bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial
Authors: Dörr Jan , Bäcker-Koduah Priscilla , Wernecke Klaus-Dieter , Becker Elke , Hoffmann Frank , Faiss Jürgen , Brockmeier Bernd , Hoffmann Olaf , Anvari Kerstin , Wuerfel Jens , Piper Sophie K , Bellmann-Strobl Judith , Brandt Alexander U , Paul Friedemann 
Published: January 2020

Background Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing–remitting MS or clinically isolated syndrome. Methods The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b. Results Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis. Conclusions The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062
Measurement of the Posterior Tibial Slope Depends on Ethnicity, Sex, and Lower Limb Alignment: A Computed Tomography Analysis of 378 Healthy Participants
Authors: Pangaud Corentin , Laumonerie Pierre , Dagneaux Louis , LiArno Sally , Wellings Peter , Faizan Ahmad , Sharma Akash , Ollivier Matthieu 
Published: January 2020

Background: There is no general consensus on the normal and pathological values for the posterior tibial slope (PTS). Purpose/Hypothesis: The primary aim of this study was to determine standard values for the PTS in healthy participants using 3-dimensional (3D) computed tomography (CT). A secondary aim was to determine the effect of demographic factors and coronal-plane lower limb alignment on the PTS measurement. The hypothesis was that the PTS would be significantly influenced by demographic factors and coronal-plane lower limb alignment. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A CT-based modeling and analytics system was used to examine and measure lower limb alignment and the PTS in 378 patients (193 male and 185 female; mean age, 58.3 ± 16.4 years [range, 18-92 years]; mean body mass index, 25.0 ± 4.4 kg/m2). The lateral, medial, and global PTS were measured for each patient. All measurements were constructed using algorithm-calculated landmarks, resulting in reproducible and consistent constructs for each specimen. The results were then evaluated based on ethnicity, sex, and hip-knee-ankle (HKA) angle. Results: The study population comprised 219 white and 159 Asian participants. The mean global, medial, and lateral PTS were 6.3° (range, –5.5° to 14.7°; 1% with ≥12°), 6.2° (range, –4.1° to 17.2°; 3% with ≥12°), and 5.3° (range, –4.7° to 16.2°; 2% with ≥12°), respectively. The lateral (Δ = –1.0° [95% CI, 0.6°-1.6°]; P < .0001) and global (Δ = –0.5° [95% CI, 0.0°-0.8°]; P = .0332) PTS were smaller in the female subpopulation. The global PTS was greater (Δ = 1.9° [95% CI, 1.5°-2.3°]; P < .0001) in the Asian subpopulation. The mean HKA angle was 179.6° (range, 170°-190°). The HKA angle was significantly correlated with the medial and global PTS. Specimens with a genu varum knee exhibited a significantly greater global (Δ = 1.2° [95% CI, 0.8°-1.7°]; P < .0001) and medial (Δ = 1.9° [95% CI, 1.3°-2.5°]; P < .0001) PTS. Conclusion: The present study gives a benchmark for the physiological values of the PTS in a healthy population and highlights several factors influencing the PTS, such as ethnicity, sex, and alignment. Anatomic variants with a PTS ≥12° were very uncommon (≤3%) in our Asian and white groups and thus could be considered as pathological. The PTS is a crucial anatomic factor for anterior cruciate ligament injuries and reconstruction. A general consensus is lacking regarding the cutoff for abnormal values, thus guiding standard of care. This study investigated the dispersion of global, medial, and lateral posterior plateau tibial angles in a large population representing a range of demographic diversity.
MPL mutations in essential thrombocythemia uncover a common path of activation with eltrombopag dependent on W491
Authors: Levy Gabriel , Carillo Serge , Papoular Benjamin , Cassinat Bruno , Zini Jean-Marc , Leroy Emilie , Varghese Leila N. , Chachoua Ilyas , Defour Jean-Philippe , Smith Steven O. , Constantinescu Stefan N. 
Published: January 2020

