bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Wearable Sensor Technology to Analyze Running Technique and Prospective Running-Related Injuries During United States Military Cadet Basic Training
Authors: Weart Amy N. , Brown Lauren C. , Florkiewicz Erin M. , Freisinger Gregory M. , East Kyle H. , Reilly Nicholas , Song Jinsup , Goss Donald L.
Published: February 2025

Background:

Running biomechanics have been linked to the development of running-related injuries in recreational and military runners.

Purpose/Hypothesis:

The purpose of this study was to determine if personal characteristics or running biomechanical variables are associated with running-related injury incidence or time to injury in military cadets undergoing training. It was hypothesized that a rearfoot strike pattern, greater rate of impact, or a lower step rate would be related to a greater running-related injury incidence and a decreased time to injury.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

Military cadets wore an on-shoe wearable sensor that analyzed biomechanical variables of foot strike pattern, rate of impact, running pace, step rate, step length, and contact time during cadet basic training (60 days). Running-related injuries during cadet basic training were determined by medical record review. Personal and running variables between the injured and uninjured cadets were compared using independent t tests and chi-square analyses. Time to injury and hazard ratios (HRs) were estimated using Kaplan-Meier survival curves and Cox proportional hazard regression models, respectively.

Results:

Of the 674 cadets who completed the study, 11% sustained a running-related injury. A significantly greater proportion of the injured participants were female (χ2 = 7.95; P = .005) and had a prior history of injury (χ2 = 7.36; P = .007). Univariate Cox proportional hazard regression models revealed greater injury risk in females (HR, 1.96; 95% CI, 1.22-3.16; P = .005) and cadets with a prior injury history (HR, 1.86; 95% CI, 1.18-2.93; P = .008). After adjusting Cox models for prior injury, females were found to be at a 1.89 times (95% CI, 1.17-3.04; P = .009) greater risk of injury. Running biomechanical variables were not associated with injury risk.

Conclusion:

Study results indicated that non-modifiable risk factors such as female sex and prior injury history increased the risk of running-related injury in cadets undergoing military training. Running biomechanical variables measured by the wearable sensor were not associated with injury in this study.
Incidence of Heterotopic Ossification Without Additional Long-Term NSAID Prophylaxis After Periacetabular Osteotomy and Concomitant Hip Arthroscopy
Authors: Helm J. Matthew , Stocks Omar , Crowley Brian , Aboulafia Alexis , Siahaan Jacob , Mansour Alfred A.
Published: February 2025

Background:

Periacetabular osteotomy (PAO) is an established treatment for hip dysplasia and has been increasingly combined with concomitant hip arthroscopy to address additional intra-articular hip pathology. Heterotopic ossification (HO) is a complication of arthroscopic and open hip procedures. Nonsteroidal anti-inflammatory drugs (NSAIDs) have become an established form of HO prophylaxis, but their use may delay bone healing.

Purpose:

To examine the incidence of HO without NSAID prophylaxis in patients after PAO with concomitant hip arthroscopy and to evaluate the impact of other variables on the development of HO in these patients.

Study Design:

Case series; Level of evidence, 4.

Methods:

Of 243 hips that underwent PAO with concomitant hip arthroscopy by a single surgeon over 11 years, 182 met the study inclusion criteria. No patients were discharged on NSAIDs for HO prophylaxis, although most took up to 6 weeks of aspirin 81 mg as part of the prophylaxis protocol for deep venous thrombosis. Radiographic images at 2 weeks, 6 weeks, and 3 months postoperatively were reviewed and graded for HO using the Brooker classification. Patient characteristics and surgical variables were recorded. The chi-square and t tests were used to determine HO incidence rates, compare groups, and identify variables associated with the presence of HO.

Results:

The incidence of radiographic HO was 6.6% (12/182 hips). Nine hips were Brooker grade 1, 2 were grade 2, and 1 was grade 3. Four patients experienced clinical symptoms of HO— including pain and restricted motion. Only 1 patient required a return trip to the operating room for surgical excision. Male patients were significantly more likely to develop HO than female patients ( P = .01). No other demographic or surgical factor influenced the development of HO. There were no cases of nonunion.

Conclusion:

There was a low incidence of HO and symptomatic HO in patients who underwent PAO with concomitant hip arthroscopy without using NSAIDs for HO prophylaxis. HO was significantly more likely to develop in male patients. Given the potential risk of NSAID use on bony union, the low incidence found in this study may obviate the need for postoperative HO prophylaxis.
Management of Isolated Partial ACL Tears: A Survey of International ACL Surgeons
Authors: Frey Christopher S. , Pierre Kinsley J. , Pham Nicole S. , Abrams Geoffrey D. , Sherman Seth L. , Spalding Tim , Safran Marc R.
Published: February 2025

Background:

Partial anterior cruciate ligament (ACL) tears, particularly injuries detected with magnetic resonance imaging (MRI) but stable on ligamentous examination, appear to be recognized more frequently; however, there remains no consensus management for this complex pathology.

