bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering the Potential Value of Coenzyme Q10 as an Adjuvant Treatment in Patients With Depression
Authors: Majmasanaye Mahnam , Mehrpooya Maryam , Amiri Hasan , Eshraghi Azadeh
Published: April 2024

Purpose/Background

Depressive disorder or mental cold is the most common mental disorder, and depression exists all over the world and in all countries and cultures. The results of several studies have shown that using compounds with antioxidant properties has been fruitful in patients with depression. Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant and exerts its antioxidant effect by directly neutralizing free radicals or reducing tocopherol and preventing the inhibition of mitochondrial activity because of oxidative stress. This study aimed to investigate the effects of oral CoQ10 in patients with depression as an adjunctive treatment.

Methods/Procedures

Sixty-nine patients with moderate and severe depression were randomly divided into 2 CoQ10 groups (36) and placebo (33). The first group of patients received CoQ10 supplements at a dose of 200 mg daily for 8 weeks along with standard interventions and treatments for depression, and the second group received standard treatments for depression along with a placebo. The change in the score of Montgomery-Åsberg Depression Rating Scale depression scale was evaluated 4 and 8 weeks after the intervention. Also, at baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity, total thiol groups, nitric oxide, malondialdehyde, and interleukin 6 were assessed.

Findings/Results

The changes in the depression score at the end of the study showed that, in the group receiving the CoQ10 supplement after 8 weeks, there was a reduction in depression symptoms, which was statistically significant compared with before the start of the study Meanwhile, no significant changes were observed in the patients of the placebo group in terms of symptom reduction. Compared with baseline and the placebo condition, serum levels of nitric oxide and total thiol groups significantly decreased and increased, respectively. Also, no statistically significant changes were observed for interleukin 6, malondialdehyde, and total antioxidant capacity.

Implications/Conclusions

A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depression and fatigue, as well as improve the quality of life of patients with depression. In addition, CoQ10 can significantly improve inflammation and oxidative stress status in patients with depression.
Symptoms, Lifetime Duration of Estrogen Exposure, and Ovarian Reserve Among Women Living With HIV: A Cross-Sectional Observational Study
Authors: Moore Scott Emory , Davey Christine Horvat , Morgan Michael , Webel Allison
Published: April 2024

This cross-sectional observational study examined associations among symptom burden, lifetime duration of estrogen exposure, and serum antimüllerian hormone (AMH) levels among women living with HIV (n = 98) using bivariate bias-corrected Pearson correlations and multiple correspondence analyses. The mostly Black (85.6%) sample of women, with a mean age of 50 years (SD 12.6 years), exhibited no significant reproductive history factors and symptom burden interrelationships or significant associations between lifetime duration of estrogen exposure and symptoms. Predictably, serum AMH levels were lower among older women; however, less predictable were its significant relationships with months living with HIV (r = −0.362), months on ART (r = −0.270), and CD4+ T-cell nadir (r = 0.347). Symptom–symptom relationships support a fatigue, pain, sleep, anxiety, and depression symptom cluster. The hypotheses were not supported by cross-sectional observation. Further studies should explore variation in relationships between HIV, estrogen exposure, ovarian reserve, and AMH levels over time.
Estimated Clinician-Patient Ratios in US Orthotic and Prosthetic Care: State-Level Trends and Discrepancies
Authors: Ronkos Charles , Mullen Ashley
Published: April 2024

Introduction

For the past 20 years, speculative studies have forewarned of a clinician shortage in the field of orthotics and prosthetics (O&P). Such predictions should emphasize the importance of monitoring potential patient and clinician populations to identify trends and intranational disparities. However, there have been no recent population-based examinations of these previously predicted shortages.

Objectives

This study estimated geographical differences and evaluated national and state-level trends in O&P care within the United States. The study used data on certified O&P clinicians, state populations, and rates of lower-limb amputation secondary to diabetes in Medicare populations.

Study Design

The original research article is a retrospective data analysis.

Methods

Clinician data from the American Board for Certification in Prosthetics Orthotics and Pedorthics, population data from the US Census Bureau, and Medicare data from the Centers for Disease Control and Prevention and the Center for Medicare and Medicaid Services were uploaded into ArcGIS mapping software and geographically weighted for examination across spatial and temporal parameters.

Results

The data show national and state-level trends and disparities. The findings reveal large differences in care environments between states.

Conclusions

Speculation on the ability for current supply to meet perceived demand is complicated, but these data update and elaborate upon previous estimations for predicted clinician scarcity in the near future. Further analysis of state-level distance-to-care discrepancies and an examination of which states would benefit most from expansion of O&P services will be necessary.

