bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a predictive signature for two trial endpoints using the cross-validated risk scores method
Authors: Cherlin Svetlana , Wason James M S 
Published: December 2020

SummaryThe existing cross-validated risk scores (CVRS) design has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using high-dimensional data (such as genetic data). The design is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure. In some settings, it is desirable to consider the tradeoff between two outcomes, such as efficacy and toxicity, or cost and effectiveness. With this motivation, we extend the CVRS design (CVRS2) to consider two outcomes. The design employs bivariate risk scores that are divided into clusters. We assess the properties of the CVRS2 using simulated data and illustrate its application on a randomized psychiatry trial. We show that CVRS2 is able to reliably identify the sensitive group (the group for which the new treatment provides benefit on both outcomes) in the simulated data. We apply the CVRS2 design to a psychology clinical trial that had offender status and substance use status as two outcomes and collected a large number of baseline covariates. The CVRS2 design yields a significant treatment effect for both outcomes, while the CVRS approach identified a significant effect for the offender status only after prefiltering the covariates.
Seasonal variation of health in Asian elephants
Authors: Franco dos Santos Diogo J , Berger Vérane , Cristofari Robin , Htut Win , Nyein U Kyaw , Aung Htoo Htoo , Reichert Sophie , Lummaa Virpi 
Published: December 2020

AbstractLong-lived species are often predicted to be buffered against seasonal variation: longevity means low annual mortality and reproductive rates and annual variability in climate may therefore have a smaller impact on population growth rates of long-lived species in comparison to short-lived ones. However, little is known of the physiological mechanisms underlying such patterns in long-lived species. In this study, we investigated seasonal variation in the health of Asian elephants living in a seasonal monsoon climate. We used two complementary methods: (i) global and (ii) trait-by-trait analyses of seasonal effects on 23 health parameters of 225 individually marked elephants with known age and reproductive and health history, with repeated measures per individual over a 26-month period. The global analysis highlighted the biggest differences in health between the hot and monsoon seasons. Our trait-specific analyses identified the physiological functions underlying such health variation in different ecological settings, including haematological, immunological, muscular, kidney and liver functions, as well as protein balance and electrolytes. Overall, the results suggest that even long-lived, large mammals may experience physiological changes in response to seasonal variation that in extreme circumstances can pose a significant health risk.
Diagnosis and management of male urinary tract infections: a need for new guidelines. Study from a French general practice electronic database
Authors: Soudais Benjamin , Lacroix-Hugues Virginie , Meunier François , Gillibert André , Darmon David , Schuers Matthieu 
Published: December 2020

Abstract

Background
The definition and the treatment of male urinary tract infections (UTIs) are imprecise. This study aims to determine the frequency of male UTIs in consultations of general practice, the diagnostic approach and the prescribed treatments.

Methods
We extracted the consultations of male patients, aged 18 years or more, during the period 2012–17 with the International Classification of Primary Care, version 2 codes for UTIs or associated symptoms from PRIMEGE/MEDISEPT databases of primary care. For eligible consultations in which all symptoms or codes were consistent with male UTIs, we identified patient history, prescribed treatments, antibiotic duration, clinical conditions, additional examinations and bacteriological results of urine culture.

Results
Our study included 610 consultations with 396 male patients (mean age 62.5 years). Male UTIs accounted for 0.097% of visits and 1.44 visits per physician per year. The UTIs most commonly identified were: undifferentiated (52%), prostatitis (36%), cystitis (8.5%) and pyelonephritis (3.5%). Fever was recorded in 14% of consultations. Urine dipstick test was done in 1.8% of consultations. Urine culture was positive for Escherichia coli in 50.4% of bacteriological tests. Fluoroquinolones were the most prescribed antibiotics (64.9%), followed by beta-lactams (17.4%), trimethoprim-sulfamethoxazole (11.9%) and nitrofurantoin (2.6%).

Conclusions
Male UTIs are rare in general practice and have different presentations. The definition of male UTIs needs to be specified by prospective studies. Diagnostic evidence of male cystitis may reduce the duration of antibiotic therapy and spare critical antibiotics.
Ultrastructural evidence for an unusual mode of ciliogenesis in mouse multiciliated epithelia
Authors: Narita Keishi , Takeda Sen 
Published: December 2020