Purpose:

To present the results of a survey of a group of international ACL experts on the management of partial ACL injuries.

Study Design:

Survey study; Level of evidence, 5.

Methods:

The ACL Study Group is an international group of orthopaedic surgeons with a special interest in the ACL. There are 169 members overall, with 135 clinically active surgeons. A branching logic survey was developed and circulated to members of the ACL Study Group via electronic mail. Categories included member demographics as well as recommended management strategies of partial ACL injuries, including recommendations on return to play.

Results:

Of the 135 clinically active surgeon members, 113 responded to the survey (84%). Nonoperative management of partial ACL injuries was selected by 92% of respondents. Of those who managed nonoperatively, 75% indicated they would not restrict weightbearing and 59% would not recommend a knee brace. When those who managed the patient nonoperatively determined criteria for return to sports (RTS), 33% would use differential knee laxity, 87% would assess functional testing, 26% would utilize imaging, and 40% selected time from injury. When using time as a guide for RTS, 13% chose RTS between 7 and 11 weeks postinjury, 56% selected no sport before 3 months, and 22% favored waiting 4 to 6 months before allowing an athlete with a partial ACL injury to RTS. With regard to function as a tool to determine RTS, painless Lachman, strength, swelling, and functional performance tests were all chosen by a majority of respondents.

Conclusion:

This study presented the results of a survey on partial ACL injury management administered to ACL Study Group active surgical members. The majority favored nonoperative management for partial ACL injuries (stable ligament examination but MRI changes in the ligament). Nonoperative treatment and RTS protocols varied and must be customized to the patient.
Combined Meniscal Saucerization and Repair Versus Subtotal Meniscectomy for Symptomatic Discoid Lateral Meniscal Tears in Children and Adolescents
Authors: Shimmyo Airi , Onishi Shintaro , Kanto Ryo , Nakayama Hiroshi , Yoshiya Shinichi , Tachibana Toshiya , Iseki Tomoya
Published: February 2025

Background:

Meniscal saucerization combined with repair of a symptomatic discoid lateral meniscus (DLM) has been expanding. However, the significance of meniscal saucerization with repair involving complex or degenerative tears remains uncertain.

Purpose/Hypothesis:

The purpose of this study was to assess the radiological and clinical outcomes of saucerization with repair performed for symptomatic DLM tears in children and adolescents in comparison with a historical control cohort undergoing subtotal meniscectomy. It was hypothesized that saucerization with repair would lead to superior outcomes compared with subtotal meniscectomy.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

This study group consisted of 27 knees in 21 patients who underwent saucerization with repair (SR group) between 2011 and 2018, while the historical control group included 22 knees in 20 patients who underwent subtotal meniscectomy (SM group) between 2005 and 2011. Patient age at the time of surgery ranged from 4 to 18 years (mean, 12.1 years). Clinical outcomes were assessed using the Lysholm score. The Tapper and Hoover classification based on Rosenberg view radiographs was adopted, and lateral joint space width was measured as a parameter for cartilage/meniscus preservation. Clinical and radiological results were evaluated preoperatively, 2 years postsurgery, and until the final follow-up.

Results:

The mean follow-up period was 50.6 ± 17.0 months in the SR group and 62.3 ± 41.0 months in the SM group. Lysholm scores significantly improved postoperatively in both groups ( P < .001). As for radiological evaluation, a progression in the Tapper and Hoover classification grade and a significant increase in lateral joint space width ( P < .001) between the right and left sides were observed in both groups at 2 years postoperatively, with no significant differences between groups. Complications included postoperative retearing in 5 cases (18.5%) from the SR group, and osteochondritis dissecans (OCD) developed after surgery in 1 knee (4%) in the SR group and 6 knees in the SM group (27%), with a significantly higher incidence in the SM group ( P = .036).

Conclusion:

Both groups showed progressive postoperative radiographic degeneration, and clinical outcomes also improved in both groups. Based on the incidence of OCD development, saucerization with repair for complex DLM tears showed advantages over subtotal meniscectomy.
Reasons for and Complications Following Revision Tibial Tubercle Osteotomy
Authors: Varady Nathan H. , Uppstrom Tyler J. , Shah Aakash , Rizy Morgan , Neijna Ava G. , Gomoll Andreas H. , Strickland Sabrina M.
Published: February 2025

Background:

While tibial tubercle osteotomy (TTO) is a highly effective treatment for patellofemoral malalignment, some patients may have recurrent symptoms after surgery. To date, there are little data on revision TTO (rTTO) and its outcomes.

Purpose:

To evaluate the (1) reasons for and (2) complications following rTTO.

Study Design:

Case series; Level of evidence, 4.

