bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated contouring and radiotherapy treatment planning of spine metastases using atlas-based auto-segmentation and knowledge-based planning approaches
Authors: Jones Emma-Louise , Oppong Porsher , Sisodia Caroline , Napoleone-Filho Carolina , Harris Victoria , Golby Christopher , Eaton David , Greener Antony
Published: February 2025

Objectives

Uncomplicated spine metastases are routinely treated with conventional external beam radiotherapy (cEBRT). In cEBRT, there is no delineation of target volumes or organs at risk (OAR), or attempt to optimise dose distribution to deliver conformal, homogeneous dose distributions with sparing of OAR. Atlas-based auto-segmentation (ABAS) for target volume and OAR delineation, followed by knowledge-based planning (KBP) could facilitate conformal planning of spine metastases.

Methods

ABAS using SmartSegmentation for delineation of thoracic and lumbar vertebrae, and OAR in their vicinity, provided target volumes and OAR for conformal treatment planning. 30 volumetric-modulated arc therapy (VMAT) treatment plans were produced using RapidPlan KBP. Plans produced using this automated approach were compared to the equivalent cEBRT treatment plans.

Results

Target volume coverage for RapidPlan VMAT generated plans was superior to cEBRT. PTV Dmean = 7.86 ± 0.16 Gy, Dmin = 3.46 ± 1.79 Gy, Dmax = 8.56 ± 0.05 Gy for RapidPlan VMAT compared to Dmean = 7.78 ± 0.24 Gy, Dmin = 1.83 ± 1.08 Gy, Dmax = 10.46 ± 0.41 Gy for cEBRT. With homogeneity index and conformity index 0.236 ± 0.215 and 1.201 ± 0.121 respectively for RapidPlan VMAT compared to 0.508 ± 0.137 and 1.789 ± 0.437 for cEBRT. Dose to dose-limiting OAR spinal cord and cauda equina was reduced for RapidPlan VMAT, with Dmax of 7.91 ± 0.16 Gy and 7.94 ± 0.13 Gy respectively compared to 8.67 ± 0.13 Gy and 8.90 ± 0.16 Gy for cEBRT. KBP was superior to cEBRT in terms of target coverage, homogeneity and conformity and was achievable in a clinically acceptable time, with improved sparing of the spinal cord and cauda equina.

Conclusions

Implementation of automated treatment planning for uncomplicated spine metastases is feasible in the clinical environment with superior plan quality compared to cEBRT.

Advances in knowledge

Automated contouring and treatment planning are feasible in the clinical environment using this approach and would allow patients conformal as opposed to conventional external beam radiotherapy for treatment of spine metastases.
32 Necrotising breast fasciitis due to empyema necessitatis
Authors: De Castro Rosa Claret , Clavell Arantxa , Cladellas Esther , Blay Lidia , Peñafiel Sebastian , Garcia Samuel , Herraiz Alba , Hugué Alex , López-de Castro Pedro , Julian Joan Francesc
Published: February 2025

The patient, a 73-year-old woman with multiple medical history, consulted the emergency department (ED) of a second-level hospital due to severe left rib pain radiating to the abdomen. Initially, it was diagnosed as postherpetic neuralgia. However, during the examination in the ED, absence of breath sounds were found in the left lung base and severe pain in the left hemithorax, leading to a chest X-ray which revealed a massive left pleural effusion. A thoracentesis was performed which confirmed the presence of empyema. The patient was admitted, treatment was started with empirical Ceftriaxone and a pleural drain was placed. Urokinase was administered for 5 days and the drain was removed. She presented a torpid evolution with persistent fever and elevation of acute phase reactants despite treatment. During admission, the patient developed inflammation of the left lower chest wall, which was diagnosed as cellulitis. Antibiotic coverage was extended to Linezolid and Imipenem. However, the patient worsened clinically, presenting hypotension and tachycardia, leading to suspicion of necrotizing fasciitis. An urgent thoracic CT scan revealed a bilateral acute pneumonic infectious process with pulmonary necrosis and signs of pleural-extraspleural fistula, which was classified as necrotizing pneumonia complicated by empyema necessitatis. Clindamycin was added to the treatment. The patient was referred to a tertiary hospital in order to be evaluated by thoracic surgeons for urgent surgical debridement. Significant fibrous pleuropulmonary adhesions were found requiring costal resection. Malodorous fluid was aspirated and pleural and thoracic drains were placed. During surgery, the patient presented poor hemodynamic and ventilatory tolerance, requiring bipulmonary ventilation and the impossibility of extubation after surgery, therefore she was admitted to the ICU. Due to a poor hemodynamic evolution, the patient required a second septic control surgery one week later. A left thoracotomy was performed and multiple fibrous pleuropulmonary adhesions were again observed. Abundant purulent material was evacuated and cultures were positive for Parvimona and mixed aero-anaerobic flora. The patient required vasoactive support during the first 72 hours, but this was subsequently withdrawn without incident. A follow-up CT scan 5 days after the second surgery showed worsening of the necrotizing pneumonia. A third urgent surgery was performed in which pleuropulmonary fibropurulent tissue was observed and removed, abundant lavage was performed and drains were placed in muscular and costal planes. Negative pressure therapy (VAC system) was performed. After a prolonged admission to the ICU presented favorable evolution and she was discharged to the ward.
Deep learning image enhancement for confident diagnosis of TMJ osteoarthritis in zero-TE MR imaging
Authors: Lee Chena , Lee Joonsung , Mandava Sagar , Fung Maggie , Choi Yoon Joo , Jeon Kug Jin , Han Sang-Sun
Published: February 2025

Objective

This study aimed to evaluate the effectiveness of deep learning method for denoising and artifact reduction (AR) in zero-TE (ZTE) magnetic resonance imaging (MRI). Also, Clinical applicability was evaluated by comparing image diagnosis to the temporomandibular joint (TMJ) cone-beam computed tomography (CBCT).

