bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide Association Analysis Across 16,956 Patients Identifies a Novel Genetic Association Between BMP6, NIPAL1, CNGA1 and Spondylosis
Authors: Zhang Yanfei , Grant Ryan A. , Shivakumar Manu K. , Zaleski Michael , Sofoluke Nelson , Slotkin Jonathan R. , Williams Marc S. , Lee Ming Ta Michael 
Published: December 2020

Study Design....
A case–control genome-wide association study (GWAS) on spondylosis.

Objective....
Leveraging Geisinger's MyCode initiative's multimodal dataset, we aimed to identify genetic associations with degenerative spine disease.

Summary of Background Data....
Degenerative spine conditions are a leading cause of global disability; however, the genetic underpinnings of these conditions remain under-investigated. Previous studies using candidate-gene approach suggest a genetic risk for degenerative spine conditions, but large-scale GWASs are lacking.

Methods....
We identified 4434 patients with a diagnosis of spondylosis using ICD diagnosis codes with genotype data available. We identified a population-based control of 12,522 patients who did not have any diagnosis for osteoarthritis. A linear-mix, additive genetic model was employed to perform the genetic association tests adjusting for age, sex, and genetic principal components to account for the population structure and relatedness. Gene-based association tests were performed and heritability and genetic correlations with other traits were investigated.

Results....
We identified a genome-wide significant locus at rs12190551 (odds ratio = 1.034, 95% confidence interval 1.022–1.046, P = 8.5 × 10–9, minor allele frequency = 36.9%) located in the intron of BMP6. Additionally, NIPAL1 and CNGA1 achieved Bonferroni significance in the gene-based association tests. The estimated heritability was 7.19%. Furthermore, significant genetic correlations with pain, depression, lumbar spine bone mineral density, and osteoarthritis were identified.

Conclusion....
We demonstrated the use of a massive database of genotypes combined with electronic health record data to identify a novel and significant association spondylosis. We also identified significant genetic correlations with pain, depression, bone mineral density, and osteoarthritis, suggesting shared genetic etiology and molecular pathways with these phenotypes.

Level of Evidence: N/A
Successful treatment of acute circulatory failure of unknown cause using critical ultrasound-guided reverse fluid resuscitation
Authors: Zhao Haotian , Long Ling , Wang Zekai , Yan Yaru , Zhao Heling 
Published: December 2020

Abstract

Rationale:
Fluid resuscitation manages shock effectively. However, shock is not always caused by hypovolemia; various types of shock have variable volumetric reactivity. Combined echocardiography and lung ultrasound (LUS) is a new technique for assessing volume status and pulmonary edema in these patients. We report a case of unexplained acute circulatory failure and acute kidney injury (AKI) aggravated by active fluid resuscitation. We used the critical consultation ultrasonic examination (CCUE) protocol for evaluation, and successfully revived the patient with reverse fluid resuscitation.

Patient concerns:
An 82-year-old man with hypertension, atrial fibrillation, and left ventricular diastolic dysfunction (LVDD) was admitted with abdominal distention and lower extremity edema. He developed symptoms of acute circulatory failure, including low blood pressure, anuria, and skin spots. After positive fluid resuscitation, the blood pressure lowered further, and moist rales were audible over both lungs.

Diagnosis:
We performed bedside critical ultrasound for evaluation. The differential diagnoses based on the findings included left atrial and right heart dilatation, low cardiac output owing to reduced left ventricular ejection consequent to excessive circulatory capacity, right heart dilation, and left ventricular compression, and pulmonary edema caused by volume overload.

Interventions:
Infusion was withheld, and tracheal intubation and mechanical ventilation were instituted to assist breathing; reverse fluid resuscitation was initiated, using continuous renal replacement therapy (CRRT) to maintain a negative fluid balance.

