bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins?
Authors: Ferenci Peter , Reiberger Thomas , Stadlbauer Vanessa , Zoller Heinz 
Published: June 2022

AbstractThe introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long‐term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short‐term (i.e. 4–8 weeks) HBIg prophylaxis after LT followed by the long‐term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co‐infected patients, the need for long‐term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post‐LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10–13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post‐LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post‐LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co‐infection did not lead to impaired overall survival or a higher recurrence rate in this long‐term follow‐up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended.
Kinetoplastid‐specific X2‐family kinesins interact with a kinesin‐like pleckstrin homology domain protein that localizes to the trypanosomal microtubule quartet
Authors: Benz Corinna , Müller Nora , Kaltenbrunner Sabine , Váchová Hana , Vancová Marie , Lukeš Julius , Varga Vladimír , Hashimi Hassan 
Published: June 2022

AbstractKinesins are motor proteins found in all eukaryotic lineages that move along microtubules to mediate cellular processes such as mitosis and intracellular transport. In trypanosomatids, the kinesin superfamily has undergone a prominent expansion, resulting in one of the most diverse kinesin repertoires that includes the two kinetoplastid‐restricted families X1 and X2. Here, we characterize in Trypanosoma brucei TbKifX2A, an orphaned X2 kinesin. TbKifX2A tightly interacts with TbPH1, a kinesin‐like protein with a likely inactive motor domain, a rarely reported occurrence. Both TbKifX2A and TbPH1 localize to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that wraps around the flagellar pocket as it extends to the cell body anterior. The proximal proteome of TbPH1 revealed two other interacting proteins, the flagellar pocket protein FP45 and intriguingly another X2 kinesin, TbKifX2C. Simultaneous ablation of TbKifX2A/TbPH1 results in the depletion of FP45 and TbKifX2C and also an expansion of the flagellar pocket, among other morphological defects. TbKifX2A is the first motor protein to be localized to the MtQ. The observation that TbKifX2C also associates with the MtQ suggests that the X2 kinesin family may have co‐evolved with the MtQ, both kinetoplastid‐specific traits.
The activity of the RGA5 sensor NLR from rice requires binding of its integrated HMA domain to effectors but not HMA domain self‐interaction
Authors: Xi Yuxuan , Chalvon Véronique , Padilla André , Cesari Stella , Kroj Thomas 
Published: June 2022

AbstractThe rice nucleotide‐binding (NB) and leucine‐rich repeat (LRR) domain immune receptors (NLRs) RGA4 and RGA5 form a helper NLR/sensor NLR (hNLR/sNLR) pair that specifically recognizes the effectors AVR‐Pia and AVR1‐CO39 from the blast fungus Magnaporthe oryzae. While RGA4 contains only canonical NLR domains, RGA5 has an additional unconventional heavy metal‐associated (HMA) domain integrated after its LRR domain. This RGA5HMA domain binds the effectors and is crucial for their recognition. Investigation of the three‐dimensional structure of the AVR1‐CO39/RGA5HMA complex by X‐ray crystallography identified a candidate surface for effector binding in the HMA domain and showed that the HMA domain self‐interacts in the absence of effector through the same surface. Here, we investigated the relevance of this HMA homodimerization for RGA5 function and the role of the RGA5HMA effector‐binding and self‐interaction surface in effector recognition. By analysing structure‐informed point mutations in the RGA5HMA‐binding surface in protein interaction studies and in Nicotiana benthamiana cell death assays, we found that HMA self‐interaction does not contribute to RGA5 function. However, the effector‐binding surface of RGA5HMA identified by X‐ray crystallography is crucial for both in vitro and in vivo effector binding as well as effector recognition. These results support the current hypothesis that noncanonical integrated domains of NLRs act primarily as effector traps and deepen our understanding of the sNLRs' function within NLR pairs.
Autoimmunity to ion channels in neurological diseases–Autoimmunity to aquaporin water channels
Authors: Tanaka Keiko , Nagaishi Akiko , Matsui Makoto 
Published: June 2022

AbstractNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease in which the majority of patients have autoantibodies against the aquaporin‐4 (AQP4) water channel. In the central nervous system (CNS), AQP4 is expressed on the cell membrane of astrocytes, and anti‐AQP4 antibodies harm AQP4 expressing astrocytes, resulting in astrocytopathy. The majority of patients are female and have acute visual disturbances and transverse myelitis, as well as brainstem and other cerebral lesions. These symptoms are frequently severe and develop quickly, resulting in substantial impairment in daily life. Patients are treated with high‐dose methylprednisolone infusions, plasma exchange, and intravenous immunoglobulin administration during the acute stage. Based on the pathogenesis of NMOSD, various effective relapse‐preventing therapies have emerged in recent years. The majority of them have been proved to have a positive impact on the patients who have been treated. They increased the number of therapy options available, albeit long‐term efficacy and safety would need to be monitored for a longer period. Through its unique fluid transport function in the CNS, knowledge of the functions of AQP4 has grown in the field of not only inflammatory disorders like NMOSD, but also other neurodegenerative disorders like Alzheimer's disease.
Evening blue‐light exposure, maternal glucose, and infant birthweight
Authors: Izci Balserak Bilgay , Hermann Renata , Hernandez Teri L. , Buhimschi Catalin , Park Chung 
Published: June 2022

AbstractMaternal–fetal consequences of exposure to blue‐wavelength light are poorly understood. This study tested the hypothesis that evening blue‐light exposure is associated with maternal fasting glucose and infant birthweight. Forty‐one pregnant women (body mass index = 32.90 ± 6.35 kg/m2; 24–39 years old; 16 with gestational diabetes mellitus [GDM]) wore actigraphs for 7 days, underwent polysomnography, and completed study questionnaires during gestational week 30 ± 3.76. Infant birthweight (n = 41) and maternal fasting glucose (n = 30; range = 16–36 weeks) were recorded from the mothers’ medical charts. Blue‐light exposure was obtained from Actiwatch‐Spectrum recordings. Adjusted and unadjusted linear regression analyses were performed to determine sleep characteristics associated with maternal fasting glucose and infant‐birthweight. The mean fasting mid‐ to late‐gestation glucose was 95.73 ± 24.68 mg/dl and infant birthweight was 3271 ± 436 g. In unadjusted analysis, maternal fasting glucose was associated with blue‐light exposure (β = 3.82, p = 0.03). In the final model of multiple linear regression for fasting glucose, evening blue‐light exposure (β = 4.00, p = 0.01) remained significant after controlling for gestational weight gain, parity, sleep duration, and GDM. Similarly, blue‐light exposure was associated with infant birthweight (69.79, p = 0.006) in the unadjusted model, and remained significant (β = 70.38, p = 0.01) after adjusting for weight gain, wakefulness after sleep onset, gestational age at delivery, and GDM. Higher blue‐light exposure in pregnancy is associated with higher fasting glucose and infant birthweight. Reduced use of electronic devices before bedtime is a modifiable behavior.
Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide‐stimulated periodontitis in vitro and in vivo
Authors: Qiao Shuwei , Li Baosheng , Cai Qing , Li Zhen , Yin Zhaoyi , He Jie , Li Yuyang , Meng Weiyan 
Published: June 2022

AbstractObjectivesFerroptosis is associated with multiple inflammatory diseases. Periodontitis is an inflammatory disease mainly caused by oral opportunistic pathogens. However, the ferroptosis–periodontitis relationship has not been thoroughly described. We here analyzed whether ferroptosis is involved in periodontitis.Materials and methodsHuman gingival fibroblasts (HGFs) were stimulated with P. gingivalis‐LPS and ferrostatin‐1 (Fer‐1, a ferroptosis inhibitor), and changes in mitochondrial morphology, ferroptosis‐related factors, and inflammation levels were detected. After the rat experimental periodontitis model was established, changes in ferroptosis‐related factors and inflammation levels were re‐evaluated in the same manner.ResultsPorphyromonas gingivalis‐LPS‐induced mitochondrial shrinkage, an increase in mitochondrial membrane density, and upregulation of reactive oxygen species in HGFs. The expression of prostaglandin‐endoperoxide synthase 2, transferrin receptor 1, and malondialdehyde and inflammation levels were upregulated, whereas the expression of solute carrier family seven member 11, glutathione peroxidase 4, superoxide dismutase, and glutathione were downregulated. Fer‐1 attenuated these aforementioned changes and inflammation levels induced by P. gingivalis‐LPS. The in vivo experiment results were consistent with the in vitro experiment results.ConclusionsFerroptosis is involved in inflammatory processes in HGFs upon P. gingivalis‐LPS stimulation. Ferroptosis is observed in the gingival tissue of periodontitis rats.
Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions
Authors: Xie Bang‐lin , Guo Run‐sheng , Liang Wen , Yang Xiao‐wei , Xu Jia‐Qiang , Wan Li‐jun , Yao Wen‐ye , Yi Zhi , Hu Ni‐ya , Zhang Bin 
Published: June 2022