Methods

For thirty patients CBCT and routine ZTE-MRI data was collected, and an additional reduced scan time-ZTE-MRI was also obtained. Scan time-reduced image sets were processed into denoised and AR image based on deep learning technique. The image quality of routine sequence, de-noised and AR image sets were compared in quantitative evaluation using signal-to-noise ratio (SNR), and in qualitative using 3-point grading system (0, poor; 1, good; 2, excellent). The presence of osteoarthritis was assessed in each imaging protocol. Diagnostic accuracy of each protocol was compared against the CBCT results, which served as the reference standard. The SNR and the qualitative scores was compared using analysis of variance test and Kruskal-Wallis test, respectively. The diagnostic accuracy was assessed using the Cohen κ (<0.5 = poor; 0.5 to < 0.75 = moderate; 0.75 to < 0.9 = good; ≥0.9 = excellent).

Results

Both denoised and AR protocol resulted the significantly enhanced SNR compared to routine protocol and AR protocol showed higher SNR than denoised one. The qualitative assessment also showed highest grade in AR protocol with statistical significance. The osteoarthritis diagnosis showed enhanced agreement with CBCT in denoised (κ=0.928) and AR images (κ=0.929) than routine images (κ=0.707).

Conclusions

A newly developed deep learning technique for both denoising and artifact reduction in ZTE-MRI presented clinical usefulness. Specifically, AR protocol showed significantly improved image quality and comparable diagnostic accuracy as CBCT. It can be expected that this novel technique would help overcome the current limitation of ZTE-MRI for replacing CBCT in bone imaging of TMJ.
Chromosome-Level Genome Assembly of the Heptageniid Mayfly Parafronurus youi (Ephemeroptera), and Its Annotation
Authors: Li Ran , Wang Ze-Kai , Liu Dong-Kai , Zhang Ying-Xue , Li Xiao-Yu , Li Hai-Xin
Published: February 2025

As a group of winged insects (Pterygota) retaining many primitive characteristics, genomic research on mayflies remains highly limited, posing challenges to the study of their origin and evolution. In this study, we present the first chromosome-level genome assembly of the Chinese endemic mayfly Parafronurus youi utilizing Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. The high-quality genome is 412.90 Mb in size with 99.07% of the sequences anchored to 11 chromosomes (ranging from 24.88 to 45.89 Mb). Genome annotation predicted 15,647 protein-coding genes with an average length of 9,934.7 bp, of which 85.9% were functionally annotated in the UniProtKB database. Repetitive elements accounted for 32.83% of the genome, including 27.33% transposable elements and 4.07% simple repeats. This study not only enriches genomic resources for mayflies but also establishes a foundation for investigating molecular mechanisms underlying ecological adaptation and evolutionary traits, contributing to the conservation of freshwater ecosystems.
Lung toxicity related to trimethoprim/sulfamethoxazole: pharmacovigilance data review
Authors: Givry F , Lebargy F , Lebrun D , Bonnet M , Ruellan A L , Hentzien M , Azzouz B , Bani-Sadr F
Published: February 2025

Background

Well-established side effects of trimethoprim/sulfamethoxazole include cutaneous and liver toxicity, hypersensitivity syndrome and blood dyscrasias. Trimethoprim/sulfamethoxazole has also been associated with severe lung toxicity (LT) but reports are scarce.

Methods

We investigated pharmacovigilance data and reviewed spontaneous reports of trimethoprim/sulfamethoxazole-related LT recorded in the French national pharmacovigilance database (FPVD) and the WHO global database of adverse events (VigiBase®) up to 31 December 2023. We performed disproportionality analysis to detect a possible pharmacovigilance signal.

Results

A total of 755 patients with trimethoprim/sulfamethoxazole-related LT were reported in VigiBase®, 17 of which were from the FPVD. In VigiBase®, interstitial lung disease was the most frequent LT pattern (30.5%). A fatal outcome was reported in 197 patients (26.1%). Significant reporting ORs were observed for the following trimethoprim/sulfamethoxazole-related LT patterns: interstitial lung disease 1.5 (95% CI: 1.3–1.7); acute respiratory distress syndrome 2.9 (95% CI: 2.5–3.5); eosinophilic pneumonia 4.1 (95% CI: 3.2–5.2); diffuse alveolar damage 3.7 (95% CI: 2.6–5.3); organizing pneumonia 2.1 (95% CI: 1.4–3.1); pulmonary toxicity 1.9 (95% CI: 1.3–2.9); acute lung injury 7.5 (95% CI: 4.9–11.6) and hypersensitivity pneumonitis 2.7 (95% CI: 1.7–4.2).

