bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Vascularized Proximal Fibular Epiphyseal Transfer For Hip Reconstruction Following Septic Necrosis In Children
Authors: El-Gammal Tarek Abdalla , El-Sayed Ali Amr , Kotb Mohamed Mostafa , Saleh Waleed Riad , Ragheb Yasser Farouk , Refai Omar Ahmed , Morsy Mohamed Mohamed , El-Gammal Yousif Tarek
Published: March 2024

Background:

Septic necrosis of the femoral head and neck in children represents a challenging problem. Several reconstructive techniques have been described but with disappointing long-term results. Vascularized epiphyseal transfer utilizing the proximal fibula have been successfully used for reconstruction of the proximal humerus and distal radius and only scarcely used for hip reconstruction. This cohort represents the largest reported series of epiphyseal transfer for hip reconstruction following septic necrosis in children.

Methods:

A total of 18 patients with an average age at surgery of 5.4 years were included. The average follow-up was 3.6 years (range 2.3 to 6.8 y).

Results:

Transient postoperative foot drop was observed in 4 patients. Radiographic resorption of the transferred fibula occurred in 2 cases. Longitudinal growth averaged 7.3 mm/year, and the physis width increased by an average of 2.7 mm/year. The rate of longitudinal growth was fastest after the age of 10 years (18.5 mm/y), which coincides with the pubertal growth spurt. All successful transfers had an open growth plate on final follow-up radiographs. Ten patients had limb length discrepancy of an average 2.8 cm (range 1 to 8 cm). Thirteen patients had satisfactory functional according to the criteria of Hunka et al. Three patients had unsatisfactory results; one had painful nonunion at the fibula-femur junction, and the other two had limited flexion range of 45 degrees. The average postoperative neck-shaft angle was 96.4 degrees which decreased by an average of 8 degrees at the final follow-up. Three patients underwent a valgus subtrochanteric osteotomy to correct a severe varus deformity. The final neck-shaft angle correlated significantly with the functional results where it averaged 96 degrees in the satisfactory group and 57 degrees in the unsatisfactory group.

Conclusion:

Vascularized epiphyseal transfer presents a promising treatment for children with septic necrosis of the femoral head and neck in whom other methods have failed to provide satisfactory long-term results. We recommend the procedure be done before the age of 5 years for optimum results.

Level of Evidence:

Level—IV.
Renal function in pediatric urologic surgical patients: Insight from the National Surgical Quality Improvement Program—Pediatric cohort
Authors: Chalfant Victor , Riveros Carlos , Stec Andrew A.
Published: March 2024

Background

Renal protection is a frequent indication for urological surgery in pediatric patients; however, preoperative assessment is not routinely performed. We assessed the rates of preoperative renal function testing and stratified outcomes after major pediatric urological surgery. Pediatric urology patients, specifically high-risk patients undergoing genitourinary surgeries, are likely to have an underdiagnosis of renal dysfunction after surgery.

Materials and methods

Cases were identified from the 2012 to 2019 National Surgical Quality Improvement Program—Pediatric database. Patients who underwent major urological surgery on an inpatient basis were included in this study. Abnormal renal function was defined as a creatinine (Cr) level of ≥0.5 mg/dL (younger than 2 years) and a glomerular filtration rate of <90 mL/min (2 years or older). Glomerular filtration rate was calculated using the bedside Schwartz equation (2 years or older): estimated glomerular filtration rate = 0.413 × (height/Cr).

Results

A total of 17,315 patients were included, of whom 3792 (21.9%) had documented Cr values. Based on the defined criteria, abnormal renal function was found in 7.3% of infants (younger than 2 years), 33.6% of children (2–9 years), and 52.5% of adolescents (10–18 years). Patients with abnormal preoperative renal function values were significantly (p < 0.001) more likely to experience readmission (10.2% vs. 5.8%), reoperation (3.7% vs. 1.6%), surgical organ/space infection (0.9% vs. 0.4%), transfusion (1.5% vs. 0.6%), renal insufficiency (1.6% vs. 0.4%), or urinary tract infection (5.1% vs. 3.6%).

Conclusions

In this pediatric population, 21.9% of the patients had documented preoperative Cr values before major urological surgery. Patients with documented abnormal preoperative renal function tests experienced higher complication rates. These patients have higher rates of progressive renal insufficiency and acute renal failure than those with normal renal function. The introduction of a standardized and unbiased risk assessment tool has the potential to offer patients benefits by pinpointing individuals with a heightened risk of complications. Further investigation is necessary to enhance the precise categorization of at-risk patients.
A novel RLBP1 gene mutation associated to a flecked retina syndrome
Authors: Issa Mohamad , Sukkarieh Georges , Bruneau Sebastien , Tadayoni Ramin
Published: March 2024

Purpose:

To present an unusual fleck retina condition associated to a novel RLBP1 gene mutation.

Methods/Results: A 25-year old male presented flecks on fundoscopic examination. Clinical presentation, multimodal imaging and ERG were compatible with the diagnosis of benign familial fleck retina. Genetic analysis detected an RLBP1 gene, a gene commonly associated with more severe retinal disease.