Methods:

This was a retrospective review of patients who underwent rTTO from a single high-volume patellofemoral surgeon between 2016 and 2023. All included patients had a minimum of 3 months of follow-up data. Demographic characteristics, indications for primary and revision surgery, operative characteristics, concomitant procedures, range of motion at 6 and 12 weeks postoperatively, radiographic data, and complications were collected.

Results:

There were 16 knees (14 patients) that underwent rTTO, including 10 (63%) for persistent malignment (all of which had chondral damage requiring concomitant intervention) and 6 (38%) for fracture/nonunion. The knees undergoing rTTO for malalignment were 90% female, compared with 33% female for fracture/nonunion ( P = .04). For persistent malalignment rTTO, the only complication (10% [1/10]) was arthrofibrosis (0°-65° at 6 weeks postoperatively), requiring arthroscopic lysis of adhesions (0°-140° at 12 weeks postoperatively). Within the follow-up available (median, 2.2 years; range, 9 months-5.3 years), there were no cases of new or recurrent patellar instability after rTTO. Similarly, at a median follow-up of 1.2 years (range, 4 months–3.0 years), all 6 knees that underwent rTTO for fracture/nonunion achieved union, with delayed union requiring percutaneous bone marrow grafting at 4 months postoperatively being the only complication in this cohort.

Conclusion:

Patients who underwent rTTO demonstrated low complication rates and high union rates in this study. There was a high prevalence of chondral damage requiring concomitant intervention among patients undergoing rTTO for persistent malalignment. While rTTO is a relatively rare procedure, these data suggest that it can be a safe and effective option for patients with recurrent symptoms or fracture/nonunion after primary TTO.
Social Anxiety, Negative Affect, and Hearing Difficulties in Adults
Authors: McClannahan Katrina (Kate) S. , McConkey Sarah , Levitan Julia M. , Rodebaugh Thomas L. , Peelle Jonathan E.
Published: February 2025

Subjective ratings of communication function reflect both auditory sensitivity and the situational, social, and emotional consequences of communication difficulties. Listeners interact with people and their environment differently, have various ways of handling stressful situations, and have diverse communication needs. Therefore, understanding the relationship between auditory and mental health factors is crucial for the holistic diagnosis and treatment of communication difficulty, particularly as mental health and communication function may have bidirectional effects. The goal of this study was to evaluate the degree to which social anxiety and negative affect (encompassing generalized anxiety, depression, and anger) contributed to subjective communication function (hearing handicap) in adult listeners. A cross-sectional online survey was administered via REDCap. Primary measures were brief assessments of social anxiety, negative affect, and subjective communication function measures. Participants were 628 adults (408 women, 220 men), ages 19 to 87 years (mean = 43) living in the United States. Results indicated that individuals reporting higher social anxiety and higher negative affect also reported poorer communication function. Multiple linear regression analysis revealed that both negative affect and social anxiety were significant and unique predictors of subjective communication function. Social anxiety and negative affect both significantly, and uniquely, contribute to how much someone feels a hearing loss impacts their daily communication function. Further examination of social anxiety and negative affect in older adults with hearing loss may help researchers and clinicians understand the complex interactions between mental health and sensory function during everyday communication, in this rapidly growing clinical population.
“‘We don’t want them to have to live out their lives in the hospital”: mixed-methods study exploring palliative care needs amongst refugees‘
Authors: Gupta Priya , Gill Ashlinder , Panza Michael , Wahoush Olive , Saeed Humaira , Chagani Jehan Ara , Owoo Christiana , Klinger Christopher
Published: February 2025

Background:

The increasing life expectancy and resultant chronic medical comorbidities have resulted in more people requiring palliative care. Unfortunately, palliative care is restricted to marginalized populations, including refugees. In Canada, refugees are only eligible for federal health insurance, which provides basic medical and social coverage until they can obtain provincial health insurance.

Objectives:

This study explored limitations in providing palliative care to refugees who had either federal or provincial health insurance in two care settings in Ontario, Canada.

Design:

An explanatory sequential mixed-methods approach guided the review of local administrative data and interview data to understand palliative care delivery for refugees.

Methods:

Local administrative data from a community health centre and an acute care hospital providing a palliative care approach were collected to review healthcare utilization for refugees with palliative care needs. Interviews from two focus groups with fourteen healthcare providers shared their care experiences in coordinating palliative care for refugees with either federal or provincial health insurance.

Results:

Refugee patients with palliative care needs appeared to be accessing acute care services frequently to meet their needs over a 5-year period. Due to a lack of citizenship or permanent residency status, many refugees have access to only federal health insurance. Compared to those with routine provincial coverage, federally insured patients were admitted more frequently. Furthermore, healthcare provider experiences revealed that refugees with only federal insurance coverage had significant barriers to accessing community palliative care support, leading to increased reliance on acute care for quality palliative care.