Clinical Relevance Statement

This research provides a rudimentary foundation for continued investigation into geographical trends and discrepancies in O&P supply and demand. The successful understanding of these metrics could inform policy and education initiatives, optimize clinical intervention for regional needs, and foster professional expansion into undertreated patient populations.
Barriers to liver transplant referral in safety net settings: A national provider survey
Authors: Hundt Melanie , Chen Ariana , Donovan John , Kim Nicole , Yilma Mignote , Tana Michele , Mehta Neil , Zhou Kali
Published: April 2024

Safety net systems care for patients with a high burden of liver disease yet experience many barriers to liver transplant (LT) referral. This study aimed to assess safety net providers’ perspectives on barriers to LT referrals in the United States. We conducted a nationwide anonymous online survey of self-identified safety net gastroenterologists and hepatologists from March through November 2022. This 27-item survey was disseminated via e-mail, society platforms, and social media. Survey sections included practice characteristics, transplant referral practices, perceived multilevel barriers to referral, potential solutions, and respondent characteristics. Fifty complete surveys were included in analysis. A total of 60.0% of respondents self-identified as White and 54.0% male. A total of 90.0% practiced in an urban setting, 82.0% in tertiary medical centers, and 16.0% in community settings, with all 4 US regions represented. Perceived patient-level barriers ranked as most significant, followed by practice-level, then provider-level barriers. Patient-level barriers such as lack of insurance (72.0%), finances (66.0%), social support (66.0%), and stable housing/transportation (64.0%) were ranked as significant barriers to referral, while medical mistrust and lack of interest were not. Limited access to financial services (36.0%) and addiction/mental health resources (34.0%) were considered important practice-level barriers. Few reported existing access to patient navigators (12.0%), and patient navigation was ranked as most likely to improve referral practices, followed by an expedited/expanded pathway for insurance coverage for LT. In this national survey, safety net providers reported the highest barriers to LT referral at the patient level and practice level. These data can inform the development of multilevel interventions in safety net settings to enhance equity in LT access for vulnerable patients.
Role of erythropoietin in the treatment of Alzheimer’s disease: the story so far
Authors: Kalluru Pavan Kumar Reddy , Bhavanthi Sushmitha , Vashist Shambhavi , Gopavaram Ravikishore Reddy , Mamilla Mahesh , Sharma Shriya , Gundoji Chethan Raj , Goguri Sumaja Reddy
Published: April 2024

This review aims to explore the potential of erythropoietin, a glycopeptide hormone, as a treatment option for Alzheimer’s disease, which is the commonest cause of dementia. Despite years of focus and research, therapeutic options for Alzheimer’s disease are not yet completely satisfactory. And as people age, they are likely to develop Alzheimer’s Disease, further pressuring the healthcare system. So, it is definite to develop treatment options that meet superior outcomes with minimal negative effects. A comprehensive review of the literature was conducted in PubMed and Google Scholar using a combination of keywords, including Alzheimer’s disease, dementia, erythropoietin, and neuroprotection. Search results were assessed for relevance before using the data for this study. The beneficial implications of erythropoietin as a therapeutic option have been explored, along with the side effects and mechanisms of erythropoietin in Alzheimer’s disease. Overall, the authors’ review indicates that erythropoietin presents a promising avenue for mitigating the progression of Alzheimer’s disease, with minimal associated side effects.
Multivariate Analysis of Risk Factors for Complications in Pediatric Tissue Expansion
Authors: Katsushima Chihiro , Sowa Yoshihiro , Sakamoto Michiharu , Abe Hiroyasu , Yamanaka Hiroki , Tsuge Itaru , Katsube Motoki , Saito Susumu , Morimoto Naoki
Published: April 2024

Background

Tissue expanders represent one of the main surgical options for skin reconstruction in cases of tumors, traumalike burn injury, scar contracture, and alopecia. However, the tissue expander device is also associated with complications such as infection and extrusion. The aim of this study was to analyze risk factors for major complications of use of tissue expanders in pediatric patients using multivariate analysis.

Methods

A retrospective, single-center observational study was performed over 10 years in pediatric patients who were treated with tissue expanders for tumors, nevus, scars, burn reconstruction, and alopecia from April 2012 to March 2022. The primary outcome was overall complications per operation and expander, including infection and extrusion. Ten predictor variables were included as risk factors based on previous studies and as new factors considered important from clinical experience. Univariate and multivariate logistic regression analyses were performed to identify risk factors for major complications such as expander infection or extrusion.

