bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of Human Immunodeficiency Virus-1 Drug Resistance During the 3-Month World Health Organization-Recommended Enhanced Adherence Counseling Period in the CART-1 Cohort Study
Authors: Brown Jennifer A , Mbunkah Herbert A , Lejone Thabo I , Ringera Isaac , Cheleboi Molisana , Klimkait Thomas , Metzner Karin J , Günthard Huldrych F , Labhardt Niklaus D , Kouyos Roger D , Tschumi Nadine 
Published: February 2021

Abstract

Background
In resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (≥80 c/mL) after EAC.

Methods
We included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL ≥80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant’s antiretroviral therapy (ART) regimen (range, 0–3; 3 indicates complete susceptibility).

Results
Among 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL ≥1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL ≥80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25–) to 0.25 (IQR = 0.25–1) during the EAC period (P = .16).

Conclusions
Despite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC.
Comparative Transcriptomics of Lowland Rice Varieties Uncovers Novel Candidate Genes for Adaptive Iron Excess Tolerance
Authors: Kar Saradia , Mai Hans-Jörg , Khalouf Hadeel , Ben Abdallah Heithem , Flachbart Samantha , Fink-Straube Claudia , Bräutigam Andrea , Xiong Guosheng , Shang Lianguang , Panda Sanjib Kumar , Bauer Petra 
Published: February 2021

AbstractIron (Fe) toxicity is a major challenge for plant cultivation in acidic waterlogged soil environments, where lowland rice is a major staple food crop. Only few studies have addressed the molecular characterization of excess Fe tolerance in rice, and these highlight different mechanisms for Fe tolerance. Out of 16 lowland rice varieties, we identified a pair of contrasting lines, Fe-tolerant Lachit and -susceptible Hacha. The two lines differed in their physiological and morphological responses to excess Fe, including leaf growth, leaf rolling, reactive oxygen species generation and Fe and metal contents. These responses were likely due to genetic origin as they were mirrored by differential gene expression patterns, obtained through RNA sequencing, and corresponding gene ontology term enrichment in tolerant vs. susceptible lines. Thirty-five genes of the metal homeostasis category, mainly root expressed, showed differential transcriptomic profiles suggestive of an induced tolerance mechanism. Twenty-two out of these 35 metal homeostasis genes were present in selection sweep genomic regions, in breeding signatures, and/or differentiated during rice domestication. These findings suggest that Fe excess tolerance is an important trait in the domestication of lowland rice, and the identified genes may further serve to design the targeted Fe tolerance breeding of rice crops.
The NAD Kinase Slr0400 Functions as a Growth Repressor in Synechocystis sp. PCC 6803
Authors: Ishikawa Yuuma , Cassan Cedric , Kadeer Aikeranmu , Yuasa Koki , Sato Nozomu , Sonoike Kintake  , Kaneko Yasuko , Miyagi Atsuko , Takahashi Hiroko , Ishikawa Toshiki , Yamaguchi Masatoshi , Nishiyama Yoshitaka , Hihara Yukako , Gibon Yves , Kawai-Yamada Maki 
Published: February 2021

Abstract
NADP+, the phosphorylated form of nicotinamide adenine dinucleotide (NAD), plays an essential role in many cellular processes. NAD kinase (NADK), which is conserved in all living organisms, catalyzes the phosphorylation of NAD+ to NADP+. However, the physiological role of phosphorylation of NAD+ to NADP+ in the cyanobacterium Synechocystis remains unclear. In this study, we report that slr0400, an NADK-encoding gene in Synechocystis, functions as a growth repressor under light-activated heterotrophic growth conditions and light and dark cycle conditions in the presence of glucose. We show, via characterization of NAD(P)(H) content and enzyme activity, that NAD+ accumulation in slr0400-deficient mutant results in the unsuppressed activity of glycolysis and tricarboxylic acid (TCA) cycle enzymes. In determining whether Slr0400 functions as a typical NADK, we found that constitutive expression of slr0400 in an Arabidopsis nadk2-mutant background complements the pale-green phenotype. Moreover, to determine the physiological background behind the growth advantage of mutants lacking slr04000, we investigated the photobleaching phenotype of slr0400-deficient mutant under high-light conditions. Photosynthetic analysis found in the slr0400-deficient mutant resulted from malfunctions in the Photosystem II (PSII) photosynthetic machinery. Overall, our results suggest that NADP(H)/NAD(H) maintenance by slr0400 plays a significant role in modulating glycolysis and the TCA cycle to repress the growth rate and maintain the photosynthetic capacity.
Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials
Authors: Dykukha Igor , Malessa Rolf , Essner Ute , Überall Michael A 
Published: February 2021

Abstract

Objective
Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain.