Conclusion:

Flecked retina syndromes and other genetic retinal diseases have a complex genotype-phenotype relation and need further research for their pathophysiology to be fully understood.
Co-occurring Usher syndrome Type 1 and Renal Failure
Authors: Le Hong , Anderson Helen , Lopez Glydel , Bayer-Vile Julie , Al-Saif Hind , Couser Natario
Published: March 2024

Purpose:

To describe a patient with a rare co-occurrence of Usher syndrome type 1C (USH1C) and renal disease, suspected to be secondary to Alport syndrome.

Method:

Case report and literature review of cases with Usher syndrome and renal failure. Clinical examination, color fundus photography, visual field tests, electroretinography and whole exome sequencing were used to diagnose and document the patient's clinical presentation.

Results:

An 18-year-old female with known history of congenital hearing loss and chronic renal failure, presents with progressive night and peripheral visual impairment suspicious for an inherited retinal disease. Visual field testing, fundus exam and electroretinography findings supported the diagnosis of Usher syndrome. Whole exome sequencing (WES) identified a novel homozygous frameshift variant (c.238del) in USH1C. WES also identified a homozygous COL4A3 variant of unknown significance, which may be responsible for concomitant Alport syndrome.

Conclusion:

By presenting this rare case of co-occurring Usher syndrome Type 1 and renal failure, we highlight the importance of conducting further investigations that could reveal an additional underlying etiology when these entities are present.
Operative Time Accuracy in the Era of Electronic Health Records: Addressing the Elephant in the Room
Authors: Elsaqa Mohamed , El Tayeb Marawan M. , Yano Stephanie , Papaconstantinou Harry T.
Published: March 2024

Goal:

Accurate prediction of operating room (OR) time is critical for effective utilization of resources, optimal staffing, and reduced costs. Currently, electronic health record (EHR) systems aid OR scheduling by predicting OR time for a specific surgeon and operation. On many occasions, the predicted OR time is subject to manipulation by surgeons during scheduling. We aimed to address the use of the EHR for OR scheduling and the impact of manipulations on OR time accuracy.

Methods:

Between April and August 2022, a pilot study was performed in our tertiary center where surgeons in multiple surgical specialties were encouraged toward nonmanipulation for predicted OR time during scheduling. The OR time accuracy within 5 months before trial (Group 1) and within the trial period (Group 2) were compared. Accurate cases were defined as cases with total length (wheels-in to wheels-out) within ±30 min or ±20% of the scheduled duration if the scheduled time is ≥ or <150 min, respectively. The study included single and multiple Current Procedural Terminology code procedures, while procedures involving multiple surgical specialties (combo cases) were excluded.

Principal Findings:

The study included a total of 8,821 operations, 4,243 (Group 1) and 4,578 (Group 2), (p < .001). The percentage of manipulation dropped from 19.8% (Group 1) to 7.6% (Group 2), (p < .001), while scheduling accuracy rose from 41.7% (Group 1) to 47.9% (Group 2), (p = .0001) with a significant reduction of underscheduling percentage (38.7% vs. 31.7%, p = .0001) and without a significant difference in the percentage of overscheduled cases (15% vs. 17%, p = .22). Inaccurate OR hours were reduced by 18% during the trial period (2,383 hr vs. 1,954 hr).

Practical Applications:

The utilization of EHR systems for predicting OR time and reducing manipulation by surgeons helps improve OR scheduling accuracy and utilization of OR resources.
Fatal Adverse Events in Femoral Neck Fracture Patients Undergoing Hemiarthroplasty or Total Hip Arthroplasty—A Retrospective Record Review Study in a Nationwide Sample of Deceased Patients
Authors: Schouten Bo , Baartmans Mees , van Eikenhorst Linda , Gerritsen Gooitzen P. , Merten Hanneke , van Schoten Steffie , Nanayakkara Prabath W.B. , Wagner Cordula
Published: March 2024

Objectives

Patient safety is a core component of quality of hospital care and measurable through adverse event (AE) rates. A high-risk group are femoral neck fracture patients. The Dutch clinical guideline states that the treatment of choice is cemented total hip arthroplasty (THA) or hemiarthroplasty (HA). We aimed to identify the prevalence of AEs related to THA/HA in a sample of patients who died in the hospital.

Methods

We used data of a nationwide retrospective record review study. Records were systematically reviewed for AEs, preventability and contribution to the patient’s death. We drew a subsample of THA/HA AEs and analyzed these cases.

Results

Of the 2998 reviewed records, 38 patients underwent THA/HA, of whom 24 patients suffered 25 AEs (prevalence = 68.1%; 95% confidence interval, 51.4–81.2), and 24 contributed to death. Patients with a THA/HA AE were of high age (median = 82.5 y) and had severe comorbidity (Charlson score ≥5). The majority of THA/HA AEs had a patient-related cause and was considered partly preventable. Examples of suggested actions that might have prevented the AEs: refraining from surgery, adhering to medication guidelines, uncemented procedures, comprehensive presurgical geriatric assessment, and better postsurgical monitoring.