Conclusions

We highlight statistically significant disproportionality for several trimethoprim/sulfamethoxazole-related LT patterns, which constitutes a pharmacovigilance signal. Trimethoprim/sulfamethoxazole-related LT is rare, but may be critical and even life-threatening. Physicians should be aware of potential trimethoprim/sulfamethoxazole-related LT and should inform their patients, since early intervention could prevent severe outcome.
Residual Feed Intake and Reproductive-related Parameters in Yearling Brangus Bulls
Authors: Venturini Mauro , de Agostini Losano Joao , Heredia Daniella , Camila López Duarte Maria , Infante Jose , Podversich Federico , McGraw Maura , Siddique Muhammad Sohail , Guertin Jillian , Poliakiwski Brette , Smith Damon J , Pohler Ky , DiLorenzo Nicolas , Daigneault Bradford W , Gonella Diaza Angela
Published: February 2025

Residual feed intake (RFI) is a widely employed metric to estimate feed efficiency, which compares actual feed intake to expected feed intake. Enhancing feed efficiency while maintaining reproductive performance is critical to maximizing the profitability of beef production systems. Published data exhibit conflicting results concerning the impact of RFI on reproductive parameters. Our objective was to evaluate the relationship between RFI and reproductive parameters in young Brangus bulls. Sixty bulls were randomly selected at the beginning of a 56-day feed efficiency test. At the start, scrotal circumference (SC) was measured, blood samples were taken for testosterone concentration analysis, and semen samples were collected by electroejaculation. Fresh semen was visually evaluated for motility, morphology, and plasma membrane integrity. Sperm kinematics and concentration were objectively determined via computer-assisted sperm analysis (CASA-IVOS II System). At the end of the test, bulls were classified as feed efficient (low RFI: LRFI) or feed inefficient (high RFI: HRFI) and grouped based on RFI divergence. Two models were constructed to analyze data: one using all bulls (Halves, n = 58) and one using the 25% extremes of the population (Tails, n = 30). Data were compared using a Completely Randomized Design (CRD). Using the halves model, only major defects (P < 0.04) and total defects (P = 0.014) were significantly affected by RFI group, with LRFI bulls showing a lower proportion of abnormal sperm cells. In the tails model, only SC (P = 0.01) was significantly affected by RFI, with LRFI bulls having a larger SC compared to HRFI bulls. The RFI group did not affect CASA-derived traits in either model. In conclusion, most fertility-related measurements were not affected by RFI status in young Brangus bulls. These results suggest that selection for feed efficiency in young bulls can be achieved without negatively impacting seminal characteristics associated with fertility.
‘And now I feel I don’t have a clear future’: Hauntings and temporal uncertainty in refugee narratives
Authors: Brøndum Tine
Published: February 2025

As a consequence of the so-called ‘paradigm shift’, that defines all refugee protection as temporary, the last decade has seen the focus for refugee administration in Denmark move from ‘integration’ towards ‘repatriation and self-provision’. Through analysis of life stories from people arriving to Denmark as refugees before and after this shift, this article examines how people seeking protection experience and make meaning of their new reality as refugees within the Danish welfare state. Drawing on the perspectives of narrativity and hauntology, that acknowledges the workings of past injustices in the present, the analysis shows that people living in temporary protection experience being kept waiting in a never-ending present. Uncertain waiting destroys people’s sense of agency and belonging and counteracts their ability to reorient themselves towards a meaningful future. The article suggests that this ongoing uncertainty conjures up ghosts from the past that reappear and continue to haunt and ruin their present lives.
Population genetic structure and human adaptation of Kaposi Sarcoma-associated Herpesvirus
Authors: Mozzi Alessandra , Forni Diego , Cagliani Rachele , Molteni Cristian , Clerici Mario , Sironi Manuela
Published: February 2025

Background

Kaposi Sarcoma-associated Herpesvirus (KSHV), the etiologic agent of Kaposi’s sarcoma, is human-specific and it is thought to have emerged from primate-infecting gammaherpesviruses. KSHV seroprevalence shows geographic variation, being highest in Sub-Saharan Africa, intermediate in the Mediterranean area, and low in most other locations. However, KSHV prevalence is also particularly high in specific regions such as the Miyako Islands (Japan).

Methods

We retrieved KSHV genomes from public repositories and we analyzed geographic patterns using principal component analysis and STRUCTURE. Adaptation to the human host was investigated by likelihood ratio tests for positive selection. Protein structures were derived from HerpesFolds.

Results

Most non-African genomes are genetically separated by the African ones and the latter are divided into two main lineages. The African genomes received most of their ancestry from two populations showing limited drift, suggesting an African origin for circulating KSHV strains. Several non-African genomes have instead most of their ancestry covered by a highly drifted ancestral population. However, some non-African genomes show similar ancestry proportions to the African ones, including those from Miyako Islands and the variant F subtype sampled in France. Molecular analysis of adaptation to the human host identified core genes as the major selection targets, including two viral enzymes that counteract human immune defenses.

