bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective two‐arm study of the testicular function in patients with COVID‐19
Authors: Enikeev Dmitry , Taratkin Mark , Morozov Andrey , Petov Vladislav , Korolev Dmitry , Shpikina Anastasia , Spivak Leonid , Kharlamova Svetlana , Shchedrina Irina , Mestnikov Oleg , Fiev Dmitry , Ganzha Timur , Geladze Marina , Mambetova Aichurok , Kogan Evgenia , Zharkov Nikolay , Demyashkin Gregory , Shariat Shahrokh F. , Glybochko Petr 
Published: February 2022

AbstractBackgroundThe COVID‐19 pandemic has led the international community to conduct extensive research into potential negative effects of the disease on multiple organs and systems in the human body. One of the most discussed areas is potential of the virus to compromise the testicular function. However, the lack of prospective studies on this topic makes it impossible to draw reliable conclusions on whether the disease affects the male reproductive system and, if so, to what extent.ObjectivesThe current trial is aimed at investigating the effect of SARS‐CoV‐2 on the testicular function, hormone levels and determining the extent of impact on spermatogenesis and damage to testicular tissue.Materials and methodsThis prospective study included healthy controls and cases of patients suffering from viral pneumonia based on chest computed tomography (CT) and a positive SARS‐CoV‐2 throat swab exhibited moderate symptoms (World Health Organization (WHO) classification). Epidemiological, clinical, laboratory and ultrasound data were collected. A semen analysis was performed in cases during their hospital stay and 3 months after the discharge home. We also assessed the testicles obtained during autopsies of patients who died of COVID‐19 (n = 20).ResultsA total of 88 participants were included (44 controls and 44 cases). Blood testosterone levels were significantly decreased in 27.3% of the cases (12/44). The mean level (7.3±2.7 nmol/L) was lower than that in the healthy controls (13.5±5.2 nmol/L, p < 0.001). An increase in luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) was also detected compared to the healthy controls (p = 0.04 and p = 0.002). The semen analysis revealed decreased motility in COVID‐19 patients (p = 0.001), and a higher number of immobile sperm (during COVID‐19: 58.8% and at 3 months 47.4%, p = 0.005). All parameters returned to normal at 3 months after discharge. Direct mixed agglutination reaction (MAR) test at 3 months showed an increase of Ig A (p = 0.03). In the majority of autopsies (18/20), structural disorders of the testicular tissue, with signs of damage to germ cells were observed.Discussion and conclusionCOVID‐19 and its management strategies significantly affect male hormone levels and sperm quality at the onset of the disease. Postmortem examination of testicular tissue confirmed inflammation and viral infiltration of the testicles. However, in patients with moderate to severe disease, the studied parameters of the testicular function returned to normal values within 3 months.
Landscape of pathogenic variants in six pre‐mRNA processing factor genes for retinitis pigmentosa based on large in‐house data sets and database comparisons
Authors: Wang Junwen , Xiao Xueshan , Li Shiqiang , Jiang Hongmei , Sun Wenmin , Wang Panfeng , Zhang Qingjiong 
Published: February 2022

AbstractPurposeVariants in six genes encoding pre‐mRNA processing factors (PRPFs) are a common cause of autosomal dominant retinitis pigmentosa (ADRP). This study aims to determine the characteristics of potential pathogenic variants (PPVs) in the six genes.MethodsVariants in six PRPF genes were identified from in‐house exome sequencing data. PPVs were identified based on comparative bioinformatics analysis, clinical phenotypes and the ACMG/AMP guidelines. The features of PPVs were revealed by comparative analysis of in‐house data set, gnomAD and previously published literature.ResultsTotally, 36 heterozygous PPVs, including 19 novels, were detected from 45 families, which contributed to 4.4% (45/1019) of RP cases. These PPVs were distributed in PRPF31 (17/45, 37.8%), SNRNP200 (12/45, 26.7%), PRPF8 (10/45, 22.2%) and PRPF3 (6/45, 13.3%) but not in PRPF6 or PRPF4. Different types of PPVs were predominant in different PRPF genes, such as loss‐of‐function variants in PRPF31 and missense variants in the five remaining genes. The clustering of PPVs in specific regions was observed in SNRNP200, PRPF8 and PRPF3. The pathogenicity for certain classes of variants in these genes, such as loss‐of‐function variants in PRPF6 and missense variants in PRPF31 and PRPF4, requires careful consideration and further validation. The predominant fundus changes were early macular involvement, widespread RPE atrophy and pigmentation in the mid‐ and far‐peripheral retina.ConclusionSystemic comparative analysis may shed light on the characterization of PPVs in these genes. Our findings provide a brief landscape of PPVs in PRPF genes and the associated phenotypes and emphasize the careful classification of pathogenicity for certain types of variants that warrant further characterization.
Supratherapeutic lithium levels in COVID‐19 infection
Authors: Rojas‐Velasquez Danilo , Lifland Brooke , Caro Mario Andres 
Published: February 2022