Discussion

Our study shows a high prevalence of (fatal) adverse events in patients undergoing THA/HA. This seems particularly valid for cemented implants in frail old patients, indicating room for improvement of patient safety in this group. Therefore, we recommend physicians to engage in comprehensive shared decision making with these patients and decide on a treatment fitting to a patient’s preexisting health status, preferences, and values.
Diagnostic Performance of Perfusion-Only SPECT/CT for Chronic Thromboembolic Pulmonary Hypertension in Comparison With Ventilation-Perfusion Planar, SPECT, and SPECT/CT Imaging
Authors: Sung Changhwan , Han Sangwon , Yoon Soyoon , Han Shin Ae , Kang Do-Yoon , Kim Dae-Hee , Park Duk-Woo , Song Jong-Min , Lee Jae Seung , Ryu Jin-Sook , Moon Dae Hyuk
Published: March 2024

Purpose

The aim of this study was to assess the diagnostic performance of perfusion-only SPECT/CT (Q SPECT/CT) in comparison with that of ventilation/perfusion planar scintigraphy (V/Q planar), perfusion SPECT with ventilation scan (V/Q SPECT), and perfusion SPECT/CT with ventilation scan (V/Q SPECT/CT) in chronic thromboembolic pulmonary hypertension (CTEPH).

Patients and Methods

Patients with pulmonary hypertension who underwent ventilation-perfusion planar and SPECT/CT were retrospectively recruited. Two nuclear medicine physicians interpreted V/Q planar, V/Q SPECT, V/Q SPECT/CT, and Q SPECT/CT according to the European Association of Nuclear Medicine criteria. The diagnostic accuracy of these modalities for CTEPH was compared using a composite reference standard of pulmonary angiography, imaging test, cardiorespiratory assessment, and follow-up.

Results

A total of 192 patients were enrolled, including 85 with CTEPH. The sensitivity of Q SPECT/CT was 98.8%, which similar to that of V/Q planar (97.6%), V/Q SPECT (96.5%), or V/Q SPECT/CT (100.0%). In contrast, Q SPECT/CT exhibited significantly lower specificity (73.8%) compared with V/Q planar (86.9%, P = 0.001), V/Q SPECT (87.9%, P < 0.001), and V/Q SPECT/CT (88.8%, P < 0.001). The significantly lower specificity of Q SPECT/CT, compared with the 3 others, was observed in the subgroup aged ≥50 years (P < 0.001 for all), but not in those <50 years.

Conclusions

Q SPECT/CT exhibited lower specificity compared with V/Q planar, V/Q SPECT, and V/Q SPECT/CT in diagnosing CTEPH. It might underscore the essential role of a ventilation scan in patients with PH, even with the introduction of SPECT/CT.
Comparison of 18F-AlF-NOTA-PRGD2 and 18F-FDG PET/CT Imaging in a Case of Primary Uveal Melanoma
Authors: Zhu Xue , Pan Donghui , Zhang Zhengwei , Wang Ke , Zou Wenjun
Published: March 2024

Uveal melanoma is the most common intraocular malignancy in adults with a high rate of metastasis and mortality. This study presented the PET/CT imaging of 18F-AlF-NOTA-PRGD2 and 18F-FDG in a patient with primary uveal melanoma. In addition to fundus photograph and ophthalmic ultrasonography, both 18F-AlF-NOTA-PRGD2 and 18F-FDG PET/CT imaging showed increased radioactive uptake in the lesions within the scan area. The tumoral lesions presented significantly higher uptake of 18F-AlF-NOTA-PRGD2 compared with that of 18F-FDG.
Pulmonary Recurrence of Colorectal Mucinous Adenocarcinoma and Sarcoidosis on 18F-FDG PET/CT
Authors: Habouzit Vincent , Maoui Khawla , Prevot Nathalie , Forest Fabien , Grange Remi
Published: March 2024

A 67-year-old woman, previously diagnosed with pulmonary sarcoidosis and sigmoid colon mucinous adenocarcinoma with pulmonary metastasis, showed an enlarged pulmonary nodule in routine follow-up. Because of the absence of treatment for either condition over the past 3 years, the nodule raised concerns of cancer recurrence or sarcoidosis progression. Its distinctive 18F-FDG PET/CT appearance, compared with other pulmonary lesions, suggested a mucinous histology. The diagnosis was confirmed by pathological examination. This emphasizes the importance of knowledge of the 18F-FDG PET/CT phenotype of neoplastic histological variants to address challenging diagnostic scenarios.
Pneumorrhachis With FDG Uptake Cervical Lesions on PET/CT of a Patient With Suspected Recurrent Hypopharyngeal Cancer
Authors: Huang Yu-Erh , Chuang Chih-Lin , Wu Shang-Heng , Chang Yu-Ming , Kao Pan-Fu
Published: March 2024

A 57-year-old man presented with odynophagia for 1 week was referred for FDG PET/CT scan to rule out recurrent hypopharyngeal cancer. The FDG PET/CT showed hypermetabolic lesions in hypopharyngeal area and adjacent cervical spine with pneumorrhachis, the presence of intraspinal air, on attenuation CT images, which might indicate a life-threatening infection. An emergency MRI confirmed the presence of cervical spondylodiscitis with an epidural abscess. The patient rapidly progressed to quadriplegia and difficulty voiding on the same day as the PET/CT scan, leading to emergent operation. The patient received antibiotics treatment and discharged 4 months later without evidence of cancer recurrence.
Exploration of Lasmiditan 200 mg Versus 100 mg for the Treatment of Migraine: A Meta-analysis Based on Aggregate Data
Authors: Wang Ting , Feng Yimo
Published: March 2024

Objectives

Lasmiditan holds important potential in treating migraine, but its ideal dose remains elusive. This meta-analysis is conducted based on aggregate data and aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for acute treatment of migraine attack.