Conclusion:

This study highlights significant gaps in palliative care access for refugees, especially those with federal health insurance. Equitable access is essential in ensuring that patient-centred, quality palliative care is available to all.
Early Saphenous Venous Graft Pseudoaneurysm, a Rare Cause of Acute Coronary Syndrome: Too Early or Too Late—A Management Dilemma
Authors: Jariwala Pankaj , Atmakur Gautam , Kulkarni Gururaj Pramod , Jariwala Anusha
Published: February 2025

A saphenous vein graft (SVG) is a bypass conduit that is frequently employed in surgical revascularization operations. One of the primary issues with SVGs is that they can encounter blockage rates of up to 25% within the first year. Saphenous venous graft aneurysms (SVGAs) are extremely uncommon, yet they can develop at any time. While early SVG degeneration may result in SVGAs, the classic indications of myocardial ischemia are often associated with late SVG degeneration. Other methods of imaging, including coronary computed tomography and graft angiography, can detect SVGA that would otherwise go undetected. This issue may cause mortality to be underestimated, resulting in fatalities that go unnoticed and uninvestigated.

The major goal of this case report was to offer a detailed account of an early SVGA episode in a patient who had a documented non-ST-segment myocardial infarction and significant myocardial ischemia, as confirmed by coronary artery angiotomography.
Sphingolipid metabolites involved in the pathogenesis of atherosclerosis: perspectives on sphingolipids in atherosclerosis
Authors: Zhao Fufangyu , Shao Mingyan , Li Mingrui , Li Tianxing , Zheng Yanfei , Sun Wenlong , Ni Cheng , Li Lingru
Published: February 2025

Atherosclerosis, with its complex pathogenesis, is a leading underlying cause of many cardiovascular diseases, which are increasingly prevalent in the population. Sphingolipids play an important role in the development of atherosclerosis. Key metabolites and enzymes in sphingolipid metabolism influence the pathogenesis of atherosclerosis in a variety of ways, including inflammatory responses and oxidative stress. Thus, an investigation of sphingolipid metabolism-related metabolites and key enzymes may provide novel insights and treatment targets for atherosclerosis. This review discusses various mechanisms and research progress on the relationship between various sphingolipid metabolites, related enzymes, and atherosclerosis. Finally, we look into the future research direction of phytosphingolipids.

Graphical Abstract
A novel roseosiphovirus infecting dinoroseobacter shibae DFL12T represents a new genus
Authors: Wei Nana , Lu Longfei , Li Yingying , Ding Bo , Cai Lanlan , Yang Yunlan
Published: February 2025

Bacteria belonging to the Roseobacter clade are key players in marine ecosystems, contributing significantly to carbon and sulfur cycles. Marine viruses, particularly those targeting Roseobacter, play crucial roles in regulating microbial communities and biogeochemical processes. Despite their importance, phages infecting organisms of the Roseobacter clade remain poorly understood. In this study, a novel roseophage, vB_DshS-R26L (R26L), infecting Dinoroseobacter shibae DFL12T, was isolated and characterized in terms of physiological and genomic properties. R26L has siphovirus morphology with an elongated head and a long, non-flexible tail. The phage has a narrow host range and demonstrates a long infection cycle with a latent period of 3.5 h and a burst size of 22 plaque-forming units (PFU cell− 1). R26L possesses a circular, double-stranded DNA genome of 79,534 bp with a G + C content of 62.6%, encoding a total of 116 open reading frames. Notably, seven auxiliary metabolic genes (AMGs), including those related to phosphate metabolism and queuosine biosynthesis, were identified. Phylogenetic and taxonomic analyses revealed that R26L represents a new genus, with its highest intergenomic similarities being 54.7% to another roseophage (R5C). By elucidating the unique characteristics of R26L, this study highlights the complexity of phage infections and the genomic diversity of roseophages, offering valuable insights into the ecological significance of Roseobacter–phage interactions in marine environments.
Autophagy is involved in the toxicity of the biocontrol agent GC16 against Tetranychus pueraricola (Acari: Tetranychidae) based on transcriptomic and proteomic analyses
Authors: He Yanyan , Du Guangzu , Wang Guang , Guan Huiming , Zhu Shusheng , Chen Bin , He Xiahong , Zhu Youyong
Published: February 2025

Background

GC16 is a novel pesticide with acaricidal properties against the spider mite Tetranychus pueraricola (Ehara & Gotoh). Its physiological mechanisms have been described previously, but its molecular mechanisms of action remain unclear. Thus, we aimed to explore the acaricidal mechanisms of GC16 through transcriptomic and proteomic analyses. The results were verified using transmission electron microscopy (TEM), immunofluorescence assay, and western blotting.

Results

Transcriptomic and proteomic analyses revealed 2717 differentially expressed genes (DEGs) and 374 differentially expressed proteins (DEPs) between the GC16-treated and control mites. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the DEGs and DEPs were enriched in the autophagy pathway. TEM showed that the number of autophagosomes and autolysosomes was higher in the GC16-treated mites than in the control mites. Immunofluorescence assay and western blot results consistently indicated that GC16 treatment significantly enhanced the relative expression of the autophagy protein LC3 in insect Sf9 cells. The intracellular calcium concentration in the GC16-treated Sf9 cells was 2.30 times higher than that in the control cells, suggesting that GC16 disrupted calcium homeostasis and potentially acted as a calcium-driven nerve agent.

