bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palmdelphin Regulates Nuclear Resilience to Mechanical Stress in the Endothelium
Authors: Sáinz-Jaspeado Miguel , Smith Ross O. , Plunde Oscar , Pawelzik Sven-Christian , Jin Yi , Nordling Sofia , Ding Yindi , Aspenström Pontus , Hedlund Marie , Bastianello Giulia , Ascione Flora , Li Qingsen , Demir Cansaran Saygili , Fernando Dinesh , Daniel Geoffrey , Franco-Cereceda Anders , Kroon Jeffrey , Foiani Marco , Petrova Tatiana V. , Kilimann Manfred W. , Bäck Magnus , Claesson-Welsh Lena 
Published: October 2021

Background:

PALMD (palmdelphin) belongs to the family of paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms in the
PALMD
locus that result in reduced expression are strong risk factors for development of calcific aortic valve stenosis and predict severity of the disease.

Methods:
Immunodetection and public database screening showed dominant expression of PALMD in endothelial cells (ECs) in brain and cardiovascular tissues including aortic valves. Mass spectrometry, coimmunoprecipitation, and immunofluorescent staining allowed identification of PALMD partners. The consequence of loss of PALMD expression was assessed in small interferring RNA-treated EC cultures, knockout mice, and human valve samples. RNA sequencing of ECs and transcript arrays on valve samples from an aortic valve study cohort including patients with the single nucleotide polymorphism rs7543130 informed about gene regulatory changes.

Results:

ECs express the cytosolic
PALMD-KKVI
splice variant, which associated with RANGAP1 (RAN GTP hydrolyase activating protein 1). RANGAP1 regulates the activity of the GTPase RAN and thereby nucleocytoplasmic shuttling via XPO1 (Exportin1). Reduced PALMD expression resulted in subcellular relocalization of RANGAP1 and XPO1, and nuclear arrest of the XPO1 cargoes p53 and p21. This indicates an important role for PALMD in nucleocytoplasmic transport and consequently in gene regulation because of the effect on localization of transcriptional regulators. Changes in EC responsiveness on loss of
PALMD
expression included failure to form a perinuclear actin cap when exposed to flow, indicating lack of protection against mechanical stress. Loss of the actin cap correlated with misalignment of the nuclear long axis relative to the cell body, observed in
PALMD
-deficient ECs,

Palmd
−/−

mouse aorta, and human aortic valve samples derived from patients with calcific aortic valve stenosis. In agreement with these changes in EC behavior, gene ontology analysis showed enrichment of nuclear- and cytoskeleton-related terms in
PALMD
-silenced ECs.

Conclusions:

We identify RANGAP1 as a PALMD partner in ECs. Disrupting the PALMD/RANGAP1 complex alters the subcellular localization of RANGAP1 and XPO1, and leads to nuclear arrest of the XPO1 cargoes p53 and p21, accompanied by gene regulatory changes and loss of actin-dependent nuclear resilience. Combined, these consequences of reduced
PALMD
expression provide a mechanistic underpinning for PALMD’s contribution to calcific aortic valve stenosis pathology.
Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients With Asymmetric Hypertrophic Cardiomyopathy
Authors: Tesic Milorad , Beleslin Branko , Giga Vojislav , Jovanovic Ivana , Marinkovic Jelena , Trifunovic Danijela , Petrovic Olga , Dobric Milan , Aleksandric Srdjan , Juricic Stefan , Boskovic Nikola , Tomasevic Miloje , Ristic Arsen , Orlic Dejan , Stojkovic Sinisa , Vukcevic Vladan , Stankovic Goran , Ostojic Miodrag , Djordjevic Dikic Ana 
Published: October 2021

Background
Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long‐term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long‐term prognostic value of CFVR on clinical outcome in HCM population.

Methods and Results

We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients’ clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow‐up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%,
P
<0.001 vs. Group 1) adverse cardiac events. By Kaplan‐Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event‐free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log‐rank 37.2,
P
<0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83–16.30,
P
<0.001), while CFVR PD was not significantly associated with outcome.