AbstractLithium levels are often checked in the inpatient setting when a patient has clear indications of acute kidney injury. Lithium levels can become supratherapeutic in COVID‐19 infection even after normalization of creatinine. Lithium levels should be checked routinely in patients with COVID‐19 infection in order to avoid supratherapeutic levels.
Pramlintide for post‐bariatric hypoglycaemia
Authors: Sheehan Amanda , Goldfine Allison , Bajwa Muhammed , Wolfs Danielle , Kozuka Chisayo , Piper Jacqueline , Fowler Kristen , Patti Mary Elizabeth 
Published: February 2022

AbstractAimsThe aim of this study was to examine the hypothesis that pramlintide would reduce hypoglycaemia by slowing gastric emptying and reducing postprandial glucagon secretion, thus limiting postprandial glycaemic excursions and insulin secretion, and thus to determine the efficacy of pramlintide on frequency and severity of hypoglycaemia in post‐bariatric hypoglycaemia (PBH).Materials and MethodsParticipants with PBH following gastric bypass were recruited from outpatient clinics at the Joslin Diabetes Center, Boston, Massachusetts for an open‐label study of pramlintide efficacy over 8 weeks. Twenty‐three participants were assessed for eligibility, 20 participants had at least one pramlintide dose, and 14 completed the study. A mixed‐meal tolerance test (MMTT) was performed at baseline and after 8 weeks of subcutaneous pramlintide with a sequential dose increase to a maximum of 120 micrograms (mean 69 ± 32 mcg) three times daily. The primary endpoint was change in glucose excursions during the MMTT. Secondary measures included MMTT insulin response, satiety and dumping score, percentage time with sensor glucose (SG) <3.9 mM, and number of days with minimum SG <3 mM, during masked continuous glucose monitoring.ResultsThere were no differences in MMTT glucose, glucagon or insulin between baseline and post treatment. We observed no significant change in satiety or dumping scores. The overall frequency of low SG values did not change, although there was substantial inter‐individual variability.ConclusionsIn PBH, pramlintide does not modulate glycaemic or insulin responses, satiety, or dumping scores during an MMTT and does not impact glycaemic excursions or decrease low SG levels in the outpatient setting.
Effects of glucagon‐like peptide‐1 receptor agonists on cardiovascular and renal outcomes: A meta‐analysis and meta‐regression analysis
Authors: Yoshiji Satoshi , Minamino Hiroto , Tanaka Daisuke , Yamane Shunsuke , Harada Norio , Inagaki Nobuya 
Published: February 2022

AbstractAimTo evaluate the cardiovascular and renal outcomes of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and the associations between these outcomes and HbA1c or weight reduction.Materials and MethodsWe searched PubMed/MEDLINE, EMBASE, and CENTRAL databases for randomized, placebo‐controlled trials of GLP‐1 RAs reporting major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, stroke, and myocardial infarction) as the primary outcome. We conducted a meta‐regression analysis of primary and secondary outcomes with HbA1c or weight reduction following a meta‐analysis with a random‐effects model for these outcomes.ResultsWe extracted data of 60 800 individuals from eight eligible studies (ELIXA, LEADER, SUSTAIN‐6, EXSCEL, HARMONY, PIONEER 6, REWIND, and AMPLITUDE‐O). GLP‐1 RAs reduced MACE (hazard ratio [HR] 0.86; 95% CI: 0.80‐0.93; P < .001) and secondary outcomes including the composite renal outcome (0.80; 0.73‐0.87; P < .001). In meta‐regression analysis, every 1% reduction in HbA1c was associated with 26% and 35% decreases in the logarithm of HR of MACE (P = .044; R2 = 0.65) and the composite renal outcome (P = .040; R2 = 0.85), respectively. On the contrary, weight reduction was not associated with any outcome, including MACE (P = .390).ConclusionsThe reduction in HbA1c, but not body weight, is associated with cardiovascular and renal outcomes. The magnitude of HbA1c reduction can be a surrogate for the cardiovascular and renal benefits of treatment with GLP‐1 RAs.
Local glucose metabolism is unaltered in reversible splenial lesion syndrome
Authors: Zöllner Johann Philipp , Wichert Jennifer , Schubert‐Bast Susanne , Hattingen Elke , Rosenow Felix , Strzelczyk Adam 
Published: February 2022

