bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of unweighting on gait kinematics during walking on a lower-body positive-pressure treadmill in patients with hip osteoarthritis
Authors: Kataoka Yoshiaki , Shimizu Tomohiro , Takeda Ryo , Tadano Shigeru , Saito Yuki , Osuka Satoshi , Ishida Tomoya , Samukawa Mina , Irie Tohru , Takahashi Daisuke , Iwasaki Norimasa , Tohyama Harukazu
Published: January 2021

Background

Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activities. Treadmills that support the body weight (BW) reduce the load on the lower limbs, and those equipped with a lower-body positive-pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device.

Methods

A total of 15 women with hip OA and 15 age-matched female controls wore a three-dimensional (3-D) motion analysis system and walked at a self-selected speed on the LBPP treadmill. Data regarding self-reported hip pain using a numeric rating scale (NRS) in which the scores 0 and 10 represented no pain and the worst pain, respectively, under three different BW conditions (100, 75, and 50%) were collected. Moreover, 3-D peak joint angles during gait under each condition were calculated and compared.

Results

In the hip OA group, the NRS pain scores at 50 and 75% BW conditions significantly decreased compared with that at 100% BW condition (50%,P = 0.002; 75%,P = 0.026), and the peak hip extension angle decreased compared with that in the healthy controls (P = 0.044). In both groups, unweighting significantly decreased the peak hip (P < 0.001) and knee (P < 0.001) flexion angles and increased the peak ankle plantar flexion angle (P < 0.001) during walking.

Conclusions

Unweighting by the LBPP treadmill decreased pain in the hip OA group but did not drastically alter the gait kinematics compared with that in the control group. Therefore, regarding the use of the LBPP treadmill for patients with hip OA, clinicians should consider the benefits of pain reduction rather than the kinematic changes.
Clinical and cost effectiveness of arthritis gloves in rheumatoid arthritis (A-GLOVES): randomised controlled trial with economic analysis
Authors: Hammond Alison , Prior Yeliz , Cotterill Sarah , Sutton Chris , Camacho Elizabeth , Heal Calvin , Adams Jo , Hough Yvonne , O’Neill Terence W. , Firth Jill
Published: January 2021

Background

Arthritis (or compression) gloves are widely prescribed to people with rheumatoid arthritis and other forms of hand arthritis. They are prescribed for daytime wear to reduce hand pain and improve hand function, and/or night-time wear to reduce pain, improve sleep and reduce morning stiffness. However, evidence for their effectiveness is limited. The aims of this study were to investigate the clinical and cost effectiveness of arthritis gloves compared to placebo gloves on hand pain, stiffness and function in people with rheumatoid arthritis and persistent hand pain.

Methods

A parallel randomised controlled trial, in adults (≥ 18 years) with rheumatoid or undifferentiated inflammatory arthritis at 16 National Health Service sites in the UK. Patients with persistent hand pain affecting function and/or sleep were eligible. Randomisation (1:1) was stratified by recent change (or not) in medication, using permuted blocks of random sizes. Three-quarter-finger length arthritis gloves (Isotoner®: applying 23-32 mmHg pressure) (intervention) were compared to loose-fitting placebo gloves (Jobskin® classic: providing no/minimal pressure) (control). Both gloves (considered to have similar thermal qualities) were provided by occupational therapists. Patients and outcome assessors were blinded; clinicians were not. The primary outcome was dominant hand pain on activity (0–10) at 12 weeks, analysed using linear regression and intention to treat principles.

Results

Two hundred six participants were randomly assigned (103 per arm) and 163 (84 intervention: 79 control) completed 12-week follow-up. Hand pain improved by 1.0 (intervention) and 1.2 (control), an adjusted mean difference of 0.10 (95% CI: − 0.47 to 0.67;p= 0.72). Adverse events were reported by 51% of intervention and 36% of control group participants; with 6 and 7% respectively, discontinuing glove wear. Provision of arthritis gloves cost £129, with no additional benefit.