Conclusions
In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.
Naricolax holinorum sp. nov. (Copepoda, Cyclopoida, Bomolochidae) parasitic in the nasal cavity of the blackhead seabream Acanthopagrus schlegelii (Bleeker, 1854) (Pisces, Sparidae) in Japan
Authors: Izawa Kunihiko 
Published: October 2021

Abstract
Naricolax holinorum sp. nov. is described based on specimens of both sexes recovered from the nasal cavity of Acanthopagrus schlegelii (Bleeker, 1854) (Pisces, Sparidae) in Japan. This species was erroneously redescribed first as N. atypicus Ho, Do & Kasahara, 1983 by Ho & Lin (2005) based on specimens of the female collected from the nasal cavity of A. schlegelii in Taiwan.
Utilizing Ice Core and Climate Model Data to Understand Seasonal West Antarctic Variability
Authors: Goddard Paul B. , Tabor Clay R. , Jones Tyler R. 
Published: October 2021

AbstractReconstructions of past West Antarctic Ice Sheet (WAIS) climate rely on the isotopologues of water recorded in ice cores which extend the local surface temperature record back tens of thousands of years. Here, we utilize continuous flow sampling and novel back-diffusion techniques with the WAIS Divide ice core (WDCobs) to construct a seasonal record of the δ18O value of the precipitation (δ18Op) at the time of deposition from 1980-2000. We then use a water isotope enabled global climate model, iCESM1, to establish seasonal drivers of WAIS climate and of δ18Op variability at the WAIS Divide location to compare with the WDCobs and MERRA2 reanalysis data. Our results show that the WAIS seasonal climate variability is driven by the position and strength of the Amundsen Sea Low (ASL) caused by variations in the Southern Annual Mode and the two Pacific-South American patterns (PSA1 and PSA2). The largest year-to-year seasonal δ18Op anomalies at the WAIS Divide location occur with respect to PSA2 during austral winter (JJA) as a result of an eastward displacement of the ASL that shifts the associated onshore winds towards the Weddell Sea, reducing temperatures and precipitation near the WAIS Divide location. Additionally, the iCESM1 experiment suggests that changes to the moisture path from the source to the WAIS Divide location is an important driver of seasonal WDCobs δ18Op variability. This work highlights the potential of using a single ice core to reconstruct past WAIS climate at seasonal timescales.
Probabilistic Predictions from Deterministic Atmospheric River Forecasts with Deep Learning
Authors: Chapman William E. , Delle Monache Luca , Alessandrini Stefano , Subramanian Aneesh C. , Ralph F. Martin , Xie Shang-Ping , Lerch Sebastian , Hayatbini Negin 
Published: October 2021

Abstract
Deep-learning (DL) postprocessing methods are examined to obtain reliable and accurate probabilistic forecasts from single-member numerical weather predictions of integrated vapor transport (IVT). Using a 34-yr reforecast, based on the Center for Western Weather and Water Extremes West-WRF mesoscale model of North American West Coast IVT, the dynamically/statistically derived 0–120-h probabilistic forecasts for IVT under atmospheric river (AR) conditions are tested. These predictions are compared with the Global Ensemble Forecast System (GEFS) dynamic model and the GEFS calibrated with a neural network. In addition, the DL methods are tested against an established, but more rigid, statistical–dynamical ensemble method (the analog ensemble). The findings show, using continuous ranked probability skill score and Brier skill score as verification metrics, that the DL methods compete with or outperform the calibrated GEFS system at lead times from 0 to 48 h and again from 72 to 120 h for AR vapor transport events. In addition, the DL methods generate reliable and skillful probabilistic forecasts. The implications of varying the length of the training dataset are examined, and the results show that the DL methods learn relatively quickly and ∼10 years of hindcast data are required to compete with the GEFS ensemble.
Relationships among Antecedents, Processes, and Outcomes for Shared Decision Making: A Cross-Sectional Survey of Patients with Lumbar Degenerative Disease
Authors: Chen Chia-Hsien , Chuang Hsin-Yi , Lee Yen , Elwyn Glyn , Hou Wen-Hsuan , Kuo Ken N. 
Published: October 2021

