bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic utility of brain MRI volumetry in comparing traumatic brain injury, Alzheimer disease and behavioral variant frontotemporal dementia
Authors: Raji Cyrus A. , Meysami Somayeh , Porter Verna R. , Merrill David A. , Mendez Mario F. 
Published: September 2024

Abstract
Background
Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments.

Objective
To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD).

Method
We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes across diagnostic groups. Discriminant analysis was done with leave-one-out cross validation on Neuroreader metrics to determine diagnostic delineation across groups.

Result
LOAD was the oldest compared to other groups (F = 27.5, p < .001). There were no statistically significant differences in sex (p = .58) with women comprising 54.7% of the entire cohort. EOAD and LOAD had the lowest Mini-Mental State Exam (MMSE) scores compared to TBI (p = .04 for EOAD and p = .01 for LOAD). LOAD had lowest hippocampal volumes (Left Hippocampus F = 13.1, Right Hippocampus F = 7.3, p < .001), low white matter volume in TBI (F = 5.9, p < .001), lower left parietal lobe volume in EOAD (F = 9.4, p < .001), and lower total gray matter volume in bvFTD (F = 32.8, p < .001) and caudate atrophy (F = 1737.5, p < .001). Areas under the curve ranged from 92.3 to 100%, sensitivity between 82.2 and 100%, specificity of 78.1-100%. TBI was the most accurately delineated diagnosis. Predictive features included caudate, frontal, parietal, temporal lobar and total white matter volumes.

Conclusion
We identified the diagnostic utility of regional volumetric differences across multiple neurocognitive disorders. Brain MRI volumetry is widely available and can be applied in distinguishing these disorders.
Association between removable prosthesis-wearing and pneumonia: a systematic review and meta-analysis
Authors: Lim Tong Wah , Li Kar Yan , Burrow Michael Francis , McGrath Colman 
Published: September 2024

Abstract
Background
A high burden of respiratory pathogens colonizing removable prosthesis surfaces suggests the potential of association between removable prosthesis-wearing and respiratory infections. Therefore, this systematic review and meta-analysis aimed to evaluate the evidence from clinical studies concerning the association between removable prosthesis-wearing and respiratory infections.

Methods
Clinical studies that reported respiratory infections associated with adult patients wearing removable prostheses in any centers (hospitals and nursing homes) or communities were included. Literature was searched across five electronic databases (MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus) to 28 May 2024. An additional search was performed for unpublished trials and references cited in related studies. The Newcastle-Ottawa Scale was employed for the quality assessment. The certainty assessment was established using GRADE. The results were pooled using a frequentist random-effects meta-analysis and the odds ratios generated.

Results
A total of 1143 articles were identified. Thirteen articles had full-text articles screening and an additional two articles were added through reference linkage. Ultimately, six non-randomized clinical studies reporting various types of pneumonia contributed to this review. Overall odds of having pneumonia among prosthesis wearers were 1.43 (95% CI: 0.76 to 2.69) and 1.27 (95% CI: 1.11 to 1.46) using the random- and fixed-effects models, respectively. The heterogeneity in the meta-analysis was substantial. In subgroup analysis according to the study design, the heterogeneity within prospective studies was much reduced, I2 = 0% (p = 0.355). The certainty of the evidence evaluated using the GRADE approach was low to very low evidence for prosthesis wearers developing pneumonia based on studies.

Conclusions
There was no conclusive evidence from the non-randomized clinical studies supporting whether prosthesis-wearing is a risk factor for pneumonia based on outcomes from this review.
Assessing resident experience of a new experiential learning health advocacy curriculum: a mixed methods study
Authors: Moledina Aliza , Ruller Sydney , Halman Samantha , Ying Yvonne 
Published: September 2024

Abstract
Background
Health Advocacy is considered one of the most difficult skills to teach. Many medical learners feel ill-equipped in social competencies and identify it as a significant gap in their medical training. Experiential learning has recently been emerging as a more effective method to teach health advocacy. The Post Graduate Medical Education (PGME) Health Advocacy Day is a new experiential learning curriculum designed to teach important competencies of health advocacy and social accountability to post-graduate medical residents at the University of Ottawa in Ottawa, Canada. The objective of this mixed-methods study was to assess resident experiences.

Methods
Second-year trainees from all adult residency programs attended the Advocacy Day as part of a mandatory academic day. All participants completed a mandatory pre-and post-session quiz to assess knowledge of key topics before and after the course. We also distributed a voluntary survey to all participants and invited residents to participate in semi-structured interviews to provide feedback on the course. We used descriptive statistics to analyze quiz scores and survey results and conducted a paired t-test of pre and post-test quiz scores. We also performed a thematic analysis of qualitative feedback, specifically survey comments and semi-structured interviews.