Results

The study included 44 patients who underwent 92 operations using 238 tissue expanders. The overall complication rate per expander was 14.3%. Univariate logistic regression analysis identified associations of younger age, number of expanders used per operation, history of infection, and tissue expander locations with a higher complication rate. In multivariate logistic regression analysis, younger age (odds ratio, 1.14; P = 0.043) was associated with a high likelihood of expander complications.

Conclusions

Younger age is an independent risk factor for tissue expander complications in pediatric patients. This factor should be considered in preoperative planning and discussions with the patient's family.
Applying the Full Endoscopic Keyhole Technique to CPA Lesions: A Single-Center Study
Authors: Cheng Dekui , Sun Hanyu , Yang Fengyu , Guo Zhongxiang , Liu Wei , Li Xin
Published: April 2024

In recent years, endoscopy has become an increasingly common tool used during neurosurgical procedures. However, its application in treating cerebellopontine angle (CPA) lesions has not progressed as rapidly. In this study, the authors present their initial experience with surgically treating CPA lesions using a fully endoscopic keyhole retrosigmoid approach. They conducted a retrospective analysis of clinical data from patients who underwent endoscopic keyhole CPA surgery at their center between May 2017 and April 2022. They provide a comprehensive explanation of this method and an overview of the strategies that have been developed to achieve better clinical outcomes. The study included 107 patients, consisting of 10 cases of vestibular schwannoma, 21 cases of epidermoid cyst, 32 cases of trigeminal neuralgia, and 44 cases of hemifacial spasm. The authors analyzed the clinicodemographic details of the patients. Among the 31 tumor cases, gross total resection was achieved in 25 patients (80.6%), while near-total resection was performed in 6 patients (19.4%). In patients with trigeminal neuralgia, facial pain resolved in 31 out of 32 patients (96.9%). Similarly, facial convulsions disappeared or were relieved in all 44 patients (100%) with hemifacial spasms after the operation. Postoperative complications included facial nerve paresis (n=9, 8.4%), with improvement observed in 6 cases during follow-up, transient facial hypoesthesia (n=3, 2.8%), cerebrospinal fluid rhinorrhea (n=3, 2.8%), transient abducens paresis (n=1, 0.9%), and postoperative hemorrhage (n=1, 0.9%). Endoscopy provides improved deep illumination and, combined with close-up observation, enhances the visualization of structures within the CPA region. The fully endoscopic keyhole technique is a safe and effective method for managing CPA lesions.
Report on Pseudoaneurysm Caused by Injury of Internal Carotid Artery During Endoscopic Pituitary Surgery and Rebleeding After Treatment With Willis Covered Stent
Authors: Xiao Kai , Chen Yu Jing , Xu Hao , Zhang Shao Jie , Chen Lang , Hu Fei , Li Pan , Chen Yang , Shao Qiang
Published: April 2024

Objective:

Report on a case of pseudoaneurysm which was caused by injury of the internal carotid artery (ICA) during endoscopic endonasal surgery (EES), which was followed by rebleeding after treatment with a Willis covered stent.

Methods:

A woman, aged 68, underwent EES for the treatment of a pituitary adenoma. During the surgery, the right ICA was injured, and successfully hemostasis by packed with cottonoid and gelatin sponge. Besides, cerebral angiography was performed in the interventional operating room for the purpose of discovering the formation of a pseudoaneurysm in the cavernous sinus segment of ICA, which was treated with a covered stent. After successfully placing the covered stent, the patient was promptly transferred to the general operating room for the removal of the cottonoid and to address the bleeding once again. The authors employ crushed muscles and cottonoid to locally compress and stop bleeding. Owing to concerns about the risk of rebleeding in the patient, after stent implantation, the patient did not utilize antiplatelet drugs. After the surgery, the patient developed occlusion of the right ICA and massive cerebral infarction in the right hemisphere. Dehydration, anti-infection, rehabilitation, hyperbaric oxygen, as well as related treatments, were given. The cottonoid was removed in EES 2 months postsurgery, and no instances of bleeding were observed. Six months after surgery, the patient had clear consciousness and hemiplegia in the left limb, with a Glasgow Outcome Scale score of 4.

Results:

The ICA was injured during EES, which resulted in the formation of a pseudoaneurysm, the Willis stent was adopted for treatment, and there was a risk of rebleeding after the nasal packing (cottonoid, crushed muscles) was removed immediately.

