bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment
Authors: Gray Simon M. , Moss Anh D. , Herzog Jeremy W. , Kashiwagi Saori , Liu Bo , Young Jacqueline B. , Sun Shan , Bhatt Aadra P. , Fodor Anthony A. , Balfour Sartor R. 
Published: August 2024

Abstract
Background
Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.

Results
Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10−/− mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10−/− mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10−/− host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10−/− mice than the distinct microbiota reassembled in non-inflamed WT hosts.

Conclusions
Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.
Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury
Authors: Singh Aditya , Gong Steven , Vu Anh , Li Scott , Obenaus Andre 
Published: August 2024

AbstractTraumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.
Soft tissue laxity is highly variable in patients undergoing total knee arthroplasty
Authors: Weiner Travis R. , Shah Roshan P. , Neuwirth Alexander L. , Geller Jeffrey A. , Cooper H. John 
Published: August 2024

Abstract
Background
One major goal of total knee arthroplasty (TKA) is to achieve balanced medial and lateral gaps in flexion and extension. While bone resections are planned by the surgeon, soft tissue laxity is largely intrinsic and patient-specific in the absence of additional soft tissue releases. We sought to determine the variability in soft tissue laxity in patients undergoing TKA.

Methods
We retrospectively reviewed 113 patients undergoing TKA. Data on preoperative knee deformity were collected. Data from a dynamic intraoperative stress examination were collected by a robotic tracking system to quantify maximal medial and lateral opening in flexion (85–95 degrees) and extension (-5–20 degrees). T-tests were used to assess the differences between continuous variables.

Results
A valgus stress opened the medial compartment a mean of 4.3 ± 2.3 mm (0.0–12.4 mm) in extension and 4.6 ± 2.3 mm (0.0–12.9 mm) in flexion. A varus stress opened the lateral compartment a mean of 5.4 ± 2.4 mm (0.3–12.6 mm) in extension and 6.2 ± 2.5 mm (0.0–13.4 mm) in flexion.
The medial compartment of varus knees opened significantly more in response to valgus stress than valgus knees in both extension (5.2 mm vs. 2.6 mm; P < 0.0001) and flexion (5.4 mm vs 3.3 mm; P < 0.0001). The lateral compartment of valgus knees opened significantly more in response to varus stress than varus knees in both extension (6.7 mm vs. 4.8 mm; P < 0.0001) and flexion (7.4 mm vs. 5.8 mm; P = 0.0003).

Conclusions
Soft tissue laxity is highly variable in patients undergoing TKA, contributing anywhere from 0–13 mm to the post-resection gap. Only a small part of this variability is predictable by preoperative deformity. These findings have implications for either measured-resection or gap-balancing techniques.

Level of Evidence
Level III.
Clarifying the relation between the marrow contusion pattern around the knee and the types of concomitant intra-articular soft tissue injuries
Authors: Faheem Mohamed H. , Saddik Ahmed R. , Refaat Medhat M. 
Published: August 2024

Abstract
Background
Acute knee injuries represent a prevalent cause of morbidity among athletes and, if overlooked, could potentially lead to the development of chronic functional limitations. This study aimed to identify marrow contusion patterns around the knee and find the relation between each pattern and the intra- and extra-articular soft tissue injuries. This was a retrospective cross-sectional study carried out on 109 patients who presented to the hospital where the study was held with recent knee joint injury, for which magnetic resonance imaging was requested from January 2017 to January 2019.

Results
The entire patient population under investigation had a mean age of 30.2 ± 9.7 years. Regarding gender distribution, the study comprised 90 males (82.6%) and 19 females (17.4%). Regarding bone marrow contusion patterns in all studied patients, it was pivot shift in 58 patients (53.2%), clip injury in 11 patients (10.1%), dashboard injury in 7 patients (6.4%), hyperextension injury in 3 patients (2.8%), lateral patellar dislocation in 15 patients (13.8%), and others in 15 patients (13.8%). In the pivot shift pattern group, anterior cruciate ligament (ACL), medial meniscus, and medial collateral ligament (MCL) injuries were most commonly seen in 94.8, 50, and 44.8% of patients, respectively. Among the clip pattern group, MCL, ACL, and medial meniscus injuries were most common in 90.9, 36.4, and 36.4%, respectively. Regarding the dashboard injury group, posterior cruciate ligament (PCL), ACL, and medial and lateral menisci were the most common injury structures (100, 57.1, 42.9, and 42.9%, respectively). Despite the hyperextension pattern being found in a small number of patients, it shows 100% medial meniscal and 66.7% PCL injuries. Within the group of lateral patellar dislocation patterns, 100% of cases exhibited injuries to the medial patellofemoral ligament.

