bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein B-100-mediated motor neuron degeneration in sporadic amyotrophic lateral sclerosis
Authors: Wong Jamie K , Roselle Anna K , Shue Taylor M , Shimshak Serena J E , Beaty Joseph M , Celestin Nadia M , Gao Ivy , Griffin Rose P , Cudkowicz Merit E , Sadiq Saud A 
Published: August 2022

Abstract
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by motor neuron degeneration. Approximately 90% of cases occur sporadically with no known cause while 10% are familial cases arising from known inherited genetic mutations. In vivo studies have predominantly utilized transgenic models harbouring amyotrophic lateral sclerosis-associated gene mutations, which have not hitherto elucidated mechanisms underlying motor neuron death or identified therapeutic targets specific to sporadic amyotrophic lateral sclerosis. Here we provide evidence demonstrating pathogenic differences in CSF from patients with sporadic amyotrophic lateral sclerosis and familial amyotrophic lateral sclerosis patients with mutations in SOD1, C9orf72 and TARDBP. Using a novel CSF-mediated animal model, we show that intrathecal delivery of sporadic amyotrophic lateral sclerosis patient-derived CSF into the cervical subarachnoid space in adult wild-type mice induces permanent motor disability which is associated with hallmark pathological features of amyotrophic lateral sclerosis including motor neuron loss, cytoplasmic TDP-43 translocation, reactive astrogliosis and microglial activation. Motor impairments are not induced by SOD1, C9orf72 or TARDBP CSF, although a moderate degree of histopathological change occurs in C9orf72 and TARDBP CSF-injected mice. By conducting a series of CSF filtration studies and global proteomic analysis of CSF, we identified apolipoprotein B-100 in sporadic amyotrophic lateral sclerosis CSF as the putative agent responsible for inducing motor disability, motor neuron degeneration and pathological translocation of TDP-43. Apolipoprotein B-100 alone is sufficient to recapitulate clinical and pathological outcomes in vivo and induce death of human induced pluripotent stem cell-derived motor neurons in vitro. Targeted removal of apolipoprotein B-100 from sporadic amyotrophic lateral sclerosis CSF via filtration or immunodepletion successfully attenuated the neurotoxic capacity of sporadic amyotrophic lateral sclerosis CSF to induce motor disability, motor neuron death, and TDP-43 translocation. This study presents apolipoprotein B-100 as a novel therapeutic target specific for the predominant sporadic form of amyotrophic lateral sclerosis and establishes proof-of-concept to support CSF pheresis as a therapeutic strategy for mitigating neurotoxicity in sporadic amyotrophic lateral sclerosis.
Brain atrophy in middle age using magnetic resonance imaging scans from Japan’s health screening programme
Authors: Mori Susumu , Onda Kengo , Fujita Shohei , Suzuki Toshiaki , Ikeda Mikimasa , Zay Yar Myint Khin , Hikage Jun , Abe Osamu , Tomimoto Hidekazu , Oishi Kenichi , Taguchi Junichi 
Published: August 2022

Abstract
Although health screening plays a key role in the management of chronic diseases associated with lifestyle choices, brain health is not generally monitored, remaining a black box prior to the manifestation of clinical symptoms. Japan is unique in this regard, as brain MRI scans have been widely performed for more than two decades as part of Brain Dock, a comprehensive health screening programme. A vast number of stored images (well over a million) of longitudinal scans and extensive health data are available, offering a valuable resource for investigating the prevalence of various types of brain-related health conditions occurring throughout adulthood.
In this paper, we report on the findings of our preliminary quantitative analysis of T1-weighted MRIs of the brain obtained from 13 980 subjects from three participating sites during the period 2015–19. We applied automated segmentation analysis and observed age-dependent volume loss of various brain structures. We subsequently investigated the effects of scan protocols and the feasibility of calibration for pooling the data. Last, the degree of brain atrophy was correlated with four known risk factors of dementia; blood glucose level, hypertension, obesity, and alcohol consumption.
In this initial analysis, we identified brain ventricular volume as an effective marker of age-dependent brain atrophy, being highly sensitive to ageing and evidencing strong robustness against protocol variability. We established the normal range of ventricular volumes at each age, which is an essential first step for establishing criteria used to interpret data obtained for individual participants. We identified a subgroup of individuals at midlife with ventricles that substantially exceeded the average size. The correlation studies revealed that all four risk factors were associated with greater ventricular volumes at midlife, some of which reached highly significant sizes.
This study demonstrates the feasibility of conducting a large-scale quantitative analysis of existing Brain Dock data in Japan. It will importantly guide future efforts to investigate the prevalence of large ventricles at midlife and the potential reduction of this prevalence, and hence of dementia risk, through lifestyle changes.
SGLT-2 inhibition by empagliflozin has no effect on experimental arterial thrombosis in a murine model of low-grade inflammation
Authors: Liberale Luca , Kraler Simon , Puspitasari Yustina M , Bonetti Nicole R , Akhmedov Alexander , Ministrini Stefano , Montecucco Fabrizio , Marx Nikolaus , Lehrke Michael , Hartmann Niels-Ulrik K , Beer Jürg H , Wenzl Florian A , Paneni Francesco , Lüscher Thomas F , Camici Giovanni G 
Published: August 2022