Conclusions

Autophagy is involved in the toxicity of GC16 against T. pueraricola and may be activated by elevated Ca2+ levels. This study reveals the molecular insecticidal mechanisms of GC16 and provides rationale for the field application of GC16 to control pest mites.
Isolated oculomotor nerve palsy due to mesencephalic infarction diagnosed by ZOOM DWI
Authors: Wang Shangpei , Cai Yajie , Wu Xiaosan , Yan Sunhong , Wang Longsheng
Published: February 2025

Background

Oculomotor nerve palsy is a common neurological presentation in daily practice.

Case presentation

A 55-year-old man presented with a 3-h history of diplopia and drooping of his bilateral especially left eyelids. Examination revealed an isolated oculomotor nerve palsy consisting of left medial rectus, inferior oblique, superior rectus, inferior rectus with intact pupillary reflexes and bilateral especially left superior palpebral levator. Conventional diffusion weighted imaging (DWI) of the brain showed a suspicious restriction in the left midbrain periaqueductal region. If the clinical symptomatology indicates a lesion in the midbrain, of which a high signal intensity was encountered from neurologically healthy older adults, the limited spatial resolution of conventional axial DWI is an enormous disadvantage. Zonally magnified oblique multislice (ZOOM) DWI correlated with apparent diffusion coefficient map providing higher accuracy for accurate diagnosis can identify signal alterations of mesencephalic interpeduncle area.

Conclusions

This is a rare presentation of isolated oculomotor nerve palsy due to pure mesencephalic infarction especially verified by ZOOM DWI.
Incidence of type 2 diabetes and metabolic syndrome by Occupation – 10-Year follow-up of the Gutenberg Health Study
Authors: Bauer Juliane , Hegewald Janice , Rossnagel Karin , Jankowiak Sylvia , Prigge Michaela , Chalabi Julian , Nübling Matthias , Freiberg Alice , Riechmann-Wolf Merle , Dietz Pavel , Wild Philipp S. , Koeck Thomas , Beutel Manfred E. , Pfeiffer Norbert , Lackner Karl J. , Münzel Thomas , Strauch Konstantin , Lurz Philipp , Tüscher Oliver , Weinmann-Menke Julia , Konstantinides Stavros , Seidler Andreas
Published: February 2025

Background

In view of demographic change, rising retirement age, and a growing shortage of skilled workers, it is increasingly important to prevent widespread diseases such as type 2 diabetes or its risk factor metabolic syndrome. Since the workplace is an important setting for preventive measures and little is known about incident cases in the working population, the aim of this study was to identify vulnerable occupational groups for whom these interventions are particularly appropriate. Therefore, we investigated the 10-year incidence of type 2 diabetes and metabolic syndrome across occupational groups in Germany.

Methods

Employees of the population-based Gutenberg-Health-Study (GHS) were examined at baseline (2007–2012) and 10 years later. We calculated age- and sex-standardised incidence rates and standardised incidence ratios (SIR) with a 95% confidence interval (CI) for occupations, job complexity levels, and supervisory and managerial positions. 5954 persons at risk for type 2 diabetes and 5103 at risk for metabolic syndrome were observed.

Results

Between baseline and follow-up, 388 cases of type 2 diabetes and 1104 cases of metabolic syndrome occurred, and standardised incidences were 6.9% and 22.6%, respectively. The highest incidence of type 2 diabetes was observed in the occupational group “food production and processing” (20.7%) with a threefold increased incidence (SIR = 3.0, 95% CI 1.8–4.7) compared to the total working population of the GHS. Employees in “metal production, processing and construction” had the highest incidence of metabolic syndrome and a two times higher SIR (48.5%; SIR = 2.1, 95% CI 1.4–2.9). There was also a high incidence of both type 2 diabetes and metabolic syndrome in “cleaners” (16.5% and 34.8%) and “drivers and mobile plant operators” (14.8% and 41.2%). An increased incidence of type 2 diabetes and metabolic syndrome was observed with decreasing job complexity levels.

Conclusions

This study shows wide differences in the incidence of type 2 diabetes and metabolic syndrome between occupational groups and highlights the vulnerability of certain occupations. As the workplace is an important platform for interventions, the findings of this study could guide the development of more nuanced and effective workplace health initiatives to promote a healthier workforce for the future.
Researcher views on returning results from multi-omics data to research participants: insights from The Molecular Transducers of Physical Activity Consortium (MoTrPAC) Study
Authors: Ormond Kelly E. , Stanclift Caroline , Reuter Chloe M. , Carter Jennefer N. , Murphy Kathleen E. , Lindholm Malene E. , Wheeler Matthew T.
Published: February 2025

Background

There is growing consensus in favor of returning individual specific research results that are clinically actionable, valid, and reliable. However, deciding what and how research results should be returned remains a challenge. Researchers are key stakeholders in return of results decision-making and implementation. Multi-omics data contains medically relevant findings that could be considered for return. We sought to understand researchers' views regarding the potential for return of results for multi-omics data from a large, national consortium generating multi-omics data.