Conclusion

The trial provides evidence of no clinically important effect of arthritis gloves on any of the trial outcomes (hand pain, function and stiffness) and arthritis gloves are not cost-effective. The clinical and cost-effectiveness results support ceasing provision of arthritis gloves in routine clinical practice. Funding: National Institute for Health Research.

Trial registration

ISRCTN,ISRCTN25892131; Registered 05/09/2016: retrospectively registered.
Patterns of coronal and sagittal deformities in adolescent idiopathic scoliosis
Authors: Mak Trixie , Cheung Prudence Wing Hang , Zhang Teng , Cheung Jason Pui Yin
Published: January 2021

Background

Thoracic scoliosis has been shown to be associated with hypokyphosis in adolescent idiopathic scoliosis (AIS). However, the relationship of sagittal spino-pelvic parameters with different coronal curve patterns and their influence on patient-perceived quality of life is unknown. This study aims to determine the association between coronal and sagittal malalignment in patients with AIS and to determine their effects on SRS-22r scores.

Methods

A cross-sectional study was conducted on 1054 consecutive patients with AIS. The coronal Cobb angle, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), PI-LL mismatch (PI-LL), pelvic tilt (PT), and sacral slope (SS) were measured on standing radiographs. The coronal Cobb angle (mild: 10–20°; moderate: > 20–40°; severe: > 40°) and PI (low: < 35°; average: 35–50°; high: > 50°) were divided into 3 sub-groups for comparison. Relationship between coronal curve magnitudes and sagittal parameters was studied as was their association with SRS-22r scores.

Results

Low PI had smaller SS (30.1 ± 8.3° vs 44.8 ± 7.7°; p < 0.001), PT (− 0.3 ± 8.1° vs 14.4 ± 7.5°; p < 0.001), and LL (42.0 ± 13.2° vs 55.1 ± 10.6°; p < 0.001), negative PI-LL mismatch (− 12.1 ± 13.1° vs 4.1 ± 10.5°; p < 0.001) as compared to large PI. There were no significant relationships with PI and TK (p = 0.905) or curve magnitude (p = 0.431). No differences in sagittal parameters were observed for mild, moderate or severe coronal Cobb angles. SRS-22r scores only correlated with coronal Cobb angle and larger Cobb angles were negatively correlated with the function, appearance and pain domains.

Conclusions

The sagittal profile for AIS is associated with the pelvic parameters especially PI but not with the coronal curve pattern. All patients have a similar TK regardless of coronal curve type. However, it appears that the coronal deformity is a greater influence on quality of life outcomes especially those > 40°.
Characterization of metabolic responses, genetic variations, and microsatellite instability in ammonia-stressed CHO cells grown in fed-batch cultures
Authors: Chitwood Dylan G. , Wang Qinghua , Elliott Kathryn , Bullock Aiyana , Jordana Dwon , Li Zhigang , Wu Cathy , Harcum Sarah W. , Saski Christopher A.
Published: January 2021

Background

As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10’s of milligrams to over 10’s of grams per liter. Most of these gains in productivity can be attributed to increasing cell densities within bioreactors. As such, strategies have been developed to minimize accumulation of metabolic wastes, such as lactate and ammonia. Unfortunately, neither cell growth nor biopharmaceutical production can occur without some waste metabolite accumulation. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a suboptimal culture environment, little is known about the genotoxic properties of these compounds that may lead to global genome instability. In this study, we examined the effects of high and moderate extracellular ammonia on the physiology and genomic integrity of Chinese hamster ovary (CHO) cells.