AbstractAimsLow-grade inflammation couples dysmetabolic states to insulin resistance and atherosclerotic cardiovascular (CV) disease (ASCVD). Selective sodium–glucose co-transporter 2 (SGLT-2) inhibition by empagliflozin improves clinical outcomes in patients with ASCVD independently of its glucose lowering effects. Yet, its mechanism of action remains largely undetermined. Here, we aimed to test whether empagliflozin affects arterial thrombus formation in baseline (BSL) conditions or low-grade inflammatory states, a systemic milieu shared among patients with ASCVD.Methods and resultsSixteen-week-old C57BL/6 mice were randomly assigned to acute administration of empagliflozin (25 mg/kg body weight) or vehicle, of which a subgroup was pre-treated biweekly over 4 weeks with super-low-dose lipopolysaccharide (LPS; 5 ng/kg body weight), before carotid thrombosis was induced by photochemical injury. The between-group difference in Doppler-flow probe detected time-to-occlusion remained within the predefined equivalence margin (Δ = |10.50|), irrespective of low-grade inflammation (95% confidence interval, –9.82 to 8.85 and –9.20 to 9.69), while glucose dropped by 1.64 and 4.84 mmoL/L, respectively. Ex vivo platelet aggregometry suggested similar activation status, corroborated by unchanged circulating platelet-factor 4 plasma levels. In concert, carotid PAI-1 expression and tissue factor (TF) activity remained unaltered upon SGLT-2 inhibition, and no difference in plasma D-dimer levels was detected, suggesting comparable coagulation cascade activation and fibrinolytic activity. In human aortic endothelial cells pre-treated with LPS, empagliflozin neither changed TF activity nor PAI-1 expression. Accordingly, among patients with established ASCVD or at high CV risk randomized to a daily dose of 10 mg empagliflozin signatures of thrombotic (i.e. TF) and fibrinolytic activity (i.e. PAI-1) remained unchanged, while plasma glucose declined significantly during 3 months of follow-up.ConclusionSGLT-2 inhibition by empagliflozin does not impact experimental arterial thrombus formation, neither under BSL conditions nor during sustained low-grade inflammation, and has no impact on proxies of thrombotic/fibrinolytic activity in patients with ASCVD. The beneficial pleiotropic effects of empagliflozin are likely independent of pathways mediating arterial thrombosis.
Prognostic value of right ventricular remodelling in patients undergoing concomitant aortic and mitral valve surgery
Authors: Tse Yi-Kei , Li Hang-Long , Yu Si-Yeung , Wu Mei-Zhen , Ren Qing-Wen , Huang Jiayi , Tse Hung-Fat , Bax Jeroen J , Yiu Kai-Hang 
Published: August 2022

Abstract

Aims
Long-term risk stratification and surgical timing remain suboptimal in concomitant aortic and mitral (double) valve surgery. This study sought to examine the predictors, changes, and prognostic implications of right ventricular (RV) remodelling in patients undergoing double-valve surgery.