Background Among musculoskeletal disorders, lumbar degenerative disease (LDD) is the leading cause of total disability-adjusted life years globally. Clinical guidelines for LDD describe multiple treatment options in which shared decision making becomes appropriate. Objectives To explore the relationships among measures of decision antecedents, process, and outcomes in patients with LDD. Methods Patients with LDD were recruited from outpatient clinics in a teaching hospital in Taiwan and administered surveys to collect measures of decision antecedents, processes, and outcomes. Multiple linear regression was conducted to assess the association between decision antecedents and the decision making process. Hierarchical linear regression was conducted to assess the relationships among decision antecedents, the decision making process, and decision outcomes. Results A total of 132 patients (mean age, 61 years) completed the survey. After adjustment for personal factors, 2 decision antecedents (namely, decision making self-efficacy and readiness) significantly predicted patients’ experiences of engaging in shared decision making (SDM). Decision making readiness and process were associated with fewer decisional conflicts and greater decision satisfaction. Limitations Models derived from cross-sectional surveys cannot establish causal relationships among decision antecedents, decision making processes, and decision outcomes. Conclusions Our results support the SDM framework, which proposes relationships among decision antecedents, the decision making process, and decision outcomes.
Distinct features of youth-onset primary antiphospholipid syndrome
Authors: Baleeiro Carla , Duran Camila SC , Signorelli Flavio , Balbi Gustavo GM , Bonfá Eloisa , Andrade Danieli CO 
Published: October 2021

Background Characteristics of primary APS (PAPS) in the youth population have never been studied. In contrast with children, pregnancy is genuinely relevant in the youth age, and understanding clinical characteristics of PAPS patients within this specific age stratum may also provide insights regarding the well-known risk of poor obstetric outcomes during the adolescence. Objective To evaluate clinical and laboratory characteristics of patients with youth-onset PAPS (15–24 years) and compare them with adult-onset PAPS (over 24 years old). Methods This was a cross-sectional study derived from two rheumatology outpatient clinics. Patients who fulfilled Sidney criteria and who were 15 years of age or older at disease onset were included. Secondary APS patients were excluded. We subdivided patients into two groups: youth- (15–24 years) and adult-onset (over 24 years) and compared them regarding demographic characteristics, criteria and non-criteria manifestations, cardiovascular risk factors, and aPL status. For the pregnancy outcomes analysis, ever-pregnant patients were divided in three groups: youth-onset, early adult-onset (25–34 years), and late adult-onset (35–49 years). Results A total of 250 consecutive PAPS patients were included. Groups had a comparable female and Caucasian distribution. We found a similar disease duration (14.0±7.9 vs 17.0±10.1 years, p = 0.079) and similar rates of thrombotic arterial (34.2% vs. 42.0%, p = 0.250) and venous events (69.7% vs. 69.5%, p = 0.975) between them. Skin ulcers were more frequent in the youth-onset group (17.1% vs. 4.0%, p = 0.001), whereas nephropathy was less common (1.3% vs. 8.0%, p = 0.039). No differences were observed for the other criteria and non-criteria manifestations. The adult-onset group presented more frequently with hypertension ( p = 0.002), hyperlipidemia ( p = 0.008), and smoking ( p = 0.003). The youth-onset group presented a higher frequency of obstetric events as the first manifestation of PAPS (30.3% vs. 21.7%, p = 0.005), with worse pregnancy outcomes, namely, fetal death (58.5% vs. 46.4% vs. 24.1%, p = 0.012) and premature delivery (35.8% vs. 19.0% vs. 10.3%, p = 0.016). Of note, all groups had a comparable number of pregnancies (2.81±2.52 vs 2.74±2.07, p = 0.899). Conclusion This study provides novel evidence that youth-onset PAPS presents a higher frequency of obstetric complications as its first manifestation, with an increased risk of fetal death and preterm delivery. Early recognition of this condition by obstetricians is essential to improve prognosis.
Comparison of Computed Tomography, Traction, and Inverted Grayscale Radiographs for Understanding Pilon Fracture Morphology
Authors: Eken Gokay , Misir Abdulhamit 
Published: October 2021

