bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reclassification of Genetic Testing Results: A Case Report Demonstrating the Need for Structured Re-Evaluation of Genetic Findings
Authors: Schott Clara , Colaiacovo Samantha , Baker Cadence , Weir Matthew A. , Connaughton Dervla M. 
Published: April 2024

Rationale: Alport Syndrome (AS) is a progressive genetic condition characterized by chronic kidney disease (CKD), hearing loss, and eye abnormalities. It is caused by mutations in the genes COL4A3, COL4A4, and COL4A5. Heterozygous mutations in COL4A4 and COL4A3 cause autosomal dominant Alport Syndrome (ADAS), and a spectrum of phenotypes ranging from asymptomatic hematuria to CKD, with variable extra-renal features. In the past, heterozygous mutations in these genes were thought to be benign, however recent studies show that about 30% of patients can progress to CKD, and 15% can progress to end stage kidney disease (ESKD). Presenting Concerns: We present a case of a woman who was noted to have microscopic hematuria pre-living kidney donation. Genetic testing revealed a heterozygous variant of uncertain significance (VUS) in the COL4A4 gene. VUSs are medically nonactionable findings and data show that VUSs can be detected in 41% of all patients who undergo clinical genetic testing. VUSs frustrate clinicians and patients alike. Although they cannot be used in medical decision-making, data suggest that reanalysis can result in the reclassification of a VUS over time. Diagnosis: Post-donation, the index patient had a higher than anticipated rise in serum creatinine, raising a concern for possible intrinsic kidney disease. Kidney biopsy was deemed high risk in the setting of a unilateral kidney thereby limiting possible diagnostic intervention to determine the cause of disease. Intervention: Re-evaluation of prior genetic testing results and reassessment of the previously identified VUS in COL4A4 was performed 5-years post-donation. These analyses, along with the addition of new phenotypic data and extended pedigree data, resulted in the reclassification of the previously identified VUS to a likely pathogenic variant. Outcomes: This case demonstrates the importance of structured, periodic re-evaluation of genetic testing results. With the ever-changing landscape of genetics in medicine, the interpretation of a VUS can be dynamic and therefore warrant caution in living kidney donor evaluations. Studies have shown that about 10% of VUSs can be upgraded to a pathogenic classification after an 18- to 36-month interval. Structured re-evaluation of genomic testing results has not yet been integrated into clinical practice and poses a unique challenge in living kidney donation. Novel findings: This case report highlights the variability of the ADAS phenotype caused by pathogenic heterozygous variants in the type 4 collagen genes. It supports the nomenclature change from a benign hematuria phenotype to ADAS, particularly when additional risk factors such as proteinuria, focal segmental glomerulosclerosis or glomerular basement membrane changes on kidney biopsy are present, or as in this case, evidence of disease in other family members.
Characteristics of Rodeo Injuries and Suggestions for Injury Prevention: A Systematic Review
Authors: Box McKenna W. , Wilson Freddie , Pasque Charles B. , Smith Chase D. 
Published: April 2024

Background: Rodeo is a globally popular sport, with its athletes prone to various types of injuries. There is no systematic review discussing rodeo injuries across all age groups. Purpose: To (1) review the published literature on incidence, types of injuries, and factors leading to injuries in rodeo athletes; (2) provide prevention recommendations for health care providers; and (3) identify gaps in the research. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of available literature was electronically performed through MEDLINE, Embase, and SPORTDiscus databases using the key terms “rodeo” and “injury” or “trauma” between 1995 and 2021. A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, which identified 116 eligible studies. Outcome data included frequency of injuries, risk factors for injury, and types of injury. Results: A total of 23 studies met the inclusion criteria (N = 2105 athletes), of which 13 were retrospective studies. In the included studies, the injury rate per competition exposure (CE) ranged from 4.2 to 19.1 injuries per 1000 CE. Sprains and strains accounted for the highest percentage of injury types, ranging from 15% to 34%. The knee was the most common location of injury, making up 11.1% to 17% of injuries. Concussions occurred in up to 15.3% of injuries for all events and up to 77% of injuries in roughstock events. Of all rodeo events reported, bull riding caused the highest percentage of injuries, making up 19.4% to 58.4% of injuries, and bareback had the second highest at 15.3% to 28.8% of injuries. Conclusion: There was a high prevalence of various injury types and mechanisms in rodeo. Improved injury surveillance and the introduction of a comprehensive standardized injury reporting system would be helpful in the future prevention, diagnosis, and treatment of rodeo injuries.
Association Between MRI Signal Intensity of the Repaired Lateral Meniscus and Residual Anterolateral Knee Laxity After ACL Reconstruction
Authors: Chiba Daisuke , Yamamoto Yuji , Kimura Yuka , Sasaki Eiji , Sasaki Shizuka , Tsuda Eiichi , Ishibashi Yasuyuki 
Published: April 2024