Methods and results
In 152 patients undergoing double-valve surgery, four RV remodelling patterns were characterized using transthoracic echocardiography: normal RV size and systolic function (Pattern 1); dilated RV (tricuspid annulus diameter &gt;35 mm) with normal systolic function (Pattern 2); normal RV size with systolic dysfunction (percentage RV fractional area change &lt;35%; Pattern 3); and dilated RV with systolic dysfunction (Pattern 4). The primary endpoint was the composite of heart failure hospitalization and all-cause mortality. Patterns 1, 2, 3, and 4 RV remodelling were present in 41, 20, 23, and 16% of patients, respectively. Patients with Stage 4 RV remodelling had worse renal function, higher EuroSCORE II, and impaired left ventricular ejection fraction. During a 3.7-year median follow up, 45 adverse events occurred. Patterns 3 and 4 RV remodelling were associated with significantly higher adverse event rates compared with Pattern 1 (37 and 75% vs. 11%, P &lt; 0.01) and had incremental prognostic value when added to clinical parameters and EuroSCORE II (χ2 increased from 30 to 66, P &lt; 0.01). At 1 year after surgery (n = 100), Patterns 3 and 4 RV remodelling had a higher risk of adverse events compared with Pattern 1.

Conclusion
Right ventricular remodelling was strongly related to adverse outcomes and deserves consideration as part of the risk and decision-making algorithms in double-valve surgery.
Functional performance of 8 small surgical aortic valve bioprostheses: an in vitro study
Authors: Sadat Najla , Scharfschwerdt Michael , Schaller Tim , Aboud Anas , Saisho Hiroyuki , Ensminger Stephan , Fujita Buntaro 
Published: August 2022

Abstract

OBJECTIVES
Selection of a surgical aortic valve (SAV) bioprosthesis model for the treatment of aortic valve disease remains controversial. The aim of this study was to characterize the functional performance of 8 SAV models in a standardized in vitro setting.

METHODS
The hydrodynamic performance of 8 SAVs with labelled size 21 mm (Avalus™, Hancock® II, Mosaic® Ultra™, Perimount®, Perimount® Magna Ease, Epic™ Supra, Trifecta™ GT; Freestyle®), was investigated in a pulse duplicator. Transvalvular pressure gradients and effective orifice area (EOA) were recorded. The geometrical orifice area and physical dimensions of the valves were determined, and new functional dimensions were introduced.

RESULTS
Mean pressure gradient (MPG) and EOA differed significantly between the analysed SAVs. The Epic presented with the lowest EOA and highest MPG, while the Trifecta showed the highest EOA and the lowest MPG. We introduce a useful way to determine the minimal internal diameter and a new measure termed ‘relative orifice area’ to characterize a valve’s performance.

CONCLUSIONS
SAVs showed significant differences in their hydrodynamic performance despite the same label size. This finding was related to the construction of the valves. We introduce a new measure that characterizes the functional performance of a valve model and size for the treatment of an aortic annulus of a specific size. Our data emphasize that SAV selection should carefully be done using an individual patient approach and that future research is necessary to improve the current generation of SAVs.
Socioeconomic impacts on Andean adolescents’ growth
Authors: Burris Mecca E , Caceres Esperanza , Chester Emily M , Hicks Kathryn A , McDade Thomas W , Sikkink Lynn , Spielvogel Hilde , Thornburg Jonathan , Vitzthum Virginia J 
Published: August 2022

AbstractBackground/ObjectivesWe evaluated potential socioeconomic contributors to variation in Andean adolescents’ growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references.MethodsAnthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0–14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno).ResultsFemale Alteños’ growth was positively associated with household and maternal income indices. Alteños’ height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents’ height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively.Conclusions/ImplicationsBoth peri-urban conditions and temporal trends contributed to gains in Alteños’ growth. Rural out-migration can alleviate migrants’ poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.
Coronary microvascular dysfunction is an independent predictor of developing cancer in patients with non-obstructive coronary artery disease
Authors: Rajai Nazanin , Ahmad Ali , Toya Takumi , Sara Jaskanwal D , Herrmann Joerg , Lerman Lilach O , Lerman Amir 
Published: August 2022

Abstract

Aims
Cardiovascular disease and cancer share common pathogenesis and risk factors. Coronary microvascular dysfunction (CMD), reflecting impaired coronary microvascular dilation in response to stress, is related to a higher risk of major cardiovascular events; however, its association with cancer has not been explored.