Background: There have been no studies evaluating the usefulness of grayscale radiographs in extremity fractures. We aimed to compare the ability and reliability of traction radiographs vs traction grayscale inversion radiographs to detect fracture fragment and comminution zones in comminuted tibia pilon fractures. Methods: Plain radiographs and grayscale inversion images of 60 patients with Orthopaedic Trauma Association/AO Foundation type C3 fracture were evaluated by 20 observers (15 orthopaedic surgeons and 5 radiologists) after traction had been applied. The anterolateral, posterolateral, and medial malleolar fragments, as well as the lateral, central, and medial column comminution zones, were identified by all physicians. Computed tomography scan images were used as the “gold standard” against which plain radiographs and grayscale inversion image interpretation were measured. Intra- and interobserver reliability and correct identification of fracture fragments and comminution zones were evaluated. Results: The interobserver reliability for 3 of the fracture fragments and comminution zones on the traction plain radiographs was moderate, whereas it was substantial on traction grayscale inversion radiographs. The lateral comminution zones ( P = .001) and presence or absence of posterolateral fragments ( P < .001) were significantly better identified in grayscale inversion radiographs compared to standard radiographs. Conclusion: After traction was applied, we found grayscale inversion radiographs are superior to plain radiographs in the identification of posterolateral fragment and lateral zone of comminution in comminuted intraarticular pilon fractures. Level of Evidence: Level III, retrospective case series.
A Mixed Methods Population Health Approach to Explore Radon-Induced Lung Cancer Risk Perception in Canada
Authors: Khan S. M. , Gomes J. , Chreim S. 
Published: October 2021

Background Radon is a predominant indoor air pollutant and second leading cause of lung cancer in radon-prone areas. Despite the gravity of the health risk, residents in Canada have inadequate perception and taken minimal protective actions. Better perception of a risk motivates people to take preventive measures. Scholarship about radon health risk perception is lacking in Canada. We applied a mixed methods population health approach to explore the determinants shaping perception and actions of a resident population in Canada. Methods We conducted mixed surveys (n = 557) and qualitative bilingual interviews (n = 35) with both homeowners and tenants of Ottawa–Gatineau areas. The study explored residents' risk perception and adaptations factors. Descriptive, correlational and regression analyses described and established associations between quantitative variables. Thematic, inductive analyses identified themes in the qualitative data. A mixed methods analysis triangulated both results to draw a holistic perception of the health risk. Results Residents’ quantitative perceptions of radon health risk, smoking at home, synergistic risk perception, social influence and care for family were associated significantly with their intention to test for radon levels in their home, actual testing and mitigation. These results were explained further with the qualitative findings. Residents who had dual cognitive and emotional awareness of the risk were motivated enough to take preventive actions. Caring for family, knowing others who contracted lung cancer and financial capability were enablers, whereas lack of awareness and homeownership, cost of mitigation and stigma were obstacles to preventive actions. We also explored the dual subjective and objective aspects of risk perception that are influenced by micro- and macro-level determinants. Conclusions Inducing protective action to reduce risk requires comprehensive population-level interventions considering dual perceptions of the risk that can modify the risk determinants. Future research can explore the dual aspects of risk perception and unequal distribution of the risk factors.
Cognitions That Support Concussion Reporting in Collegiate Athletes: An Analysis of a Worksheet Activity
Authors: Kneavel Meredith , Ernst William 
Published: October 2021