Methods

Researchers from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) were recruited for in-depth semi-structured interviews. To assess understanding of potential clinical utility for types of data collected and attitudes towards return of results in multi-omic clinical studies, we devised an interview guide focusing on types of results generated in the study for hypothetical return based on review of the literature and professional expertise of team members. The semi-structured interviews were recorded, transcribed verbatim and co-coded. Thematic trends were identified for reporting.

Results

We interviewed a total of 16 individuals representative of 11 sites and 6 research roles across MoTrPAC. Many respondents expressed positive attitudes regarding hypothetical multi-omics results return, citing participant rights to their data and perception of minimal harm. Ethical and logistical concerns around the return of multi-omics results were raised, and they often mirrored those in the published literature for genomic return of results including: uncertain clinical validity, a lack of expertise to communicate results, and an unclear obligation regarding whether to return multi-omics results. With the exception of privacy concerns, respondents were able to give examples within multi-omics of how each point was relevant. Further, researchers called for more guidance from funding agencies and increased researcher education regarding return of results.

Conclusion

Overall, researchers expressed positive attitudes toward multi-omic return of results in principle, particularly if medically actionable. However, competing ethical considerations, logistical constraints, and need for more external guidance were raised as key implementation concerns. Future studies should consider views and experiences of other relevant stakeholders, specifically clinical genomics professionals and study participants, regarding the clinical utility of multi-omics information and multi-omics results return.
Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma
Authors: Pham Dinh-Xuan , Hsu Tien
Published: February 2025

Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of kidney malignancy. ccRCC is considered a major health concern worldwide because its numbers of incidences and deaths continue to rise and are predicted to continue rising in the foreseeable future. Therefore new strategy for early diagnosis and therapeutics for this disease is urgently needed. The discovery of cancer stem cells (CSCs) offers hope for early cancer detection and treatment. However, there has been no definitive identification of these cancer progenitors for ccRCC. A majority of ccRCC is characterized by the loss of the von Hippel-Lindau (VHL) tumor suppressor gene function. Recent advances in genome analyses of ccRCC indicate that in ccRCC, tumor-initiating cells (TICs) and metastasis-initiating cells (MICs) are two distinct groups of progenitors. MICs result from various genetic changes during subclonal evolution, while TICs reside in the stem of the ccRCC phylogenetic tree of clonal development. TICs likely originate from kidney tubule progenitor cells bearing VHL gene inactivation, including chromatin 3p loss. Recent studies also point to the importance of microenvironment reconstituted by the VHL-deficient kidney tubule cells in promoting ccRCC initiation and progression. These understandings should help define the progenitors of ccRCC and facilitate early detection and treatment of this disease.
Prevalence of malaria and associated factors among febrile children under 15 years at Bududa General Hospital, Eastern Uganda
Authors: Okongo Benson , Asiimwe Daisy , Olong Clinton , Muwanguzi Enoch , Wagubi Robert
Published: February 2025

Background

A significant portion of malaria-related deaths occur in Africa, and Uganda is an endemic region where malaria remains a public health concern. This study aimed to determine the prevalence of malaria and its associated factors among febrile children under 15 years of age at Bududa General Hospital, Eastern Uganda.

Methods

This cross-sectional study was conducted between April and June 2023. Informed consent was obtained from parents/guardians before 250 febrile children below 15 years were enrolled in this study. A structured questionnaire was administered to parents/guardians to collect sociodemographic characteristics and identify factors associated with malaria. Venous blood samples were collected from the children and screened for the presence of malaria parasitaemia using blood smear microscopy. The data collected were entered into an Excel spreadsheet and analysed using STATA version 14. Logistic regression models were used to determine the factors associated with malaria, and we considered ≤ 0.05 as the level of significance.

Results

Out of the 250 study participants, the overall prevalence of malaria was 111(44.4%). Among the children who tested positive for malaria, 98 (88.3%) had Plasmodium falciparum, 11 (9.9%) had Plasmodium malariae, and (1.8%) had Plasmodium ovale infection. The mean parasite count was 21,951 parasites/µL of blood. The highest parasite count was 154,387 parasites/µL of blood, and the lowest count was 146 parasites/µL of blood. The prevalence rates of low, moderate, and high malaria parasitaemia were 46.8%, 28.0%, and 25.2%, respectively. In the multivariate analysis, the factors associated with malaria infections were older age; 1 to 5 years (p = 0.013), 6 to 10 years (p = 0.000), 11 to 15 years (p = 0.000), secondary education (p = 0.050), and no use of insecticide-treated bed nets (p = 0.002).