Results

Through whole genome sequencing, we discovered 2394 variant sites within functional genes comprised of both single nucleotide polymorphisms and insertion/deletion mutations as a result of ammonia stress with high or moderate impact on functional genes. Furthermore, several of these de novo mutations were found in genes whose functions are to maintain genome stability, such as Tp53, Tnfsf11, Brca1, as well as Nfkb1. Furthermore, we characterized microsatellite content of the cultures using the CriGri-PICR Chinese hamster genome assembly and discovered an abundance of microsatellite loci that are not replicated faithfully in the ammonia-stressed cultures. Unfaithful replication of these loci is a signature of microsatellite instability. With rigorous filtering, we found 124 candidate microsatellite loci that may be suitable for further investigation to determine whether these loci may be reliable biomarkers to predict genome instability in CHO cultures.

Conclusion

This study advances our knowledge with regards to the effects of ammonia accumulation on CHO cell culture performance by identifying ammonia-sensitive genes linked to genome stability and lays the foundation for the development of a new diagnostic tool for assessing genome stability.
A qualitative study of bereaved family caregivers: feeling of security, facilitators and barriers for rural home care and death for persons with advanced cancer
Authors: Barlund Anne Sæle , André Beate , Sand Kari , Brenne Anne-Tove
Published: January 2021

Background

For cancer patients and their family, an important factor that determines the choice to die at home is the caregivers’ feeling of security when caring for the patient at home. Support to caregivers from healthcare professionals is important for the feeling of security. In rural areas, long distances and variable infrastructure may influence on access to healthcare services. This study explored factors that determined the security of caregivers of patients with advanced cancer who cared for the patients at home at the end of life in the rural region of Sogn og Fjordane in Norway, and what factors that facilitated home death.

Methods

A qualitative study using semi-structured in-depth interviews with bereaved with experience from caring for cancer patients at home at the end of life was performed. Meaning units were extracted from the transcribed interviews and divided into categories and subcategories using Kvale and Brinkmann’s qualitative method for analysis.

Results

Ten bereaved caregivers from nine families where recruited. Five had lived together with the deceased. Three main categories of factors contributing to security emerged from the analysis: “Personal factors”, “Healthcare professionals” and “Organization” of healthcare. Healthcare professionals and the organization of healthcare services contributed most to the feeling of security.

Conclusion

Good competence in palliative care among healthcare professionals caring for patients with advanced cancer at home and well- organized palliative care services with defined responsibilities provided security to caregivers caring for advanced cancer patients at home in Sogn og Fjordane.
Perceived usefulness and ease of use of fundoscopy by medical students: a randomised crossover trial of six technologies (eFOCUS 1)
Authors: Dunn H. P. , Kang C. J. , Marks S. , Witherow J. L. , Dunn S. M. , Healey P. R. , White A. J.
Published: January 2021

Background

Fundoscopy outside ophthalmology is in decline, and the technical demands of the traditional direct ophthalmoscope examination are likely contributing. Alternative fundoscopy technologies are increasingly available, yet valid comparisons between fundoscopy technologies are lacking. We aimed to assess medical students’ perceptions of usefulness and ease of use of traditional and contemporary fundus-viewing technologies including smartphone fundoscopy.

Methods

One hundred forty-six second-year medical students participated in a cross-sectional, randomised, cross-over study of fundoscopy methods. Medical students completed small group training sessions using six current fundoscopy technologies including: a non-mydriatic fundus camera; two types of direct fundoscopy; and three types of smartphone fundoscopy. A novel survey of perceived usefulness and ease of use was then completed by students.

Results

Repeated-measures ANOVA found students rated both the perceived usefulness (p< 0.001) and ease of use (p< 0.001) of smartphone fundoscopy significantly higher than both the non-mydriatic camera and direct fundoscopy.

Conclusions

Smartphone fundoscopy was found to be significantly more useful and easier to use than other modalities. Educators should optimise student access to novel fundoscopy technologies such as smartphone fundoscopy which may mitigate the technical challenges of fundoscopy and reinvigorate use of this valuable clinical examination.
Out-of-pocket costs and time spent attending antenatal care services: a case study of pregnant women in selected rural communities in Zinder, Niger
Authors: Ouédraogo Césaire T. , Vosti Stephen A. , Wessells K. Ryan , Arnold Charles D. , Faye M. Thierno , Hess Sonja Y.
Published: January 2021

Background

Despite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance.