Results
One hundred and eighty-three residents participated in the Advocacy Day and 112 (61.2%) completed the post-course survey. Ten residents volunteered to be interviewed. Respondents were generally satisfied by the session and felt it was of good quality. Most residents felt the course enhanced their ability to advocate for individual patients or communities (N = 80; 71.5%) and understand patients and families’ lived experience with illness (N = 87; 77.5%). Most residents also felt the course improved their knowledge of the impact of social determinants of health (N = 91; 81.2%) and increased their awareness of local resources that can support patients and their families (N = 88; 78.3%). Visiting community sites in-person and meeting persons with lived experiences were highlighted as the most valuable components of the course.

Conclusion
Experiential learning can be integrated within post-graduate medical curricula to teach health advocacy competencies. Future studies should examine the longitudinal impact of the curricula, to determine whether shifts in perspectives persist over time.
FgCWM1 modulates TaNDUFA9 to inhibit SA synthesis and reduce FHB resistance in wheat
Authors: Zhang Yazhou , Yao Danyu , Yu Xinyu , Cheng Xinyao , Wen Lan , Liu Caihong , Xu Qiang , Deng Mei , Jiang Qiantao , Qi Pengfei , Wei Yuming 
Published: September 2024

Abstract
Background
Fusarium head blight (FHB) significantly impacts wheat yield and quality. Understanding the intricate interaction mechanisms between Fusarium graminearum (the main pathogen of FHB) and wheat is crucial for developing effective strategies to manage and this disease. Our previous studies had shown that the absence of the cell wall mannoprotein FgCWM1, located at the outermost layer of the cell wall, led to a decrease in the pathogenicity of F. graminearum and induced the accumulation of salicylic acid (SA) in wheat. Hence, we propose that FgCWM1 may play a role in interacting between F. graminearum and wheat, as its physical location facilitates interaction effects.

Results
In this study, we have identified that the C-terminal region of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) could interact with FgCWM1 through the yeast two-hybrid assay. The interaction was further confirmed through the combination of Co-IP and BiFC analyses. Consistently, the results of subcellular localization indicated that TaNDUFA9 was localized in the cytoplasm adjacent to the cell membrane and chloroplasts. The protein was also detected to be associated with mitochondria and positively regulated complex I activity. The loss-of-function mutant of TaNDUFA9 exhibited a delay in flowering, decreased seed setting rate, and reduced pollen fertility. However, it exhibited elevated levels of SA and increased resistance to FHB caused by F. graminearum infection. Meanwhile, inoculation with the FgCWM1 deletion mutant strain led to increased synthesis of SA in wheat.

Conclusions
These findings suggest that TaNDUFA9 inhibits SA synthesis and FHB resistance in wheat. FgCWM1 enhances this inhibition by interacting with the C-terminal region of TaNDUFA9, ultimately facilitating F. graminearum infection in wheat. This study provides new insights into the interaction mechanism between F. graminearum and wheat. TaNDUFA9 could serve as a target gene for enhancing wheat resistance to FHB.
Has multimorbidity and frailty in adult hospital admissions changed over the last 15 years? A retrospective study of 107 million admissions in England
Authors: Faitna Puji , Bottle Alex , Klaber Bob , Aylin Paul P. 
Published: September 2024

Abstract
Background
Few studies have quantified multimorbidity and frailty trends within hospital settings, with even fewer reporting how much is attributable to the ageing population and individual patient factors. Studies to date have tended to focus on people over 65, rarely capturing older people or stratifying findings by planned and unplanned activity. As the UK’s national health service (NHS) backlog worsens, and debates about productivity dominate, it is essential to understand these hospital trends so health services can meet them.

Methods
Hospital Episode Statistics inpatient admission records were extracted for adults between 2006 and 2021. Multimorbidity and frailty was measured using Elixhauser Comorbidity Index and Soong Frailty Scores. Yearly proportions of people with Elixhauser conditions (0, 1, 2, 3 +) or frailty syndromes (0, 1, 2 +) were reported, and the prevalence between 2006 and 2021 compared. Logistic regression models measured how much patient factors impacted the likelihood of having three or more Elixhauser conditions or two or more frailty syndromes. Results were stratified by age groups (18–44, 45–64 and 65 +) and admission type (emergency or elective).