Background: Anterolateral knee laxity (ALLx) has been linked to tears of the lateral meniscus (LM) and anterior cruciate ligament (ACL) injury. Purpose: To investigate the longitudinal relationship between the signal intensity (SI) of the repaired LM on magnetic resonance imaging (MRI) and residual ALLx after ACL reconstruction (ACLR). Study Design: Cohort study; Level of evidence, 3. Methods: Included were 87 patients who underwent double-bundle ACLR and lateral meniscal repair (mean age, 23.5 years; body mass index, 23.7 kg/m2; 56 women) at a single institution between 2010 and 2019. Proton density-weighted (PDW) and T2-weighted (T2W) MRI was performed at 3, 6, and 12 months postoperatively, and the SI ratio (SIR) was calculated as ( SI of the repaired LM)/( SI of the posterior cruciate ligament). At the 12-month follow-up, ALLx was evaluated using the pivot-shift test; an International Knee Documentation Committee grade ≥1 indicated residual ALLx. Results: Overall, 12 patients (13.8%) exhibited ALLx at 12 months postoperatively. At 3 months postoperatively, the SIR on PDW images (SIR-PDW) was significantly higher in patients with ALLx versus those without ALLx (1.98 ± 0.77 vs 1.49 ± 0.52, respectively; P = .007); there was no difference in the SIR on T2W images between the groups. SIR-PDW at 3 months postoperatively was correlated negatively with patient age ( r = -0.308, P = .004). When patients were stratified into a younger (≤22 years; n = 53; ALLx = 7 [13.2%]) and an older (>22 years; n = 34; ALLx = 5 [14.7%]) group, the area under the receiver operating characteristic curves (AUCs) for SIR-PDW in the younger group were statistically significant for predicting the prevalence of ALLx at all follow-up times (AUCs, 0.733-0.788) with optimal cutoff values of 2.00 at 3 months, 1.50 at 6 months, and 1.50 at 12 months. Logistic regression analysis revealed that if younger patients consistently had higher SIR-PDW values than the cutoff values, they were more likely to have residual ALLx (odds ratios, 10.24-23.57). Conclusion: For younger patients who underwent both ACLR and lateral meniscal repair, higher MRI SI of the repaired LM was associated with a higher prevalence of residual ALLx.
The Effect of First Metatarsal Shortening and Sagittal Displacement on Forefoot Pressure in MIS Hallux Valgus Correction
Authors: Lopez Andres , Haupt Edward T. , Porter Giselle M. , Bakaes Yianni , Shi Glenn , Jackson J. Benjamin , Myers Paisley , Gonzalez Tyler 
Published: April 2024