Methods and results
A retrospective study on 1042 patients with non-obstructive coronary artery diseases (NOCADs) was performed. Data regarding demographic, clinical history, diagnostic coronary reactivity test, and cancer occurrence were collected. Coronary microvascular dysfunction was defined as coronary flow reserve (the ratio of hyperaemic blood flow to resting blood flow) ≤2.5. Thirty-four per cent had CMD (67.4% female and the average age was 52.4 ± 12.2 years). Of 917 patients with no history of cancer, 15.5% developed cancer during follow-up [median of 9 (4, 16) years]. Kaplan–Meier analysis showed that CMD patients had lower cancer-free survival compared with those without CMD (log-rank P = 0.005). Cox proportional hazard analyses showed that after adjusting for age, sex, hypertension, diabetes, smoking, and glomerular filtration rate, CMD is independently associated with cancer [hazard ratio, 1.4; 95% confidence interval (CI), 1.09–2.04; P = 0.04]. The rate of major adverse cardiovascular events (MACE) was significantly higher in CMD patients compared with that in non-CMD patients who had a previous history of cancer [odds ratio (OR), 2.5; 95% CI, 1–6.2; P = 0.04] and those with no history of cancer (OR, 1.4; 95% CI, 1.01–1.9; P = 0.044).

Conclusion
Coronary microvascular dysfunction is associated with cancer incidence in patients presenting with NOCADs. This study emphasizes follow-up in patients with CMD to evaluate the risk of MACE as well as potential malignant diseases.
The Time-Varying Link of Public Timber REITs with Private Timberland, Real Estate, and Financial Assets
Authors: Baral Srijana , Mei Bin 
Published: August 2022

Abstract
We examined the relationship between public timber real estate investment trusts (REIT), private timberland, real estate, and financial asset returns using a multi-factor model and investigated the time-varying volatility of timber REITs under the state space framework. We first orthogonalized explanatory variables to obtain pure factors. Then we decomposed REIT volatility into S&P500, private-equity timberland, real estate, bond, and idiosyncratic risk components. Results reveal that timber REITs are positively sensitive to large-cap stocks and bonds. Volatility contributions of the large-cap stock factor are consistent and high whereas those of idiosyncratic risk factors decline over time. Private-equity timberland, real estate, and bonds exhibit negligible contribution to the volatility of timber REITs. We conclude that timber REIT characteristics change with time and the timber REIT market is not mature. Thus, the results contribute to our understanding of the risk and return features of public-equity timberland investments.
The cAMP-PKA pathway regulates prey sensing and trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora
Authors: Chen Sheng-An , Lin Hung-Che , Hsueh Yen-Ping 
Published: August 2022

Abstract
Sensing environmental factors and responding swiftly to them is essential for all living organisms. For instance, predators must act rapidly once prey is sensed. Nematode-trapping fungi (NTF) are predators that use “traps” differentiated from vegetative hyphae to capture, kill, and consume nematodes. These traps undergo drastic and rapid morphological changes upon nematode induction. Multiple signaling hubs have been shown to regulate this remarkable process. Here, we demonstrate that the conserved cAMP-PKA signaling pathway exerts a crucial role in trap morphogenesis of the nematode-trapping fungi Arthrobotrys oligospora. A gene deletion mutant of the PKA catalytic subunit TPK2 proved insensitive toward nematode presence. Moreover, we show that the G protein alpha subunit GPA2 acts upstream of adenylate cyclase, with GPA2 deletion resulting in substantially reduced trap formation, whereas exogenous provision of cAMP rescued the prey-sensing and trap morphogenesis defects of a gpa2 mutant. Thus, we show that cAMP production triggered by G protein signaling and downstream PKA activity are vital for prey-sensing and trap development in A. oligospora, demonstrating that this highly conserved signaling pathway is critical for nematode-trapping fungi and nematode predator–prey interactions.
Pericardioperitoneal shunt for the treatment of refractory non-malignant pericardial effusion
Authors: Masaru Ishida , Tetsuya Kajiyama , Hisashi Satoh 
Published: August 2022