Abstract
Mutations in the MPL gene encoding the human thrombopoietin receptor (TpoR) drive sporadic and familial essential thrombocythemias (ETs). We identified 2 ET patients harboring double mutations in cis in MPL, namely, L498W-H499C and H499Y-S505N. Using biochemical and signaling assays along with partial saturation mutagenesis, we showed that L498W is an activating mutation potentiated by H499C and that H499C and H499Y enhance the activity of the canonical S505N mutation. L498W and H499C can activate a truncated TpoR mutant, which lacks the extracellular domain, indicating these mutations act on the transmembrane (TM) cytosolic domain. Using a protein complementation assay, we showed that L498W and H499C strongly drive dimerization of TpoR. Activation by tryptophan substitution is exquisitely specific for position 498. Using structure-guided mutagenesis, we identified upstream amino acid W491 as a key residue required for activation by L498W or canonical activating mutations such as S505N and W515K, as well as by eltrombopag. Structural data point to a common dimerization and activation path for TpoR via its TM domain that is shared between the small-molecule agonist eltrombopag and canonical and novel activating TpoR mutations that all depend on W491, a potentially accessible extracellular residue that could become a target for therapeutic intervention.
How I treat obese patients with oral anticoagulants
Authors: Wang Tzu-Fei , Carrier Marc 
Published: January 2020

AbstractObesity has become a major threat to health worldwide. The prevalence of obesity is rapidly increasing, so much so that the World Health Organization has declared obesity as a global epidemic. Obesity is associated with multiple health problems, including venous thromboembolism and atrial fibrillation, both of which are treated with anticoagulation. However, obesity and treatments for obesity such as bariatric surgery can influence absorption, excretion, pharmacokinetics, and pharmacodynamics of various anticoagulants. This results in uncertainty regarding the best antithrombotic strategies in this population, particularly in the morbidly obese. In the recent years, several studies have attempted to investigate anticoagulation use in this population and provided more insight. Herein, we present 4 cases of anticoagulant use in the obese to illustrate the common challenges faced by clinicians and discuss our approach. Whenever possible, we provide a review of the literature and base our recommendations on the best available evidence.
Thrombin activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease
Authors: Sparkenbaugh Erica M. , Chen Chunsheng , Brzoska Tomasz , Nguyen Julia , Wang Shaobin , Vercellotti Gregory M. , Key Nigel S. , Sundd Prithu , Belcher John D. , Pawlinski Rafal 
Published: January 2020

Abstract
Vaso-occlusive crisis (VOC) is the primary cause of morbidity and hospitalization in sickle cell disease (SCD); however, only 4 therapies (hydroxyurea, l-glutamine, crizanlizumab, and voxeletor) are currently approved in SCD. These agents limit the duration, severity, and frequency of crises. Activation of coagulation is a hallmark of SCD. Studies in animal models of SCD have shown that coagulation contributes to the chronic inflammation and end-organ damage associated with the disease; however, it is unknown whether coagulation directly contributes to the microvascular stasis that causes VOC. Herein, we demonstrate that inhibition of tissue factor (TF) and the downstream coagulation proteases factor Xa and thrombin significantly attenuates heme-induced microvascular stasis in mouse models of VOC. Pharmacologic inhibition of the principal thrombin receptor, protease activated receptor-1 (PAR-1), as well as deficiency of PAR-1 in all nonhematopoietic cells, also reduces stasis in sickle mice. PAR-1 deficiency was associated with reduced endothelial von Willebrand factor expression, which has been shown to mediate microvascular stasis. In addition, TF inhibition reduces lung vaso-occlusion in sickle mice mediated by arteriolar neutrophil-platelet microemboli. In sum, these results suggest that prophylactic anticoagulation might attenuate the incidence of VOC.
N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm
Authors: Craver Brianna M. , Ramanathan Gajalakshmi , Hoang Summer , Chang Xinyue , Mendez Luque Laura F. , Brooks Stefan , Lai Hew Yeng , Fleischman Angela G. 
Published: January 2020

Abstract
Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN. Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute pulmonary thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice. Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN.
Combined effects of ocean acidification and hypoxia on the early development of the thick shell mussel Mytilus coruscus
Authors: Wang Xinghuo , Shang Yueyong , Kong Hui , Hu Menghong , Yang Jinlong , Deng Yuewen , Wang Youji 
Published: January 2020