Abstract
Multiciliogenesis is a cascading process for generating hundreds of motile cilia in single cells. In vertebrates, this process has been investigated in the ependyma of brain ventricles and the ciliated epithelia of the airway and oviduct. Although the early steps to amplify centrioles have been characterized in molecular detail, subsequent steps to establish multicilia have been relatively overlooked. Here, we focused on unusual cilia-related structures previously observed in wild-type mouse ependyma using transmission electron microscopy and analyzed their ultrastructural features and the frequency of their occurrence. In the ependyma, $\sim$5% of cilia existed as bundles; while the majority of the bundles were paired, bundles of more than three cilia were also found. Furthermore, apical protrusions harboring multiple sets of axonemes were occasionally observed (0–2 per section), suggesting an unusual mode of ciliogenesis. In trachea and oviduct epithelia, ciliary bundles were absent, but protrusions containing multiple axonemes were observed. At the base of such protrusions, certain axonemes were completely enwrapped by membranes, whereas others remained incompletely enwrapped. These data suggested that the late steps of multiciliogenesis might include a unique process underlying the development of cilia, which is distinct from the ciliogenesis of primary cilia.
Public health emergencies of international concern: a historic overview
Authors: Wilder-Smith Annelies , Osman Sarah 
Published: December 2020

Abstract

Rationale
The International Health Regulations (IHR) have been the governing framework for global health security since 2007. Declaring public health emergencies of international concern (PHEIC) is a cornerstone of the IHR. Here we review how PHEIC are formally declared, the diseases for which such declarations have been made from 2007 to 2020 and justifications for such declarations.

Key findings
Six events were declared PHEIC between 2007 and 2020: the 2009 H1N1 influenza pandemic, Ebola (West African outbreak 2013–2015, outbreak in Democratic Republic of Congo 2018–2020), poliomyelitis (2014 to present), Zika (2016) and COVID-19 (2020 to present). Poliomyelitis is the longest PHEIC. Zika was the first PHEIC for an arboviral disease. For several other emerging diseases a PHEIC was not declared despite the fact that the public health impact of the event was considered serious and associated with potential for international spread.

Recommendations
The binary nature of a PHEIC declaration is often not helpful for events where a tiered or graded approach is needed. The strength of PHEIC declarations is the ability to rapidly mobilize international coordination, streamline funding and accelerate the advancement of the development of vaccines, therapeutics and diagnostics under emergency use authorization. The ultimate purpose of such declaration is to catalyse timely evidence-based action, to limit the public health and societal impacts of emerging and re-emerging disease risks while preventing unwarranted travel and trade restrictions.
Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study
Authors: Van den Bosch Ines , Bouillon Thomas , Verhamme Peter , Vanassche Thomas , Jacquemin Marc , Coemans Maarten , Kuypers Dirk , Meijers Björn 
Published: December 2020

Abstract

Background
Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population.

Methods
We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day.

Results
Apixaban 5 mg resulted in higher area under the curve (AUC0–48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0–48 pre-dialysis were on average 48% (2.5 mg) and 26% (5 mg) lower than the AUC0–48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0–48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg group pre-dialysis (P = 0.02).

Conclusions
Our data suggest that exposure to apixaban in patients on maintenance haemodialysis is dependent not only on drug dose but also on timing of intake relative to the haemodialysis procedure.
Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease
Authors: Roodenrijs Nadia M T , van der Goes Marlies C , Welsing Paco M J , Tekstra Janneke , Lafeber Floris P J G , Jacobs Johannes W G , van Laar Jacob M 
Published: December 2020

Abstract

Objectives
Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease.

Methods
Consecutive RA patients were enrolled and categorized as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis.

Results
Fifty-two RA patients were classified as D2T and 100 as non-D2T. Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA [odds ratio (OR) 1.97 (95%CI 1.08–3.61)]. Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than in non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient’s and rheumatologist’s wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: (i) ‘non-adherent dissatisfied patients’; (ii) patients with ‘pain syndromes and obesity’; (iii) patients closest to the concept of ‘true refractory RA’.

Conclusions
This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.
The Moderating Effect of Age on the Association Between High-Performance Work Systems and Employee Performance in Different Work Roles
Authors: Pahos Nikolaos , Galanaki Eleanna , Van der Heijden Beatrice I J M , de Jong Jeroen 
Published: December 2020

AbstractHigh performance work systems (HPWS) have been shown to associate with performance at diverse levels. In this article, we study the effects of employee age on the relationship between HPWS and employee performance. We use a role-based measurement of employee performance, which introduces five roles that an employee can hold within an organization, namely the roles of Job holder, Career seeker, Innovator, Team member, and Organization member. Integrating social exchange theory with lifespan theories (i.e., future time perspective and socio-emotional selectivity theory), we propose that HPWS have different associations with job roles for older employees. Using 342 pairs of supervisors and their subordinates, that are nested in 111 service organizations, multilevel analyses show that HPWS positively associate with employee performance in the Organization member role. Moreover, the relationships between HPWS and performance in the Job holder and the Career seeker roles are weaker for older than for younger employees. The results are discussed in the light of the challenges they pose for the management of an aging workforce.
Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality
Authors: Solcà Marco , Krishna Vibhor , Young Nicole , Deogaonkar Milind , Herbelin Bruno , Orepic Pavo , Mange Robin , Rognini Giulio , Serino Andrea , Rezai Ali , Blanke Olaf 
Published: December 2020