Methods

Data were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations.

Results

The mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (− 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not.

Conclusion

OPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC.

Trial registration

The NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688. Registered 16 April 2013.
An updated tribal classification of Lamiaceae based on plastome phylogenomics
Authors: Zhao Fei , Chen Ya-Ping , Salmaki Yasaman , Drew Bryan T. , Wilson Trevor C. , Scheen Anne-Cathrine , Celep Ferhat , Bräuchler Christian , Bendiksby Mika , Wang Qiang , Min Dao-Zhang , Peng Hua , Olmstead Richard G. , Li Bo , Xiang Chun-Lei
Published: January 2021

Background

A robust molecular phylogeny is fundamental for developing a stable classification and providing a solid framework to understand patterns of diversification, historical biogeography, and character evolution. As the sixth largest angiosperm family, Lamiaceae, or the mint family, consitutes a major source of aromatic oil, wood, ornamentals, and culinary and medicinal herbs, making it an exceptionally important group ecologically, ethnobotanically, and floristically. The lack of a reliable phylogenetic framework for this family has thus far hindered broad-scale biogeographic studies and our comprehension of diversification. Although significant progress has been made towards clarifying Lamiaceae relationships during the past three decades, the resolution of a phylogenetic backbone at the tribal level has remained one of the greatest challenges due to limited availability of genetic data.

Results

We performed phylogenetic analyses of Lamiaceae to infer relationships at the tribal level using 79 protein-coding plastid genes from 175 accessions representing 170 taxa, 79 genera, and all 12 subfamilies. Both maximum likelihood and Bayesian analyses yielded a more robust phylogenetic hypothesis relative to previous studies and supported the monophyly of all 12 subfamilies, and a classification for 22 tribes, three of which are newly recognized in this study. As a consequence, we propose an updated phylogenetically informed tribal classification for Lamiaceae that is supplemented with a detailed summary of taxonomic history, generic and species diversity, morphology, synapomorphies, and distribution for each subfamily and tribe.

Conclusions

Increased taxon sampling conjoined with phylogenetic analyses based on plastome sequences has provided robust support at both deep and shallow nodes and offers new insights into the phylogenetic relationships among tribes and subfamilies of Lamiaceae. This robust phylogenetic backbone of Lamiaceae will serve as a framework for future studies on mint classification, biogeography, character evolution, and diversification.

Graphical abstract
Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems
Authors:   Local Burden of Disease HIV Collaborators
Published: January 2021

Background

Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico.

Methods

We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017.

Results

All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017.

Conclusions

Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.
Conceptions of the pathophysiology of happy hypoxemia in COVID-19
Authors: Dhont Sebastiaan , Derom Eric , Van Braeckel Eva , Depuydt Pieter , Lambrecht Bart N.
Published: January 2021

In their letter-to-the-editor entitled “Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19”, Tobin et al. (Respir Res 21:249, 2020) debated our views on happy hypoxemia in COVID-19 (Respir Res 21:198, 2020). We thank the authors for their interesting comments and alternative viewpoints, and we would like to clarify several important aspects raised.
A study of patients’ quality of life more than 5 years after trauma: a prospective follow-up
Authors: Vardon-Bounes Fanny , Gracia Romain , Abaziou Timothée , Crognier Laure , Seguin Thierry , Labaste François , Geeraerts Thomas , Georges Bernard , Conil Jean-Marie , Minville Vincent
Published: January 2021

Background

The long-term fate of severely injured patients in terms of their quality of life is not well known. Our aim was to assess the quality of life of patients who have suffered moderate to severe trauma and to identify primary factors of long-term quality of life impairment.