AbstractBackground and purposeTransient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES.MethodsWe retrospectively analysed patients with RESLES after reductions in antiseizure medications during in‐hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests.ResultsLocal glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p = 0.902 and p = 0.535, respectively).ConclusionWe found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible.
Validation of an equine fitness tracker: ECG quality and arrhythmia detection
Authors: ter Woort Fe , Dubois Guillaume , Tansley Grace , Didier Marie , Verdegaal Elisabeth‐Lidwien , Franklin Samantha , Van Erck‐Westergren Emmanuelle 
Published: February 2022

SummaryBackgroundCardiac arrhythmias in exercising horses are the focus of much interest, both in terms of what is considered normal and potential associations with poor performance and sudden cardiac death. One barrier to performing large‐scale studies is the lack of an easily applicable device, to allow recording of large numbers of high‐quality exercising electrocardiograms (ECGs). The EquimetreTM is a new wearable device, which records a single lead ECG, among other parameters. Validation of such wearable devices is essential before further studies are undertaken.ObjectivesTo evaluate the quality of ECG using the EquimetreTM and compare arrhythmia detection during exercise with the reference TelevetTM system.Study designProspective blinded clinical study.MethodsSimultaneous ECGs were recorded with both systems in 49 healthy horses during exercise. High‐intensity exercise (>40 km/h) was performed by 29 racehorses, and lower‐intensity exercise for the remainder of the racehorses and show jumpers. Tracings were excluded if >10% artefact was present (duration of artefact relative to duration of exercise). For included ECGs, the duration of artefact was recorded and compared. ECGs were evaluated using Kubios premium software. Arrhythmia detection (yes/no) and arrhythmia classification (sinus arrhythmia, narrow complex of similar morphology to the sinus complexes or wide complex with a different morphology) were compared using Cohen's Kappa coefficient.ResultsNine TelevetTM ECGs and 3 EquimetreTM ECGs were excluded due to artefact >10%. TelevetTM ECGs included significantly more artefact during exercise than EquimetreTM ECGs (5% vs. 0.25% P < .001). Arrhythmia analysis was performed on 38 horses’ paired ECGs. The kappa coefficient was excellent for arrhythmia detection (K = 0.97) and arrhythmia classification (K = 0.93).Main limitationsRelatively low numbers of horses with arrhythmias (n = 21) were included. The ECG recordings only provided one lead, making arrhythmia classification challenging in some cases.ConclusionsThe Equimetre device provides a reliable ECG for arrhythmia detection during exercise. This system may be useful clinically and for future large‐scale investigations into the occurrence and significance of exercising arrhythmias.
Do small‐scale fisheries have the capacity to provide food security to coastal populations?
Authors: Canty Steven W. J. , Deichmann Jessica L. 
Published: February 2022