Abstract
Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, requiring sometimes the addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatiotemporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, 15 patients with severe chronic pain and an SCS implant underwent congruent SCS-VR (personalized visual feedback of the perceived SCS-induced paresthesia displayed on the patient's virtual body) and 2 control conditions (incongruent SCS-VR and VR alone). We demonstrate the efficacy of neuromodulation-enhanced VR for the treatment of chronic pain by showing that congruent SCS-VR reduced pain ratings on average by 44%. Spinal cord stimulation–VR analgesia was stronger than that in both control conditions (enabling stronger analgesic effects than incongruent SCS-VR analgesia or VR alone) and kept increasing over successive stimulations, revealing the selectivity and consistency of the observed effects. We also show that analgesia persists after congruent SCS-VR had stopped, indicating carry over effects and underlining its therapeutic potential. Linking latest VR technology with recent insights from the neuroscience of body perception and SCS neuromodulation, our personalized new SCS-VR platform highlights the impact of immersive digiceutical therapies for chronic pain.
Registration: clinicaltrials.gov, Identifier: NCT02970006.
Rallying All Resources
Authors: O'Glasser Avital Y. , Stroup Scott , Merkel Matthias J. , Lahti Elizabeth , Kubik Sharon , Vaughn Kristi , Reback Erin , Rumberger Ruth , Hayes Mariah , Backer Jennifer , Solani Tee , Halvorson Stephanie 
Published: December 2020

Background:
The COVID-19 pandemic resulted in the need for hospitals to plan for a potential “surge” of COVID-19 patients.

Problem:
Prior to the onset of the COVID-19 pandemic, our hospital adult acute care capacity ranged 90% to 100%, and a potential hospital surge was projected for Oregon that would exceed existing capacity.

Approach:
A multidisciplinary team with stakeholders from nursing leadership, nursing units, nurse-led case management, and physicians from hospital medicine was convened to explore the conversion of an ambulatory surgical center to overflow patient acute care capacity.

Outcomes:
A protocol was rapidly created and implemented, ultimately transferring 12 patients to an ambulatory surgery unit.

Conclusions:
This project highlighted the ability for stakeholders and innovators to work together in an interprofessional, multidisciplinary way to rapidly create an overflow unit. While this innovation was designed to address COVID-19, the lessons learned can be applied to any other emerging infectious disease or acute care capacity crisis.
Technical Report: A New Method for Determining Image Distance for Stand Magnifiers
Authors: Lewerenz David , Hanson Kara , Hopkins Gregory 
Published: December 2020

SIGNIFICANCE
Low vision rehabilitation clinicians must sometimes evaluate stand magnifiers to determine their true optical properties. A novel method is described for measuring the image distance of stand magnifiers.

PURPOSE
We describe a new method for determining the image distance of stand magnifiers, which has some advantages over previously described methods.

METHODS
Diverging light emerging from a stand magnifier is brought to a focus on the ceiling or other flat surface using convex lenses placed on the top of the stand magnifier lens. Knowing the power of this convex lens and the distance from the magnifier lens to the imaging surface, one can calculate the degree to which the emerging light is diverging and, from that, the image distance. Each author evaluated three stand magnifiers using this method and compared our results with each other and with the values for image distance published by the manufacturer.

RESULTS
Our method produced measurements that were consistent between three clinicians, with emerging divergence values differing by no more than 0.37 D and image distance differing by 0.6 to 3.1 cm for the three magnifiers evaluated. Our measured values also corresponded favorably with the published image distances listed in the manufacturer's catalog, deviating by a maximum of 3.7 cm and a mean of 1.3 cm. When the manufacturer's image distances were converted to dioptric divergence, our measurements varied by a maximum of 0.48 D and a mean of 0.17 D.