Methods

A prospective monocentric study conducted on a number of patients who were victims of moderate to severe injuries during the year 2012. Patients were selected based on an Injury Severity Score (ISS) more than or equal to 9. Quality of life was assessed by the MOS SF-36 and NHP scores as a primary evaluation criterion. The secondary evaluation criteria were the determination of the socio-economic impact on quality of life and the identification of factors associated with disability.

Results

Two hundred and eight patients were contacted by e-mail or telephone. Fifty-five patients participated in this study (with a participation level of 26.4%), including 78.2% men, with a median age of 46. Significant alterations in quality of life were observed with the NHP and MOS SF-36 scale, including physical and psychological components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10), 20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores ≤ 85 on the physical functioning variable of the MOS SF 36 scale was associated with disability.

Conclusion

More than five years after a moderate to severe injury, patients’ quality of life was significantly impacted, resulting in significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score ≤ 85 on the physical functioning dimension of the MOS SF-36 scale. This study raises the question of whether or not early rehabilitation programs should be implemented in order to limit the long-term impact of major trauma.
Predictors of long-term post-thrombotic syndrome following high proximal deep vein thrombosis: a cross-sectional study
Authors: Engeseth Marit , Enden Tone , Sandset Per Morten , Wik Hilde Skuterud
Published: January 2021

Background

Post-thrombotic syndrome (PTS) is a frequent chronic complication of proximal deep vein thrombosis (DVT) of the lower limb, but predictors of PTS are not well established. We aimed to examine predictors of PTS in patients with long-term PTS following proximal DVT.

Methods

During 2006–09, 209 patients with a first time acute upper femoral or iliofemoral DVT were randomized to receive either additional catheter-directed thrombolysis or conventional therapy alone. In 2017, the 170 still-living participants were invited to participate in a cross-sectional follow-up study. In the absence of a gold standard diagnostic test, PTS was defined in line with clinical practice by four mandatory, predefined clinical criteria: 1. An objectively verified DVT; 2. Chronic complaints (> 1 month) in the DVT leg; 3. Complaints appeared after the DVT; and 4. An alternative diagnosis was unlikely. Possible predictors of PTS were identified with multivariate logistic regression.

Results

Eighty-eight patients (52%) were included 8–10 years following the index DVT, and 44 patients (50%) were diagnosed with PTS by the predefined clinical criteria. Younger age and higher baseline Villalta score were found to be independent predictors of PTS, i.e., OR 0.96 (95% CI, 0.93–0.99), and 1.23 (95% CI, 1.02–1.49), respectively. Lack of iliofemoral patency at six months follow-up was significant in the bivariate analysis, but did not prove to be significant after the multivariate adjustments.

Conclusions

In long-term follow up after high proximal DVT, younger age and higher Villalta score at DVT diagnosis were independent predictors of PTS.
Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice
Authors: Menees Kelly B. , Earls Rachael H. , Chung Jaegwon , Jernigan Janna , Filipov Nikolay M. , Carpenter Jessica M. , Lee Jae-Kyung
Published: January 2021

Background

Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood.

Results

Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis.

Conclusions

This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.
Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet
Authors: Daniel Sarah , Phillippi Danielle , Schneider Leah J. , Nguyen Kayla N. , Mirpuri Julie , Lund Amie K.
Published: January 2021

Background

Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study.

Results

Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment.

Conclusions

Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.
A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia
Authors: Howard Dena R. , Hockaday Anna , Brown Julia M. , Gregory Walter M. , Todd Susan , Munir Tahla , Oughton Jamie B. , Dimbleby Claire , Hillmen Peter
Published: January 2021

Background

The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success.

Methods

FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial.

Results

The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres.

Conclusions

FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community.

Trial registration

ISRCTN Registry ISRCTN01844152. Registered on August 08, 2014
Recruitment and retention of participant and study partner dyads in two multinational Alzheimer’s disease registration trials
Authors: Bernstein Olivia M. , Grill Joshua D. , Gillen Daniel L.
Published: January 2021

Background

Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk.

Methods

We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia.

Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout.

Results

Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model.