Introduction/Purpose: Minimally invasive surgical (MIS) treatment of hallux valgus (HV) deformity is increasing in popularity. A 2mm-diameter burr is used to create a distal first metatarsal osteotomy prior to capital fragment translation and fixation. The metatarsal will shorten by the burr’s diameter (2mm). Plantar or dorsal capital fragment displacement may also cause load transference and possibly transfer metatarsalgia. In this study, we examine the effect of MIS HV on forefoot loading mechanics with respect to metatarsal shortening and sagittal plane displacement. Methods: Four lower-limb cadaveric specimens were studied. A pedobarography pressure-sensing mat was used to record forefoot plantar pressure in a controlled weightbearing stance position.10 Control and post-osteotomy measurements were obtained with the capital fragment fixated in 3 possible positions: 0mm, 5mm dorsal, and 5mm plantar displacement. Pedobarography data yielded pressure data within measurable graphical depictions. Raw mean contact pressure measurements were taken under the first and fifth metatarsal heads to establish medial and lateral forefoot loading pressure ratios. A priori power analysis was performed based on previous peer-reviewed pedobarographic data and our study was adequately powered. Results: 40 measurements were recorded and ratios of medial-to-lateral forefoot loading were constructed. Medial forefoot pressure change control versus 0mm displacement, and control versus dorsal displacement was not found to be statistically significant (p=0.525, p=0.55 respectively). Significant medial pressure increase was identified comparing control versus plantar displacement (p=0.006). Lateral pressure increased significantly with dorsal displacement of the osteotomy (p=0.013). Conclusion: MIS hallux valgus correction does not appear to cause increase in lateral forefoot pressure loading when sagittal plane displacements are controlled. Plantar displacement increases medial loading, and dorsal displacement increases lateral loading. The clinician must consider metatarsal head position post-osteotomy, as decrease in medial loading and subsequent increase in lateral loading may lead to lateral forefoot pain and transfer metatarsalgia.
Nature as Medicine and Classroom: Evaluating an Innovative, Outdoor Course for Medical and Dental Students
Authors: Trudel Sierra M. , Winter Emily L. , Guerrera Mary P. 
Published: April 2024

Background There is a growing, global awareness and recognition of the important, interdependent relationships between our natural world and human health. Several contemporary health organizations have placed calls to action and emphasize an urgent need for collaboration and interdisciplinary research, education, and clinical work to address the increasing degradation of our planetary and human health. With more research dedicated to nature’s health impacts, health professions schools would benefit by including such training in their programs while also cultivating a comprehensive mind-body health perspective to support both the health of student practitioners and their future patients. Objective The present program evaluation investigates a five-day outdoor mini-course covering nature-based health techniques at a medical and dental school in the American Northeast. This unique outdoor course combines nature, creativity, and reflection within the context of modern medicine. Methods A concurrent mixed-method design using descriptive statistics, quantitative and qualitative data from students’ anonymous final course evaluations and final reflection projects are evaluated. Results Data suggests that students benefitted from their experience during this five-day course. Students provided feedback reinforcing the enjoyment and transformative outcomes gleaned from the course experiences. Students entered the course describing feeling stressed, overwhelmed, and overextended, not uncommon for learners in medical and dental school, and completed the course describing the acquisition of applicable skills, increased attention and mindfulness, creativity, and connection to the natural world. Conclusions Students described a positive experience of the course. Several areas of personal and professional development were also described, such as improvements within cognitive domains, enhanced connection with nature, others, and themselves, increased mindfulness, and overall improved well-being. Findings have implications for medical and dental programs on how such innovative training may lean into the work of nature-based care to provide for the whole person.
Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies
Authors: Langerbeins Petra , Giza Adam , Robrecht Sandra , Cramer Paula , von Tresckow Julia , Al-Sawaf Othman , Fink Anna Maria , Fürstenau Moritz , Kutsch Nadine , Simon Florian , Goede Valentin , Hoechstetter Manuela , Niemann Carsten Utoft , da Cunha-Bang Caspar , Kater Arnon , Dubois Julie , Gregor Michael , Staber Philipp Bernhard , Tausch Eugen , Schneider Christof , Stilgenbauer Stephan , Eichhorst Barbara , Fischer Kirsten , Hallek Michael 
Published: April 2024