Methods

PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model or fixed-effect model based on the heterogeneity. The primary outcome was pain free at 2 hours. Secondary outcomes included pain relief at 2 hours, pain free at 24 hours, most bothersome symptom free at 2 hours, and adverse events.

Results

Seven randomized controlled trials and 6515 patients were included in this meta-analysis. Compared with lasmiditan 100 mg for migraine patients, lasmiditan 200 mg was able to significantly improve pain free at 2 hours (odd ratio [OR], 1.28; 95% confidence interval [CI], 1.14–1.44; P < 0.0001) and pain free at 24 hours (OR, 1.35; 95% CI, 1.14–1.60; P = 0.0005), but showed no effect on pain relief at 2 hours (OR, 1.00; 95% CI, 0.90–1.12; P = 0.98) or most bothersome symptom free at 2 hours (OR, 0.93; 95% CI, 0.83–1.03; P = 0.17). Lasmiditan 200 mg was associated with the increase in adverse events compared with lasmiditan 100 mg (OR, 1.28; 95% CI, 1.15–1.43; P < 0.0001).

Conclusions

Lasmiditan 200 mg is more effective to improve pain free at 2 hours and 24 hours than lasmiditan 100 mg for the acute treatment of migraine patients.
Transition to Permitless Open Carry and Association with Firearm-Related Suicide
Authors: Grimsley Emily A , Torikashvili Johnathan V , Janjua Haroon M , Read Meagan D , Kuo Paul C , Diaz Jose J
Published: March 2024

BACKGROUND:

Firearm-related death rates continue to rise in the US. As some states enact more permissive firearm laws, we sought to assess the relationship between a change to permitless open carry (PLOC) and subsequent firearm-related death rates, a currently understudied topic.

STUDY DESIGN:

Using state-level data from 2013 to 2021, we performed a linear panel analysis using a state fixed-effects model. We examined total firearm-related death, suicide, and homicide rates separately. If a significant association between OC law and death rate was found, we then performed a difference-in-difference (DID) analysis to assess for a causal relationship between changing to PLOC and increased death rate. For significant DID results, we performed confirmatory DID separating firearm and nonfirearm death rates.

RESULTS:

Nineteen states maintained a no OC or permit-required law, whereas 5 changed to permitless and 26 had a PLOC before 2013. The fixed-effects model indicated more permissive OC law that was associated with increased total firearm-related deaths and suicides. In DID, changing law to PLOC had a significant average treatment effect on the treated of 1.57 (95% CI 1.05 to 2.09) for total suicide rate but no significant average treatment effect for the total firearm-related death rate. Confirmatory DID results found a significant average treatment effect on the treated of 1.18 (95% CI 0.90 to 1.46) for firearm suicide rate.

CONCLUSIONS:

OC law is associated with total firearm-related death and suicide rates. Based on our DID results, changing to PLOC is indeed strongly associated with increased suicides by firearm.
Barriers to Black Medical Students and Residents Pursuing and Completing Surgical Residency in Canada: A Qualitative Analysis
Authors: Akuffo-Addo Edgar , Dalson Jaycie , Agyei Kwame , Mohsen Samiha , Yusuf Safia , Juando-Prats Clara , Simpson Jory S
Published: March 2024

BACKGROUND:

The limited available data suggest that the Canadian surgical workforce does not reflect the racial diversity of the patient population it serves, despite the well-established benefits of patient-provider race concordance. There have been no studies to date that characterize the systemic and individual challenges faced by Black medical students in matching to and successfully finishing training in a surgical specialty within a Canadian context that can explain this underrepresentation.

STUDY DESIGN:

Using critical qualitative inquiry and purposive sampling to ensure sex, geographical, and student or trainee year heterogeneity, we recruited self-identifying Black medical students and surgical residents across Canada. Online in-depth semistructured interviews were conducted and transcribed verbatim. Transcripts were analyzed through an inductive reflexive narrative thematic process by 4 analysts.

RESULTS:

Twenty-seven participants including 18 medical students and 9 residents, were interviewed. The results showed 3 major themes that characterized their experiences: journey to and through medicine, perceptions of the surgical culture, and recommendations to improve the student experience. Medical students identified lack of mentorship and representation as well as experiences with racism as the main barriers to pursuing surgical training. Surgical trainees cited systemic racism, lack of representation, and insufficient safe spaces as the key deterrents to program completion. The intersection with sex exponentially increased these identified barriers.

