bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?
Authors: Cleary Megan , Ndhlovu Lishomwa C. , Sacha Jonah B.
Published: November 2024

Purpose of review

Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.

Recent findings

Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 (ccr5Δ32), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.

Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.
A retrospective study on the relationship between plasma β-hydroxybutyric acid levels and short-term prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure
Authors: Wang Jinxin , Zou Dan , Song Xiaoshuai , Gao Luyao , Chi Kai , Xu Ping , Rui Haiying , Yu Huaxiang , Liu Lulu , Wu Xuting , Zou Wenyi , Wang Fengxin , Li Yuting , Li Anqi , Li Ran , Xue Li , Chen Yuguo
Published: November 2024

Background

Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption; however, its role in the short-term prognosis of patients with acute myocardial infarction combined with heart failure has not been clearly elucidated. The aim of this study was to investigate the effect of β-hydroxybutyric acid, the main component of ketone bodies, on the short-term prognosis of patients with acute myocardial infarction combined with heart failure.

Methods

This was a retrospective observational study that enrolled patients admitted to the Qilu Hospital of Shandong University for acute myocardial infarction combined with heart failure between January 1, 2019, and December 31, 2022. According to whether β-hydroxybutyric acid was elevated or not, subjects were divided into a β-hydroxybutyric acid elevated and nonelevated groups, to observe the difference in cardiac function improvement between the two groups.

Results

This study included a total of 260 patients, of which 170 exhibited elevated levels of β-hydroxybutyric acid. Compared to the patients in the nonelevated group, patients in the elevated β-hydroxybutyric acid group had higher plasma levels of creatine kinase myocardial band and greater Gensini scores. Multivariate logistic regression analysis indicated that an increase in β-hydroxybutyric acid levels (odds ratio: 2.517; 95% confidence intervals: 1.394–4.597; P = 0.002) is an independent protective factor affecting the prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure.

Conclusion

In patients with acute myocardial infarction combined with heart failure, plasma β-hydroxybutyric acid serves as an independent protective factor for short-term improvement in cardiac function.
Trauma team activation criteria for potential major trauma in the adult population: a narrative review
Authors: Garrido Callén Alberto , Pérez Torres Manuel , Vasco Castaño Dovami , Cui Liu Cui Jie , González Gómez María , Muñoz Varea María , Bardal Ruiz Alfredo , López Cuenca Sonia , Martin Pellicer Ana , Merino Vega Carmen Débora , Fernandéz Martín-Caro Ignacio , Maqueda Lluva Diego , Pérez Marquéz Manuel
Published: November 2024

Traumatic disease is a common cause of death and disability in the young population. The presence of a trauma team ensures the quality of patient management, thus improving patient outcomes. Therefore, triage is an essential part of trauma care, especially for potential major trauma patients, who present significant challenges due to the lack of universal and centralized criteria. This narrative review aimed to present an overview of the main studies conducted thus far, focusing on the screening of adult patients in both prehospital and in-hospital settings, along with the latest guidelines published in 2021. Our approach involved a nonsystematic literature review, with a particular emphasis on systematic reviews and meta-analyses of observational studies published in the PubMed, Embase, and Cochrane databases. We analyzed the different tools proposed for patient screening and incorporated them into our protocol for triaging potential trauma patients who could benefit from early trauma team activation. In conclusion, our review underscores the importance of incorporating accurate physiological criteria and suspected injury patterns into a trauma team activation protocol. We also highlight the ongoing challenges in refining the mechanistic aspects of trauma and special considerations. Moving forward, continued research with new machine learning models and collaboration among trauma experts may be crucial for enhancing the precision and effectiveness of trauma triage, ultimately leading to improved patient outcomes and optimal resource allocation.
Impact of COVID-19 on Exercise-Based Pulmonary Rehabilitation
Authors: Borghi-Silva Audrey , Goulart Cássia da Luz , Silva Rebeca Nunes , Back Guilherme Dionir , Camargo Patrícia Faria , Trimer Renata , Teles Stephanny Nascimento , Sampaio Luciana Maria Malosa
Published: November 2024