Conclusions:

The ICA was injured during EES after bleeding was controlled by packing with cottonoid, crushed muscles, etc, subsequently, the patient was given intravascular treatment, it is advised to make thorough preparations and, after a suitable period, remove nasal packing in the hybrid operating room to address unexpected situations and unforeseen circumstances.
Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study
Authors: Estroff Jordan M. , Devlin Joseph , Hoteit Lara , Hassoune Adnan , Neal Matthew D. , Brown Joshua B. , Lu Liling , Kotch Shannon , Hazelton Joshua P. , Christian Ashton B. , Yeates Eric O. , Nahmias Jeffry , Jacobson Lewis E. , Williams Jamie , Schuster Kevin M. , O’Connor Rick , Semon Gregory R. , Straughn Angela D. , Cullinane Daniel , Egodage Tanya , Kincaid Michelle , Rollins Allison , Amdur Richard , Sarani Babak
Published: April 2024

BACKGROUND

Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC.

METHODS

We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior.

RESULTS

Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79–1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53–2.02) units compared with AA.

CONCLUSION

PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Characterizing trauma patients with delays in orthopedic process measures
Authors: Gohel Nishant , Khambete Pranav , Gerhardinger Laura J. , Miller Anna N. , Wolinsky Philip R. , Jarman Molly P. , Scott John W. , Vaidya Rahul , Hemmila Mark R. , Oliphant Bryant W.
Published: April 2024

INTRODUCTION

Early operative intervention in orthopedic injuries is associated with decreased morbidity and mortality. Relevant process measures (e.g., femoral shaft fixation <24 hours) are used in trauma quality improvement programs to evaluate performance. Currently, there is no mechanism to account for patients who are unable to undergo surgical intervention (i.e., physiologically unstable). We characterized the factors associated with patients who did not meet these orthopedic process measures.

METHODS

A retrospective cohort study of patients from 35 American College of Surgeons Committee on Trauma–verified level 1 and level 2 trauma centers was performed using quality collaborative data (2017–2022). Inclusion criteria were adult patients (18 years or older), Injury Severity Score ≥5, and a closed femoral shaft or open tibial shaft fracture classified via the Abbreviated Injury Scale version 2005. Relevant factors (e.g., physiologic) associated with a procedural delay >24 hours were identified through a multivariable logistic regression, and the effect of delay on inpatient outcomes was assessed. A subanalysis characterized the rate of delay in “healthy patients.”

RESULTS

We identified 5,199 patients with a femoral shaft fracture, and 87.5% had a fixation procedure, of which 31.8% had a delay, and 47.1% of those delayed were “healthy.” There were 1,291 patients with an open tibial shaft fracture, 92.2% had fixation, 50.5% had an irrigation and debridement, and 11.2% and 18.7% were delayed, respectively. High Injury Severity Score, older age, and multiple medical comorbidities were associated with a delay in femur fixation, and those delayed had a higher incidence of complications.

CONCLUSION

There is a substantial incidence of surgical delays in some orthopedic trauma process measures that are predicted by certain patient characteristics, and this is associated with an increased rate of complications. Understanding these factors associated with a surgical delay, as well as effectively accounting for them, is key if these process measures are to be used appropriately in quality improvement programs.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Favorable Outcome After Single-kidney Transplantation From Small Donors in Children: A Match-controlled CERTAIN Registry Study
Authors: Schild Raphael , Carvajal Abreu Karla , Büscher Anja , Kanzelmeyer Nele , Lezius Susanne , Krupka Kai , Weitz Marcus , Prytula Agnieszka , Printza Nikoleta , Berta László , Saygili Seha Kamil , Sellier-Leclerc Anne-Laure , Spartà Giuseppina , Marks Stephen D. , Kemper Markus J. , König Sabine , Topaloglu Rezan , Müller Dominik , Klaus Günter , Weber Stefanie , Oh Jun , Herden Uta , Carraro Andrea , Dello Strologo Luca , Ariceta Gema , Hoyer Peter , Tönshoff Burkhard , Pape Lars
Published: April 2024

Background.

Kidney transplantation (KTx) from small donors is associated with inferior graft survival in registry studies, whereas single-center studies show favorable results.

Methods.

We compared 175 pediatric KTx from small donors ≤20 kg (SDKTx) with 170 age-matched recipients from adult donors (ADKTx) from 20 centers within the Cooperative European Paediatric Renal Transplant Initiative registry. Graft survival and estimated glomerular filtration rate (eGFR) were analyzed by Cox regression and mixed models. Detailed data on surgical and medical management were tested for association with graft survival.

Results.