CONCLUSIONS:

Except for a few surgical programs, medical schools across Canada do not offer a safe space for Black students and trainees to access and complete surgical training. An urgent change is needed to provide diverse mentorship that is transparent, acknowledges the real challenges related to systemic racism and biases, and is inclusive of different racial and ethnic backgrounds.
Title of Manuscript: Prevalence of SARS- CoV-2 virus in saliva, stool, and urine samples of COVID-19 patients in Bihar, India
Authors: Meghna Nupur , Archana Archana , Bhushan Divendu , Kumar Abhyuday , Sarfraz Asim , Naik Bijaya Nanda , Pati Binod Kumar
Published: March 2024

Introduction

The coronavirus illness caused by SARS- CoV-2 can cause multiple organ involvement, with varying degrees of severity. Besides, inhalation as a route for transmission, feco-oral has also been proposed. Its transmission to sewage systems is a growing public health issue.

Objective

To detect SARS-CoV-2 RNA in non-respiratory samples (saliva, urine, and stool) collected from COVID-19 cases, in Bihar.

Materials and methods

This Cross-Sectional observational study was conducted from January 2021 to March 2022 on human non-respiratory samples. A total of 345 samples including saliva (116), stool (97), and urine (132) were collected from 143 covid-19 cases. Samples were analyzed for SARS-CoV-2 by multiplex RT-PCR targeted against E, ORF 1ab, and RdRp gene.

Results

In this study, out of 143 cases, a total of 107(74.8%) were positive for SARS-CoV-2 RNA in at least one of the non-respiratory samples.

Conclusion

There is a high prevalence of SARS-CoV-2 virus in non-respiratory samples.
Occurrence and persistence of pseudo-tail spots in the barn swallow
Authors: Hasegawa Masaru
Published: March 2024

While numerous studies have confirmed sexual selection for ornamental traits in animals, it remains unclear about how animals exaggerate ornamentation beyond their original traits. I found that some Asian barn swallowsHirundo rustica gutturalispossessed pseudo-tail spots in their undertail coverts. A close inspection showed its remarkable resemblance to the white tail spots, a well-known sexual signal in this species, although pseudo-tail spots in the undertail covers do not incur any flight cost, unlike the white tail spots on the tail itself. Presence of pseudo-tail spots can thus represent an initial stage of a deceptive elaboration as predicted by sexual selection theory. The frequency of pseudo-tail spots in the study population remained low even a decade after the first observation (ca. 7%), but was higher compared to other populations (e.g., 1% in another Japanese population). The slow progress of evolution, perhaps due to the low detectability of the trait, provides a unique opportunity to observe contemporary evolution of ornament exaggeration across traits.
Mean exercise torque is a critical factor influencing neuromuscular fatigability induced by exhausting contractions
Authors: Lebesque Loïc , Scaglioni Gil , Manckoundia Patrick , Martin Alain
Published: March 2024

PURPOSE

To get a more detailed description of neuromuscular fatigability, maximal torque sustainability (i.e., the ability to maintain a high torque level) can be assessed in addition to the classically used maximal voluntary contraction (MVC). Since this parameter appears to be affected by mean exercise torque (MET), the present study aims to examine the relationship between MET and neuromuscular fatigability induced by exhausting contractions.

METHODS

Thirteen participants sustained a plantar flexors MVC for 1 min (MVC1-MIN) before and after exhausting exercises designed to produce a similar MET (30% MVC), and following a 10-min rest period. Exercises consisted of intermittent (INT), continuous (CON) or variable (continuous contraction alternating between moderate and low intensity, VAR) contractions performed until task failure.

RESULTS

Although the INT resulted in greater exercise duration and torque-time integral than CON and VAR, MVC similarly decreased after all exercises due to neural and muscular impairments. The torque loss during the MVC1-MINincreased after all exercises to a similar extent, mainly because of neural alterations. Contrary to MVC, the torque loss during the MVC1-MINreturned to baseline value after the recovery period.

CONCLUSION

By considering both maximal torque production and sustainability, INT, CON and VAR exercises, performed with identical mean torque and until exhaustion, led to a similar neuromuscular fatigability. Results confirm the independence of maximal torque production from the contraction pattern and support the impact of MET on maximal torque sustainability. The present findings are crucial to consider for the management of neuromuscular fatigability in both athletes and patients.
Non-invasive MRI of Blood-Cerebrospinal Fluid-Barrier Function: a Functional Biomarker of Early Alzheimer’s Disease Pathology
Authors: Perera Charith , Cruz Renata , Shemesh Noam , Carvalho Tania , Thomas David L. , Wells Jack , Ianus Andrada
Published: March 2024

INTRODUCTION

Choroid plexus (CP) dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer’s disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods capable of assessing CP function.

METHODS

Here, we harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the blood cerebrospinal fluid barrier (BCSFB) as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD progression in the widely used triple transgenic mouse model (3Tg), which recapitulates aspects of disease pathology.

RESULTS

Total BCSFB-mediated water delivery is significantly higher in 3Tg mice (>50%) from 8 weeks (preclinical stage), while tissue parameters such as CBF and T1 are not different between groups at all ages.

DISCUSSION

Our work shows changes in BCSFB function in the early stages of AD, providing a novel biomarker of pathology.
Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe
Authors: Delhaye Guillaume , van der Linde Sietse , Bauman David , Orme C. David L. , Suz Laura M. , Bidartondo Martin I.
Published: March 2024

Aim

Ecoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.

Location

Europe.

Time period

2008 – 2015.