The Coronavirus Disease 2019 (COVID-19) pandemic had a major global impact on health care, including the delivery, modality, and importance of outcomes in pulmonary rehabilitation (PR). This review discusses the impact of the pandemic on PR and the changes that were required to maintain its delivery. This article reviews the current evidence on PR during the COVID-19 pandemic period, focusing on delivery models, modalities, outcomes, perspectives, and barriers. A search of the MEDLINE, Embase, and SciELO databases and the Cochrane Library on this topic was conducted between December 1, 2019 and August 1, 2023. Studies were reviewed and relevant topics were included in this narrative. Rehabilitation of patients with severe acute COVID-19 and symptoms of long COVID has been challenging. The number of rehabilitation programs worldwide is still low, and community-based programs are still rare. Integrated programs with a multidisciplinary approach and exercise therapy with individualized prescription based on symptoms have been an interesting strategy. Telerehabilitation and outpatient rehabilitation are both effective in the treatment of patients with chronic obstructive pulmonary disease. However, the uptake of PR remains considerably low, and technological barriers for patients and lack of technological resources in low-income countries affect the delivery of these services in much of the world.
A RETROSPECTIVE STUDY ON THE OUTCOMES OF PNEUMATIC VITREOLYSIS FOR THE TREATMENT OF VITREOMACULAR TRACTION
Authors: De Clerck Ivo , Bivort Juliette , Van Calster Joachim , Stalmans Peter
Published: November 2024

Purpose:

To study the effectiveness and safety of pneumatic vitreolysis (PVL) for the treatment of symptomatic vitreomacular traction (VMT) and macular holes (MHs) with VMT.

Methods:

This was a retrospective, monocentric analysis of 92 consecutive VMT (±MH) patients treated with pneumatic vitreolysis at University Hospitals Leuven between January 2022 and March 2024.

Results:

Release of VMT occurred in 60% of the patients who had VMT and in 86% of the patients who had MHs. MH closure occurred in 29% of the small MHs. Lens status was the only predictor of VMT release, with an odds ratio of 0.232 for pseudophakia (P = 0.013). Successful pneumatic vitreolysis was associated with significant improvements in the best-corrected visual acuity in patients with VMT (P = 0.007) and in patients with MHs (P = 0.034). Two patients (2.2%) suffered a retinal tear, one of which led to retinal detachment. Two patients with VMT (3.17%) developed a MH.

Conclusion:

Pneumatic vitreolysis using the injection of 0.2 cc of C2F6 and subsequent posturing seems to be beneficial with limited complications for symptomatic focal VMT and for (very) small MHs with VMT, especially in phakic patients. The complication rate in this study was lower than that previously reported.
Intrastromal Corneal Ring Segments and Keratoconus Progression: A Case Series Study
Authors: Benito-Pascual Blanca , Arriola-Villalobos Pedro , Rodríguez-Quet Olivia , Termine Vittoria , Cuiña-Sardiña Ricardo , Díaz-Valle David
Published: November 2024

Objective:

To assess keratoconus (KC) progression following the implant of intrastromal corneal ring segments (ICRSs) in young patients.

Materials and methods:

Retrospective, longitudinal, observational, controlled nonrandomized case series study. Keratoconus patients aged 25 years or younger who underwent uneventful ICRS surgery and completed at least 3 years of follow-up were enrolled. Controls were of similar age and treatment-naive patients with KC. The following Pentacam imaging (Oculus, Wetzlar, Germany) data were analyzed: keratometric (maximum, in-flattest meridian, in-steepest meridian, and mean), aberrometric (higher-order aberrations and coma), pachymetric (thinnest corneal thickness), and elevation (maximum posterior elevation). The main outcome measure was KC progression.

Results:

The study sample comprised 20 eyes of 18 cases (age 20.20 ± 3.70 years, nine right eyes, 14 male patients) and 30 eyes of 24 controls (age 20.80 ± 3.20 years, 15 right eyes, 21 male patients). The mean follow-up duration was 4.90 ± 1.70 years (range 3–8 years) for cases and 4.50 ± 1.40 years (range 3–8 years) for controls. Four cases and two controls met criteria for KC progression.

Conclusions:

Intrastromal corneal ring segments did not have significant impact on KC progression in the cohort.
Evaluation of the Microbiology of Removed Punctal Plugs and Intracanalicular Devices
Authors: Meyer Jay J. , Culbreath Karissa , Ager Edward , Esmaili Neda , Fowler William C. , Gilligan Peter , Fowler Amy M.
Published: November 2024

Objective:

The purpose of this observational study was to characterize the microorganisms colonizing punctal plugs and intracanalicular stents.