One-year graft survival was lower after SDKTx compared with ADKTx (90.9% versus 96.5%; odds ratio of graft loss, 2.92; 95% confidence interval [CI], 1.10-7.80; P = 0.032), but 5-y graft survival was comparable (90.9% versus 92.7%; adjusted hazard ratio of graft loss 1.9; 95% CI, 0.85-4.25; P = 0.119). SDKTx recipients had an annual eGFR increase of 8.7 ± 6.2 mL/min/1.73 m² compared with a decrease of 6.9 ± 5.7 mL/min/1.73 m² in ADKTx recipients resulting in a superior 5-y eGFR (80.5 ± 25.5 in SDKTx versus 65.7 ± 23.1 mL/min/1.73 m² in ADKTx; P = 0.008). At 3 y posttransplant, eGFR after single SDKTx was lower than after en bloc SDKTx (86.6 ± 20.4 versus 104.6 ± 35.9; P = 0.043) but superior to ADKTx (68.1 ± 23.9 mL/min/1.73 m²). Single-kidney SDKTx recipients had a lower rate of hypertension at 3 y than ADKTx recipients (40.0% versus 64.7%; P = 0.008).

Conclusions.

Compared with ADKTx, 5-y graft function is superior in SDKTx and graft survival is similar, even when performed as single KTx. Utilizing small donor organs, preferably as single kidneys in experienced centers, is a viable option to increase the donor pool for pediatric recipients.
Organ Donation and Transplantation Registries Across the Globe: A Review of the Current State
Authors: Rampersad Christie , Ahn Curie , Callaghan Chris , Dominguez-Gil Beatriz , Ferreira Gustavo F. , Kute Vivek , Rahmel Axel O. , Sarwal Minnie , Snyder Jon , Wang Haibo , Wong Germaine , Kim S. Joseph ,   on behalf of the Global Data Harmonization Committee of the Transplantation Society
Published: April 2024

Background.

The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally.

Methods.

We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured.

Results.

We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics).

Conclusions.

This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors.
Antibiotic Use and Antimicrobial Resistance: KAP survey of medical students to evaluate undergraduate training curriculum
Authors: Saksena Rushika , Parida Annapurna , Jain Madhura , Gaind Rajni
Published: April 2024

Introduction: A better understanding of knowledge, attitude and practices of undergraduate medical students towards antimicrobial resistance (AMR) is necessary to identify gaps in current training curriculum.
Methods: A 20-point Likert scale-based questionnaire divided three parts on knowledge, attitude and practices relating to antibiotic use and resistance was devised. Students attending each year of undergraduate medical program were approached to participate in the study over a one-week-period. KAP scores of each year were compared through logistic ordinal regression and Kruskal-Wallis (KW) test.
Results: Two hundred and eight students participated in the study. Overall, knowledge of about intended use of antibiotics, fixed drug combinations and awareness about AMR was good (average score of 73.75%). Steady improvement in knowledge scores was observed from first year (-0.441) to final year (0.00). The medical students had favorable attitude towards rational antimicrobial use (Likert score ³4) including the need to spread awareness about AMR amongst  students and public and following doctor’s prescription. Self-medication was reported by 28.4% of students and hoarding of leftover doses by 49.1%. Attitude score had a direct correlation with the knowledge score on KW test (χ2 =29.6, p≤0.5) but had no significant correlation with antimicrobial practices (χ2 =3.9, p≥0.5). The gaps identified in students’ practices included self-medication, skipping of dosing, hoarding of leftover medication.
Conclusion: As improvement in knowledge did not correlate with better personal behaviours regarding antibiotics, current curriculum needs to include AMR as a focus area to ensure good antibiotic prescribing practices in future practitioners.
Hidden Challenges in Evaluating Spillover Risk of Zoonotic Viruses using Machine Learning Models
Authors: Kawasaki Junna , Suzuki Tadaki , Hamada Michiaki
Published: April 2024

Machine learning models have been deployed to assess the zoonotic spillover risk of viruses by identifying their human infectivity potential. However, the scarcity of comprehensive datasets poses a major challenge, limiting the predictable range of viruses. Our study addressed this limitation through two key strategies: constructing expansive datasets across 26 viral families and developing new models leveraging large language models pre-trained on extensive nucleotide sequences. Our approaches substantially boosted our model performance. This enhancement was particularly notable in segmented RNA viruses, which are involved with severe zoonoses but have been overlooked due to limited data availability. Furthermore, models trained on data up to 2018 displayed strong generalization capability for viruses emerging post-2018. Nonetheless, we also found remaining challenges in alerting the zoonotic potential of specific viral lineages, including SARS-CoV-2. Our study elaborates on the models and datasets for predicting viral infectivity and highlights the unresolved issues to fully exploit machine learning in preparing for future zoonotic threats.
Leveraging AI for improved reproducibility of mathematical disease models: insights from a retinitis pigmentosa case study
Authors: Greugny Éléa Thibault , Ratto Nicolas , Etheve Loïc , Gourlet Jean-Baptise , Cogny Frédéric , Monteiro Claudio
Published: April 2024