Outcomes:
Within 72 hours of fluid withdrawal, the blood pressure reverted to normal, symptoms of pulmonary edema were alleviated, and the circulation and tissue perfusion were restored. The symptoms of acute renal injury are relieved and allowing urine formation without support.

Lessons:
Not all patients with acute circulatory failure require positive fluid resuscitation. Fluid balance should be closely monitored and managed. Potential intolerance to the rapid increase in volume may lead to biventricular interaction, ultimately leading to acute circulatory failure. The shock caused by volume overload should be treated with reverse fluid resuscitation. Combined echocardiography and LUS is a powerful tool for the differential diagnosis of circulatory and respiratory dysfunction.
Development of the Prostate Cancer Treatment Decision Framework
Authors: Owens Otis L. , Dawson Robin M. , Thomas Tracey 
Published: December 2020

Background
Over the past 2 decades, numerous decision-making interventions have been developed to guide the prostate cancer (PrCA) treatment choices of patients and families. These interventions are often supported by economic decision frameworks, which do not account for the role of emotions in treatment decisions. In some instances, emotion-driven decisions can override an individual’s cognitive evaluation of a decision, leading to unfavorable outcomes such as decision regret.

Objectives
To produce a Prostate Cancer Treatment Decision Framework based on the Risk-as-Feelings Hypothesis.

Methods
The authors reviewed seminal research in emotion and decision-making in an effort to create a context-specific decision framework.

Results
Five variables, not germane to the Risk-as-Feelings Hypothesis, play prominent roles in PrCA decision-making including age, spirituality, family support, healthcare provider communication, and perception of treatment outcomes. While family support only affects decision outcomes by influencing emotion and cognitive evaluation of a PrCA decision, age, spirituality, and healthcare provider communication can have direct effects on an individual’s perception of treatment outcomes.

Conclusions
The Prostate Cancer Treatment Decision Framework combines new variables with older models to explain the PrCA treatment decision-making process and elucidate relationships affecting treatment outcomes and survivors’ perceptions of these outcomes. The core premise of this model can be applied to other high-risk health decisions.

Implications for Practice
Healthcare providers have the greatest influence on PrCA treatment decision-making. Using a shared decision-making approach, providers should take into account a patient’s personal characteristics and values, in addition to clinical presentation, to help patients with treatment decisions.
Aerosol generation in children undergoing high flow nasal cannula therapy
Authors: Gall Elliott T. , Laguerre Aurélie , Noelck Michelle , Van Meurs Annalise , Austin Jared A , Foster Byron A. 
Published: December 2020

AbstractObjectiveHigh flow nasal cannula therapy (HFNC) may increase aerosol generation, putting health care workers at increased risk of infection, including from SARS-CoV-2. This study examined whether use of HFNC increases near-field aerosols and if there is a relationship between flow rate and near-field aerosol concentrations.Patients and MethodsSubjects between 30 days and 2 years of age were enrolled. Each child received HFNC therapy at different flow rates over time. Three sampling stations with particle counters were deployed to measure aerosol generation and dispersion in the room: station one within 0.5 m of the subject, station two at 2 m, and station three on the other side of the room. We also measured carbon dioxide (CO2) and relative humidity. Station three (far-field) measurements were used to adjust the station one (near-field) measurements for room conditions.ResultsWe enrolled ten children ranging from 6-24 months (median 9 months), two with respiratory illness. Elevated CO2 indicated the near-field measurements were in the breathing plane of the subjects. Near-field breathing plane concentrations of aerosols with diameter 0.3 – 10 µm are elevated by the presence of the patient with no HFNC flow, relative to the room far-field, by 0.45 #/cm3. While we observed variability between subjects in their emission and dispersion of particles, we did not find an association between HFNC and near-field elevations of particle counts.ConclusionNear-patient levels of particles with diameter in the 0.3-10 µm range was not affected by the use of HFNC in healthy patients. Further study on older children and children with increased mucus production may be warranted.
Evaluation of a novel approach to community health care delivery in Ifanadiana District, Madagascar
Authors: Razafinjato Bénédicte , Rakotonirina Luc , Andriantahina Jafeta Benony , Cordier Laura F. , Andriamihaja Randrianambinina , Rasoarivao Anna , Andrianomenjanahary Mamy , Marovavy Lanto , Hanitriniaina Feno , Mayfield Alishya , Palazuelos Daniel , Ihantamalala Felana , Rakotonanahary Rado J.L. , Miller Ann , Garchitorena Andres , McCarty Meg G. , Bonds Matthew H. , Finnegan Karen E. 
Published: December 2020