Results
The study included 107 million adult inpatient hospital episodes. Overall, the proportion of admissions with one or more Elixhauser conditions rose for acute and elective admissions, with the trend becoming more prominent as age increased. This was most striking among acute admissions for people aged 65 and over, who saw a 35.2% absolute increase in the proportion of admissions who had three or more Elixhauser conditions. This means there were 915,221 extra hospital episodes in the last 12 months of the study, by people who had at least three Elixhauser conditions compared with 15 years ago. The findings were similar for people who had one or more frailty syndromes. Overall, year, age and socioeconomic deprivation were found to be strongly and positively associated with having three or more Elixhauser conditions or two or more frailty syndromes, with socioeconomic deprivation showing a strong dose–response relationship.

Conclusions
Overall, the proportion of hospital admissions with multiple conditions or frailty syndromes has risen over the last 15 years. This matches smaller-scale and anecdotal reports from hospitals and can inform how hospitals are reimbursed.
Addressing the credibility crisis in Mendelian randomization
Authors: Burgess Stephen , Woolf Benjamin , Mason Amy M. , Ala-Korpela Mika , Gill Dipender 
Published: September 2024

Abstract
Background
Genome-wide association studies have enabled Mendelian randomization analyses to be performed at an industrial scale. Two-sample summary data Mendelian randomization analyses can be performed using publicly available data by anyone who has access to the internet. While this has led to many insightful papers, it has also fuelled an explosion of poor-quality Mendelian randomization publications, which threatens to undermine the credibility of the whole approach.

Findings
We detail five pitfalls in conducting a reliable Mendelian randomization investigation: (1) inappropriate research question, (2) inappropriate choice of variants as instruments, (3) insufficient interrogation of findings, (4) inappropriate interpretation of findings, and (5) lack of engagement with previous work. We have provided a brief checklist of key points to consider when performing a Mendelian randomization investigation; this does not replace previous guidance, but highlights critical analysis choices. Journal editors should be able to identify many low-quality submissions and reject papers without requiring peer review. Peer reviewers should focus initially on key indicators of validity; if a paper does not satisfy these, then the paper may be meaningless even if it is technically flawless.

Conclusions
Performing an informative Mendelian randomization investigation requires critical thought and collaboration between different specialties and fields of research.
Characterization of spatiotemporal and kinetic gait variables in dogs with hindlimb ataxia and bilateral hindlimb lameness
Authors: Park Clair , Sawyere Dominique M. , Pancotto Theresa E. , Lanz Otto I. , Werre Stephen R. 
Published: September 2024

Abstract
Background
Discriminating the underlying cause of gait abnormalities can be challenging in a clinical setting, especially in the presence of bilateral disease. Pressure-sensitive walkways (PSWs) have been utilized to characterize the gait of dogs with various neurologic or orthopaedic conditions. The potential use of the PSW includes the discrimination of conditions that can be similar in clinical presentation, such as bilateral hindlimb lameness and hindlimb ataxia. The primary aim of this study was to describe the spatial, temporal, and kinetic gait parameters of dogs with hindlimb ataxia or bilateral hindlimb lameness and compare them to those of normal dogs. Forty-six dogs were prospectively recruited. The normal group included 20 dogs with normal neurologic and orthopaedic exams. The orthopaedic group included 15 dogs with bilateral hindlimb orthopaedic diseases with weight-bearing hindlimb lameness and normal neurologic exams. The neurologic group included 11 dogs with ambulatory paraparesis and normal orthopaedic exams. Each dog was walked across the PSW, and at least 3 valid trials were collected. The stride time, stance time, swing time, stride length, gait velocity, peak vertical force (PVF), vertical impulse (VI), and limb symmetry were recorded. The mean values of all parameters from the valid trials were calculated and used for data analysis. The outcomes were compared among all groups.

Results
Compared with the normal group, the orthopaedic group had a significantly greater percent body weight distribution (%BWD) and vertical impulse distribution (VID) in the forelimbs. When comparing the spatiotemporal parameters, the neurologic group showed an increase in forelimb stance time compared to that of the normal group. Compared with that in the normal group, the stride velocity in the forelimbs in the orthopaedic group was greater. There were no significant differences in the kinetic parameters between the neurologic group and the normal group, nor in stride time or stride length among the groups.

Conclusion
The gait parameters obtained by PSW demonstrated that the orthopaedic and neurologic groups may have different compensatory mechanisms for their gait deficiencies. These parameters can potentially be used to construct a predictive model to evaluate PSW as a diagnostic tool in future studies.
Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells
Authors: Chandrasekaran Venkataragavan , Andersson Karin M. E. , Erlandsson Malin , Li Shuxiang , Olsson Torbjörn Nur , Garcia-Bonete Maria-Jose , Malmhäll-Bah Eric , Johansson Pegah , Katona Gergely , Bokarewa Maria I. 
Published: September 2024

Abstract
Background
Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFNγ effects in CD4+ cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4+ cells in rheumatoid arthritis (RA).