Mathematical modeling of disease and drug action is becoming an indispensable component of drug development, underscored by recent examples of models predicting trial results. To be able to rely on such approaches, decision-makers need to be able to verify those results independently with in silico confirmatory studies. Artificial Intelligence (AI) offers a valuable avenue for improving the reproducibility of complex models, enabling their swift and software-agnostic deployment. This paper highlights AI’s impact through a case study on an Ordinary Differential Equation (ODE) model of Retinitis Pigmentosa (RP). We use a version of Chat GPT 4, a sophisticated large language model (LLM) developed by OpenAI, as customized by Mathpix company with additional capabilities. This setup facilitated the extraction of equations from the PDF and converted into a human-readable, text-based definition language called Antimony, which is part of the Python package tellurium. Subsequently, the model was converted into Systems Biology Markup Language (SBML) using tellurium and uploaded onto the jinkō platform for simulation. The RP model was efficiently and accurately implemented using AI techniques. Furthermore, we were able to reproduce the model behavior presented in the literature. Our findings advocate for the broader application of AI in mathematical model re-implementations to ensure reliability and reproducibility of the results.
Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19
Authors: Baker Candice N. , Duso Debra , Kothapalli Nagarama , Hart Tricia , Casey Sean , Cookenham Tres , Kummer Larry , Hvizdos Janine , Lanzer Kathleen , Vats Purva , Shanbhag Priya , Bell Isaac , Tighe Mike , Travis Kelsey , Szaba Frank , Bedard Olivia , Oberding Natalie , Ward Jerrold M. , Adams Mark D. , Lutz Cathleen , Bradrick Shelton S. , Reiley William W. , Rosenthal Nadia
Published: April 2024

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a limited range of other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad range of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.
A Novel Association Between Human Papillomavirus and Thyroid Eye Disease
Authors: Garg Ishita , Meyer Benjamin I. , Gallo Ryan A. , Wester Sara T. , Pelaez Daniel
Published: April 2024

Context

Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R).

Objective

To explore the potential involvement of viral infections in TED pathogenesis.

Methods

Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, includingPapillomaviridae,Paramyxoviridae,Herpesviridae,Enterovirus,Polyomaviridae, andRhabdoviridae. Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed.

Results

Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control (M= 0.9387,SD= 0.3548), chronic TED (M= 2.305,SD= 1.064), and active acute TED (M= 4.087,SD= 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV.

Conclusions

This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED’s pathogenesis, opening new avenues for understanding and managing the disease.
Common and Specific Intrinsic Functional Network Related to Episode Dynamics during Treatment in Bipolar Spectrum
Authors: Liu Xiaobo , Liu Zhen-Qi , Wan Bin , Liu Lang , Xiao Jinming , Meng Yao , Weng Chao , Gao Yujun
Published: April 2024

A significant challenge in bipolar disorder (BD) is to understand the neural substrates of emotional fluctuations (i.e., episode phases) along the spectrum including manic (BipM), depressive (BipD), and remission states (rBD). Here, We constructed intrinsic functional connectome for 117 subjects with BD (BipM: 38, BipD: 42, and rBD: 37) and 35 healthy controls, then associated connectivities with emotional fluctuations to identify the common and specific patterns, and finally probed their biological underpinnings. We uncovered the common altered pattern in the salience-attention network and the specific pattern in the default mode-salience network specific for BipM and sensory-prefrontal network specific for BipD and rBD. These pathological patterns can accurately delineate the various episodes episodes types of bipolar disorder and forecast the corresponding clinical symptoms associated with each episodes type. Both common and specific patterns exhibited significant genetic stability and centered regions were enriched in multiple receptors such as MOR, NMDA, and H3 for specific pathology while A4B2, 5HTT, and 5HT1a for common pathology. Gene expression was enriched in PLEKHO1, SCN2A, POU3F2, and ANK3. Our study provides new insights into possible neurobiological interpretation for episode phases in the bipolar spectrum and holds promise for advancing personalized precision medicine approaches targeting various episodes of the condition.
The potential impact of removing a ban on electronic nicotine delivery systems using the Mexico smoking and vaping model (SAVM)
Authors: Sánchez-Romero Luz María , Li Yameng , Zavala-Arciniega Luis , Gallegos-Carrillo Katia , Thrasher James F. , Meza Rafael , Levy David T.
Published: April 2024

Objective

To develop the Mexico Smoking and Vaping Model (Mexico SAVM) to estimate cigarette and electronic nicotine delivery systems (ENDS) prevalence and the public health impact of legalizing ENDS use.