CONCLUSIONS
Our method provides an expedient and clinically accurate way to evaluate the divergence and image distance of a stand magnifier. Knowing the image distance is valuable by itself, but the divergence of the emerging light is also critical in determining the stand magnifier's enlargement ratio.
Use of Magnetic Resonance Imaging for Orthopedic Trauma and Infection in the Emergency Department
Authors: Huntley Joseph H. , Huntley Samuel R. , Greif Dylan N. , Marshall Danielle C. , Desai Sohil , Rodriguez Jose , Jose Jean 
Published: December 2020

Abstract
Conditions affecting the musculoskeletal system constitute a significant portion of medical emergencies in the United States, with traumatic injury and infection being two of the most common etiologies. Although physical examination and plain radiographs are often sufficient to guide diagnosis and treatment, there are myriad traumatic and infectious pathologies that are commonly missed or simply not detectable on plain radiographs. Advanced imaging is subsequently warranted for additional workup.
Magnetic resonance imaging (MRI) has become an increasingly used imaging modality for musculoskeletal complaints in the emergency department due to its superior visualization of soft tissues, focal edematous changes, and occult osseous insults often not visible on plain radiographs. Although multiple studies have evaluated its utility in the workup of emergency musculoskeletal complaints, there remains a dearth of literature examining the use of MRI for certain occult diagnoses.
Radiologists, emergency clinicians, and orthopedic surgeons must be knowledgeable of the indications for MRI in the emergency setting, as delayed diagnosis may contribute to increased morbidity and possibly mortality. This review summarizes the use of MRI in diagnoses relating to trauma or infection among patients presenting to the emergency department with a musculoskeletal complaint.
H3K4 trimethylation is required for postnatal pancreatic endocrine cell functional maturation
Authors: Campbell Stephanie A. , Bégin Jocelyn , McDonald Cassandra L. , Vanderkruk Ben , Stephan Tabea L. , Hoffman Brad G. 
Published: December 2020

SummaryDuring pancreas development, endocrine progenitors differentiate into the islet-cell subtypes, which undergo further functional maturation in postnatal islet development. In islet β-cells, genes involved in glucose-stimulated insulin secretion are activated and glucose exposure increases the insulin response as β-cells mature. Here, we investigated the role of H3K4 trimethylation in endocrine cell differentiation and functional maturation by disrupting TrxG complex histone methyltransferase activity in mouse endocrine progenitors. In the embryo, genetic inactivation of TrxG componentDpy30in NEUROG3+ cells did not affect the number of endocrine progenitors or endocrine cell differentiation. H3K4 trimethylation was progressively lost in postnatal islets and the mice displayed elevated random and fasting glycemia, as well as impaired glucose tolerance by postnatal day 24. Although postnatal endocrine cell proportions were equivalent to controls, islet RNA-sequencing revealed a downregulation of genes involved in glucose-stimulated insulin secretion and an upregulation of immature β-cell genes. Comparison of histone modification enrichment profiles in NEUROG3+ endocrine progenitors and mature islets suggested that genes downregulated by loss of H3K4 trimethylation more frequently acquire active histone modifications during maturation. Taken together, these findings suggest that H3K4 trimethylation is required for the activation of genes involved in the functional maturation of pancreatic islet endocrine cells.
Deletion of INPP5E in the murine retina impairs axoneme formation and prevents photoreceptor disc morphogenesis
Authors: Sharif Ali S. , Gerstner Cecilia D. , Cady Martha A. , Arshavsky Vadim Y. , Mitchell Christina , Ying Guoxin , Frederick Jeanne M. , Baehr Wolfgang 
Published: December 2020

ABSTRACTINPP5E (pharbin) is a ubiquitously-expressed, farnesylated phosphatidylinositol polyphosphate 5’-phosphatase which modulates the phosphoinositide composition of membranes. INPP5E resides in primary cilia, and mutations or loss of INPP5E are associated with ciliary dysfunction. INPP5E missense mutations of the phosphatase catalytic domain cause Joubert syndrome in humans, a syndromic ciliopathy affecting multiple tissues including brain, liver, kidney and retina. We show that, differing from other primary cilia, INPP5E is present in the wildtype photoreceptor inner segment and absent in the outer segment--a modified primary cilium dedicated to phototransduction. We generatedInpp5eF/F;Six3Cre (in short,retInpp5e-/-) mice which exhibit a rapidly progressing rod-cone degeneration nearly completed by postnatal day 21 (P21) in the central retina. Mutant cone outer segments contain vesicles instead of discs as early as P8. While P10 mutant outer segments contain phototransduction and structural proteins, they do not form axonemes and fail to elaborate disc membranes. Connecting cilia ofretInpp5e-/-rods appear normal, although IFT-B/A particles accumulate at their distal ends suggesting disrupted intraflagellar transport. These results show that ablation of INPP5E does not impair the secretory pathway responsible for delivery of outer segment-specific proteins, but blocks axonemal extension and prevents disc morphogenesis.