AbstractOcean acidification has become serious, and seawater hypoxia has become evident in acidified waters. The combination of such stressors may have interactive effects on the fitness of marine organisms. In order to investigate the interactive effects of seawater acidification and hypoxia on the early development of marine bivalves, the eggs and sperm of the thick shell musselMytilus coruscuswere exposed to combined treatments of pH (8.1, 7.7, 7.3) and dissolved oxygen (2, 6 mg/L) for 96 h culture observation to investigate the interactive effects of seawater acidification and hypoxia on the early development of marine bivalves. Results showed that acidification and hypoxia had significant negative effects on various parameters of the early development of the thick shell mussel. However, hypoxia had no effect on fertilization rate. Significant interactions between acidification and hypoxia were observed during the experiment. Short-term exposure negatively influenced the early development of the thick shell mussel but did not affect its survival. The effects of long-term exposure to these two environmental stresses need further study.
The radiological assessment, hazard evaluation, and spatial distribution for a hypothetical nuclear power plant accident at Baiji potential site
Authors: Mohammed Saeed Ismael Mohammed , Saleh Muneer Aziz Mohammed , Hashim Suhairul , Hama Younis Mohammed Salih , Hamza Khaidzir , Al-Shatri Shwan Hassan 
Published: January 2020

Abstract
Background
The safety assessment in site selection for a new nuclear power plant is an essential issue for human health. It could be improved by predicting the consequences for a hypothetical accident. This paper is contextual with the nuclear safety regarding the risk upon human health from the hazard constituted by the emission of radioactive material due to a hypothetical nuclear power plant accident. HYSPLIT model used and configured based on terrestrial and meteorological conditions for this purpose.

Results
It presents an analysis of the time-series and spatial distribution for dispersed radioactive contaminants from a hypothetical accident at Baiji potential site. This is based on the geological and meteorological specifications of the potential site. Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model configured to simulate the atmospheric dispersion of fission emissions, then assesses the public health consequences of a hypothetical nuclear accident. Results indicate that the total individual dose intake by the population living around the potential site from the hypothetical accident exceeded 1 Sv, greater than the allowed dose limits by International Commission on Radiological Protection (ICRP). The probability of cancer incidence at regions on directions of southeast to northeast along 30 km from the potential site was high (0.0378 to 0.00131) risk/person. However, the areas that laid on the west and south-west of the site recorded higher levels of influence compared to regions on other directions. Also, the reduction of exposure dose with the distance from the site presented. The north-direction regions from the Baiji site recorded a rapid reduction of exposure dose to become zero at 40 km distance.

Conclusions
Finally, to minimize the radiological impacts on population, emergency procedures are required at the regions that laid on the west and south-west of the site. These countermeasure remedy actions should include evacuation, sheltering, ban the sale of local agriculture productions, and long-range resettlement of the population. Since the plume of radioactive contaminants did not arrive at the regions on east and northeast, 40 km away from Baiji site, these areas could be categorized as a support zone.
Towards a synthesis of the Caribbean biogeography of terrestrial arthropods
Authors: Crews Sarah C. , Esposito Lauren A. 
Published: January 2020

AbstractBackgroundThe immense geologic and ecological complexity of the Caribbean has created a natural laboratory for interpreting when and how organisms disperse through time and space. However, competing hypotheses compounded with this complexity have resulted in a lack of unifying principles of biogeography for the region. Though new data concerning the timing of geologic events and dispersal events are emerging, powerful new analytical tools now allow for explicit hypothesis testing. Arthropods, with varying dispersal ability and high levels of endemism in the Caribbean, are an important, albeit understudied, biogeographic model system. Herein, we include a comprehensive analysis of every publicly available genetic dataset (at the time of writing) of terrestrial Caribbean arthropod groups using a statistically robust pipeline to explicitly test the current extent of biogeographic hypotheses for the region.ResultsOur findings indicate several important biogeographic generalizations for the region: the South American continent is the predominant origin of Caribbean arthropod fauna; GAARlandia played a role for some taxa in aiding dispersal from South America to the Greater Antilles; founder event dispersal explains the majority of dispersal events by terrestrial arthropods, and distance between landmasses is important for dispersal; most dispersal events occurred via island hopping; there is evidence of ‘reverse’ dispersal from islands to the mainland; dispersal across the present-day Isthmus of Panama generally occurred prior to 3 mya; the Greater Antilles harbor more lineage diversity than the Lesser Antilles, and the larger Greater Antilles typically have greater lineage diversity than the smaller islands; basal Caribbean taxa are primarily distributed in the Greater Antilles, the basal-most being from Cuba, and derived taxa are mostly distributed in the Lesser Antilles; Jamaican taxa are usually endemic and monophyletic.ConclusionsGiven the diversity and deep history of terrestrial arthropods, incongruence of biogeographic patterns is expected, but focusing on both similarities and differences among divergent taxa with disparate life histories emphasizes the importance of particular qualities responsible for resulting diversification patterns. Furthermore, this study provides an analytical toolkit that can be used to guide researchers interested in answering questions pertaining to Caribbean biogeography using explicit hypothesis testing.
Does manual therapy affect functional and biomechanical outcomes of a sit-to-stand task in a population with low back pain? A preliminary analysis
Authors: Carpino Giancarlo , Tran Steven , Currie Stuart , Enebo Brian , Davidson Bradley S. , Howarth Samuel J. 
Published: January 2020