Conclusions

After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.
A methodological review protocol of the use of Bayesian factor analysis in primary care research
Authors: Zhang Hao , Schuster Tibor
Published: January 2021

Background

The development of questionnaires for primary care practice and research is of increasing interest in the literature. In settings where valuable prior knowledge or preliminary data is available, Bayesian factor analysis can be used to incorporate such information when conducting questionnaire construct validation. This protocol outlines a methodological review that will summarize evidence on the current use of Bayesian factor analysis in the primary care literature.

Methods

A comprehensive search strategy has been developed and will be used to identify relevant literature (research studies in primary care) indexed in MEDLINE, Scopus, EMBASE, CINAHL, and Cochrane Library. The search strategy includes terms and synonyms for Bayesian factor analysis and primary care. The reference lists of relevant articles being identified will be screened to find further relevant studies. At least two reviewers will independently extract data and resolve discrepancies through consensus. Descriptive analyses will summarize the use and reporting of Bayesian factor analysis approaches for validating questionnaires applicable to primary care.

Discussion

This methodological review will provide a comprehensive overview of the current use and reporting of Bayesian factor analysis in primary care and will provide recommendations for its proper future use.

Systematic review registration

PROSPERO CRD42018114978
Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis
Authors: Cheng Yangfan , Chen Yongping , Shang Huifang
Published: January 2021

Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21],p= 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73],p< 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05],p< 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67],p< 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90],p= 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88],p= 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.
Correction to: Experimental Study and Analytical Modeling on Fatigue Properties of Pervious Concrete Made with Natural and Recycled Aggregates
Authors: Chen Xudong , Shi Dandan , Shen Nan , Li Shengtao , Liu Saisai
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
An exploration of perceptions and preferences for healthy eating in Dutch consumers: a qualitative pilot study
Authors: Coumans Juul M. J. , Bolman Catherine A. W. , Lechner Lilian , Oenema Anke
Published: January 2021

Background

Unhealthy dietary patterns are highly prevalent in Western countries, and they have been associated with depression, hypertension, heart disease, cancer, type 2 diabetes, and obesity. Many dietary interventions have been developed to promote healthier dietary behavior, yet most do not achieve the intended dietary change. This study aims to provide a better understanding of what Dutch consumers perceive as a healthy diet, how this relates to the current Dutch nutrition guidelines, and their preferences for how to eat more healthily. This is an essential consideration for the development of tailored interventions aimed to help people adopt changes in their dietary behavior.

Methods

Seventy-eight participants filled in an online questionnaire containing both open-ended and closed-ended questions. The qualitative data was analyzed using content analysis resulting in a classification scheme. Two students then identified to which category each part of a participant’s answer belonged.

Results

For both the perception of a healthy diet and how to eat healthily, four major categories and a residual category were identified: dietary patterns, food processing, food products, content/nutrients, and non-food. These major categories consisted of several categories. The results showed that how people perceived a healthy diet was mostly represented at the level of food product (vegetables and fruit) and the content/nutrient level (carbohydrates), whereas how they would like to eat healthily was mostly represented at the level of food processing (preparation), food product (vegetables), and dietary patterns (amount).

Conclusions

Our findings are mostly in line with how the Dutch dietary guidelines are communicated (“product level”). However, consumers primarily mention single aspects instead of naming the guidelines as a whole. Health policymakers can use this insight in future communications regarding the guidelines to the general public. A challenge for future (eHealth) diet interventions is how to implement and tailor dietary information that optimally connects with the perceptions of the target population.
Cotton germplasm improvement and progress in Pakistan
Authors: RAZZAQ Abdul , ZAFAR Muhammad Mubashar , ALI Arfan , HAFEEZ Abdul , BATOOL Wajeeha , SHI Yuzhen , GONG Wankui , YUAN Youlu
Published: January 2021