Conclusion

The prevalence of malaria among febrile children in this study was high, with nearly half of the participants showing severe infections. Health education on the correct use of insecticide-treated mosquito nets should be prioritized to help control malaria.
Deciphering TCOF1 mutations in Chinese Treacher Collins syndrome patients: insights into pathogenesis and transcriptional disruption
Authors: Jiang Zhuoyuan , Mao Ke , Wang Bingqing , Zhu Hao , Liu Jiqiang , Lang Ruirui , Xiao Baichuan , Shan Hailin , Chen Qi , Li Ying , Zhao Shouqin , Zhang Qingguo , Liu Huisheng , Zhang Yong-Biao
Published: February 2025

Background

Treacher Collins syndrome (TCS, MIM #154500), a severe congenital disorder, predominantly involves dysplasia of craniofacial bones and is characterized by features such as downslanting palpebral fissures, lower eyelid colobomas, microtia, and other craniofacial anomalies. Despite its clinical importance, the underlying pathogenic mutations in TCS remain largely uncharacterized, representing a critical knowledge gap for researchers in the field.

Results

To address this, we performed mutation screening on a familial TCS case (trio) and 11 sporadic cases from a Chinese population. We identified 11 mutations predominantly localized to the central repeat domain (CRD) and the C-terminal domain (CTD, including the nuclear localization sequence) of TCOF1. The de novo frameshift mutation identified in the trio led to TCOF1 truncation, disrupting the central repeat domain crucial for binding transcriptional factors. Immunoprecipitation assays revealed that this pathogenic mutation attenuates the interaction between TCOF1 and transcription-related proteins, such as Pol II. Furthermore, cellular luciferase assays demonstrated that the mutation compromises the nuclear localization capability of TCOF1.

Conclusions

Our findings establish TCOF1 as the primary pathogenic gene in this Chinese TCS cohort, with mutations predominantly in the CRD and CTD, thereby expanding the known mutation spectrum of TCS and informing its prevention strategies.
Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice
Authors: Yousefian-Jazi Ali , Kim Suhyun , Chu Jiyeon , Choi Seung-Hye , Nguyen Phuong Thi Thanh , Park Uiyeol , Kim Min-gyeong , Hwang Hongik , Lee Kyungeun , Kim Yeyun , Hyeon Seung Jae , Rhim Hyewhon , Ryu Hannah L. , Lim Grewo , Stein Thor D. , Lim Kayeong , Ryu Hoon , Lee Junghee
Published: February 2025

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.

Methods

Convolutional neural network was used to identify an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element. To examine the alteration of MEF2C transcription by the SNP, we generated HEK293T cells carrying the major or minor allele by CRISPR-Cas9. To verify the role of MEF2C-knockdown (MEF2C-KD) in mice, we developed AAV expressing shRNA for MEF2C based on AAV-U6 promoter vector. Neuropathological alterations of MEF2C-KD mice with mitochondrial dysfunction and motor neuronal damage were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through longitudinal study by tail suspension, inverted grid test and automated gait analysis.

Results

Here, we show that enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits.

Conclusions

Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.
Dysbiosis and extraintestinal cancers
Authors: He Ruishan , Qi Pingqian , Shu Linzhen , Ding Yidan , Zeng Peng , Wen Guosheng , Xiong Ying , Deng Huan
Published: February 2025

The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens. The dissemination of pathogens through the circulation may contribute to the establishment of an immune-suppressive environment that promotes carcinogenesis in extraintestinal organs either directly or indirectly. The oncogenic cascade always engages in the disruption of hormonal regulation and inflammatory responses, the induction of genomic instability and mutations, and the dysregulation of adult stem cell proliferation. This review aims to comprehensively summarize the existing evidence that points to the potential role of dysbiosis in the malignant transformation of extraintestinal organs such as the liver, breast, lung, and pancreas. Additionally, we delve into the limitations inherent in current methodologies, particularly the challenges associated with differentiating low loads gut-derived microbiome within tumors from potential sample contamination or symbiotic microorganisms. Although still controversial, an understanding of the contribution of translocated intestinal microbiota and their metabolites to the pathological continuum from chronic inflammation to tumors could offer a novel foundation for the development of targeted therapeutics.
Childhood occasional hypertension and its association with size at birth and early growth: a population-based retrospective cohort study from China
Authors: Zhang Shuang , Wang Leishen , Zhang Tao , Qiao Yijuan , Li Wei , Li Weiqin
Published: February 2025

Background

Hypertension has recently shown a rapid rise in prevalence among children and adolescents. It can track into adulthood and tend to manifest at an earlier age. It should be prevented urgently and efficiently.