Methods:

Devices were removed from participants who previously underwent placement of punctal plugs for tear insufficiency and lacrimal stents for dacryocystorhinostomy and canalicular reconstruction procedures. After removal of the devices, they were cultured for organisms both with and without sonication to loosen any biofilms or adherent microorganisms. Primary outcome measures included culture positivity, identification of isolated microorganisms, recovery of microorganisms from culture after sonication, and clinical evidence of ocular infection.

Results:

There were no cases of clinical infection. A total of 181 specimens were processed (174 punctal plugs, seven intracanalicular stents), of which 98 (54%) were culture positive. Of the punctal plugs, 92 (52.9%) were culture positive, including 42 with a single organism isolated, whereas 22 yielded two organisms, 7 yielded three organisms, and the remaining 21 yielded a polymicrobial culture with four or more organisms. The most common isolates from punctal plugs were coagulase negative staphylococci (27.6%), diphtheroids (16.4%), and streptococcus viridans (10.2%). Those plugs with polymicrobial culture results grew a mixture of organisms most consistent with skin or upper respiratory flora. Of the intracanalicular stents, 6 (85.6%) were culture positive.

Conclusions:

Punctal plugs and intracanalicular devices can become colonized with bacteria composed of oropharyngeal flora, skin flora, and other rare but potentially significant pathogens.
KINGELLA KINGAE SEQUENCE TYPE 25 MENINGITIS IN AN IMMUNOCOMPETENT TODDLER: CLINICAL AND MOLECULAR APPROACH
Authors: Syrogiannopoulos George A. , Bidet Philippe , Michoula Aspasia N. , Goutzourelas Athanasios D. , Syrogiannopoulou Theoni G. , Anthracopoulos Michael B. , Bonacorsi Stéphane , Grivea Ioanna N.
Published: November 2024

Kingella kingae is a cause of bacteremia, endocarditis, and the leading cause of osteoarticular infections between 6 and 48 months of life. We report on a rare case of K. kingae meningitis in the absence of endocarditis and immune deficiency in a 26-month-old boy emphasizing the distinct genomic determinants of the strain which may be of importance to the pathogenesis of the disease.
High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma
Authors: Peng Fangli , Igawa Takuro , Urata Tomohiro , Kobayashi Hiroki , Isoda Tetsuya , Ono Sawako , Tanaka Takehiro , Ennisshi Daisuke , Maeda Yoshinobu , Yamamoto Hidetaka
Published: November 2024

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2/BCL6/c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B, was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P<0.01) and double-expressor cases (20/32, 62.5%; P=0.01) compared with the MYD88/CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type (P=0.03), showing poorer outcomes in overall survival (P=0.02) and progression-free survival (P=0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.
Effect of Jinfeng Pill on ovarian function of Tripterygium wilfordii polyglycoside tablets induced poor ovarian response rats
Authors: Li Yi , Wang Jian-Fang , Yan Xiao-Hong , Ji Xiao-Lei , Zhang Heng-Yuan , Wu Rong-Feng , Li You-Zhu
Published: November 2024

Objective:

This study aimed to assess the effects of the Jinfeng pill on ovarian volume and endocrine function in rats with poor ovarian response and to elucidate the gene expression changes that contribute to the Jinfeng pill’s role in improving ovarian function.

Methods:

Thirty 8-week-old specific pathogen-free (SPF) female rats were randomly assigned to five groups: control, model, estradiol, Jinfeng pill, and Jinfeng pill + estradiol, with six rats in each group. All groups, except the control were administered Tripterygium glycoside tablets. After establishing the poor ovarian response model, the three intervention groups (estradiol, Jinfeng pill, and Jinfeng pill + estradiol) received their respective drug interventions. Hematoxylin-eosin staining was employed to assess follicle distribution, and immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor and endostatin in rat ovaries. Hormone levels were measured using ELISA.

Results:

The uterine and total ovarian masses in the three intervention groups were higher than those in the model group; however, the differences were not statistically significant. The ovaries of the Jinfeng pill and Jinfeng pill + estradiol groups contained more follicles at various developmental stages. The three intervention groups showed significantly increased vascular endothelial growth factor expression and decreased endostatin expression compared with the model group, with the Jinfeng pill + estradiol group exhibiting the most pronounced differences. Anti-Müllerian hormone levels were slightly elevated in the Jinfeng pill group compared to the model group. However, only the Jinfeng pill + estradiol group showed a statistically significant decrease in follicle-stimulating hormone levels compared to the model group (P = 0.01).