Conclusions
Precise localization of the marrow contusion around the knee and defining its pattern help to anticipate the most probable associated soft tissue injuries and, thus, can increase our sensitivity in their detection. This can have a better impact on patients' management outcomes.
Assessment of right ventricular systolic function using speckle tracking strain imaging in patients with severe tricuspid regurgitation: a validation study with cardiac magnetic resonance
Authors: Moon Inki , Kwak Soongu , Kim MinKwan , Lee Seung-Pyo , Kim Hyung-Kwan , Kim Yong-Jin , Park Jun-Bean 
Published: August 2024

Abstract
Background
Right ventricular (RV) systolic dysfunction is an established prognostic factor in patients with severe tricuspid regurgitation (TR). However, accurate assessment of RV systolic function using conventional echocardiography remains challenging. We investigated the accuracy of strain measurement using speckle tracking echocardiography (STE) for evaluating RV systolic function in patients with severe TR.

Methods
We included consecutive patients with severe TR who underwent echocardiography and cardiac magnetic resonance imaging (CMR) within 30 days between 2011 and 2023. Two-dimensional STE was used to measure RV free wall longitudinal strain (RVFWLS) and global longitudinal strain (RVGLS). These values were compared with the RV ejection fraction (RVEF) from CMR. RV systolic dysfunction was defined as a CMR-derived RVEF < 35%.

Results
A total of 87 patients with severe TR were identified during the study period. Among echocardiographic RV strain measurements, RVFWLS was the best correlate of CMR-derived RVEF (r = –0.37, P < 0.001), followed by RVGLS (r = –0.27, P = 0.012). Receiver operating characteristic (ROC) curve analysis revealed that RVFWLS provided better discrimination of RV systolic dysfunction, yielding an area under the ROC curve (AUC) of 0.770 (95% confidence interval [CI], 0.696–0.800) than RV fractional area change (AUC, 0.615; 95% CI, 0.500–0.859).

Conclusions
In patients with severe TR, STE-derived RVFWLS showed the best correlation with RVEF on CMR and displayed superior discrimination of RV systolic dysfunction compared with the RV fractional area change. This study suggests the potential usefulness of STE in assessing RV systolic function in this population.
Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials
Authors: Verheijden Rik J. , de Groot Jolien S. , Fabriek Babs O. , Hew Miki N. , May Anne M. , Suijkerbuijk Karijn P.M. 
Published: August 2024

PURPOSE
Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials.

METHODS
A post hoc analysis was performed on individual patient data from the anti–programmed cell death-1 (anti–PD-1) + anti–cytotoxic T lymphocyte–associated protein-4 (anti–CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex.

RESULTS

Of the 1,959 patients who received anti–PD-1 + anti–CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HR
adj
), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HR
adj
, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HR
adj
, 1.21 (95% CI, 1.06 to 1.39) and HR
adj
, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HR
adj
of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS.

CONCLUSION
Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.
Sleep Disturbances in Type 1 Diabetes and Mitigating Cardiovascular Risk
Authors: Abu Irsheed Ghada , Martyn-Nemeth Pamela , Baron Kelly Glazer , Reutrakul Sirimon 
Published: August 2024