Major taxa studied

Ectomycorrhizal fungi.

Methods

We used a large dataset of ∼ 24,000 ectomycorrhizas, assigned to 1,350 operational taxonomic units, collected from 129 forest plots via a standardised protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses, and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.

Results

Ecoregions predict large-scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short-distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.

Main conclusions

Ecoregions are useful units to investigate eco-evolutionary processes in mycorrhizal fungal communities and for conservation decision-making that includes fungi.
Learning tissue representation by identification of persistent local patterns in spatial omics data
Authors: Tanevski Jovan , Vulliard Loan , Hartmann Felix , Saez-Rodriguez Julio
Published: March 2024

Spatial omics data provide rich molecular and structural information about tissues, enabling novel insights into the structure-function relationship. In particular, it facilitates the analysis of the local heterogeneity of tissues and holds promise to improve patient stratification by association of finer-grained representations with clinically relevant features. Here, we introduce Kasumi, a method for the identification of spatially localized neighborhoods of intra- and intercellular relationships, persistent across samples and conditions. We learn compressed explainable representations while preserving relevant biological signals that are readily deployable for data exploration and hypothesis generation, facilitating translational tasks. We address tasks of patient stratification for disease progression and response to treatment in cancer on data coming from different spatial antibody-based multiplexed proteomics platforms. Kasumi outperforms related neighborhood analysis approaches and offers explanations at the level of cell types or directly from the measurements, of the spatial coordination and multivariate relationships underlying observed disease progression and response to treatment. We show that persistent local patterns form spatially contiguous regions of different sizes. However, the abundance of the persistent local patterns is not associated with their relative importance in downstream tasks. We show that non-abundant, localized structural and functional relationships in the tissue are strongly associated with unfavorable outcomes in disease progression and response to treatment.
Ecological diversification in sexual and asexual lineages
Authors: Chaparro-Pedraza P. Catalina , Roth Gregory , Melián Carlos J.
Published: March 2024

The presence or absence of sex can have a strong influence on the processes whereby species arise. Yet, the mechanistic underpinnings of this influence are poorly understood. To gain insights into the mechanisms whereby the reproductive mode may influence diversification, we investigate how natural selection, genetic mixing and the reproductive mode interact and how this interaction affects the evolutionary dynamics of diversifying lineages. To do so, we formulate and analyze trait-based eco-evolutionary models of ecological diversification for sexual and asexual lineages, in which diversification is driven by intraspecific resource competition. We find that the reproductive mode strongly influences the diversification rate and thus the ensuing diversity of a lineage. Our results reveal that natural selection is stronger in asexual lineages because asexual organisms have a higher reproductive potential than sexual ones. As a consequence, an asexual population can reach a higher population density than a sexual population under the very same ecological conditions. This causes competition, and thus ecologically-based selection, to be stronger in asexual lineages, promoting faster diversification. However, a small amount of genetic mixing accelerates the trait expansion process in sexual lineages, overturning the effect of selection alone and enabling a faster niche occupancy than asexual lineages. As a consequence, sexual lineages can occupy more ecological niches, eventually resulting in higher diversity. This suggests that sexual reproduction may be widespread among species because it increases rates of diversification.
U-FISH: a universal deep learning approach for accurate FISH spot detection across diverse datasets
Authors: Xu Weize , Cai Huaiyuan , Zhang Qian , Mueller Florian , Ouyang Wei , Cao Gang
Published: March 2024

In the rapidly advancing landscape of fluorescence in situ hybridization (FISH) technologies, there is a critical need for sophisticated yet adaptable methods for spot detection. This study introduces U-FISH, a deep learning approach that significantly improves accuracy and generalization capabilities. Our method utilizes a U-Net model to transform noisy and ambiguous FISH images into a standardized representation with consistent signal characteristics, facilitating efficient spot detection. For the training and evaluation of the U-FISH model, we have constructed a comprehensive dataset comprising over 4,000 images and more than 1.6 million manually annotated spots, sourced from both experimental and simulated environments. Our benchmarks demonstrate that U-FISH outperforms existing methods for FISH spot detection, offering improved versatility by eliminating the need for laborious manual parameter adjustments. This allows for its application across a broad spectrum of datasets and formats. Furthermore, U-FISH is designed for high scalability and is capable of processing 3D data, supporting the latest generation of file formats for large and complex datasets. To promote community adoption and ensure accessibility, we provide a user-friendly interfaces: Napari plugin, web application and command-line interface. The complete training dataset is made publicly available, laying a solid foundation for future research in this field.
Lit-OTAR Framework for Extracting Biological Evidences from Literature
Authors: Tirunagari Santosh , Saha Shyamasree , Venkatesan Aravind , Suveges Daniel , Carmona Miguel , Buniello Annalisa , Ochoa David , McEntyre Johanna , McDonagh Ellen , Harrison Melissa
Published: March 2024