AbstractDespite the widespread global adoption of community health (CH) systems, there are evidence gaps in how to best deliver community-based care aligned with global best practice in remote settings where access to health care is limited and community health workers (CHWs) may be the only available providers. PIVOT partnered with the Ministry of Public Health to pilot a new two-pronged approach for care delivery in rural Madagascar: one CHW provided care at a stationary CH site while 2-5 additional CHWs provided care via proactive household visits. The pilot included professionalization of the CHW workforce (i.e. recruitment, training, financial incentive) and twice monthly supervision of CHWs. We evaluated the impact of the CH pilot on utilization and quality of integrated community case management (iCCM) in the first six months of implementation (October 2019-March 2020).We compared utilization and proxy measures of quality of care (defined as adherence to the iCCM protocol for diagnosis, classification of disease severity, treatment) in the intervention commune and five comparison communes, using a quasi-experimental study design and relying on routinely collected programmatic data. Average per capita monthly under-five visits were 0.28 in the intervention commune and 0.22 in the comparison communes. In the intervention commune, 40.0% of visits were completed at the household via proactive care. CHWs completed all steps of the iCCM protocol in 77.8% of observed visits in the intervention commune (vs 49.5% in the comparison communes, p-value=<0.001). A two-pronged approach to CH delivery and professionalization of the CHW workforce increased utilization and demonstrated satisfactory quality of care. National stakeholders and program managers should evaluate program re-design at a local level prior to national or district-wide scale-up.
Targeted T cell receptor gene editing provides predictable T cell product function for immunotherapy
Authors: Müller Thomas R. , Jarosch Sebastian , Hammel Monika , Grassmann Simon , Effenberger Manuel , Andrae Immanuel , Chaudhry M. Zeeshan , Cicin-Sain Luka , Steinberger Peter , Neuenhahn Michael , Schober Kilian , Busch Dirk H. 
Published: December 2020

AbstractAdoptive transfer of T cells expressing a transgenic T cell receptor (TCR) has the potential to revolutionize immunotherapy of infectious diseases and cancer. However, the generation of defined TCR-transgenic T cell medicinal products with predictable in vivo function still poses a major challenge and limits broader and more successful application of this ‘living drug’. Here, by studying 51 different TCRs, we show that conventional genetic engineering by viral transduction leads to variable TCR expression and T cell product functionality as a result of interference with the endogenous TCR, variable transgene copy numbers, and un-targeted transgene integration. In contrast, CRISPR/Cas9-mediated TCR gene editing enables defined, targeted TCR insertion with concomitant knock-out of the endogenous receptor. Thereby, T cell products display more homogenous and physiological TCR expression which results in increased functionality and – importantly – less variable in vivo T cell responses in comparison to conventionally generated T cells. Hence, targeted TCR gene editing increases the predictability of TCR-transgenic T cell product function, which represents a crucial aspect for clinical application in adoptive T cell immunotherapy.BRIEF SUMMARYSafer, more functional and predictable transgenic T cell products for immunotherapy can be generated via CRISPR/Cas9-mediated targeted TCR engineering
Pupil-based states of brain integration across cognitive states
Authors: Mäki-Marttunen Verónica 
Published: December 2020