ObjectiveTo study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens.MethodsThis experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In‐hospital infection of clean limb incision, II, In‐hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non‐motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram‐positive bacteria (G+, mainly including Staphylococcus) and Gram‐negative bacteria (G‐, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two‐way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05.ResultsThere was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G‐ were resistant to the first‐ and the second‐generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third‐generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta‐lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria.ConclusionIn open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out‐of‐hospital infection was lower than that of hospital infection.
Long‐term outcomes of a time to isolation – based strategy for cryoballoon ablation compared to radiofrequency ablation in patients with symptomatic paroxysmal atrial fibrillation
Authors: Wei Yue , Chen Lin , Cao Jiang , Liu Shaowen , Ling Tianyou , Huang Xinmiao , Zhou Genqing , Lin Changjian , Xie Yun , Bao Yangyang , Luo Qingzhi , Ye Jiawen , Zhang Ning , Jin Qi , Wu Liqun 
Published: June 2022

AbstractBackgroundCryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long‐term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF.MethodsIn this observational study, symptomatic patients with drug‐refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) – based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia >30 s following a 90‐day blanking period. The secondary endpoint was procedure‐related complications and procedure parameters.ResultsA total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow‐up of 778 days, the atrial tachyarrhythmia‐free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p < .001) and left atrial dwell time (60.1 min vs. 109.9 min, p < .001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p < .001).ConclusionCompared to RFA, our TTI‐based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF.
The earliest enzyme replacement for infantile‐onset Pompe disease in Japan
Authors: Tocan Vlad , Mushimoto Yuichi , Kojima‐Ishii Kanako , Matsuda Akane , Toda Naoko , Toyomura Daisuke , Hirata Yuichiro , Sanefuji Masafumi , Sawada Takaaki , Sakai Yasunari , Nakamura Kimitoshi , Ohga Shouichi 
Published: June 2022

AbstractBackgroundInfantile‐onset Pompe disease (IOPD) is the most severe phenotype of a lysosomal storage disorder caused by acid alpha‐glucosidase (GAA) deficiency. An enzymatic newborn screening (NBS) program started regionally in Japan in 2013 for early enzyme replacement therapy (ERT). We report the ERT responses of the first NBS‐identified Japanese IOPD case and of another case diagnosed prior to NBS, to discuss the problems of promptly starting ERT in Japan.MethodsAcid alpha‐glucosidase activity was measured by fluorometric assay in both patients. The diagnosis of IOPD was confirmed by next‐generation followed by Sanger‐method sequencing (patient 1) or direct sequencing of polymerase chain reaction (PCR)‐amplified products (patient 2) of the GAA gene.ResultsA female infant identified by NBS had a novel out‐of‐frame (p.F181Dfs*6) variant and a reported pathogenic (p.R600C) variant, along with two pseudodeficiency variants. Enzyme replacement therapy was started at age 58 days when the infant had increased serum levels of creatine kinase and slight myocardial hypertrophy. Clinical and biochemical markers improved promptly. She has been alive and well without delayed development at age 14 months. Patient 2, a Japanese male, received a diagnosis of IOPD at age 5 months before the NBS era. He had a homozygotic variant of GAA (p.R608X), later registered as a cross‐reactive immunological material (CRIM)‐negative genotype, and developed a high titer of anti‐rhGAA antibodies. The patient has survived myocardial hypertrophy with continuous respiratory support for 12 years of ERT.ConclusionsEnzyme replacement therapy should not be delayed over the age of 2 months for reversible cardiac function, although CRIM‐negative cases may hamper turnaround time reduction.
Ventricular depolarization and repolarization variability in children with type 1 diabetes mellitus
Authors: Bezen Diğdem , Türkmenoğlu Yelda , İrdem Ahmet 
Published: June 2022

AbstractBackgroundArrhythmias can be seen as a sign of cardiac autonomic neuropathy in type 1 diabetes mellitus. We aimed to evaluate pulmonary artery pressure, ventricular depolarization and repolarization variability in children with type 1 diabetes mellitus.MethodsWe investigated 78 children with type 1 diabetes mellitus (mean age 11.6 ± 3.6 years) and 68 age‐gender matched healthy children as control group. All type 1 diabetes mellitus patients were divided into three subgroups according to glycated hemoglobin (HbA1c) levels and the duration of disease. Electrocardiogram and transthoracic echocardiograms were performed on both groups.ResultsIn patients with type 1 diabetes mellitus, there was an elongation in P, Pd, PR, QTc, QTd, QTcd, JT, JTc, JTd, Tp‐Te and Tp‐Te/QT, Tp‐Te/QTc, Tp‐Te/JT, Tp‐Te/JTc ratios were higher (P < 0.05). In patients with type 1 diabetes mellitus, pulmonary artery pressure was higher than control group (P = 0.001). Prolongation of QTc, thickness of left ventricle end‐diastolic diameter and left ventricle posterior wall diameter were higher in the HbA1c ≥9% subgroup. When adjusted for age there was no significant correlation between left ventricle parameters and HbA1c.ConclusionsAtrial conduction delay and impairment of ventricular repolarization were significantly high and there was a predisposition for the development of pulmonary artery hypertension in children with type 1 diabetes mellitus. Poor glycemic control was not a risk factor for propensity of left ventricle hypertrophy and left ventricle dysfunction.
Higher quality rather than superior quantity of oocytes determine the amount of fertilizable oocytes in two outbred Dummerstorf high‐fertility mouse lines
Authors: Calanni‐Pileri Michela , Weitzel Joachim M. , Langhammer Martina , Michaelis Marten 
Published: June 2022