Design
Systematic review and meta-analysis.

Methods
A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges’ g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2).

Results
Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of −0.40 (95% confidence interval [CI]: −.59 to −.21; FE, P &lt; .0001) or −0.44 (95% CI: −.70 to −.19; RE, P = .0006). A SMD of −0.21 (95% CI: −.32 to −.10; FE) or −0.26 (95% CI: −.42 to −.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses.

Conclusions
Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.
Probabilistic Proofs, Lottery Propositions, and Mathematical Knowledge
Authors: Hamami Yacin 
Published: February 2021

Abstract
In mathematics, any form of probabilistic proof obtained through the application of a probabilistic method is not considered as a legitimate way of gaining mathematical knowledge. In a series of papers, Don Fallis has defended the thesis that there are no epistemic reasons justifying mathematicians’ rejection of probabilistic proofs. This paper identifies such an epistemic reason. More specifically, it is argued here that if one adopts a conception of mathematical knowledge in which an epistemic subject can know a mathematical proposition based solely on a probabilistic proof, one is then forced to admit that such an epistemic subject can know several lottery propositions based solely on probabilistic evidence. Insofar as knowledge of lottery propositions on the basis of probabilistic evidence alone is denied by the vast majority of epistemologists, it is concluded that this constitutes an epistemic reason for rejecting probabilistic proofs as a means of acquiring mathematical knowledge.
Effectiveness of Telerehabilitation in Physical Therapy: A Rapid Overview
Authors: Seron Pamela , Oliveros María-Jose , Gutierrez-Arias Ruvistay , Fuentes-Aspe Rocío , Torres-Castro Rodrigo C , Merino-Osorio Catalina , Nahuelhual Paula , Inostroza Jacqueline , Jalil Yorschua , Solano Ricardo , Marzuca-Nassr Gabriel N , Aguilera-Eguía Raul , Lavados-Romo Pamela , Soto-Rodríguez Francisco J , Sabelle Cecilia , Villarroel-Silva Gregory , Gomolán Patricio , Huaiquilaf Sayen , Sanchez Paulina 
Published: February 2021

Abstract

Objective
The purpose of this article was to summarize the available evidence from systematic reviews on telerehabilitation in physical therapy.

Methods
We searched Medline/PubMed, EMBASE, and Cochrane Library databases. In addition, the records in PROSPERO and Epistemonikos and PEDro were consulted. Systematic reviews of different conditions, populations, and contexts—where the intervention to be evaluated is telerehabilitation by physical therapy—were included. The outcomes were clinical effectiveness depending on specific condition, functionality, quality of life, satisfaction, adherence, and safety. Data extraction and risk of bias assessment were carried out by a reviewer with non-independent verification by a second reviewer. The findings are reported qualitatively in the tables and figures.

Results
Fifty-three systematic reviews were included, of which 17 were assessed as having low risk of bias. Fifteen reviews were on cardiorespiratory rehabilitation, 14 on musculoskeletal conditions, and 13 on neurorehabilitation. The other 11 reviews addressed other types of conditions and rehabilitation. Thirteen reviews evaluated with low risk of bias showed results in favor of telerehabilitation versus in-person rehabilitation or no rehabilitation, while 17 reported no differences between the groups. Thirty-five reviews with unclear or high risk of bias showed mixed results.

Conclusions
Despite the contradictory results, telerehabilitation in physical therapy could be comparable with in-person rehabilitation or better than no rehabilitation for conditions such as osteoarthritis, low-back pain, hip and knee replacement, and multiple sclerosis and also in the context of cardiac and pulmonary rehabilitation. It is imperative to conduct better quality clinical trials and systematic reviews.

Impact
Providing the best available evidence on the effectiveness of telerehabilitation to professionals, mainly physical therapists, will impact the decision-making process and therefore yield better clinical outcomes for patients, both in these times of the COVID-19 pandemic and in the future. The identification of research gaps will also contribute to the generation of relevant and novel research questions.
Ban Bedcentricity: A Multifaceted Innovation to Reduce Sedentary Behavior of Patients During the Hospital Stay
Authors: Koenders Niek , Potkamp-Kloppers Sandra , Geurts Yvonne , Akkermans Reinier , Nijhuis-van der Sanden Maria W G , Hoogeboom Thomas J 
Published: February 2021

Abstract

Objective
The purpose of this study was to explore differences in sedentary behavior, length of hospital stay, and discharge destination of patients before and after the Ban Bedcentricity implementation at ward level.