Methods

SAVM, a cohort-based discrete-time simulation model, compares two scenarios. TheENDS-Restricted Scenarioestimates smoking prevalence and associated mortality outcomes under the current policy of an ENDS ban, using Mexico-specific population projections, death rates, life expectancy, and smoking and e-cigarette prevalence.The ENDS-Unrestricted Scenarioprojects smoking and vaping prevalence under a hypothetical scenario where ENDS use is allowed. The impact of legalizing ENDS use is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the ENDS-Restricted and Unrestricted scenarios.

Results

Compared to a national ENDS ban, The Mexico SAVM projects that legalizing ENDS use could decrease smoking prevalence by 40.1% in males and 30.9% in females by 2049 compared to continuing the national ENDS ban. This reduction in prevalence would save 2.9 (2.5 males and 0.4 females) million life-years and avert almost 106 (91.0 males and 15.5 females) thousand deaths between 2025 and 2049. Public health gains decline by 43% to 59,748 SVADs averted when the switching rate is reduced by half and by 24.3% (92,806 SVADs averted) with a 25% ENDS risk level from that of cigarettes but increased by 24.3% (121,375 SVADs averted) with the 5% ENDS risk.

Conclusions

Mexico SAVM suggests that greater access to ENDS and a more permissive ENDS regulation, simultaneous with strong cigarette policies, would reduce smoking prevalence and decrease smoking-related mortality. The unanticipated effects of an ENDS ban merit closer scrutiny, with further consideration of how specific ENDS restrictions may maximize public health benefits.
Inpatient treatment for severe obesity: a retrospective cohort study in Brazil
Authors: Rios Domingos L. S. , Oliveira Márcia C. A. M. , Braga Sérgio Q. , Chamorro Matheus J. , Cunha Beatriz L. B. , Reis Ana C. R. , Guimarães Ana P. , Silva Ana D. N. , Silva Dandara A. R. , Araújo Edilene M. Q. , Pimentel Magno M. W.
Published: April 2024

Introduction

Very low-calorie diets with hospitalization have demonstrated promise as a viable therapeutic option for severe obesity and its associated comorbidities. However, large studies providing a comprehensive longitudinal observation of patients undergoing this therapy are lacking. We evaluated the effectiveness of treating severe obesity in hospitalized patients, using very low-calorie diets and clinical support to develop lifestyle changes.

Methods

A retrospective cohort study with a pre-post quasi-experimental design analyzed secondary data from 2016–2022 medical records of patients with severe obesity (grade II or III) treated in a Brazilian obesity specialist hospital. The patients underwent a very low-calorie diet (500–800 kCal/day) and immersive changes in lifestyle habits, monitored by a multidisciplinary team. At 3 months, 777 patients presented complete data and 402 presented complete data at 6 months. The study compared changes in bioimpedance and laboratory tests, between men and women and age groups (elderly vs. non-elderly).

Results

Three months of hospitalization yielded significant reductions in weight, body mass index (BMI), body fat, skeletal muscle mass, glucose, inflammatory, and lipid parameters. These reductions were more pronounced after 6 months, nearly doubling those observed at 3 months. In women, BMI and fat mass reduced by 10.4% and 15.2% at 3 months and 20.4% and 31.3% at 6 months, respectively. In men, BMI and fat mass decreased by 12.9% and 25.3 at 3 months and 23.6% and 45.3% at 6 months, respectively. Elderly individuals (aged ≥ 60 years) had smaller reductions in BMI and fat mass than non-elderly individuals (aged < 60 years) but still presented significant improvements.