AbstractDummerstorf fertility lines FL1 and FL2 represent two models of enhanced fertility characterized by the doubling of the litter size compared with an unselected control population (ctrl line, Dummerstorf FztDU). Both biodiverse FLs managed to reach this goal by increasing the ovulation rate per cycle, even showing decreased pregnancy rate and irregular oestrous cycle and metabolic hormone levels, compared with ctrl. The aim of the present study was to analyse oocytes in terms of quality and quantity by comparing the entire pool of oocytes per ovary, with those from the antral follicles within the same animal. We performed Brilliant Cresyl Blue staining as a non‐invasive marker of oocyte quality in combination with an analysis of additional morphological indicators, e.g. cytoplasm clarity, cumulus cell layers, nuclear anatomy, size and shape. We compared our fertility lines with the unselected control population and with another independent line selected from the same founder population, showing lower litter size (DU6P). Our results suggest that fertility lines show decreased number of oocytes per ovary compared with DU6P but increased number of high‐quality oocytes before ovulation. Hence, the raise in the ovulation rate and litter size of those super fertile mouse lines are not associated with an increased number of oocytes per ovary but rather with an increased number of higher quality fertilizable oocytes per cycle. In addition, the most conspicuous method to acquire oocytes with the highest quality in our lines is to assess their morphology, rather than their status after staining. All these discoveries together may be of fundamental importance for further studies in livestock farm animals showing some similar characteristics, e.g. irregular cycle or hormonal misbalances, to improve production while lowering costs, and in humans to increase the possibilities of successful pregnancies for couples undergoing in vitro fertilization (IVF).
Justifying a presumed standing for environmental NGOs: A legal assessment of Article 9(3) of the Aarhus Convention
Authors: Danthinne Audrey , Eliantonio Mariolina , Peeters Marjan 
Published: June 2022

AbstractThe Aarhus Convention is a well‐known cornerstone of environmental law on the European continent. Nevertheless, interpretative dilemmas have arisen, particularly in relation to access to justice for environmental nongovernmental organizations (ENGOs). More precisely, while the standing criterion in Article 9(2) of the Convention is formulated in a rather precise and generous way for ENGOs, the standing criterion in Article 9(3) has been deliberately kept vague and makes no reference to ENGOs. In the meantime, some courts, both at the national and European Union (EU) level, have linked the scope ratione personae of Article 9(2) to that of Article 9(3), thus recognizing a presumed and therefore generous standing for ENGOs under both provisions. Because the Aarhus Convention explicitly provides for such an advantageous presumption only under Article 9(2), this article seeks to assess whether these remarkable judicial interpretations nonetheless find a convincing basis in EU law or in the Aarhus Convention respectively.
Coastal proximity and individual living standards: Econometric evidence from georeferenced household surveys in sub‐Saharan Africa
Authors: Wild Frederik , Stadelmann David 
Published: June 2022

AbstractWe investigate georeferenced household‐level data consisting of up to 128,609 individuals living in 11,261 localities across 17 coastal sub‐Saharan African countries over 20 years. We analyze the relevance of coastal proximity, measured by the geographic distance to harbors, as a predictor of individual economic living standards. Our setting allows us to account for country‐time fixed effects as well as individual‐specific controls. Results reveal that individuals living further away from the coast are significantly poorer, measured along an array of welfare indicators. Our findings are robust to the inclusion of other geographic covariates of development such as climate (e.g., temperature, precipitation) or terrain conditions (e.g., ruggedness, land suitability). We also explore mechanisms through which coastal proximity may matter for individual welfare and decompose the estimated effect of coastal proximity via formal mediation analysis. Our results highlight the role of human capital, urbanization, and infrastructural endowments in explaining within‐country differences in individual economic welfare.