malig Rep, 14, 2019, 302). Chief among these is ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), which produces deep, durable responses in CLL with good tolerability (Haematologica, 103, 2018 and e204). Though prolonged exposure to the drug can exert selective pressure on CLL cells and allow for the emergence of drug‐resistant clones, primary ibrutinib treatment failure is rare (Expert Rev Hematol, 11 and 2018, 185; N Engl J Med, 370, 2014 and 2352; N Engl J Med, 373, 2015 and 25, 2425; Blood, 128, 2016 and 2199). Activating mutations in the gene PLCG2, which encodes a downstream target of BTK, appear to enable constitutive BCR signaling and have been associated with ibrutinib resistance (Int J Cancer, 146 and 2020, 85; J Clin Oncol, 35, 2017 and 1437; Blood, 126, 2015 and 61). In recent years, novel investigational agents have targeted other components of the BCR pathway. Among these is entospletinib, an orally bioavailable, selective inhibitor of splenic tyrosine kinase (SYK) (Blood, 126, 2015 and 1744), which lies upstream of the enzyme phospholipase C‐gamma‐2 (PLCG2). Here, we describe a patient who was found to harbor a novel somatic variant of PLCG2 and experienced a lack of treatment response to both ibrutinib and entospletinib.
The Framingham cardiovascular risk score and 5‐year progression of multiple sclerosis
Authors: Petruzzo Martina , Reia Antonio , Maniscalco Giorgia T. , Luiso Fabrizio , Lanzillo Roberta , Russo Cinzia Valeria , Carotenuto Antonio , Allegorico Lia , Palladino Raffaele , Brescia Morra Vincenzo , Moccia Marcello 
Published: October 2020

AbstractBackground and purposeCardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10‐year risk of developing macrovascular disease. Our objectives were to evaluate the possible association between the Framingham risk score at baseline and MS relapses, disability, and disease‐modifying therapy (DMT) choices over a 5‐year follow‐up.MethodsThis is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability, and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HRs).ResultsA one‐point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR = 1.31; 95% confidence interval [CI] = 1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR = 1.19; 95% CI = 1.05, 3.01), and 62% higher risk of DMT escalation (HR = 1.62; 95% CI = 1.22, 3.01).ConclusionsHigher cardiovascular risk was associated with higher risk of relapses, disability, and DMT escalation in MS. Early identification, correction, and treatment of cardiovascular comorbidities should be carefully considered within MS management.
Short‐term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue
Authors: Dommerholt Marleen B. , Blankestijn Maaike , Vieira‐Lara Marcel A. , van Dijk Theo H. , Wolters Henk , Koster Mirjam H. , Gerding Albert , van Os Ronald P. , Bloks Vincent W. , Bakker Barbara M. , Kruit Janine K. , Jonker Johan W. 
Published: October 2020

Dietary protein restriction has been demonstrated to improve metabolic health under various conditions. However, the relevance of ageing and age‐related decline in metabolic flexibility on the effects of dietary protein restriction has not been addressed. Therefore, we investigated the effect of short‐term dietary protein restriction on metabolic health in young and aged mice. Young adult (3 months old) and aged (18 months old) C57Bl/6J mice were subjected to a 3‐month dietary protein restriction. Outcome parameters included fibroblast growth factor 21 (FGF21) levels, muscle strength, glucose tolerance, energy expenditure (EE) and transcriptomics of brown and white adipose tissue (WAT). Here, we report that a low‐protein diet had beneficial effects in aged mice by reducing some aspects of age‐related metabolic decline. These effects were characterized by increased plasma levels of FGF21, browning of subcutaneous WAT, increased body temperature and EE, while no changes were observed in glucose homeostasis and insulin sensitivity. Moreover, the low‐protein diet used in this study was well‐tolerated in aged mice indicated by the absence of adverse effects on body weight, locomotor activity and muscle performance. In conclusion, our study demonstrates that a short‐term reduction in dietary protein intake can impact age‐related metabolic health alongside increased FGF21 signalling, without negatively affecting muscle function. These findings highlight the potential of protein restriction as a strategy to induce EE and browning of WAT in aged individuals.
Hepatocellular carcinoma and other complications of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in Japan: A structured review of published works
Authors: Eguchi Yuichiro , Wong Gabriel , Lee I‐Heng , Akhtar Omar , Lopes Ricardo , Sumida Yoshio 
Published: October 2020

AimsHepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non‐malignant complications among Japanese NAFLD and NASH patients.MethodsAn English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria.ResultsHepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%–20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality.Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH‐HCC). With longer follow‐up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH‐HCC patients also have a higher post‐operative mortality than HCV‐HCC patients.Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non‐NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients.ConclusionHepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.