Conclusions

We suggest that the genetic diversity of extant strains reflects relatively recent demographic events associated with viral lineage extinctions, which may have influenced KSHV epidemiology. Adaptation to the human host involved changes in core genes, possibly a strategy to optimize protein-protein interactions.
Meeting evaluation criteria based on authorship positions by gender, academic age, and research field: the Spanish case
Authors: Chinchilla-Rodríguez Zaida , Escabias Manuel , Morillo Fernanda
Published: February 2025

This study aims to provide an overview of the distribution of the Spanish scientific workforce focusing on differences in authorship position by gender, academic age, number of authors, and research field. The results show some degree of parity in younger age cohorts and areas such as biomedicine, but little participation of females in the oldest age cohort and areas such as mathematics. In addition, the presence of women undergoes significant changes in certain areas and decreases in oldest age cohorts. This circumstance leads to a low probability of finding women or junior researchers in relevant authorship positions. Policymakers should know that inequalities in the scientific workforce must be considered when addressing/proposing scientific evaluation criteria.
Recently reported SARS-CoV-2 genomes suggested to be intermediate between the two early main lineages are instead likely derived
Authors: Pekar Jonathan E , Moshiri Niema , Lemey Philippe , Crits-Christoph Alexander , Débarre Florence , Goldstein Stephen A , Hensel Zach , Rambaut Andrew , Worobey Michael , Holmes Edward C , Wertheim Joel O
Published: February 2025

Understanding the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the outset of the coronavirus disease 2019 (COVID-19) pandemic can provide insight into the circumstances leading to its emergence. Early SARS-CoV-2 genomic diversity has been classified into two distinct viral lineages, denoted “A” and “B”, which we hypothesized were separately introduced into humans. Recently published data contain two genomes with a haplotype suggested to be an evolutionary intermediate to these two lineages, known as “T/T”. We used a phylodynamic approach to analyze SARS-CoV-2 genomes from early 2020 to determine whether these two T/T genomes represent an evolutionarily intermediate haplotype between lineages A and B, or if they are a later descendent of either of these two lineages. We find that these two recently published T/T genomes do not represent an evolutionarily intermediate haplotype and were, instead, derived from either lineage A or B. However, we cannot conclusively determine from which lineage they were derived. After including additional data from the start of the pandemic, including these two T/T genomes, we again find a discrepancy in the molecular clock when inferring the ancestral haplotype of SARS-CoV-2, corroborating existing evidence for the separate introductions of SARS-CoV-2 lineages A and B into the human population in late 2019.
A Rare Case of Combined Merkel Cell Cancer and Squamous Cell Carcinoma of the Face in an Older Woman of Southern Italy
Authors: Mariniello Domenico , D’Antonio Santolo , Castellaneta Francesco , Grieco Michele , Fabrizio Tommaso
Published: February 2025

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin tumor, whereas squamous cell carcinoma (SCC) is a more common form of skin cancer. Both tumors share similar risk factors, including advanced age, sun exposure, and fair skin. Cases of synchronous MCC and SCC are rare, and there are no established guidelines for their combined management. We report the case of an 85-year-old White woman from Southern Italy, presenting with a nodular lesion on her right forehead and a flat keratotic lesion on her right zygomatic region. The patient was treated with surgical excision and close postoperative follow-up. Histopathological analysis confirmed 2 distinct tumor populations in the forehead lesion: poorly differentiated neuroendocrine cells, consistent with MCC, and squamous cells with invasive characteristics. The zygomatic lesion contained only squamous cells. Despite surgical intervention and multidisciplinary postoperative care, the patient experienced recurrence within 4 months and died. This case illustrates a rare occurrence of combined MCC and SCC, presenting challenges in diagnosis and treatment. Given the lack of guidelines for managing dual diagnoses, this case highlights the need for further studies to establish standardized treatment protocols. The aggressive nature of these tumors underscores the importance of early detection and ongoing research to improve outcomes.
Causal relationship between gut microbiota and dental caries: A Mendelian randomization analysis
Authors: Jiang Yongyuan , Jin Huan , Liang Qian , Zhu Xuan
Published: February 2025

The onset of dental caries is associated with multiple factors, including oral microbiota, dietary sugars, the defensive mechanisms of saliva and teeth, oral hygiene practices, and socioeconomic factors. However, its relationship with the gut microbiota remains to be further explored. It remains crucial to establish a definitive causal link between the gut microbiota and the development of dental caries. This study aimed to investigate the causal relationship between gut microbiota and the risk of dental caries, focusing on identifying specific microbial communities potentially implicated in its pathogenesis. Gut microbiota data from genome-wide association studies (GWAS) conducted by the MiBioGen consortium were utilized as the exposure variable, with dental caries as the outcome variable. A Mendelian randomization (MR) approach was employed, leveraging comprehensive, publicly available GWAS summary data from European populations. The primary analytical method was the inverse variance weighted method, supplemented by additional techniques such as the weighted median model, MR-Egger, simple mode, and weighted mode, to ensure the robustness of the results. Heterogeneity was evaluated using Cochran Q test, and potential pleiotropy was assessed through MR-Egger regression. Sensitivity analyses were performed using the leave-one-out method to further validate the findings. The results revealed that a higher relative abundance of Christensenellaceae, FamilyXIII, Ruminococcaceae, and Senegalimassilia was associated with a reduced risk of dental caries. In contrast, a higher relative abundance of Erysipelotrichia, Erysipelotrichales, Pasteurellales, Erysipelotrichaceae, Pasteurellaceae, Methanobrevibacter, Roseburia, and Terrisporobacter was linked to an elevated risk of dental caries. This study provides compelling evidence for a causal relationship between gut microbiota and the development of dental caries, offering novel insights into the potential role of specific gut microbial communities in the pathogenesis of dental caries.
Acute abdominal pain as the initial presenting symptom of pediatric Burkitt lymphoma: A case report and literature review
Authors: Tan Qing-Lin , Tang Qing , Chen Xiu-Qi , Huang Li , Yun Xiang , Shan Qing-Wen
Published: February 2025

Rationale:

Acute abdominal pain is a prevalent clinical symptom in pediatric patients, primarily attributed to pediatric acute abdomen. However, there are rare exceptional instances where neoplastic diseases may cause acute abdominal pain.