Methods
We performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4+ cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4+ cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4+ cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.

Results
We identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within cis-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4+ cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFNγ in CD4+ cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4+ cells.

Conclusions
BvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4+ cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.
Twelve-month outcomes of a community-based, father-daughter physical activity program delivered by trained facilitators
Authors: Ashton Lee M. , Rayward Anna T. , Pollock Emma R. , Kennedy Stevie-Lee , Young Myles D. , Eather Narelle , Barnes Alyce T. , Lee Daniel R. , Morgan Philip J. 
Published: September 2024

Abstract
Background
Dads and Daughters Exercising and Empowered (DADEE) is a program targeting fathers/father-figures to improve their daughters’ physical activity and well-being. Previous randomised controlled efficacy and effectiveness trials of DADEE demonstrated meaningful improvements in a range of holistic outcomes for both fathers and daughters in the short-term. This study aims to assess the long-term impact (12-months) of the program when delivered in the community by trained facilitators.

Methods
Fathers/father-figures and their primary school-aged daughters were recruited from Newcastle, Australia into a single-arm, non-randomised, pre-post study with assessments at baseline, 10-weeks (post-intervention) and 12-months. The 9-session program included weekly 90-min educational and practical sessions, plus home-based tasks. The primary outcome was fathers’ and daughters’ days per week meeting national physical activity recommendations (≥ 30 min/day of MVPA for fathers, ≥ 60 min/day MVPA for daughters). Secondary outcomes included physical activity, screen time, self-esteem, father-daughter relationship, social-emotional well-being, parenting measures, and process outcomes (including recruitment, attendance, retention and program acceptability).

Results
Twelve programs were delivered with 257 fathers (40.0 ± 9.2 years) and 285 daughters (7.7 ± 1.9 years). Mixed effects regression models revealed significant intervention effects for the primary outcome, with fathers increasing the days/week meeting physical activity recommendations by 27% at 10-weeks (p < 0.001) and by 19% at 12-months (p < 0.001) compared with baseline. Likewise, for daughters there was a significant increase by 25% at 10-weeks (p < 0.001) and by 14% at 12-months (p = 0.02) when compared to baseline. After conducting a sensitivity analysis with participants unaffected by COVID-19 lockdowns (n = 175 fathers, n = 192 daughters), the primary outcome results strengthened at both time-points for fathers and at 12-months for daughters. Additionally, the sensitivity analysis revealed significant intervention effects at post-program and 12-months for all secondary outcomes in both fathers and daughters. Furthermore, the process outcomes for recruitment capability, attendance, retention and satisfaction levels were high.

Conclusions
Findings provide support for a sustained effect of the DADEE program while delivered in a community setting by trained facilitators. Further investigation is required to identify optimised implementation processes and contextual factors to deliver the program at scale.

Trial registration
ACTRN12617001450303. Date registered: 12/10/2017.
Operational description of rare diseases: a reference to improve the recognition and visibility of rare diseases
Authors: Wang Chiuhui Mary , Whiting Amy Heagle , Rath Ana , Anido Roberta , Ardigò Diego , Baynam Gareth , Dawkins Hugh , Hamosh Ada , Le Cam Yann , Malherbe Helen , Molster Caron M. , Monaco Lucia , Padilla Carmencita D. , Pariser Anne R. , Robinson Peter N. , Rodwell Charlotte , Schaefer Franz , Weber Stefanie , Macchia Flaminia 
Published: September 2024

AbstractImproving health and social equity for persons living with a rare disease (PLWRD) is increasingly recognized as a global policy priority. However, there is currently no international alignment on how to define and describe rare diseases. A global reference is needed to establish a mutual understanding to inform a wide range of stakeholders for actions. A multi-stakeholder, global panel of rare disease experts, came together and developed an Operational Description of Rare Diseases. This reference describes which diseases are considered rare, how many persons are affected and why the rare disease population demands specific attention. The operational description of rare diseases is framed in two parts: a core definition of rare diseases, complemented by a descriptive framework of rare diseases. The core definition includes parameters that permit the identification of which diseases are considered rare, and how many persons are affected. The descriptive framework elaborates on the impact and burden of rare diseases on patients, their caregivers and families, healthcare systems, and society overall. The Operational Description of Rare Diseases establishes a common point of reference for decision-makers across the world who strive to understand and address the unmet needs of persons living with a rare disease. Adoption of this reference is essential to improving the visibility of rare conditions in health systems across the world. Greater recognition of the burden of rare diseases will motivate new actions and policies to address the unmet needs of the rare disease community.