Conclusions:

Jinfeng pill modulates ovarian protein expression, increases ovarian volume, and improves blood circulation. Additionally, it may elevate hormone levels and enhance ovarian response function in rats with poor ovarian function.
Using Machine Learning to Examine Pre-Transplant Factors InfluencingDe novoHLA-Specific Antibody Development Post-Kidney Transplant
Authors: Rothwell Alex , Nita George , Howse Matthew , Ridgway Dan , Hammad Abdul , Mehra Sanjay , Jones Andrew R , Goldsmith Petra
Published: November 2024

The development ofde novodonor-specific antibodies (DSAs) against HLA is associated with premature graft failure in kidney transplantation. However, rates and factors influencingde novoDSA formation vary widely across the literature. We aimed to identify pre-transplant factors influencing the development ofde novoHLA-specific antibodies following kidney transplantation using machine learning.

Data from 460 kidney transplant recipients at a single centre between 2009-2014 were analysed. Pre-transplant variables were collected, and post-transplant sera were screened for HLA antibodies. Positive samples were investigated using Single Antigen Bead (SAB) testing. Machine learning models (Classification and Regression Trees, Random Forest, XGBoost, CatBoost) were trained on a training set of pre-transplant data to predictde novoDSA formation, with and without SMOTE oversampling. Model performance was evaluated on an independent testing set using F1 scores, and feature importance was assessed using SHAP.

In the full cohort analysis, XGBoost models performed the best, with F1 scores of 0.54-0.59 without SMOTE and 0.72-0.79 with SMOTE. The strongest predictors were pre-transplant HLA antibodies, number of kidney transplants, cold ischemia time (CIT), recipient age and female gender. SHAP dependence plots showed that pre-existing HLA antibodies and past transplants increased the risk ofde novoDSA development. In the unsensitised subgroup analysis, model performance was poor.

Machine learning models can be used to identify pre-transplant risk factors forde novoHLA-specific antibody development in kidney transplantation. Monitoring and risk-stratifying patients based on these factors may help guide preventive immunological strategies and recipient selection to improve long-term allograft outcomes.

Translational statement

This study identified pre-transplant risk factors for the development ofde novoHLA-specific antibody in kidney transplantation. Monitoring and risk-stratifying patients based on these factors may help guide preventive immunological strategies and recipient selection to improve long-term allograft outcomes.
Defective glycosylation and ELFN1 binding of mGluR6 congenital stationary night blindness mutants
Authors: Pindwarawala Mustansir , Abid Faiyaz A. K. , Lee Jaeeun , Miller Michael L. , Noppers Juliet S. , Rideout Andrew P. , Agosto Melina A.
Published: November 2024

Synaptic transmission from photoreceptors to ON-bipolar cells (BCs) requires the postsynaptic metabotropic glutamate receptor mGluR6, located at BC dendritic tips. Binding of the neurotransmitter glutamate initiates G-protein signaling that regulates the TRPM1 transduction channel. mGluR6 also interacts with presynaptic ELFN adhesion proteins, and these interactions are important for mGluR6 synaptic localization. The mechanisms of mGluR6 trafficking and synaptic targeting remain poorly understood. In this study, we investigated mGluR6 missense mutations from patients with congenital stationary night blindness (CSNB), which is associated with loss of synaptic transmission to ON-BCs. We found that multiple CSNB mutations in the extracellular ligand-binding domain of mGluR6 impart a trafficking defect leading to lack of complex N-glycosylation but efficient plasma membrane insertion, suggesting a Golgi bypass mechanism. These mutants fail to bind ELFN1, consistent with lack of a necessary modification normally acquired in the Golgi. The same mutants were mislocalized in bipolar cells, explaining the loss of function in CSNB. The results reveal a key role of Golgi trafficking in mGluR6 function, and suggest a role for the extracellular domain in Golgi sorting.
Apparent digestibility and nutritional performance of bakery waste produced in Punjab Pakistan forLabeo rohitafingerlings
Authors: Hussain Syed Shafat , Khan Noor , Rasool Fayyaz , Davies Simon John , Naveed Saima
Published: November 2024