Patient concerns:

The present study encompasses a case of pediatric Burkitt lymphoma wherein acute abdominal pain manifested as the initial symptom, erroneously diagnosed as acute appendicitis.

Diagnoses:

The immunohistochemistry results of laparoscopic biopsy revealed Burkitt lymphoma, characterized by positive expression of CD20, CD79a, CD10, BCL-6, MUM1, and strong positive expression of CD38, c-myc, cyclinD1, and Ki-67 positive index >90%+.

Interventions:

The child underwent regular chemotherapy according to the SCCCG-BL/DLBCL-2017 regimen.

Outcomes:

During the 13-month follow-up period, the patient’s obtained complete remission by Positron emission tomography–computed tomography scan.

Lessons:

The objective of this study is to enhance the awareness of clinical pediatricians regarding cases of acute abdominal pain caused by lymphoma.
Intracranial phosphaturic mesenchymal tumor: A rare case report and systematic review
Authors: Song Shuyue , Zhao Yuyang , Wang Yiquan , Zhao Yujing , Liu Wenqiang , Wang Zhe
Published: February 2025

Rationale:

Phosphaturic mesenchymal tumors (PMTs) are rare soft-tissue and bone tumors that can occur intracranially. Low incidence, nonspecific symptoms, and diverse histomorphology of PMTs contribute to a high rate of misdiagnosis.

Patient concerns:

This report presents a rare case of an intracranial PMT located in the posterior cranial fossa. In addition, a systematic review of previously reported intracranial PMT cases was conducted and summarized.

Diagnoses:

Incorporating clinical symptoms, laboratory findings, and imaging features, the definitive diagnosis of PMT was based on pathological examination.

Interventions:

The patient underwent consultations in endocrinology, orthopedics, and neurosurgery, and ultimately had a surgical procedure to remove the intracranial tumor.

Outcomes:

After tumor resection, the patient’s laboratory values returned to normal, his symptoms improved, and he could walk again.

Lessons:

Due to the rarity and high misdiagnosis rate of PMTs, no unified diagnosis and treatment standards have been established. Early identification, accurate diagnosis, and timely treatment are essential for optimal management. Surgical resection remains the preferred treatment for PMTs, with total tumor resection strongly recommended. In case of incomplete resection, tumor recurrence and persistent symptoms may necessitate adjunctive drug therapy and radiation therapy.
The causal relationship between hallux valgus and endogenous pathogenic factors: A 2-sample Mendelian randomization
Authors: Xie Yuan Lei , Liang Jia Yuan , Du Gen Fa , Lu Hui Jun , Luo Wei Jie , Wu Jia Heng , Sheng Zhao Hui
Published: February 2025

Notably, several factors are associated with hallux valgus (HV); however, their causal relationship remains unclear. In this study, a 2-sample Mendelian randomization (MR) analysis was performed to investigate the casual relationship between 9 endogenous risk factors and HV, aiming to provide a foundation for the clinical management of HV. Exposure factors such as body mass index (BMI), BMI (male), BMI (female), acquired flatfoot, rheumatoid arthritis, gout, knee osteoarthritis, hip osteoarthritis, and Ehlers–Danlos syndrome were considered, with HV as the outcome. Exposure and outcome data were obtained from the IEU Open Genome-wide association study project, UK Biobank, and FinnGen project. Strongly correlated (P < 5×10−08/5×10−06) single nucleotide polymorphisms (SNPs) were selected from the exposure dataset, and those associated with exposure were selected from the HV dataset. The intersection of these SNPs was used as instrumental variables. Five modes were used for the analysis: inverse variance-weighted (IVW), MR-Egger regression, weighted median (WME), simple mode, and weighted mode. MR analysis results of BMI show that except for MR-Egger, the other 4 modes are significant (P < .05), and the β directions are consistent among the 5 methods. For the 4 BMI (male) methods, except for the simple mode, the P- and β-values of the other results all suggest a positive causal relationship between BMI (male) and HV. Flatfoot-IVW and WME results were <.05, indicating statistical significance, whereas MR-Egger, simple mode, and median mode had no statistical significance. However, their β-values were consistent with those of IVW and WME. Further mediation MR analysis suggested that the effect mediated by HV accounts for 13.33% [95% CI (0.03–0.24)] of the total causal effect between the BMI and flatfoot, indicating HV as a mediator of the causal relationship between the BMI and flatfoot. However, the remaining 6 factors had no direct causal association with HV (P < .05). Flatfoot in all patients and elevated BMI in males are directly associated with HV. Therefore, treating acquired flatfoot and controlling the BMI to prevent HV are recommended.
Association Between Vascular Calcifications on Joint Radiographs and Calcium Pyrophosphate Crystal Arthritis
Authors: Brikman Shay , Tannous Hani , Novofastovski Irina , Abuhasira Ran , Mader Reuven , Bieber Amir
Published: February 2025

Objective

Previous studies have shown an association between chondrocalcinosis (CC) and vascular calcifications (VCs). This study aimed to investigate the association of VCs detected on joint radiographs (XRs) of older patients diagnosed with calcium pyrophosphate (CPP) arthritis compared with a control group with osteoarthritis (OA).

