bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of geographical access and factors influencing travel time to emergency obstetric care in the urban state of Lagos, Nigeria
Authors: Banke-Thomas Aduragbemi , Wong Kerry L M , Collins Lindsey , Olaniran Abimbola , Balogun Mobolanle , Wright Ololade , Babajide Opeyemi , Ajayi Babatunde , Afolabi Bosede Bukola , Abayomi Akin , Benova Lenka 
Published: August 2021

AbstractPrevious efforts to estimate the travel time to comprehensive emergency obstetric care (CEmOC) in low- and middle-income countries (LMICs) have either been based on spatial models or self-reported travel time, both with known inaccuracies. The study objectives were to estimate more realistic travel times for pregnant women in emergency situations using Google Maps, determine system-level factors that influence travel time and use these estimates to assess CEmOC geographical accessibility and coverage in Lagos state, Nigeria. Data on demographics, obstetric history and travel to CEmOC facilities of pregnant women with an obstetric emergency, who presented between 1st November 2018 and 31st December 2019 at a public CEmOC facility were collected from hospital records. Estimated travel times were individually extracted from Google Maps for the period of the day of travel. Bivariate and multivariate analyses were used to test associations between travel and health system-related factors with reaching the facility &gt;60 minutes. Mean travel times were compared and geographical coverage mapped to identify ‘hotspots’ of predominantly &gt;60 minutes travel to facilities. For the 4005 pregnant women with traceable journeys, travel time ranges were 2–240 minutes (without referral) and 7–320 minutes (with referral). Total travel time was within the 60 and 120 minute benchmark for 80 and 96% of women, respectively. The period of the day of travel and having been referred were significantly associated with travelling &gt;60 minutes. Many pregnant women living in the central cities and remote towns typically travelled to CEmOC facilities around them. We identified four hotspots from which pregnant women travelled &gt;60 minutes to facilities. Mean travel time and distance to reach tertiary referral hospitals were significantly higher than the secondary facilities. Our findings suggest that actions taken to address gaps need to be contextualized. Our approach provides a useful guide for stakeholders seeking to comprehensively explore geographical inequities in CEmOC access within urban/peri-urban LMIC settings.
The autism risk gene CNTN4 modulates dendritic spine formation
Authors: Zhao Rongjuan , Zhu Tengfei , Liu Qiong , Tian Qi , Wang Meng , Chen Jingjing , Tong Dali , Yu Bin , Guo Hui , Xia Kun , Qiu Zilong , Hu Zhengmao 
Published: August 2021

Abstract
Contactin 4 (CNTN4) is a crucial synaptic adhesion protein that belongs to the contactin superfamily. Evidence from both human genetics and mouse models suggests that synapse formation and structural deficits strongly correlate with neurodevelopmental disorders, including autism. In addition, several lines of evidence suggest that CNTN4 is associated with the risk of autism. However, the biological functions of CNTN4 in neural development and disease pathogenesis are poorly understood. In this study, we investigated whether and how CNTN4 is autonomously involved in the development of dendrites and dendritic spines in cortical neurons. Disruption of Cntn4 decreased the number of excitatory synapses, which led to a reduction in neural activity. Truncated proteins lacking the signal peptide, FnIII domains or GPI domain lacked the ability to regulate dendritic spine formation, indicating that CNTN4 regulates dendritic spine density through a mechanism dependent on FnIII domains. Importantly, we revealed that autism-related variants lacked the ability to regulate spine density and neural activity. In conclusion, our study suggests that CNTN4 is essential for promoting dendrite growth and dendritic spine formation and that disruptive variants of CNTN4 interfere with abnormal synapse formation and may increase the risk of autism.
A Minimal Framework for Describing Living Systems: A Multi-Dimensional View of Life Across Scales
Authors: Caetano-Anollés Kelsey , Ewers Brent , Iyer Shilpa , Lucas Jeffrey R , Pavlic Theodore P , Seale Andre P , Zeng Yu 
Published: August 2021