Abstract
Introduction
Manual therapy (MT) hypothetically affects discrepant neuromuscular control and movement observed in populations with low back pain (LBP). Previous studies have demonstrated the limited influence of MT on movement, predominately during range of motion (ROM) testing. It remains unclear if MT affects neuromuscular control in mobility-based activities of daily living (ADLs). The sit-to-stand (STS) task represents a commonly-performed ADL that is used in a variety of clinical settings to assess functional and biomechanical performance.

Objective
To determine whether MT affects functional performance and biomechanical performance during a STS task in a population with LBP.

Methods
Kinematic data were recorded from the pelvis and thorax of participants with LBP, using an optoelectronic motion capture system as they performed a STS task before and after MT from November 2011 to August 2014. MT for each participant consisted of two high-velocity low-amplitude spinal manipulations, as well as two grade IV mobilizations of the lumbar spine and pelvis targeted toward the third lumbar vertebra and sacroiliac joint in a side-lying position; the order of these treatments was randomized. Pelvis and thorax kinematic data were used to derive the time-varying lumbar angle in the sagittal plane for each STS trial. The difference between the maximum and minimum lumbar angles during the STS trial determined the sagittal ROM that was used as the biomechanical outcome. Time to complete each STS trial was used as a functional measure of performance. Pre-MT and post-MT values for the lumbar sagittal ROM and time to completion were statistically analysed using paired samples t-tests.

Results
Data were obtained from 40 participants with 35 useful datasets (NRS = 3.3 ± 1.2; 32.4 ± 9.8 years; 16 females, 19 males). After MT, lumbar sagittal ROM increased by 2.7 ± 5.5 degrees (p = 0.007). Time to complete the STS test decreased by 0.4 ± 0.4 s (p < 0.001).

Discussion
These findings provide preliminary evidence that MT might influence the biomechanical and functional performance of an STS task in populations with LBP. The MT intervention in this study involved a combination of spinal manipulations and mobilizations. Future work will expand upon these data as a basis for targeted investigations on the effects of either spinal manipulation and mobilization on neuromuscular control and movement in populations with LBP.
Scurvy may occur even in children with no underlying risk factors: a case report
Authors: Gallizzi Romina , Valenzise Mariella , Passanisi Stefano , Pajno Giovanni Battista , De Luca Filippo , Zirilli Giuseppina 
Published: January 2020

Abstract
Background
Since ancient times, scurvy has been considered one of the most fearsome nutritional deficiency diseases. In modern developed countries, this condition has become very rare and is only occasionally encountered, especially in the pediatric population. Underlying medical conditions, such as neuropsychiatric disorders, anorexia nervosa, celiac disease, Crohn disease, hemodialysis, and severe allergies to food products may enhance the risk of developing scurvy.

Case presentation
We report the case of an otherwise healthy 3-year-old white boy who developed scurvy due to a selective restrictive diet derived from his refusal to try new food. He presented to our clinic with asthenia and refusal to walk. During hospitalization he developed severe anemia and hematochezia. A diagnosis of scurvy was assessed on the basis of nutritional history, clinical features, radiographic findings, and laboratory findings. Supplementation of ascorbic acid enabled a prompt resolution of symptoms.

Conclusions
Scurvy is caused by vitamin C deficiency. Cutaneous bleeding, mucosal bleeding, and anemia represent typical manifestations of the disease. These symptoms are directly connected to ascorbic acid involvement in collagen biosynthesis. Some radiographic findings can be useful for the diagnosis. Treatment aims to normalize serum levels of vitamin C in order to counteract the deprivation symptoms. The present case report demonstrates that scurvy may sporadically occur in pediatric patients, even in individuals with no predisposing medical conditions and/or potential risk factors.