AbstractArousal is a potent mechanism that provides the brain with functional flexibility and adaptability to external conditions. Within the wake state, arousal levels driven by activity in the neuromodulatory systems are related to specific signatures of neural activation and brain synchrony. However, direct evidence is still lacking on the varying effects of arousal on macroscopic brain characteristics and across a variety of cognitive states in humans. Using a concurrent fMRI-pupillometry approach, we used pupil size as a proxy for arousal and obtained patterns of brain integration associated with increasing arousal levels. We carried out this analysis on resting-state data and data from two attentional tasks implicating different cognitive processes. We found that an increasing level of arousal was related to a non-linear pattern of brain integration, with increasing brain integration from intermediate to larger arousal levels. This effect was prominent in the salience network in all tasks, while other regions showed task-specificity. Furthermore, task performance was also related to arousal level, with accuracy being highest at intermediate levels of arousal across tasks. Taken together, our study provides evidence in humans for pupil size as an index of brain network state, and supports the role of arousal as a switch that drives brain coordination in specific brain regions according to the cognitive state.
Social capital and business model innovation in SMEs: do organizational learning capabilities and entrepreneurial orientation really matter?
Authors: Khan Samar Hayat , Majid Abdul , Yasir Muhammad , Javed Asad 
Published: December 2020

PurposeThis research aims to concentrate on the important concern that how social capital (SC) influences business model innovation (BMI) in the course of the mediating role of organizational learning capabilities (OLC) and the moderating role of entrepreneurial orientation (EO). In the context of small and medium enterprises (SMEs), this study empirically tested a theoretical model of BMI to advocate a mechanism for the analysis of its significant determinants.Design/methodology/approachIn order to achieve the objective of the research, survey method was utilized, and data were collected from 521 CEOs, MDs and the owners of ICT sector SMEs. Correlation, causal step approach and regression analysis were used to test the proposed model.FindingsFinding of the research advocates that OLC mediate the relationship between SC and BMI. In addition, stronger EO augments the association between OLC and BMI.Practical implicationsThe study adds to the literature by providing insights regarding the impact of SC, OLC and EO on BMI of small firms.Originality/valueThis research enriches the existing knowledge by testing a mediating role of OLC between SC-BMI link and, therefore, makes an important addition to the existing knowledge in the context of SMEs by concentrating on the relationship between SC, OLC, BMI and EO.
Retinal vessel diameters, flicker‐induced retinal vasodilation and retinal oxygen saturation in high‐ and low‐risk pregnancy
Authors: Sharifizad Mozhgan , Schmidl Doreen , Werkmeister René M. , Zeisler Harald , Told Reinhard , Binder Julia , Küssel Lorenz , Garhöfer Gerhard , Schmetterer Leopold 
Published: December 2020

AbstractPurposeTo compare retinal vascular parameters between high‐risk and low‐risk pregnant women over time during pregnancy.MethodsIn a longitudinal study, we included pregnant women with normal blood pressure and normal body mass index (BMI, group 1), pregnant women with systemic hypertension and/or overweight (group 2) and age‐matched nonpregnant healthy women (group 3). Using the dynamic vessel analyser (DVA) we investigated flicker‐induced vasodilation in retinal arteries (FLA) and veins (FLV), central retinal arterial and vein equivalent (CRAE, CRVE), arterio‐venous ratio (AVR) and retinal arterial and venous oxygen saturation (SartO2, SveinO2). Study visits were scheduled 2nd trimester (TP 2), 3rd trimester (TP 3) and postpartum (PP).ResultsData from 29 women in group 1, 25 women in group 2 and 33 women in group 3 were included for analysis. FLA, FLV, CRAE, CRVE, AVR and SveinO2 were altered in group 2 (p‐values between < 0.001 and 0.009). At TP 3 the differences between groups were most pronounced. In contrast, there were only minor differences between group 1 and 3. Changes in retinal parameters were independently associated with systemic blood pressure and BMI.ConclusionsThe present analysis indicates that flicker‐induced retinal vasodilation, retinal vessel diameters and retinal oxygen saturation are altered in high‐risk pregnant women. Hence, these parameters are candidate biomarkers for pregnancy complications, a hypothesis that deserves further study.
Stoma‐related complications: a report from the Stoma‐Const randomized controlled trial
Authors: Correa Marinez Adiela , Bock David , Carlsson Eva , Petersén Charlotta , Erestam Sofia , Kälebo Peter , Rosenberg Jacob , Haglind Eva , Angenete Eva 
Published: December 2020