Methods

A medical records review study of joint radiographs (knee and wrist) was conducted. CPP crystal arthritis was diagnosed based on at least 1 documented episode of arthritis with synovial fluid analysis positive for CPP crystals or imaging showing CC at 1 or more sites, with no alternative inflammatory arthritis diagnosis. The control group comprised patients with OA and no CC, matched 1:1 for age and sex. All participants were over 60 years of age. XRs were reviewed for CC, OA, and VCs at the affected joint by 2 independent observers.

Results

A total of 98 patients were enrolled in both the CPP arthritis group and the OA group. VCs adjacent to the affected joint were detected in 69 patients of the CPP group and 19 patients of the control group (70.4% vs 19.4%, p < 0.001). Among patients aged 60 to 80 years, the presence of VCs on XRs was highly indicative of CPP, demonstrating a specificity of 89.2% (95% confidence interval: 79.1%–95.6%). In the CPP group, patients with VCs had a significantly higher prevalence of cardiovascular (CV) comorbidities.

Conclusions

The detection of VCs on XRs was strongly associated with CPP crystal arthritis. The presence of VCs may further serve as a biomarker for an increased burden of CV comorbidities.
Diagnostic investigations in adults with suspected stroke—improvement of door-to-imaging time: a best practice implementation project
Authors: Licenik Radim , Sedova Petra , Ismail Tahir , Khaled Hasan Muhammad , Klugar Miloslav , Riad Abanoub , Klugarová Jitka
Published: February 2025

Objectives:

This evidence implementation project aimed to assess and improve compliance with evidence-based neuroimaging criteria for adult patients with suspected stroke.

Introduction:

Stroke is the second leading cause of mortality and severe disability, requiring timely and accurate diagnosis. Clinical guidelines recommend brain imaging within 60 minutes of hospital arrival for suspected stroke patients. This project involved hospitals in North West Anglia NHS Foundation Trust, UK, serving 850,000 people with over 800 admissions annually.

Methods:

The JBI Evidence Implementation Framework was used to guide this project. JBI software, the Practical Application of Clinical Evidence System (PACES), as well as JBI's Getting Research into Practice (GRiP) approach, were used to conduct the audit and implementation phases. The project followed three stages: (1) implementation planning, (2) baseline assessment and implementation, and (3) impact evaluation. Three audit criteria were used to represent best practices for diagnosing suspected stroke patients.

Results:

The baseline audit revealed low compliance with the first criterion, with only 2.9% (1/35) of patients receiving a CT head scan within 1 hour of admission. In the follow-up audit, compliance improved to 45.2% (14/31). The other two criteria, diagnosis by a trained health care professional and baseline ECG assessment, had already achieved 100% compliance in the baseline audit.

Conclusions:

Compliance with evidence-based neuroimaging criteria improved after implementing targeted educational strategies and training. The rate of CT scans conducted within 1 hour increased, although door-to-imaging times remain suboptimal compared with achievable benchmarks of ≤ 20 minutes. Ongoing education and training are crucial for sustaining high compliance and improving stroke patient outcomes.

Spanish abstract:

http://links.lww.com/IJEBH/A324
Reconstructing the Huang Surname and Its Related Lineages: A Comprehensive Analysis of Molecular Genetics and Historical Genealogies
Authors: Huang Shi
Published: February 2025

The origin of the Huang surname is complex, but according to historical texts such asShiji, it can be traced back to the Yellow Emperor (Huang Di) and his descendant, Bo Yi, who played a key role in controlling the floods during the Xia Dynasty and was granted the surname Ying. Bo Yi had two sons who each established a state, one named Huang and the other Xu. After the fall of Huang, its people adopted Huang as their surname and migrated to Hubei. Similarly, after the fall of Xu, its people adopted Xu as their surname, spreading throughout Jiangsu. Further descendants of Bo Yi also gave rise to 12 other surnames, including the Liang surname. Given that the narratives of ancient texts are often regarded as legendary, we aim to independently verify the authenticity of the historical records by analyzing the paternal haplotypes of the Huang surname and its related surnames using scientific methods. We analyzed the surname genetic data of 207,333 Han Chinese males published by 23Mofang and combined it with independent sequencing research. In 189 Y chromosome haplotype branches, each containing at least five individuals with the surnames Huang, Xu, or Liang, and formed around 4,000 years ago, we analyzed the proportion of samples with the Huang surname from Hubei among all samples nationwide with the Huang surname. Branches with a high proportion in Hubei are likely to represent the Hubei-specific lineage of the Huang surname. We similarly analyzed the proportion of samples with the Xu surname in the Jiangsu area and of samples with the Liang surname in the Hebei area. We further applied two criteria to identify the ancestral genotype of a specific surname in a given region: first, the surname should appear at a high frequency among all surnames within that genotype; second, the proportion of samples of the region among nationwide samples should be high. The results showed that the Hubei-specific Huang surname likely carries the MF14296/MF15137 haplotype downstream of the supergrandfather O-M117-F8-F2137-A16635-A16636. Our independent sampling study found that A16636 is the dominant haplotype among the Huang surname population in nine neighboring Huang surname villages around Luohansi in Huangpi, Hubei. The Jiangsu-specific Xu surname likely carries the MF38096/SK1726 haplotype under the A16636 sister branch F15823, while the Hebei-specific Liang surname likely carries the F15823 related MF14287/MF15398/MF14963 haplotype. This conclusion aligns with the historical records, providing strong genetic evidence that supports the authenticity of these ancestral claims regarding the Huang and Xu states and the Xia dynasty.
BrAIn: A comprehensive artificial intelligence-based morphology analysis system for brain organoids and neuroscience
Authors: Kahveci Burak , Polatli Elifsu , Evranos Ali Eren , Güner Hüseyin , Bastanlar Yalin , Karakülah Gökhan , Güven Sinan
Published: February 2025