The lit-OTAR framework, developed through a collaboration between Europe PMC and Open Targets, leverages deep learning to revolutionise drug discovery by extracting evidence from scientific literature for drug target identification and validation. This novel framework combines Named Entity Recognition (NER) for identifying gene/protein (target), disease, organism, and chemical/drug within scientific texts, and entity normalisation to map these entities to databases like Ensembl, Experimental Factor Ontology (EFO), and ChEMBL. Continuously operational, it has processed over 39 million abstracts and 4.5 million full-text articles and preprints to date, identifying more than 48.5 million unique associations that significantly help accelerate the drug discovery process and scientific research (> 29.9m distinct target-disease, 11.8m distinct target-drug and 8.3m distinct disease-drug relationships). The results are made accessible through the Open Targets Platform (https://platform.opentargets.org/) as well as Europe PMC website (SciLite web app) and annotations API (https://europepmc.org/annotationsapi).
High-resolution climate data reveals increased risk of Pierce’s Disease for grapevines worldwide
Authors: Giménez-Romero Àlex , Moralejo Eduardo , Matías Manuel A.
Published: March 2024

Range shifts in plant disease distributions are sensitive to scaling processes, but few crop case studies have included these predictions under climate change. High-quality wines are increasingly produced in topographically heterogeneous river valleys, whereby disease models that capture steep relief gradients become especially relevant. Here we show how non-linear epidemiological models more accurately reflect the threat of an emerging grapevine pathogen in areas with significant spatial gradients. By comparing the results of simulations using climate data with different spatial resolutions, we identify an increased risk of Pierce’s disease (PD), caused by the vector-borne bacteriumXylella fastidiosa, in wine regions globally. Over 100,000 vine presence records worldwide were analysed with respect to their closer risk-grid cell, observing an increase from 21.8% to 41.2% of the area at risk in European vineyards, from 5.6% to 47.2% in South Africa and to a lesser extent in other wine-growing regions. This general trend has been preceded by an accelerating rate of increase in risk within wine-growing areas. Our analysis demonstrates the importance of microclimatic conditions, highlighting previously unresolved risk zones in areas close to rivers and valleys, and the insufficiency of lower resolution data sets to capture complex climatic variations.
High Frequency Terahertz Stimulation Alleviates Neuropathic Pain by Inhibiting the Pyramidal Neuron Activity in the Anterior Cingulate Cortex of mice
Authors: Peng Wenyu , Wang Pan , Tan Chaoyang , Zhao Han , Chen Kun , Si Huaxing , Tian Yuchen , Lou Anxin , Zhu Zhi , Yuan Yifang , Wu Kaijie , Chang Chao , Wu Yuanming , Chen Tao
Published: March 2024

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7–10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximate 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions.In vivoandin vitroresults demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex through enhancing the voltage-gated K+and also the leak K+conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising application in other nervous system diseases.
Longevity of Implantable Silicon-ICs for Emerging Neural Applications: Evaluation of Bare Die and PDMS-Coated ICs After Accelerated Aging and Implantation Studies
Authors: Nanbakhsh Kambiz , Idil Ahmad Shah , Lamont Callum , Dücső Csaba , Akgun Ömer Can , Horváth Domonkos , Tóth Kinga , Ulbert István , Mazza Federico , Constandinou Timothy G. , Serdijn Wouter , Vanhoestenberghe Anne , Donaldson Nick , Giagka Vasiliki
Published: March 2024

Silicon integrated circuits (ICs) are central to the next-generation miniature active neural implants, whether packaged in soft polymers for flexible bioelectronics or implanted as bare die for neural probes. These emerging applications bring the IC closer to the corrosive body environment, raising reliability concerns, particularly for long-term clinical use. Here, we evaluated the long-term electrical and material stability of silicon-ICs from two foundries, after one-year acceleratedin vitroandin vivoanimal studies. The ICs featured various custom-designed test structures and were partially PDMS coated, creating two regions on each chip, uncoated “bare die” and “PDMS-coated”. During the acceleratedin vitrostudy, ICs were electrically biased and periodically monitored. Results demonstrated stable electrical performance for at least a year, suggesting that bare die ICs can function in the body for months. Despite electrical stability, material analysis revealed chemical and electrically driven degradation of the IC passivation in the bare die regions. In contrast, PDMS-coated regions revealed no such degradation, making PDMS a highly suitable encapsulant for ICs intended for years-long implantation. Based on the new insights, guidelines are proposed that may enhance the longevity of implantable ICs, significantly broadening their applications in the biomedical field.
Clinical factors associated with SFTS diagnosis and severity in cats
Authors: Osako Hiromu , Xu Qiang , Nabeshima Takeshi , Balingit Jean Claude , Nwe Khine Mya , Yu Fuxun , Inoue Shingo , Hayasaka Daisuke , Tun Mya Myat Ngwe , Morita Kouichi , Takamatsu Yuki
Published: March 2024

Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonosis caused by SFTS virus (SFTSV). In addition to tick bites, animal-to-human transmission of SFTSV has been reported, but little is known about feline SFTSV infection. In this study, we analyzed data on 187 cats with suspected SFTS to identify biomarkers for SFTS diagnosis and clinical outcome., Body weight, red and white blood cell and platelet counts, serum aspartate aminotransferase and total bilirubin levels, were useful for SFTS diagnosis, and alanine aminotransferase, aspartate aminotransferase and serum SFTSV RNA levels were associated with the clinical outcome. We developed a scoring model to predict SFTSV infection. In addition, we performed a phylogenetic analysis to reveal the relationship between disease severity and viral strain. This study provides comprehensive information on feline SFTS and could contribute to the protection of cat owners, community members, and veterinarians from the risk of cat-transmitted SFTSV infection.
Screening of functional maternal-specific chromatin regulators in early embryonic development
Authors: Liu Guifen , Wang Yiman , Wang Xiangxiu , Wang Wen , Cao Zheng , Zhang Yong
Published: March 2024