Methods
The Ban Bedcentricity innovation and implementation procedure were implemented at the cardiothoracic surgery, cardiology, and orthopedics-traumatology wards. Sedentary behavior data were collected 2 weeks before and after the implementation using behavioral observations and analyzed with Pearson chi-square. Length of hospital stay and discharge destination data were collected from all admitted patients and analyzed with multiple and logistic regression analyses.

Results
Behavioral observations showed that in 52% of the observations, patients were lying in bed before implementation and 40% after implementation at the cardiothoracic surgery, 64% and 46% at the cardiology, and 53% and 57% at the orthopedics-traumatology wards, respectively. The mean length of hospital stay after implementation (compared with implementation before) was 5.1 days at the cardiothoracic surgery (n = 1923; mean = +0.13 days, 95% CI = −0.32 to 0.60), 2.6 days at the cardiology (n = 2646; mean = −0.22 days, 95% CI = −0.29 to −0.14), and 2.4 days at the orthopedics-traumatology wards (n = 1598; mean = +0.28 days, 95% CI = 0.06 to 0.50). After the implementation, more patients were discharged home from the cardiothoracic surgery (odds ratio [OR = 1.23], 95% CI = 1.07 to 1.37) and cardiology wards (OR = 1.37, 95% CI = 1.22 to 1.49), and no statistically significant difference was found at the orthopedics-traumatology ward (OR = 1.09, 95% CI = 0.88 to 1.27).

Conclusion
The results indicate beneficial outcomes after the implementation with less sedentary behavior and proportionately more patients being discharged home compared with before the implementation. However, little information is available about the adoption and fidelity of Ban Bedcentricity; therefore, outcomes should be interpreted with caution.

Impact
This multifaceted innovation to reduce sedentary behavior of patients during the hospital stay seems to be promising, with outcomes indicating less sedentary behavior in patients and more patients being discharged home after the implementation.

Lay Summary
We introduced Ban Bedcentricity, an intervention to reduce the amount of time patients lie in the hospital bed during their hospitalization. This study shows that after the introduction of Ban Bedcentricity, patients lie in bed less and are more often discharged home.
Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study
Authors: Salliot Carine , Nguyen Yann , Gusto Gaëlle , Gelot Amandine , Gambaretti Juliette , Mariette Xavier , Boutron-Ruault Marie-Christine , Seror Raphaèle 
Published: February 2021

Abstract

Objective
To assess the relationships between female hormonal exposures and risk of RA in a prospective cohort of French women.

Methods
E3N (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) is an on-going French prospective cohort that included 98 995 women aged 40–65 years in 1990. Every 2–3 years, women completed mailed questionnaires on their lifestyles, reproductive factors and health conditions. Cox proportional hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% CIs were estimated. Effect modification by smoking history was investigated.

Results
A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (&lt;22 vs ≥27 years; HR = 1.34; 95% CI 1.0, 1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95% CI 1.0, 1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95% CI 1.0, 2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95% CI 0.2, 0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (&gt;24 vs 0 months; multi-adjusted HR = 0.77; 95% CI 0.6, 0.9).

Conclusions
These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.
Association of particulate matter with autoimmune rheumatic diseases among adults in South Korea
Authors: Park Jun Seok , Choi Seulggie , Kim Kyuwoong , Chang Jooyoung , Kim Sung Min , Kim Seong Rae , Lee Gyeongsil , Son Joung Sik , Kim Kyae Hyung , Lee Eun Young , Park Sang Min 
Published: February 2021

Abstract

Objective
The primary objective of this study was to investigate adverse effects of ambient particulate matter of various sizes on the incidence of the prevalent autoimmune rheumatic diseases (AIRDs): RA, AS and SLE.

Methods
We investigated 230 034 participants in three metropolitan cities of South Korea from the National Health Insurance Service–National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. The 2008–2009 respective averages of particulate matter2.5 (&lt;2.5 μm) and particulate mattercoarse (2.5 μm to 10 μm) were linked with participants’ administrative district codes. Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox regression analysis in one- and two-pollutant models.