Abstract
We evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug–treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high), and 78.7% (very high). Differences between consecutive CLL-IPI risk groups were observed for intermediate vs low and high vs intermediate, but not very high vs high. CLL-IPI factors β2-microglobulin, immunoglobulin heavy variable (IGHV) status, and TP53 status each retained prognostic value for PFS. The 3-year overall survival (OS) rates by CLL-IPI risk groups were 100%, 96%, 93.9%, and 89.4%, respectively, with no differences between consecutive risk groups. Age, Binet stage, β2-microglobulin, and TP53 status each retained prognostic value for OS. In chemoimmunotherapy patients (median observation time, 66.9 months), 3-year PFS rates for CLL-IPI risk groups were 78.1%, 51.4%, 40.1%, and 16.5%, respectively; corresponding 3-year OS rates were 97.4%, 93.1%, 81.8%, and 57.3%. In a matched-pair analysis, PFS differences in targeted therapies (n = 812) vs chemoimmunotherapy (n = 812) across all risk groups and OS differences in all but patients at low risk were demonstrated. The CLL-IPI maintains its prognostic value in predicting PFS outcomes with targeted drugs, but its impact in predicting survival appears diminished. Targeted therapies showed enhanced outcomes over chemoimmunotherapy, highlighting their effectiveness across various risk groups. Our findings support ongoing assessment of prognostic tools in CLL treatment evolution. These trials were registered at www.ClinicalTrials.gov as #NCT02345863, #NCT02401503, #NCT02689141, #NCT02445131, #NCT02758665, #NCT02950051, #NCT02242942, #NCT00262782, #NCT00281918, and #NCT01010061.
Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions
Authors: Neuhaus Emily , Rea Hannah , Jones Elizabeth , Benavidez Hannah , Miles Conor , Whiting Alana , Johansson Margaret , Eayrs Curtis , Kurtz-Nelson Evangeline C. , Earl Rachel , Bernier Raphael A. , Eichler Evan E. 
Published: April 2024

Abstract
Background
Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD – ADNP, CHD8, and DYRK1A – with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes.

Methods
Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features.

Results
Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group.

Conclusions
Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.
Correlated evolution between body size and echolocation in bats (order Chiroptera)
Authors: Castro Mario G. , Amado Talita Ferreira , Olalla-Tárraga Miguel Á. 
Published: April 2024

Abstract
Background
Body size and echolocation call frequencies are related in bats. However, it is unclear if this allometry applies to the entire clade. Differences have been suggested between nasal and oral emitting bats, as well as between some taxonomic families. Additionally, the scaling of other echolocation parameters, such as bandwidth and call duration, needs further testing. Moreover, it would be also interesting to test whether changes in body size have been coupled with changes in these echolocation parameters throughout bat evolution. Here, we test the scaling of peak frequency, bandwidth, and call duration with body mass using phylogenetically informed analyses for 314 bat species. We specifically tested whether all these scaling patterns differ between nasal and oral emitting bats. Then, we applied recently developed Bayesian statistical techniques based on large-scale simulations to test for the existence of correlated evolution between body mass and echolocation.

Results
Our results showed that echolocation peak frequencies, bandwidth, and duration follow significant allometric patterns in both nasal and oral emitting bats. Changes in these traits seem to have been coupled across the laryngeal echolocation bats diversification. Scaling and correlated evolution analyses revealed that body mass is more related to peak frequency and call duration than to bandwidth. We exposed two non-exclusive kinds of mechanisms to explain the link between size and each of the echolocation parameters.

Conclusions
The incorporation of Bayesian statistics based on large-scale simulations could be helpful for answering macroevolutionary patterns related to the coevolution of traits in bats and other taxonomic groups.
In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns
Authors: Hou Bochen , Zhang Honglan , Zhou Lina , Hu Biao , Tang Wenyi , Ye Bo , Wang Cui , Xu Yongmei , Zou Lingyun , Hu Jun 
Published: April 2024

Abstract
Background
Severe burns may alter the stability of the intestinal flora and affect the patient’s recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers.

Methods
We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis.

Results
We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy.

Conclusions
Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.