The early stages of embryonic development rely on maternal products for proper regulation. However, systematic screening for functional maternal-specific factors has been challenging due to the time- and labor-intensive nature of traditional approaches. Here, we combined a computational pipeline and F0 homozygous mutation technology to screen for functional maternal-specific chromatin regulators in zebrafish embryogenesis and identified Mcm3l, Mcm6l, and Npm2a as playing essential roles in DNA replication and cell division. Our results contribute to understanding the molecular mechanisms underlying early embryo development and highlight the importance of maternal-specific chromatin regulators in this critical stage.
3D quantification of viral transduction efficiency in living human retinal organoids
Authors: Rogler Teresa S. , Salbaum Katja A. , Sonntag Selina M. , James Rebecca , Shelton Elijah R. , Brinkop Achim T. , Klopstock Thomas , Babutzka Sabrina , Michalakis Stylianos , Serwane Friedhelm
Published: March 2024

The development of therapeutics relies on testing their efficiency and specificity in animals and humanin vitromodels. To optimize the efficiency of a gene therapy, for example, fluorescent reporters expressed by treated cells are often utilized as readouts. Traditionally, the overall fluorescence signal provides an estimate for the global transduction efficiency. However, detailed analysis of the transduction efficiency in individual cells within a tissue remains a challenge. Readout on a single cell level can be realized via fluorescence-activated cell sorting at the cost of tissue dissociation into single cells and loss of spatial information. Complementary, spatial information is accessible via immunofluorescence characterization of fixed samples. However, those approaches impede time-dependent studies and prevent the recording of the dynamic interplay between the viral vector and the target cells in a 3D tissue.

Here, we provide a quantitative, three-dimensional characterization of viral transduction efficiencies in living retinal organoids. We combine engineered adeno-associated virus (AAV) vectors, confocal live-imaging, and deep learning-based image segmentation to establish a quantitative test platform for gene delivery. To establish this, we transduced human retinal organoids with specific AAV vectors and imaged the fluorescent reporter expression in 3D. We measured a faster onset (7 days) and higher transduction efficiency (82%) of an AAV vector with optimized serotype (AAV2.NN) compared to two other AAV serotypes (AAV2.7m8, AAV9.NN). This highlights the practicality and functionality of our platform as a testbed for future treatments. The combination of optimized viral vectors, live-imaging, and deep learning-based image processing has the potential to guide the development of therapies in a variety of biomedical applications.
Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling
Authors: Lee Kuo Hao , Won Sung Joon , Oyinloye Precious , Shi Lei
Published: March 2024

The dopamine transporter (DAT) plays a critical role in the central nervous system and has been implicated in numerous psychiatric disorders. The ligand-based approaches are instrumental to decipher the structure-activity relationship (SAR) of DAT ligands, especially the quantitative SAR (QSAR) modeling. By gathering and analyzing data from literature and databases, we systematically assemble a diverse range of ligands binding to DAT, aiming to discern the general features of DAT ligands and uncover the chemical space for potential novel DAT ligand scaffolds. The aggregation of DAT pharmacological activity data, particularly from databases like ChEMBL, provides a foundation for constructing robust QSAR models. The compilation and meticulous filtering of these data, establishing high-quality training datasets with specific divisions of pharmacological assays and data types, along with the application of QSAR modeling, prove to be a promising strategy for navigating the pertinent chemical space. Through a systematic comparison of DAT QSAR models using training datasets from various ChEMBL releases, we underscore the positive impact of enhanced data set quality and increased data set size on the predictive power of DAT QSAR models.
Functional Diversification of Gene Duplicates under the Constraint of Protein Structure
Authors: Guo Kangning , Yang Yuqing , You Tingting , Zhu Kangli
Published: March 2024

Gene differentiation following duplication plays a crucial role in evolution, driving the emergence of new functional genes. This process involves changes in key gene traits, such as protein structure, expression patterns, subcellular localization, and enzymatic activity, which together contribute to the development of novel functions. Here, we identified a group of homologous Glycoside Hydrolase Family 50 (GH50) agarases in the deep-sea bacteriumAgarivorans ablusstrain JK6, providing an ideal model for studying gene differentiation following duplication. Phylogenetic analysis revealed that these enzymes arose through gene duplication and subsequent divergence. Experimental assays demonstrated that, while they retained similar glycoside hydrolase activity, their agarolytic activity diverged significantly. We further explored their structural variations constrained by the protein’s 3D structural limitations, the development of specific localization linked to changes in enzymatic activity, and distinct expression patterns induced by different sugars. Notably, structural variations were primarily concentrated in the active site, while the overall backbone remained highly conserved. This study highlights gene differentiation following duplication as a key evolutionary strategy, facilitating the transition from single enzymes to complex functional systems.