Results
Adjusted for age, sex, region, and household income, in the two-pollutant model, RA incidence was positively associated with the 10 μg/m³ increment of particulate matter2.5 (aHR = 1.74, 95% CI: 1.06, 2.86), but not with particulate mattercoarse (aHR = 1.27, 95% CI: 0.87, 1.85). In the one-pollutant model, the elevated incidence rate of RA was slightly attenuated (particulate matter2.5 aHR = 1.61, 95% CI: 0.99, 2.61; particulate mattercoarse aHR = 1.13, 95% CI: 0.80, 1.61), with marginal statistical significance for particulate matter2.5. The RA incidence was also higher in the 4th quartile group of particulate matter2.5 compared with the first quartile group (aHR = 1.83, 95% CI: 1.07, 3.11). Adverse effects from particulate matter were not found for AS or SLE in either the one- or two-pollutant models.

Conclusion
The important components of particulate matter10 associated with RA incidence were the fine fractions (particulate matter2.5); no positive association was found between particulate matter and AS or SLE.
Non-adherence in difficult-to-treat rheumatoid arthritis from the perspectives of patients and rheumatologists: a concept mapping study
Authors: Roodenrijs Nadia M T , van der Goes Marlies C , Welsing Paco M J , van Oorschot Eline P C , Nikiphorou Elena , Nijhof Nienke C , Tekstra Janneke , Lafeber Floris P J G , Jacobs Johannes W G , van Laar Jacob M , Geenen Rinie 
Published: February 2021

Abstract

Objectives
Treatment non-adherence is more frequent among difficult-to-treat (D2T) than among non-D2T RA patients. Perceptions of non-adherence may differ. We aimed to thematically structure and prioritize barriers to (i.e. causes and reasons for non-adherence) and facilitators of optimal adherence from the patients’ and rheumatologists’ perspectives.

Methods
Patients’ perceptions were identified in semi-structured in-depth interviews. Experts selected representative statements regarding 40 barriers and 40 facilitators. Twenty D2T and 20 non-D2T RA patients sorted these statements during two card-sorting tasks: first, by order of content similarity and, second, content applicability. Additionally, 20 rheumatologists sorted the statements by order of content applicability to the general RA population. The similarity sorting was used as input for hierarchical cluster analysis. The applicability sorting was analysed using descriptive statistics, prioritized and the results compared between D2T RA patients, non-D2T RA patients and rheumatologists.

Results
Nine clusters of barriers were identified, related to the healthcare system, treatment safety/efficacy, treatment regimen and patient behaviour. D2T RA patients prioritized adverse events and doubts about effectiveness as the most important barriers. Doubts about effectiveness were more important to D2T than to non-D2T RA patients (P = 0.02). Seven clusters of facilitators were identified, related to the healthcare system and directly to the patient. All RA patients and rheumatologists prioritized a good relationship with the healthcare professional and treatment information as the most helpful facilitators.

Conclusions
D2T RA patients, non-D2T RA patients and rheumatologists prioritized perceptions of non-adherence largely similarly. The structured overviews of barriers and facilitators provided in this study may guide improvement of adherence.
Segmental Series and Size: Clade-Wide Investigation of Molar Proportions Reveals a Major Evolutionary Allometry in the Dentition of Placental Mammals
Authors: Billet Guillaume , Bardin Jérémie 
Published: February 2021

AbstractIterative segments such as teeth or limbs are a widespread characteristic of living organisms. While their proportions may be governed by similar developmental rules in vertebrates, there is no emerging pattern as regards their relation to size. Placental mammals span eight orders of magnitude in body size and show a wide spectrum of dietary habits associated with size and reflected in their dentitions, especially molars. Although variation in size constitutes an important determinant for variation in biological traits, few major allometric trends have been documented on placental molars so far. Molar proportions have been intensively explored in placentals in relation to developmental models, but often at a small phylogenetic scale. Here, we analyzed the diversity of upper molar proportions in relation to absolute size in a large sample of placental species ($n = 299$) encompassing most of the group’s dental diversity. Our phylogenetically informed analyses revealed a 2-fold pattern of evolutionary integration among upper molars: while molars covary in size with each other, their proportions covary with the absolute size of the entire molar field. With increasing absolute size, posterior molars increase in size relative to anterior ones, meaning that large-sized species have relatively large rear molars while the opposite is true for small-sized species. The directionality of proportional increase in the molar row exhibits a previously unsuspected allometric patterning among placentals, showing how large-scale variations in size may have influenced variation in dental morphology. This finding provides new evidence that processes regulating the size of individual molars are integrated with overall patterns of growth and calls for further testing of allometric variation in the dentition and in other segmental series of the vertebrate body. [Dentition; evolution; model; phylogeny; segmentation; size.]