Methods

This study assesses the prevalence of occasional hypertension (OHTN) at 5 ~ 6 years old and evaluates its association with size at birth and BMI at 2 and 5 ~ 6 years old in full-term children. We conducted a population-based cohort study of 12,564 children from 66 kindergartens in Tianjin, China. Information on birth weight, body mass index (BMI) at 2 and 5 ~ 6 years old, and blood pressure at 5 ~ 6 years old was retrospectively collected.

Results

The prevalence of childhood OHTN (SBP or DBP ≥ P95 percentile for sex, age, and height) was 17.0%. At birth, SGA has a high risk of OHTN (AOR 1.36, 95%CI 1.10–1.68). In the SGA subgroup, although children are of normal weight at 5 ~ 6 years old, excessive catch-up growth (BMI ≥75th at 2 years old) was still attributed to OHTN (OR 1.51, 95%CI 1.03–2.24). Obesity (BMI ≥2SD at 5 ~ 6 years old) was a vital risk factor for OHTN (AOR 2.93, 95%CI 2.56–3.36) unregarding with birthweight (OR 95%CI: SGA 3.23(1.66 ~ 6.27), AGA 2.83 (2.42–3.31), LGA 3.52 (2.65–4.68)). The co-presence of moderate or excessive catch-up growth before 2 years old and obesity at 5 ~ 6 years old significantly increased the risk of childhood OHTN (OR from 2.74 (1.65–4.54) to 6.53 (2.68–15.90)).

Conclusions

Preschool obesity, low birth weight, and excessive catch-up growth increased the risk of OHTN in childhood.
Molecular imprinted polymer-based potentiometric approach for the determination of carvedilol and ivabradine hydrochloride in dosage form, spiked human plasma and in presence of their oxidative degradates
Authors: Fares Nermine V. , El Fiky Haitham A. , Ahmed Dina A. , El Ghany Maha F. Abd , Badawey Amr M. , Tantawy Mahmoud A.
Published: February 2025

Carivalan® pharmaceutical formulation, which includes carvedilol and ivabradine hydrochloride, is commonly prescribed for alleviating pain associated with angina. Solid contact ion-selective electrodes with wide range of applications have been developed for analysis of these two active ingredients. Those types of electrodes have common drawbacks. Aside from development of aqueous layer, the incorporated ion exchanger in plasticized membrane is usually unable to differentiate in sensing between two similarly charged lipophilic organic ions. These flaws impeded simultaneous quantification of carvedilol and ivabradine hydrochloride in their dosage form. First, attempts were made to stabilize possible signals by synthesizing hydrophobic multiwall carbon nanotubes-based carbon paste. Precipitation polymerization was used to create molecular imprinted polymers (MIPs) for each drug. MIPs’ graved cavities serve as artificial host-tailored receptors that are able to recognize and bind to individual drugs. Carvedilol MIP-based sensor showed Nernstian slope of 55.30 mV/decade while the corresponding value for ivabradine one was 55.50 mV/decade. The respective LODs were 7.0 × 10− 8 M and 6.0 × 10− 7 M. Interference from excipients of pharmaceutical formulation, common plasma ions, and possible oxidation byproducts was not witnessed, permitting direct and simultaneous measurement of carvedilol and ivabradine in their tablet solution and spiked human plasma. Furthermore, the proposed technique was compared favorably with the official titrimetric and reported spectrophotometric methods for analyzing carvedilol and ivabradine, respectively.
Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids
Authors: Zhu Lu , Yang Wenhao , Luo Jiaxin , Lu Danli , Hu Yanan , Zhang Rui , Li Yan , Qiu Li , Chen Zelian , Chen Lina , Liu Hanmin
Published: February 2025

Background

The nasal epithelium, as part of a continuous and integrated airway epithelium, provides a more accessible sample source than the bronchial epithelium. However, the similarities and differences in gene expression patterns and immune responses between these two sites have not been extensively studied.

Results

Four lines of matched nasal and bronchial airway epithelial cells obtained from the four patients were embedded in Matrigel and cultured in thechemically defined medium to generate patient-derived nasal organoids (NO) and bronchial organoids (BO). Histologic examination of nasal organoid tissue revealed high similarity and a reduced ciliary beat frequency compared to bronchial organoid tissue. Whole exome sequencing revealed that over 99% of single nucleotides were shared between the NO and matched BO and there was a 95% overlap in their RNA transcriptomes. RNA sequencing analysis of differentially expressed genes indicated a significant reduction in the immune response in NO. RSV infection revealed more productive replication in NO, with a downregulated immune pathway identified by RNA sequencing analysis and upregulated levels of pro-inflammatory cytokines in culture supernatants in NO compared to BO.

Conclusions

NO and BO serve as robust in vitro models, faithfully recapitulating the biological characteristics of upper respiratory epithelial cells. The different regions of respiratory epithelial cells exhibit distinct immune responses, underscoring their complementary roles in exploring airway immune mechanisms and disease pathophysiology.