Cotton (Gossypium spp.) contributes significantly to the economy of cotton-producing countries. Pakistan is the fourth-largest producer of cotton after China, the USA and India. The average yield of cotton is about 570.99 kg.hm− 2 in Pakistan. Climate change and different biotic stresses are causing reduction in cotton production. Transgenic approaches have unique advantage to tackle all these problems. However, how to confer permanent resistance in cotton against insects through genetic modification, is still a big challenge to address. Development of transgenic cotton has been proven to be effective. But its effectiveness depends upon several factors, including heterogeneity, seed purity, diffusion of varieties, backcrossing and ethical concerns. Cotton biotechnology was initiated in Pakistan in 1992–1993 with a focus on acquiring cotton leaf curl virus (CLCuV)-resistant insect-resistant, and improving fiber quality. This review summarizes the use of molecular markers, QTLs, GWAS, and gene cloning for cotton germplasm improvement, particularly in Pakistan.
The porcine respiratory microbiome: recent insights and future challenges
Authors: Pirolo Mattia , Espinosa-Gongora Carmen , Bogaert Debby , Guardabassi Luca
Published: January 2021

Understanding the structure of the respiratory microbiome and its complex interactions with opportunistic pathogenic bacteria has become a topic of great scientific and economic interest in livestock production, given the severe consequences of respiratory disease on animal health and welfare. The present review focuses on the microbial structures of the porcine upper and lower airways, and the factors that influence microbiome development and onset of respiratory disease. Following a literature search on PubMed and Scopus, 21 articles were selected based on defined exclusion criteria (20 studies performed by 16S rRNA gene sequencing and one by shotgun metagenomics). Analysis of the selected literature indicated that the microbial structure of the upper respiratory tract undergoes a remarkable evolution after birth and tends to stabilise around weaning. Antimicrobial treatment, gaseous ammonia concentration, diet and floor type are amongst the recognized environmental factors influencing microbiome structure. The predominant phyla of the upper respiratory tract are Proteobacteria and Firmicutes with significant differences at the genus level between the nasal and the oropharyngeal cavity. Only five studies investigated the lower respiratory tract and their results diverged in relation to the relative abundance of these two phyla and even more in the composition of the lung microbiome at the genus level, likely because of methodological differences. Reduced diversity and imbalanced microbial composition are associated with an increased risk of respiratory disease. However, most studies presented methodological pitfalls concerning specimen collection, sequencing target and depth, and lack of quality control. Standardization of sampling and sequencing procedures would contribute to a better understanding of the structure of the microbiota inhabiting the lower respiratory tract and its relationship with pig health and disease.
Can dynamic magnetic resonance imaging replace static magnetic resonance sequences in evaluation of temporomandibular joint dysfunction?
Authors: Kamel Zeinab Sobhy Ahmed Sayed Ahmed , El-Shafey Mohammad Hassan Rashad , Hassanien Omar Ahmed , Nagy Hanan Ahmad
Published: January 2021

Background

Static MRI was used as an effective tool for diagnosis of temporomandibular joint dysfunction instead of invasive techniques such as arthroscopy and arthrography. The purpose of this study was to detect whether dynamic MRI can be used instead of static MRI in diagnosis of TMJ dysfunction or not.

Results

According to disc displacement, anterior disc displacement was detected in 29 joints (36.25%) by both static and dynamic MRIs, and medial and lateral disc displacements were detected only by static MRI. Regarding disc mobility, dynamic MRI detects stuck disc in 4 joints versus 2 joints detected by static MRI (p value 0.008). Condylar translation was abnormal in 18 joints (22.5%) by static MRI and in 26 joints (32.5%) by dynamic MRI (p value < 0.001). The detection rate of articular disc for dynamic MRI was 87.5% versus static MRI 92.5% (p value 0.038), and the detection rate of condylar head for dynamic MRI was 97.5% versus static MRI 100% (p value 0.012).

Conclusion

Dynamic MRI cannot replace static MRI in evaluation of TMJ dysfunction; both of them support each other for accurate diagnosis and better image quality.