AbstractAimThe impact of construction techniques on the development of stoma complications is partly undiscovered. The aim of this paper was to report and analyse the impact of the three surgical techniques in a randomized controlled trial Stoma‐Const on stoma‐related complications as well as identifying risk factors and patient‐reported stoma function as a planned secondary analysis.MethodsThis was a randomized, multicenter trial where all patients scheduled to receive an end colostomy were invited to participate. Patients were randomized to one of three techniques for stoma construction; cruciate fascial incision, circular incision or prophylactic mesh. Stoma complications were assessed by a surgeon and stoma care nurses within 1 year postoperatively.ResultsTwo hundred and nine patients were randomized. Patient demographics were similar in all three groups. Data on stoma‐related complications were available for analysis in 201 patients. A total of 127 patients (63%) developed some type of stoma complication within 1 year after surgery. The risk ratio (95% CI) for stoma complications was 0.93 (0.73; 1.2) between cruciate vs. circular incision groups and 1.02 (0.78; 1.34) between cruciate vs. mesh groups. There were no statistically significant differences between the groups regarding parastomal hernia rate and no risk factors could be identified.ConclusionThis randomized trial confirmed a high prevalence of stoma‐related complications but could not identify an impact of surgical technique or identify modifiable risk factors for stoma‐related complications.
Retrospective Analysis Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation Offers Improvements in Efficiency of the Design of Volunteer Infection Studies for Antimalarial Drug Development
Authors: Andrews Kayla Ann , Owen Joel S. , McCarthy James , Wesche David , Gobeau Nathalie , Grasela Thaddeus H. , Möhrle Jörg J. 
Published: December 2020

Volunteer infection studies using the induced blood stage malaria (IBSM) model have been shown to facilitate antimalarial drug development. Such studies have traditionally been undertaken in single‐dose cohorts, as many as necessary to obtain the dose‐response relationship. To enhance ethical and logistic aspects of such studies, and to reduce the number of cohorts needed to establish the dose‐response relationship, we undertook a retrospective in silico analysis of previously accrued data to improve study design. A pharmacokinetic (PK)/pharmacodynamic (PD) model was developed from initial fictive‐cohort data for OZ439 (mixing the data of the three single‐dose cohorts as: n = 2 on 100 mg, 2 on 200 mg, and 4 on 500 mg). A three‐compartment model described OZ439 PKs. Net growth of parasites was modeled using a Gompertz function and drug‐induced parasite death using a Hill function. Parameter estimates for the PK and PD models were comparable for the multidose single‐cohort vs. the pooled analysis of all cohorts. Simulations based on the multidose single‐cohort design described the complete data from the original IBSM study. The novel design allows for the ascertainment of the PK/PD relationship early in the study, providing a basis for rational dose selection for subsequent cohorts and studies.
Impact of clinical photographs on the accuracy and confidence in the histopathological diagnosis of mycosis fungoides
Authors: Hadi Rouba , Miller Timothy I. , May Caitlin , Lehman Julia S. , Bennett Daniel D. , Piliang Melissa , Chang Oliver , Shinohara Michi M. 
Published: December 2020

AbstractBackgroundThe histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies.MethodsWe provided photomicrographs to board‐certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF.ResultsWe found that access to clinical photographs improved diagnostic accuracy in both MF and non‐MF (distractors); the degree of improvement was significantly higher in the non‐MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available.ConclusionThese findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.