AbstractThe almost limitless complexity of biology has led to two general approaches to understanding biological phenomena. One approach is dominated by reductionism in which high-level phenomena of whole systems are viewed as emerging from relatively simple and generally understood interactions at a substantially lower level. Although this approach is theoretically general, it can become intractable in practice when attempting to simultaneously explain a wide range of systems. A second approach is for specialists to investigate biological phenomena within one of many different hierarchical levels of description that are separated to decouple from concerns at other levels. Although this approach reduces the explanatory burden on specialists that operate within each level, it also reduces integration from insights gained at other levels. Thus, as beneficial as these approaches have been, they limit the scope and integration of knowledge across scales of biological organization to the detriment of a truly synoptic view of life. The challenge is to find a theoretical and experimental framework that facilitates a broader understanding of the hierarchy of life—providing permeability for the exchange of ideas among disciplinary specialists without discounting the peculiarities that have come to define those disciplines. For this purpose, coarse-grained, scale-invariant properties, and resources need to be identified that describe the characteristic features of a living system at all spatiotemporal scales. The approach will be aided by a common vernacular that underscores the realities of biological connections across a wide range of scales. Therefore, in this vision paper, we propose a conceptual approach based on four identified resources—energy, conductance, storage, and information (ECSI)—to reintegrate biological studies with the aim of unifying life sciences under resource limitations. We argue that no functional description of a living system is complete without accounting for at least all four of these resources. Thus, making these resources explicit will help to identify commonalities to aid in transdisciplinary discourse as well as opportunities for integrating among the differently scoped areas of specialized inquiry. The proposed conceptual framework for living systems should be valid across all scales and may uncover potential limitations of existing hypotheses and help researchers develop new hypotheses addressing fundamental processes of life without having to resort to reductionism.
Birth outcomes following unexpected job loss: a matched-sibling design
Authors: Gailey Samantha , Knudsen Elias Stapput , Mortensen Laust H , Bruckner Tim A 
Published: August 2021

Abstract

Background
Research documents social and economic antecedents of adverse birth outcomes, which may include involuntary job loss. Previous work on job loss and adverse birth outcomes, however, lacks high-quality individual data on, and variation in, plausibly exogenous job loss during pregnancy and therefore cannot rule out strong confounding.

Methods
We analysed unique linked registries in Denmark, from 1980 to 2017, to examine whether a father’s involuntary job loss during his spouse’s pregnancy increases the risk of a low-weight (i.e. &lt;2500 grams) and/or preterm (i.e. &lt;37 weeks of gestational age) birth. We applied a matched-sibling design to 743 574 sibling pairs.

Results
Results indicate an increased risk of a low-weight birth among infants exposed in utero to fathers’ unexpected job loss [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.07, 1.75]. Sex-specific analyses show that this result holds for males (OR = 1.70, 95% CI: 1.14, 2.53) but not females (OR = 1.24, 95% CI: 0.80, 1.91). We find no relation with preterm birth.

Conclusions
Findings support the inference that a father’s unexpected job loss adversely affects the course of pregnancy, especially among males exposed in utero.
Examining the effects of heterospecific abundance on dispersal in forest small mammals
Authors: Denomme-Brown Simon T , Cottenie Karl , Falls J Bruce , Falls E Ann , Brooks Ronald J , McAdam Andrew G 
Published: August 2021

AbstractThe effects of conspecific densities on dispersal have been well documented. However, while positive and negative density-dependent dispersal based on conspecific densities often are shown to be the result of intraspecific competition or facilitation, respectively, the effects of heterospecific densities on dispersal have been examined far less frequently. This gap in knowledge warrants investigation given the potential for the analogous processes of interspecific competition and heterospecific attraction to influence dispersal patterns and behavior. Here we use a long-term live-trapping study of deer mouse (Peromyscus maniculatus), eastern chipmunk (Tamias striatus), red-backed vole (Myodes gapperi), and jumping mice (Napaeozapus insignis and Zapus hudsonius) to examine the effects of variation in conspecific and heterospecific abundances on dispersal frequency. In terms of conspecific abundance, jumping mice were more likely to disperse from areas with fewer conspecifics, while red-backed voles and chipmunks did not respond to variation in conspecific abundances in their dispersal frequencies. While there were no statistically significant effects of variation in heterospecific abundances on dispersal frequency, some effect sizes for heterospecific abundance effects on dispersal met or exceeded those of conspecific abundances. Conspecific abundances clearly can affect dispersal by some species in this system, but the effects of heterospecific abundances on dispersal frequency are less clear. Based on effect sizes, it appears that there may be potential for heterospecific effects on dispersal by some species in the community, although the strength and causes of these relationships remain unclear.
The high reported accuracy of the standardized field sobriety test is a property of the statistic not of the test
Authors: Kane Greg , Kane Elizabeth 
Published: August 2021