Human-induced pluripotent stem cells (iPSCs) offer transformative potential for biomedical research, with iPSC-derived organoids providing more physiologically relevant models than traditional 2D cell cultures. Among these, brain organoids are particularly valuable for drug screening, disease modeling, and investigations into molecular pathways. Accurate representation of brain morphology is critical, as more complex organoid structures better mimic the human brain. Deep learning (DL) and machine learning (ML) approaches have become integral to analyzing organoid morphology, yet tools for comprehensive, time-resolved assessments are scarce. Here, we introduceBrAIn, a DL-based application for analyzing the developmental progression of brain organoids. BrAIn tracks their evolution from embryoid bodies and quantifies parameters including area, Feret diameter, perimeter, roundness, and circularity. It also classifies budding and abnormal morphologies of 3D organoids and detects monolayer neural rosette structures, key features of neuronal differentiation. Designed with accessibility in mind, BrAIn provides a no-code interface, enabling researchers of all technical backgrounds to conduct advanced morphological analyses with ease. Our study demonstrates the application of BrAIn to evaluate the effects of different growth conditions - static, orbital shaker, and microfluidic chip-based - on brain organoid development. Orbital shaker cultures resulted in the largest organoids, while chip-based systems achieved more homogeneous growth. Both conditions produced organoids with greater morphological complexity compared to static culture. BrAIn emerges as a robust, user-friendly tool to quantify brain organoid development and explore how versatile growth conditions influence their morphology and maturation.
Disentangling urbanisation, climate effects and their interaction on ornamental colourations
Authors: Sandmeyer Lisa , Lopez-Idiaquez David , Fargevieille Amelie , Giovannini Pablo , Perret Samuel , Del Rey Maria , Charmantier Anne , Doutrelant Claire , Gregoire Arnaud
Published: February 2025

Research on urbanisation and climate change has shown that they affect phenotype expression across taxa. Most evidence collated so far has focused on exploring these two phenomena on isolation. Currently, the combined effects of climate change and urbanisation remain underexplored, despite being among the greatest challenges faced by biodiversity. Here, we use a decade-long, individual-based study of urban and forest great tits (Parus major) to analyse urbanisation, climate and their interactive effects on yellow breast colouration, a carotenoid-based trait. We find that urban birds exhibit duller colourations than forest counterparts, being 10-20% less chromatic, with first-year birds and males being more negatively impacted in cities. Additionally, birds in the city are more sexually dichromatic than in the forest. Over the decade, colouration differences between habitats remain stable, following a similar quadratic temporal pattern. Finally, while climate has a weak effect on colouration, urban birds appear more sensitive to its influence than forest birds. Our results indicate urbanisation has a stronger impact than climate on great tit colouration, though both factors may interact. The heightened sensitivity of first-year birds and increased sexual dichromatism in cities may alter the strength of natural and sexual selection on this trait in urban environments.
The novel SCN5A-P1891A mutation is associated with left ventricular hypertrabeculation and links Nav1.5 to cardiomyocyte proliferation and disrupted 3D cardiac tissue formation
Authors: Majid Qasim A. , Prajapati Chandra , Liu Xiaonan , Kari-Koskinen Julia , Pohjolainen Lotta , Karhu S. Tuuli , Ruskoaho Heikki , Varjosalo Markku , Aalto-Setälä Katriina , Talman Virpi
Published: February 2025

Background

Left ventricular hypertrabeculation (LVHT) is a heterogenous cardiac condition with a complex and poorly understood aetiology. We comprehensively characterised the effect of a novel P1891A mutation in theSCN5Agene, which encodes the voltage-gated sodium channel Nav1.5, identified in a Finnish family diagnosed with LVHT.

Methods

We generatedSCN5A-P1891A mutation-carrying human induced pluripotent stem cell-derived cardiomyocytes (P1891A-hiPSC-CMs) and performed electrophysiological assessments, including patch-clamp studies, and fluorescent calcium imaging, to determine the mutation’s effect on hiPSC-CM electrophysiology. We also evaluated the impact of the mutation on the proliferative capacity in response to mitogenic stimuli and on the hypertrophic response following cyclic mechanical stretch or endothelin-1 treatment. Further, we assessed the effect on contractile parameters in three-dimensional (3D) contractile hydrogels (engineered heart tissues, EHTs) and conducted advanced proteomics to understand the consequences of the mutation on Nav1.5 protein-protein interactions.