Abstract
We report the case of a 74-year-old man treated for refractory non-malignant pericardial effusion using a pericardioperitoneal shunt. After the failure of conventional pericardiocentesis, a pericardioperitoneal shunt using a Denver shunt was inserted to drain the pericardial effusion into the peritoneal cavity. At 3-year follow-up, the effusion was well controlled and the shunt remained patent.
Comparison of Fibrinogen Concentrations Determined by the Clauss Method with Prothrombin-Derived Measurements on an Automated Coagulometer
Authors: Guven Berrak , Can Murat , Tekin Abdulkadir 
Published: August 2022

Abstract

Background
This research aims to compare fibrinogen results, obtained from the Clauss and PT-derived method on the Cobas t511 analyzer, in patients with specific categories of disease. A second aim was to determine the reference range for these 2 methods.

Methods
We retrospectively compared fibrinogen concentrations of 914 patients obtained by the Clauss and PT-derived methods on the Cobas t511 coagulation analyzer from the laboratory information system. Fibrinogen data was segregated into a healthy outpatient population and those populations with possible fibrinogen abnormalities including pregnancy, chronic illness, liver disease, heart and vascular diseases, and clinical suspicion of COVID-19. All data were analyzed using Passing–Bablok regression and Bland–Altman analysis. Reference ranges were determined from fibrinogen results of the healthy outpatient population who presented for a clinic check-up.

Results
All fibrinogen results were grouped and compared according to fibrinogen values (low, normal, and high), international normalized ratio (INR) values (&lt;1.2, 1.2–2.0, and &gt;2.0), and diagnosis. There were statistically significant positive correlations in all groups (P &lt; 0.05), except for low fibrinogen values (P = 0.96). Results with INR value &lt;1.2 had the highest correlation between 2 methods.

Conclusion
The PT-derived method can be used alone in the Cobas t511 analyzer, especially in patients with an INR &lt;1.2. Reported new reference ranges of the PT-derived method could help to determine and compare the clinical significance of fibrinogen methods. Further studies must be focused on the conditions in which PT-derived fibrinogen results should be directed to the Clauss test.
Differential RNA aptamer affinity profiling on plasma as a potential diagnostic tool for bladder cancer
Authors: Fjelstrup Søren , Dupont Daniel M , Bus Claus , Enghild Jan J , Jensen Jørgen B , Birkenkamp-Demtröder Karin , Dyrskjøt Lars , Kjems Jørgen 
Published: August 2022

Abstract
The molecular composition of blood is a signature of human health, reflected in the thousands of blood biomarkers known for human diseases. However, establishing robust disease markers is challenging due to the diversity of individual samples. New sequencing methods have simplified biomarker discovery for circulating DNA and RNA while protein profiling is still laborious and costly. To harness the power of high-throughput sequencing to profile the protein content of a biological sample, we developed a method termed APTASHAPE that uses oligonucleotide aptamers to recognize proteins in complex biofluids. We selected a large pool of 2′Fluoro protected RNA sequences to recognize proteins in human plasma and identified a set of 33 cancer-specific aptamers. Differential enrichment of these aptamers after selection against 1 μl of plasma from individual patients allowed us to differentiate between healthy controls and bladder cancer-diagnosed patients (91% accuracy) and between early non-invasive tumors and late stage tumors (83% accuracy). Affinity purification and mass spectrometry of proteins bound to the predictive aptamers showed the main target proteins to be C4b-binding protein, Complement C3, Fibrinogen, Complement factor H and IgG. The APTASHAPE method thus provides a general, automated and highly sensitive platform for discovering potential new disease biomarkers.
Equity Issuance Methods and Dilution
Authors: Burkart Mike , Zhong Hongda 
Published: August 2022

Abstract
We analyze rights and public offerings when informed shareholders strategically choose to subscribe. Absent wealth constraints, rights offerings achieve the full information outcome and dominate public offerings. When some shareholders are wealth constrained, rights offerings lead to more dilution of their stakes and lower payoffs, despite the income from selling these rights. In both rights and public offerings, there is a trade-off between investment efficiency and wealth transfers among shareholders. When firms can choose the flotation method, either all firms choose the same offer method or high and low types opt for rights offerings, while intermediate types select public offerings. (JEL G32)