Abstract
OBJECTIVE In the 1990s as the legal blood alcohol limit for driving changed, validation studies reported the Standardized Field Sobriety Test (SFST) to be accurate at discriminating between Blood Alcohol Concentrations (BAC) above or below several legal limits: 0.10, 0.08, 0.05 and 0.04%. We investigated the contribution of the validation studies’ choice of accuracy statistic to the SFST’s reported accuracy. METHODS Using the data set from a commonly cited SFST validation study, we calculated the arrest accuracy and overall accuracy of the SFST at identifying BACs above or below 31 different target BACs from 0.00 to 0.30%. RESULTS At target BAC 0.30% the arrest accuracy of the SFST is 1%; at BAC 0.15%, 34%; at BAC 0.00%, 100%. The statistics arrest accuracy and overall accuracy describe the SFST, a test designed to identify changes caused by alcohol, as less accurate when the changes are severe, more accurate when changes are mild, and as 100% (arrest) and 93% (overall) accurate when there are no changes at all. CONCLUSION The statistics overall accuracy and arrest accuracy to not quantify the probability that impaired driving defendants who failed the SFST had an elevated BAC or were impaired.
Saturation mutagenesis charts the functional landscape ofSalmonellaProQ and reveals a gene regulatory function of its C-terminal domain
Authors: Rizvanovic Alisa , Kjellin Jonas , Söderbom Fredrik , Holmqvist Erik 
Published: August 2021

AbstractThe global RNA-binding protein ProQ has emerged as a central player in post-transcriptional regulatory networks in bacteria. While the N-terminal domain (NTD) of ProQ harbors the major RNA-binding activity, the role of the ProQ C-terminal domain (CTD) has remained unclear. Here, we have applied saturation mutagenesis coupled to phenotypic sorting and long-read sequencing to chart the regulatory capacity of Salmonella ProQ. Parallel monitoring of thousands of ProQ mutants allowed mapping of critical residues in both the NTD and the CTD, while the linker separating these domains was tolerant to mutations. Single amino acid substitutions in the NTD associated with abolished regulatory capacity strongly align with RNA-binding deficiency. An observed cellular instability of ProQ associated with mutations in the NTD suggests that interaction with RNA protects ProQ from degradation. Mutation of conserved CTD residues led to overstabilization of RNA targets and rendered ProQ inert in regulation, without affecting protein stability in vivo. Furthermore, ProQ lacking the CTD, although binding competent, failed to protect an mRNA target from degradation. Together, our data provide a comprehensive overview of residues important for ProQ-dependent regulation and reveal an essential role for the enigmatic ProQ CTD in gene regulation.
Cis regulation within a cluster of viral microRNAs
Authors: Vilimova Monika , Contrant Maud , Randrianjafy Ramy , Dumas Philippe , Elbasani Endrit , Ojala Päivi M , Pfeffer Sébastien , Fender Aurélie 
Published: August 2021

Abstract
MicroRNAs (miRNAs) are small regulatory RNAs involved in virtually all biological processes. Although many of them are co-expressed from clusters, little is known regarding the impact of this organization on the regulation of their accumulation. In this study, we set to decipher a regulatory mechanism controlling the expression of the ten clustered pre-miRNAs from Kaposi's sarcoma associated herpesvirus (KSHV). We measured in vitro the efficiency of cleavage of each individual pre-miRNA by the Microprocessor and found that pre-miR-K1 and -K3 were the most efficiently cleaved pre-miRNAs. A mutational analysis showed that, in addition to producing mature miRNAs, they are also important for the optimal expression of the whole set of miRNAs. We showed that this feature depends on the presence of a canonical pre-miRNA at this location since we could functionally replace pre-miR-K1 by a heterologous pre-miRNA. Further in vitro processing analysis suggests that the two stem-loops act in cis and that the cluster is cleaved in a sequential manner. Finally, we exploited this characteristic of the cluster to inhibit the expression of the whole set of miRNAs by targeting the pre-miR-K1 with LNA-based antisense oligonucleotides in cells either expressing a synthetic construct or latently infected with KSHV.
Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia
Authors: Heerspink Hiddo J L , Stack Austin G , Terkeltaub Robert , Greene Tom A , Inker Lesley A , Bjursell Magnus , Perl Shira , Rikte Tord , Erlandsson Fredrik , Perkovic Vlado 
Published: August 2021

ABSTRACT

Background
Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia.

Methods
Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months.

Conclusions
This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.
Patterns of renal osteodystrophy 1 year after kidney transplantation
Authors: Jørgensen Hanne Skou , Behets Geert , Bammens Bert , Claes Kathleen , Meijers Bjorn , Naesens Maarten , Sprangers Ben , Kuypers Dirk R J , D’Haese Patrick , Evenepoel Pieter 
Published: August 2021

Abstract

Background
Renal osteodystrophy is considered common, but is not well characterized in contemporary kidney transplant recipients. This study reports extensively on bone phenotype by bone histomorphometry, bone densitometry and novel bone biomarkers 1 year after kidney transplantation.

Methods
A transiliac bone biopsy and dual-energy X-ray absorptiometry scans were performed in 141 unselected kidney transplant recipients in this observational cohort study. Blood and 24-h urine samples were collected simultaneously.