Background Sports related concussions continue to be a public health concern and improving reporting behavior a focus of educational programs. While educational programs have addressed changes in knowledge of concussion symptoms, it has been challenging to design educational programs which have lasting effects on reporting behavior. Aims The current analysis describes an intervention in which thoughts about reporting behavior are actively written down in a worksheet exercise to “pre-arm” athletes with cognitions designed to enhance reporting behavior prior to the injury event. Method A total of 503 male and female college athletes participating in collision (football, field hockey, ice hockey, lacrosse, and soccer) and contact sports (baseball, basketball, and softball) from 7 colleges/universities competing across all three NCAA divisions provided data collected during a randomized trial of a peer concussion education program. Results Qualitative analysis revealed 10 themes that would improve reporting including short-term benefits, faster recover, safe and healthy return to play, reporting helps the team, reporting protects the brain, risk aversion, long-term benefits, coach will be supportive, teammates will be supportive and understanding, and academic performance will be affected. Discussion Athletes had awareness of key risks involved in concussions and understood both short- and long-term consequences. Conclusion These findings have important implications for understanding how to change athletes’ thoughts about reporting concussions.
Risk of Depression Among MMT Patients: Does Coping Strategies and Perceived Social Support Play a Role?
Authors: Wahab Suzaily , Chun Keat Tee , Azmi Amirul Danial , Mahadevan Raynuha , Muhamed Ramli Eni Rahaiza , Kian Boon Law 
Published: October 2021

Introduction: Patients receiving methadone maintenance therapy (MMT) experience higher level of stress and are at greater risk of developing mental health problems such as depression which could potentially affect both quality of life and treatment outcomes. This cross-sectional study is aimed at understanding the relationship between psychosocial factors such as social support, coping, and depression among patients receiving MMT in a Malaysian Hospital. Methods: One hundred and ninety-six patients attending MMT program were recruited. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depression, Multidimensional Scale of Perceived Social Support (MSPSS) was used to assess participants’ perceived social support, and the Brief COPE questionnaire was used to assess coping strategies. The diagnosis of depression was made using Mini-International Neuropsychiatric Interview (MINI). Results: About 13.8% of our sample were diagnosed with depression. From our analysis, it was found that having higher levels of perceived social support (OR = 0.462, 95% CI 0.238-0.899, P < .05), the use of active and emotion focused coping mechanism (OR = 0.231, 95% CI 0.095-0.565, P < .005), and support seeking and self-distraction coping mechanism (OR = 0.196, 95% CI 0.074-0.521, P < .001) was associated with lower likelihood of depression. On the contrary, the use of dysfunctional coping strategies such as denial, behavioral disengagement, and self-blame was associated with increased likelihood of depression (OR = 9.384, 95% CI 3.081-28.581, P < .001). Conclusion: Active and emotion focused along with support and self-distraction coping strategies, and higher levels of perceived social support may serve as a buffer against depression in patients receiving MMT.
Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study
Authors: Giovannoni Gavin , Singer Barry A , Issard Delphine , Jack Dominic , Vermersch Patrick 
Published: October 2021

Background: No evidence of disease activity (NEDA-3) is a patient-centric outcome increasingly used as the goal of multiple sclerosis treatment. Objective: Determine treatment durability of cladribine tablets beyond 2 years considering the variable bridging interval of 0.1–116.0 weeks between CLARITY and CLARITY Extension. Methods: Between CLARITY and CLARITY Extension, patients transitioned from cladribine tablets 3.5 mg/kg to placebo (CP3.5 group, n = 98) or continued further treatment with cladribine tablets 3.5 mg/kg (CC7.0 group, n = 186). Treatment assignment was randomized and blinded in both CLARITY and CLARITY Extension. Results: The 2-year NEDA-3 in CLARITY Extension (encompassing both years of CLARITY Extension) was 29.6% in the CP3.5 group and 32.8% in the CC7.0 group. There was no evidence that treatment effect differed with varying bridging intervals. For patients in the CP3.5 group with a bridging interval of ⩽48 weeks, 1 year NEDA-3 (the first year of CLARITY Extension) was 44.4% (28/63) compared with 31.4% (11/35) in patients with a bridging interval of >48 weeks. Conclusion: Treatment with cladribine tablets in CLARITY, followed by either placebo or cladribine tablets in CLARITY Extension, produced sustained benefits for NEDA-3 and its constituent elements for a follow up period up to 6 years from CLARITY baseline.