This study aimed to examine the impact of bakery waste supplementation on the nutrient digestibility and performance metrics of rohu (Labeo rohita) juveniles. Fish were fed with seven different diets containing bakery waste products (biscuits, cream cake, bread, and dry rusk) in combination with rice polish and wheat flour. Chromic oxide (1%) was added to the diet as an inert marker to measure nutrient digestibility. The results indicated a significant difference (p < 0.05) in the digestibility of crude protein, lipid, gross energy, and dry matter among the dietary groups. Fish fed with rice polish had the lowest apparent digestibility value of protein (16.13 ± 1.86), whereas fish fed wheat flour had the highest (77.70 ± 0.05). Moreover, it was shown that fish fed rusk waste had better growth. It has been concluded that bakery wastes could be used as a cheaper fish feed ingredient source for the manufacturing of cost-effective feed forL. rohita. This investigation was discussed within the context of providing cost effective ingredients for sustainable aquaculture production in Pakistan.
COCOMO2: A coarse-grained model for interacting folded and disordered proteins
Authors: Jussupow Alexander , Bartley Divya , Lapidus Lisa J. , Feig Michael
Published: November 2024

Biomolecular interactions are essential in many biological processes, including complex formation and phase separation processes. Coarse-grained computational models are especially valuable for studying such processes via simulation. Here, we present COCOMO2, an updated residue-based coarse-grained model that extends its applicability from intrinsically disordered peptides to folded proteins. This is accomplished with the introduction of a surface exposure scaling factor, which adjusts interaction strengths based on solvent accessibility, to enable the more realistic modeling of interactions involving folded domains without additional computational costs. COCOMO2 was parameterized directly with solubility and phase separation data to improve its performance on predicting concentration-dependent phase separation for a broader range of biomolecular systems compared to the original version. COCOMO2 enables new applications including the study of condensates that involve IDPs together with folded domains and the study of complex assembly processes. COCOMO2 also provides an expanded foundation for the development of multi-scale approaches for modeling biomolecular interactions that span from residue-level to atomistic resolution.

Table of Contents Figure
Altered renal vascular patterning reduces ischemic kidney injury and limits vascular loss associated with aging
Authors: McLarnon Sarah R. , Honeycutt Samuel E. , N’Guetta Pierre-Emmanuel Y. , Xiong Yubin , Li Xinwei , Abe Koki , Kitai Hiroki , Souma Tomokazu , O’Brien Lori L.
Published: November 2024

The kidney vasculature has a complex arrangement, which runs in both series and parallel to perfuse the renal tissue and appropriately filter plasma. Recent studies have demonstrated that the development of this vascular pattern is dependent on netrin-1 secreted by renal stromal progenitors. Mice lacking netrin-1 develop an arterial tree with stochastic branching, particularly of the large interlobar vessels. The current study investigated whether abnormalities in renal vascular pattern altered kidney function or response to injury. To examine this, we analyzed kidney function at baseline as well as in response to recovery from a model of bilateral ischemic injury and measured vascular dynamics in aged mice. We found no differences in kidney function or morphology at baseline between mice with an abnormal arterial pattern compared to control. Interestingly, male and female mutant mice with stochastic vascular patterning showed a reduction in tubular injury in response to ischemia. Similarly, mutant mice also had a preservation of perfused vasculature with aging compared to a reduction in the control group. These results suggest that guided and organized patterning of the renal vasculature may not be required for normal kidney function; thus, modulating renal vascular patterning may represent an effective therapeutic strategy. Understanding how patterning and maturation of the arterial tree affects physiology and response to injury or aging has important implications for enhancing kidney regeneration and tissue engineering strategies.
The relationship between voluntary and involuntary muscle contractile properties in young women
Authors: Fry Madison J. , Zoughaib William S. , Hoffman Richard L. , Coggan Andrew R.
Published: November 2024

Isokinetic dynamometry and neuromuscular electrical stimulation (NMES) are two commonly used approaches for quantifying muscle contractile properties. Few studies, however, have investigated the relationship between such testing procedures, particularly in women.

PURPOSE

To determine the relationship between voluntary isometric and isokinetic torque and torque during involuntary, electrically evoked contractions of the knee extensor muscles.