Abstract
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in persons with type 1 diabetes (T1D). Despite control of known cardiovascular (CV) risk factors and better glycemic management, persons with T1D still face heightened CVD risk, suggesting additional contributing factors. Sleep has recently been recognized as a CV risk factor; however; the role of sleep in CVD specifically in T1D population has only started to emerge. Extensive evidence suggests that persons with T1D often encounter sleep disturbances. This review aims to comprehensively explore the relationship between sleep disturbances and CVD in T1D, proposed possible mediators including glycemic control, which has been studied more extensively, and less studied factors such as blood pressure, lipid metabolism, and weight management. Stress and self-care behaviors likely also play a role in the relationship between sleep disturbances and CVD. The evidence regarding sleep interventions in the context of T1D in mitigating these CV risk factors has recently been shown in early, small-scale studies. Sleep assessments should be a part of the standard of care in persons with T1D. Further research should focus on understanding the impact and mechanistic pathways of sleep disturbances on CV risk and developing T1D-specific sleep interventions to reduce CVD burden in this population.
(Re)montagem do mundo
Authors: Sarinho Rafaela Travassos , Costa Carlos Eduardo Felix da 
Published: August 2024

O que é um atlas? Como um percurso epistemológico em torno dessa figura pode ser produtivo para as diversas disciplinas voltadas para o pensamento visual? O presente trabalho aborda algumas dessas questões e elabora, na esteira de Didi Huberman (2018), uma genealogia do atlas, entendendo-o não apenas como aquilo que reúne e agrupa os objetos do conhecimento, mas como um método operativo de elaboração e montagem de mundo no qual o sujeito assume o protagonismo, fissurando ordens do discurso comuns a partir da inclusão de suas experiências, estabelecendo conexões entre o passado e o presente, sem visar nenhum sentido previamente definido.
Demand and capacity for hip and knee replacements in NHS Wales before the COVID-19 pandemic: implications for future planning
Authors: Royce Robert 
Published: August 2024

Background/Aims Joint replacement services in Wales were particularly affected by the COVID-19 pandemic, but waiting times had been high for several years before this. This study aimed to explore the hip and knee replacement activity in NHS Wales between 2000 and 2019 to indicate whether an existing gap between capacity and demand exacerbated the impact of the pandemic on waiting times. Methods A retrospective review was performed using publicly available databases, including the Patient Episode Database Wales and Stats Wales. Data relating to the number of hip and knee replacement operations performed between 2000 and 2019 and average waiting times were extracted and analysed. Data on the number of patients who underwent a hip or knee replacement during the study period after waiting over 36 weeks from referral were obtained by request to the Patient Episode Database Wales. Data were analysed descriptively. Results The 36-week referral to treatment target was not achieved for any year during the study period. Activity increased each year from 2000 to 2009, but varied substantially year to year afterwards. Average waiting times were at their lowest in 2009, but rose substantially after this point. Conclusions There had been a long-term lack of capacity for hip and knee replacements in NHS Wales for 20 years before 2020, which may have exacerbated the impact of the COVID-19 pandemic on waiting times for these services. Implementing more nuanced waiting time targets, based on the clinical effectiveness of procedures, may be more appropriate than blanket waiting time guarantees.
AN EXPLORATION OF MOVEMENT AND HANDLING BY PHYSIOTHERAPISTS IN A REHABILITATION SETTING: A MOTION ANALYSIS STUDY
Authors: Johnson Katharine , Pavlova Anastasia , Swinton Paul , Cooper Kay 
Published: August 2024

Purpose and BackgroundWork-related musculoskeletal disorders (WRMSD) can affect 56–80% of physiotherapists. Patient handling is reported as a significant risk factor for developing WRMSD with the back most frequently injured. Physiotherapists perform therapeutic handling to manually assist and facilitate patients’ movement to aid rehabilitation, which can increase physiotherapists risk of experiencing high forces during patient handling.Methods and ResultsA descriptive cross-sectional study was completed to explore and quantitatively measure the movement of ten physiotherapists during patient handling, over one working day, in a neurological setting. A wearable 3-dimensional motion analysis system, Xsens (Movella, Henderson, NV), was used to measure physiotherapist movement and postures in the ward setting during patient treatment sessions. The resulting joint angles were reported descriptively and compared against a frequently used ergonomic assessment tool, the Rapid Upper Limb Assessment (RULA).Physiotherapists adopted four main positions during patient handling tasks: 1) kneeling; 2) half-kneeling; 3) standing; and 4) sitting. Eight patient handling tasks were identified and described: 1) Lie-to-sit; 2) sit-to-lie; 3) sit-to-stand; facilitation of 4) upper limb; 5) lower limb; 6) trunk; and 7) standing treatments; and 8) walking facilitation. Kneeling and sitting positions demonstrated greater neck extension and greater lumbosacral flexion during treatments which scores highly with the RULA.ConclusionThis research identified that patient treatment tasks were more often performed in kneeling or sitting positions than standing. Current moving and handling guidance teaches moving and handling in a standing position; loading and stresses experienced by the physiotherapists may differ in sitting or kneeling positions.Conflicts of interestNoneSources of fundingNoneThis work has been presented as a poster at the CSP conference Glasgow 2023.
MENOPAUSE AND PARITY ARE ASSOCIATED WITH LUMBAR SPINE CURVATURE
Authors: Saunders F.R. , Parkinson J. , Aspden R.M. , Cootes T. , Gregory J.S. 
Published: August 2024