Conclusion

This study suggests the viability of treating severe obesity by hospitalization with low-calorie diets and immersive lifestyle changes. This treatment modality significantly improves anthropometric measurements, glucose, lipids, and inflammatory markers, thereby reducing cardiovascular risk.
Receptor binding and tissue architecture explain the morphogen local-to-global mobility transition
Authors: Zhu Shiwen , Loo Yi Ting , Veerapathiran Sapthaswaran , Loo Tricia Y. J. , Tran Bich Ngoc , Teh Cathleen , Zhong Jun , Matsudaira Paul , Saunders Timothy E. , Wohland Thorsten
Published: April 2024

Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realisticin silicoarchitecture of the extracellular spaces of the zebrafish brain using light and electron microscopy data. Simulations on realistic architectures demonstrate that tortuosity and receptor binding within these spaces are sufficient to reproduce experimentally measured morphogen dynamics. Importantly, this work demonstrates that hindered diffusion is a viable mechanism for gradient formation, without requiring additional regulatory control.

SIGNIFICANCE

Measurements of morphogen diffusivity vary significantly depending on experimental approach. Such differences have been used to argue against diffusion as a viable mechanism of morphogen gradient formation. Here, we demonstrate that accounting for the local tissue architecture in concert with including receptor binding is sufficient to explain a range of biological observations. This demonstrates that (hindered) diffusion-driven transport is a viable mechanism of gradient formation.
Disorganized Inhibitory Dynamics in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice
Authors: Herrlinger Stephanie A. , Rao Bovey Y , Paredes Margaret E. Conde , Tuttman Anna L. , Arain Haroon , Varol Erdem , Gogos Joseph A. , Losonczy Attila
Published: April 2024

Individuals with the 22q11.2 deletion syndrome, one of the strongest genetic risk factors for schizophrenia, demonstrate cognitive impairments including episodic memory dysfunction. Place cell activity of excitatory pyramidal neurons in the hippocampus supporting episodic memory are impaired in a mouse model for the 22q11.2 deletion (Df(16)A+/-). While excitatory dynamics are under tight inhibitory control by multiple subtypes of GABAergic interneurons, previous studies have predominantly focused on a single subtype of PV-expressing interneurons; there have not yet been studies describing the functional relationships between molecularly identified inhibitory types inDf(16)A+/-mice. Here, we examined interneuron subtype-specific activity dynamics in the dorsal hippocampal area CA1 ofDf(16)A+/-mice during random foraging and spatial reward learning tasks. Capitalizing on 3D acousto-optical deflector two-photon microscopy withpost hocimmunohistochemical identification, we found that multiple interneuron types exhibit aberrant responses to reward locations and delayed reward enrichment extinction.Df(16)A+/-inhibitory interneurons also carry markedly reduced spatial information in a subtype-dependent manner. We observed task-dependent changes in the correlation structure and coactivity among multiple GABAergic subtypes, suggesting a broadly disorganized microcircuit functionality in mutant mice. Overall, we identify widespread and heterogeneous subtype-specific alterations in interneuron dynamics during spatial reward learning, reflecting impaired flexibility and organization in CA1 inhibitory microcircuits. Our study provides critical insights into how schizophrenia-risk mutations affect local-circuit interactions among diverse cell types in the mouse hippocampus during learning and spatial navigation.
Google Trends and Online Q&A site Reveal Surging Demand for Endemic Pet Reptiles in Japan
Authors: Digirolamo Richard
Published: April 2024

The global trade in pet reptiles is substantial, with Japan being a major importer. Understanding pet reptile preferences is crucial for conservation, as overexploitation of wild populations can occur. This study aimed to determine Japan’s most popular pet reptiles, including traded and endemic species, using the largest question-answering website in Japan, Yahoo! Chiebukuro and Google Trends as data sources. We analysed data from 2004 to 2023, focusing on recent periods (2020-2023) for a comprehensive assessment of public interest in 20 different pet reptile species. Data revealed a significant overlap between the two tools in identifying popular species. Leopard geckos were consistently the most popular, aligning with trade data. Surprisingly, the endemic Japanese grass lizard surpassed the popularity of traditionally favoured species like central bearded dragons. A concerning preference for invasive turtles (Chinese pond turtles, red-eared sliders) was also noted. These findings highlight the popularity of both traded and readily available endemic species within Japan’s pet market. This emphasises the need to monitor domestic trends alongside the traditional trade focus to ensure the sustainability of wild reptile populations. Yahoo! Chiebukuro and Google Trends offer valuable tools for such monitoring. Google Trends’ regional data pinpointed Okinawa prefecture’s high interest in leopard geckos, raising concerns about potential invasiveness. This study demonstrates the importance of a comprehensive approach to understanding pet reptile popularity. The combined use of these tools and the adaptable methodology provide a template for monitoring trends in Japan and other countries, contributing to proactive conservation efforts within the global pet trade.