METHODS

Thirty young women (age 23 ± 5 y) performed maximal knee extensions on an isokinetic dynamometer at angular velocities of 0, 1.57, 3.14, 4.71, and 6.28 rad/s. Following this testing, NMES of the quadriceps (400 V, 200 µs) was used to determine unpotentiated and potentiated twitch contractile properties. The quadriceps were also stimulated with 1 s trains at 1, 5, 10, 15, 20, 25, 30, 35, 40, 60, 80, and 100 Hz to determine the torque-frequency relationship.

RESULTS

Voluntary torques at 1.57 and 3.14 rad/s were significantly correlated (i.e., multiplicity-adjusted P≤0.01) with the rate of torque development during potentiated twitches (r = 0.60 and 0.55, respectively). No other significant correlations were found between voluntary and involuntary muscle contractile properties, including various measures of the torque-frequency relationship.

CONCLUSION

Although there is some relationship between voluntary and NMES indices of muscle contractility, such results are only moderately well-correlated at best. The two techniques should therefore be considered complementary rather than interchangeable.

Abstract Figure
The Role of Prompt Engineering for Multimodal LLM Glaucoma Diagnosis
Authors: Agbareia Reem , Omar Mahmud , Zloto Ofira , Chandala Nisha , Tai Tania , Glicksberg Benjamin S , Nadkarni Girish N , Klang Eyal
Published: November 2024

Background and Aim

This study evaluates the diagnostic performance of multimodal large language models (LLMs), GPT-4o and Claude Sonnet 3.5, in detecting glaucoma from fundus images. We specifically assess the impact of prompt engineering and the use of reference images on model performance.

Methods

We utilized the ACRIMA public dataset, comprising 705 labeled fundus images, and designed four prompt types, ranging from simple instructions to more refined prompts with reference images. The two model were tested across 5640 API runs, with accuracy, sensitivity, specificity, PPV, and NPV assessed through non-parametric statistical tests.

Results

Claude Sonnet 3.5 achieved a highest sensitivity of 94.92%, a specificity of 73.46%, and F1 score of 0.726. GPT-4o reached a highest sensitivity of 81.47%, a specificity of 50.49%, and F1 score of 0.645. The incorporation of prompt engineering and reference images improved GPT-4o’s accuracy by 39.8% and Claude Sonnet 3.5’s by 64.2%, significantly enhancing both models’ performance.

Conclusion

Multimodal LLMs demonstrated potential in diagnosing glaucoma, with Claude Sonnet 3.5 achieving a sensitivity of 94.92%, far exceeding the 22% sensitivity reported for primary care physicians in the literature. Prompt engineering, especially with reference images, significantly improved diagnostic performance. As LLMs become more integrated into medical practice, efficient prompt design may be key, and training doctors to use these tools effectively could enhance clinical outcomes.
Cholinergic neurotransmission in the anterior cingulate cortex is associated with cognitive performance in healthy older adults: Baseline characteristics of the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial
Authors: de Figueiredo Pelegrino Ana , Attarha Mouna , Toussaint Paule-Joanne , Ouellet Lydia , Grant Sarah-Jane , Van Vleet Thomas , de Villers-Sidani Etienne
Published: November 2024

Aging is associated with dysfunction in the cholinergic system, including degeneration of basal forebrain cholinergic terminals that innervate the cortex, which directly contributes to age- and disease-related cognitive decline. In this study, we used [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) imaging to assess the effect of age on cholinergic terminal integrity in predefined regions of interest and its relationship to cognitive performance in healthy older adults who underwent neuropsychological assessment and FEOBV PET brain imaging. Our results showed age-related reductions in FEOBV binding, particularly in the anterior cingulate cortex-our primary region of interest-as well as in the striatum, posterior cingulate cortex, and primary auditory cortex. Notably, FEOBV binding in the anterior cingulate cortex was positively correlated with cognitive performance on the NIH EXAMINER Executive Composite Score. These findings suggest that [18F]FEOBV PET imaging can be used as a reliable biomarker to assess cholinergic changes in the human brain and indicate that preserving the cholinergic integrity of the basal forebrain may help maintain cognitive function and protect against age-related cognitive decline.
Bilingualism measures in children: A critical review of content overlap, development, and pragmatic quality
Authors: Leung Kai Ian , Molnar Monika
Published: November 2024

Purpose

A variety of assessment tools (e.g., questionnaires) measure the type and degree of bilingualism in children in both research and clinical settings. Although these tools are often assumed to evaluate the same constructs and be interchangeable, this may not be the case, as indicated by other recent reviews. This review critically evaluated existing measures of child bilingualism, focusing on item-content overlap, measure development, and pragmatic quality.