BackgroundLateral lumbar spine statistical shape models (SSM) have been used previously to describe associations with osteoarthritis and back pain. However, associations with factors such as osteoporosis, menopause and parity have not been explored.Methods and ResultsA 143-point SSM, describing L1 to the top of L5, was applied to lateral spine iDXA scans from UK Biobank. Associations with self-reported osteoporosis, menopause, parity and back pain and the first 10 modes of variation were examined using adjusted binary logistic regression or linear regression (adjusted for age, height, weight and total spine BMD). We report odds ratios with 95% confidence intervals for each standard deviation change in mode.Complete data were available for 2494 women. Mean age was 61.5 (± 7.4) years. 1369 women reported going through menopause, 96 women self-reported osteoporosis and 339 women reported chronic back pain. 80% of women reported at least 1 live birth.Lumbar spine shape was not associated with back pain in this cohort. Two modes were associated with menopause (modes 1 & 2), 1 mode with parity (mode 1) and 2 modes with osteoporosis (modes 3 & 5). Mode 1 (43.6% total variation), describing lumbar curvature was positively associated with both menopause [OR 1.15 95% CI 1.00–1.33, p=0.05] and parity [OR 1.058 95% CI 1.03–1.0, p=0.01]. Mode 3, describing decreased vertebral height was positively associated with osteoporosis [OR 1.40 95% CI 1.14–1.73, p=0.001].ConclusionMenopause and parity were associated with a curvier lumbar spine and osteoporosis with decreased vertebral height. Shape was not associated with back pain.No conflicts of interest Sources of fundingWellcome Trust collaborative award ref 209233
POTENTIAL CAUSAL ASSOCIATION BETWEEN HUMAN CYTOMEGALOVIRUS INFECTION AND CHRONIC BACK PAIN: A ONE-SAMPLE MENDELIAN RANDOMIZATION STUDY
Authors: Naeini M. Kazemi , Freidin M.B. , Smith I. Granville , Ward S. , Williams F.M.K. 
Published: August 2024

BackgroundChronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP.MethodUK Biobank participants provided information on CMV seropositivity and CBP status, which were available for both traits in 5,140 participants. We used EBV seropositivity as a negative control to identify confounding and inaccurate causal inference. A one-sample Mendelian randomization (MR) based on independent genetic variants predicting CMV and EBV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS).ResultsCMV GWAS revealed 86 independent SNPs having p-value < 2 × 10−4 for the one-sample MR. These SNPs were used to define genetically-predicted categories of CMV infection risk. CMV infection risk categories were significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, p-value = 0.043), findings which were confirmed using the CMV PRS (OR = 1.299; 95% CI: 1.141–1.479, p-value = 0.001). There was no causal association between EBV and CBP (p-value = 0.17).ConclusionOur results provide further evidence for a causal relationship between CMV infection and CBP. These results suggest a stratified approach to CBP may be useful, particularly in clinical trials and they shed light on underlying mechanisms in CBP.Conflicts of interestNo conflicts of interestSources of fundingNo funding obtainedAcknowledgementUKBB data were obtained under the project #18219Some aspects of this work have been previously presented at The Challenge of Chronic Pain: From Genomics to Therapy in UK and first 1st Danish International Conference on Personalised Medicine in Denmark.