Results
The median age was 57 ± 11 years, 71% were men and all were of Caucasian ethnicity. Bone turnover was normal in 71% of patients, low in 26% and high in just four cases (3%). Hyperparathyroidism with hypercalcaemia was present in 13% of patients, of which only one had high bone turnover. Delayed bone mineralization was detected in 16% of patients, who were characterized by hyperparathyroidism (137 versus 53 ρg/mL), a higher fractional excretion of phosphate (40 versus 32%) and lower levels of phosphate (2.68 versus 3.18 mg/dL) and calcidiol (29 versus 37 ng/mL) compared with patients with normal bone mineralization. Osteoporosis was present in 15–46% of patients, with the highest prevalence at the distal skeleton. The proportion of osteoporotic patients was comparable across categories of bone turnover and mineralization.

Conclusions
The majority of kidney transplant recipients, including patients with osteoporosis, have normal bone turnover at 1-year post-transplant. Low bone turnover is seen in a substantial subset, while high bone turnover is rare. Vitamin D deficiency and hypophosphataemia represent potential interventional targets to improve bone health post-transplant.
Community Perspectives on Patient Credibility and Provider Burden in the Treatment of Chronic Pain
Authors: Tait Raymond C , Chibnall John T 
Published: August 2021

Abstract

Objective
This study examined factors influencing lay perceptions of a provider’s clinical burden in providing care to a person with chronic pain.

Design
In a between-subjects design that varied three levels of pain severity (4, 6, or 8 out of 10) with two levels of medical evidence (low/high), participants rated the credibility of pain reported by a hypothetical patient and the psychosocial factors expected to mediate the effects of evidence and severity on a provider’s burden of care.

Setting
A randomized vignette study in which community participants were recruited via Amazon Mechanical Turk.

Subjects
337 community participants.

Methods
Using a Qualtrics platform, participants read one of six vignettes describing a hypothetical patient with varying levels of medical evidence and pain severity and then rated perceived pain severity, pain credibility, psychosocial variables, and burden.

Results
Serial mediation models accounted for all effects of medical evidence and pain severity on burden. Low medical evidence was associated with increased burden, as mediated through lower pain credibility and greater concerns about patient depression, opioid abuse, and learning pain management. Higher levels of reported pain severity were associated with increased burden, as mediated through greater pain discounting and concerns about opioid abuse.

Conclusions
The lay public is skeptical of chronic pain that is not supported by medical evidence or is reported at high levels of severity, raising concerns about psychosocial complications and drug seeking and expectations of higher burden of care. Such negative stereotypes can pose obstacles to people seeking necessary care if they or others develop a chronic pain condition.
Early Pain Catastrophizing Exacerbates Impaired Limb Loading and 6-Minute Walk Test Distance 12 Months After Lower Extremity Fracture
Authors: Van Wyngaarden Joshua J , Archer Kristin R , Spencer Alex , Matuszewski Paul E , Brightwell Benjamin , Jacobs Cale , Noehren Brian 
Published: August 2021

Abstract

Objective
Disability is common after lower extremity fracture (LEF). Although psychosocial factors have been associated with patient-reported outcomes after LEF, they have not been associated with objective measures of function. Aberrant gait patterns are important markers of function, but are poorly defined after LEF. The primary purpose of this study was to explore whether pain catastrophizing and fear of movement 6 weeks after surgery were associated with injured limb loading outcomes and 6-minute walk test (6MWT) distance 12 months after femur or tibia fracture. The secondary purpose was to determine if limb loading characteristics differed between injured and uninjured limbs.

Methods
At 6 weeks after LEF, patients completed validated measures of pain catastrophizing, fear of movement, and depression. At 12 months, patients completed a 6MWT while wearing instrumented insoles that recorded the limb loading outcomes of stance time, impulse, and loading rate. Bivariate correlations assessed how patient and psychosocial characteristics at 6 weeks were associated with injured limb loading outcomes and 6MWT distance. Multivariable regression analyses were performed to determine if psychosocial variables were associated with each outcome after controlling for depression and patient demographic and clinical characteristics. Finally, paired t tests compared limb loading outcomes between limbs.

Results
Forty-seven participants completed the 6MWT at 12 months (65%), and 38 completed the 6MWT with the instrumented insoles. Fear of movement carried a poor relationship (r = 0.11–0.32) and pain catastrophizing a moderate relationship (r = 0.46–0.54) with 12-month outcomes. The regression results indicated that pain catastrophizing continued to be associated with all outcomes. Finally, the injured limb had significantly lower limb loading outcomes than the uninjured limb at 12 months (Cohen d = 0.54–0.69).

Conclusion
Pain catastrophizing early after LEF was associated with impaired limb loading and 6MWT distance at 12 months.

Impact
Impaired limb loading persists 12 months after LEF. Further research is needed to determine whether rehabilitative efforts focused on pain catastrophizing can restore limb loading after LEF.