AbstractWhilst total global fisheries landed catches declined from 1950 to 2016, small‐scale fisheries (SSFs) landed catches increased. Amongst SSFs landed catches, approximately 95% are consumed domestically. Taken together, these highlight the importance of the potential for SSFs to contribute to food security and well‐being of coastal populations, particularly in Developing Economy Countries (DECs). We used the Sea Around Us database to evaluate long‐term trends of marine SSFs landed catches in 85 DECs. We analyse whether yields from SSFs have the capacity to provide the coastal populations of DECs with a recommended annual intake (RAI) of 10.6 kg of fish per person, and how that capacity has changed over the period of 1960 to 2016. We show that landed catches of SSFs increased in the majority of DECs evaluated from 1950 to 2016. However, in 2016, over one‐third of SSFs in DECs assessed did not have the capacity to provide the RAI of fish to coastal communities, and 64% of all SSFs assessed are exhibiting significant declines in their capacity to fulfil this need. Regional trends in providing RAI were highly variable, putting the long‐term sustainability and capacity of SSFs to contribute meaningfully to food security in doubt. This study demonstrates that landed catches of SSFs alone are not a useful proxy for food security. Implementation of proven effective management practices, policies to improve accessibility and consumption patterns, and the prioritization of small‐scale wild‐caught fisheries are needed to ensure the food security of billions of people in coastal communities.
Separation of powers, opposition strength, and chief executives' strategy
Authors: Lee Don S. , Magyar Zsuzsanna B. 
Published: February 2022

AbstractOne of the main questions about presidential democracies is to what extent the legislature influences executive governance. However, less well‐known in this literature is the influence of opposition parties in policy‐making and government formation processes. We argue that, in multiparty presidential governments, more concentrated opposition forces in the legislature, as opposed to more fragmented, lead to higher government spending and greater chances of coalition formation. Facing more united opposition, presidents who are concerned about passing their agenda in the legislature are willing to pay the price to hold their ruling party or governing coalition together in tighter unity. We test this logic by analyzing data on government spending and cabinet formation in all multiparty presidential democracies in East and Southeast Asia and find strong support for it, controlling for several political and economic variables. Our analysis further shows that chief executives' electoral incentives strongly shape their budget spending and cabinet appointments.
Exploration of the molecular mechanisms underlying the antibiotic resistance of Helicobacter pylori: A whole‐genome sequencing‐based study in Southern China
Authors: Li Ying , Huang Zhixin , Shang Yanyan , Xie Xinqiang , Yang Runshi , Chen Huizhen , Wang Zhi , Xue Liang , Pang Rui , Zhang Jumei , Ding Yu , Chen Moutong , Wang Juan , Chen Jianhui , Wu Qingping 
Published: February 2022

AbstractBackgroundAlthough antimicrobial resistance (AMR) in Helicobacter pylori is a global threat to human health and the underlying molecular mechanisms have been explored previously, only a few of them are fully elucidated.Materials and MethodsIn the present study, we isolated 54 Helicobacter pylori strains from Southern China and assessed their susceptibility to five antibiotics using the agar dilution assay. Whole‐genome sequencing was performed to screen the AMR genotypes of the Helicobacter pylori isolates.ResultsOur study revealed a high prevalence of resistance to clarithromycin (CLR), levofloxacin (LVX), and metronidazole (MTZ) in the Chinese isolates, 55.56% of which showed multidrug‐resistant phenotypes. We screened for the 94 types of previously reported AMR mutations in 12 genes, but only a few of them were related to the AMR phenotype. Furthermore, we discovered four new mutations in the 23S rRNA gene and one mutation in infB related to CLR resistance. Another three mutations in gyrA and one in gyrB were closely correlated with the AMR pattern against LVX. We also demonstrated that the mutations R16C/H in rdxA, V56I in rpsU, and D54A in sodB might contribute to resistance to MTZ, which were previously reported in laboratory experiments but not found in clinical strains. We examined the concordance between the genotype and phenotype of AMR and identified several potential molecular biomarkers for predicting CLR and LVX resistance.ConclusionsOur study explored the molecular mechanisms underlying the antibiotic resistance of Helicobacter pylori isolates from Southern China. We propose further epidemiologic investigations in China.
Prevalence and predictors of bradyarrhythmias requiring permanent pacing in patients with Anderson–Fabry disease
Authors: Tassetti Luigi , Fumagalli Carlo , Argirò Alessia , Zampieri Mattia , Gori Martina , Verrillo Federica , Zocchi Chiara , Cappelli Francesco , Olivotto Iacopo 
Published: February 2022