Results

TheSCN5A-P1891A mutation reduced the sodium current densities and increased both the sodium window current and arrhythmogenicity; however, action potential parameters were unaffected. Advanced proteomics characterised, for the first time, the complete Nav1.5 interactome and revealed that theSCN5A-P1891A mutation negated interactions with fibroblast growth factor 12 (FGF12) and FGF13, that are known to modulate sodium channel activity. Baseline proliferation was unchanged, although aged P1891A-hiPSC-CMs demonstrated enhanced proliferative capacity following mitogenic stimulation. Further, P1891A-hiPSC-CMs exhibited a heightened stress response upon mechanical stretch, resulting in the upregulation of heart failure-associated genes. Strikingly, EHTs derived from P1891A-hiPSC-CMs yielded disparate phenotypes. Whilst the majority condensed only partially and failed to beat synchronously, a small subset condensed fully yet exhibited weak contractile properties, alongside age-associated functional decline. In contrast, EHTs derived from healthy control hiPSC-CMs consistently condensed fully and demonstrated a positive correlation between post-fabrication age and contractile properties

Conclusions

Our study presents a unique aetiology of LVHT and reveals a novel association betweenSCN5Amutations and enhanced human cardiomyocyte proliferation. Further, the inability of P1891A-hiPSC-CMs to consistently form fully condensed 3D cardiac tissues may be linked to their abnormal response to mechanical stretch and provides a powerful 3D model for future mechanistic research and drug development studies to better understand and treat LVHT.
Perspectives of persons with lived experience on acceptable outcome after traumatic brain injury
Authors: Bodien Yelena , Borsi Lydia , Pier Ellyn , Kanny Samantha , Droscha Lillian , Choi William , Filoramo Ryan , Burnetta Danielle , McColgan Kathleen , Patel Bhumi , Spring Mallory , Vazquez Rivera Jean Paul , Wolfe Jessica , Quilico Enrico , Campbell Tiffany , Merner Amanda , Lazaro-Munoz Gabriel , Wilson Lindsay , Giacino Joseph
Published: February 2025

Importance: Current approaches to functional outcome assessment in persons with severe traumatic brain injury (TBI) may not reflect the perspectives of persons with TBI or TBI caregivers. Objective: Determine the lowest level of functional recovery after severe TBI that is perceived to be acceptable by persons with TBI and TBI caregivers. Design: Cross-sectional crowdsourcing online survey disseminated May-July 2024. Setting: United States. Participants: Persons with a history of TBI requiring assistance with basic daily activities and TBI caregivers. Exposure(s): History of severe TBI. Outcome(s)/Measure(s): An expanded version of the Glasgow Outcome Scale-Extended (GOSE) designed to determine the level of acceptability of 11 TBI outcome milestones and the minimally acceptable outcome (MAO). Results: The survey was completed by 252 persons with TBI (mean[SD] age 39.8[13.5] years; 67% female; 75% white; 11.9[12.0] years post-TBI) and 256 TBI caregivers (41.0[12.1] years; 57% female; 65% white). Among the outcomes selected most frequently as the MAO by persons with TBI (i.e., "recovery of yes/no communication" and "conscious, but does not communicate") and TBI caregivers (i.e., "recovery of yes/no communication" and "alive, but permanently unconscious"), recovery of reliable yes/no communication was selected as acceptable by most respondents (persons with TBI: 36% vs 12%; Z=-7.1, p<0.0001; TBI caregivers 40% vs 14%, Z=-7.1, p=<0.0001). Recovery of reliable yes/no communication was therefore identified as the MAO by both cohorts. This outcome was rated as acceptable or somewhat acceptable by 65% of persons with TBI and 72% of caregivers. Outcomes representing disability greater than "completely independent in the home" were selected as the MAO more frequently than this common cut-off for "favorable" outcome, which was selected as the MAO by 5.6% and 3.9% persons with TBI and caregivers, respectively. Conclusions/Relevance: Persons with TBI and TBI caregivers identified recovery of yes/no communication, an outcome that is well below the traditional cut-off for "favorable," as the MAO. Persons with lived experience appear more accepting of a greater burden of disability than TBI investigators and providers. Recognizing this disparity in perspectives may influence clinical decision-making regarding goals of care and suggests the need for a more person-centered approach to TBI outcome assessment.
Mechanisms and Pathways Linking Depression and Type 2 Diabetes Outcomes: A Scoping Review
Authors: Derese Andualem , Sirgu Sisay , G/Egziabhere Yohannes , Hanlon Charlotte
Published: February 2025

Aims People with diabetes experience a significantly higher prevalence of mental health issues, particularly depression. This adversely affects their diabetes management and overall health. This scoping review aims to develop a conceptual framework for understanding the connection between depression and diabetes outcomes globally, specifically focusing on intermediary factors that may influence this relationship. Methods PubMed, EMBASE, PsycINFO, and Global Index Medicus were searched using relevant keywords on 17th May 2024. The inclusion criteria encompassed peer-reviewed studies involving adults diagnosed with Type 2 diabetes that assessed depression and analysed its impact on diabetes outcomes through various pathways Results The review identified 30 studies examining the association between depression and diabetes outcomes. Results indicate that while depression is linked to poorer diabetes outcomes, the mechanisms are complex and often mediated by factors such as self-efficacy, social support, and diabetes-related distress. Notably, self-efficacy emerged as a critical mediator in the relationship between depression and self-management behaviours. Furthermore, social support was identified as a protective factor that can reduce the adverse effects of depression on glycaemic control. Conclusions Addressing mental health concerns in diabetes care is essential for improving patient outcomes. This review underscores the need for integrated interventions that consider psychosocial factors to enhance self-management and glycaemic control among individuals with Type 2 diabetes. Future research should focus on exploring these relationships in diverse populations to inform tailored strategies for effective diabetes management. Keywords: Type 2 Diabetes Mellitus, Depression, self-efficacy, glycaemic control, psychosocial factors