AbstractIntroductionBradyarrhythmias are an established red flag for storage cardiac conditions including Anderson–Fabry disease (AFD). The prevalence of bradyarrhythmias requiring a pacemaker (PM) and their timing in AFD is unresolved.MethodsWe evaluated the prevalence and predictors of PM requirement in a large AFD cohort, investigating the occurrence of bradyarrhythmias as initial versus late manifestation. We retrospectively evaluated 82 consecutive AFD patients referred to our multidisciplinary referral center from 1994 to 2020 with a median follow‐up of 6.9 years, identifying those requiring pacing. Univariable analysis was performed to identify cardiac features associated with PM implantation.ResultsFive of 82 (6%) AFD patients required PM implantation (5/39, i.e., 13% of those with cardiac involvement), always in the context of advanced cardiomyopathy. In none, bradyarrhythmias were the presenting feature. Indications included sick sinus syndrome in three patients, advanced atrioventricular block in two patients. QRS prolongation during follow‐up strongly correlated with the onset of bradyarrhythmias.ConclusionSevere bradyarrhythmias are relatively frequent in patients with AFD cardiomyopathy, but do not represent a mode of presentation, occurring late in the disease course and always in the context of advanced cardiac involvement. Monitoring QRS variations over time may help to identify patients requiring pacing.
Early adversities accelerate epigenetic aging into adulthood: a 10‐year, within‐subject analysis
Authors: Copeland William E. , Shanahan Lilly , McGinnis Ellen W. , Aberg Karolina A. , van den Oord Edwin J.C.G. 
Published: February 2022

BackgroundLongitudinal studies are needed to clarify whether early adversities are associated with advanced methylation age or if they actually accelerate methylation aging. This study test whether different dimensions of childhood adversity accelerate biological aging from childhood to adulthood, and, if so, via which mechanisms.Methods381 participants provided one blood sample in childhood (average age 15.0; SD = 2.3) and another in young adulthood (average age 23.1; SD = 2.8). Participants and their parents provided a median of 6 childhood assessments (total = 1,950 childhood observations), reporting exposures to different types of adversity dimensions (i.e. threat, material deprivation, loss, unpredictability). The blood samples were assayed to estimate DNA methylation age in both childhood and adulthood and also change in methylation age across this period.ResultsCross‐sectional associations between the childhood adversity dimensions and childhood measures of methylation age were non‐significant. In contrast, multiple adversity dimensions were associated with accelerated within‐person change in methylation age from adolescence to young adulthood. These associations attenuated in model testing all dimensions at the same time. Accelerated aging increased with increasing number of childhood adversities: Individuals with highest number of adversities experienced 2+ additional years of methylation aging compared to those with no exposure to childhood adversities. The association between total childhood adversity exposure and accelerated aging was partially explained by childhood depressive symptoms, but not anxiety or behavioral symptoms.ConclusionsEarly adversities accelerate epigenetic aging long after they occur, in proportion to the total number of such experiences, and in a manner consistent with a shared effect that crosses multiple early dimensions of risk.
Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism?
Authors: Bomer Nils , Pavez‐Giani Mario G. , Grote Beverborg Niels , Cleland John G. F. , van Veldhuisen Dirk J. , van der Meer Peter 
Published: February 2022

AbstractHeart failure is a devastating clinical syndrome, but current therapies are unable to abolish the disease burden. New strategies to treat or prevent heart failure are urgently needed. Over the past decades, a clear relationship has been established between poor cardiac performance and metabolic perturbations, including deficits in substrate uptake and utilization, reduction in mitochondrial oxidative phosphorylation and excessive reactive oxygen species production. Together, these perturbations result in progressive depletion of cardiac adenosine triphosphate (ATP) and cardiac energy deprivation. Increasing the delivery of energy substrates (e.g., fatty acids, glucose, ketones) to the mitochondria will be worthless if the mitochondria are unable to turn these energy substrates into fuel. Micronutrients (including coenzyme Q10, zinc, copper, selenium and iron) are required to efficiently convert macronutrients to ATP. However, up to 50% of patients with heart failure are deficient in one or more micronutrients in cross‐sectional studies. Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation, moving our view of the failing myocardium away from an “an engine out of fuel” to “a defective engine on a path to self‐destruction.” This summary of evidence suggests that supplementation with micronutrients—preferably as a package rather than singly—might be a potential therapeutic strategy in the treatment of heart failure patients.