Method

A database and manual search identified studies on child bilingualism measure development, which were then appraised using the Psychometric and Pragmatic Evidence Rating Scale and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN).

Result

Analysis across the six identified measures showed weak between-measure content overlap, with less than one quarter of items shared on average, suggesting they assess different constructs.

Ratings indicated varied pragmatic quality, especially in assessor burden (training, interpretation). COSMIN evaluations also highlighted shortcomings in measure design and development.

Conclusion

The findings underscore the need for improved content validity and better pragmatic criteria for the clinical use of these tools. We offer recommendations for measure selection dependent on use case (e.g., setting-specific needs) and suggestions for future bilingualism measure development, prioritizing a pragmatic approach.
Applications of Synthetic Data Integration for Deep Learning for Volumetric Analysis and Segmentation in Thoracic CT Imaging
Authors: Zeyrek Ali , Navarro Sergio M
Published: November 2024

This study presents a framework for processing Digital Imaging and Communications in Medicine (DICOM) medical imaging data by integrating synthetic objects for volumetric analysis and simulation for applications in assessment of computed tomography (CT) imaging used in thoracic surgery. Functions are designed to generate synthetic objects including geometric shapes such as spheres, cubes, rectangular prisms, cylinders, and blobs with known volumes. Validation is performed through test functions to ensure accuracy and consistency. Additionally, the use of UNet models for segmenting various chest pathologies, such as hemothorax and pneumothorax, as well as organs, is demonstrated. The created framework is used to generate synthetic data to address the scarcity of publicly available hemothorax CT imaging data. Models achieved high performance, assessed by various metrics. The framework and models provide a robust tool for data augmentation and analysis in medical imaging, potentially enhancing clinical decision-making and supporting research in thoracic surgery and related fields.
RGFSAMNet: An interpretable COVID-19 detection and classification by using the deep residual network with global feature fusion and attention mechanism
Authors: Ul Karim S M Rakib , Bala Diponkor , Rasul Rownak Ara , Goggins Sean
Published: November 2024

Artificial intelligence has shown considerable promise in fields like medical imaging. Existing testing limitations necessitate reliable approaches for screening COVID-19 and measuring its adverse effects on the lungs. CT scans and chest X-ray images are vital in quantifying and accurately classifying COVID-19 infections. One significant advantage of deep learning models in medical image analysis for detection and classification is that they are a top-notch way to diagnose diseases. For this purpose, we have utilized the power of a deep residual learning network with a global feature fusion technique and attention mechanism to develop our proposed model named “RGFSAMNet” in this study to diagnose the COVID-19 infected patient accurately from a CT scan and chest X-ray images. We have used two publicly available datasets named “SARS-COV-2,” which consists of 2482 CT scan images with two classes, and another chest X-ray dataset that contains 12,576 images with three classes. To check the effectiveness of our model, we have trained and tested the model on two different types of datasets. We also generated the Grad-CAM, LIME, and SHAP visualization based on our proposed model, which can represent the identification of the affected area’s regions in images and describe the model’s interpretability level. These experimental results show that the proposed model architecture can achieve accurate classification of COVID-19 affected CT scans and X-ray images despite a lack of data, with the highest accuracy of 99.60% on test data for CT scans and 99.48% on X-ray image detection and classification. We also developed a web-based User Interface (UI) for the model validation to detect and classify COVID-19 images. Our proposed model exceeds some previous state-of-the-art performance levels. We think our contributions will help clinicians detect and classify COVID-19 images effectively and save human lives.
Healthcare Expenditure on Atrial Fibrillation in the United States: The Medical Expenditure Panel Survey 2016-2021
Authors: See Claudia , Grubman Scott , Shah Nisarg , Hu Jiun-Ruey , Nanna Michael , Freeman James V. , Murugiah Karthik
Published: November 2024

Objectives

To provide a contemporary nationally representative assessment of atrial fibrillation (AF) and atrial flutter (AFL) expenditures in the United States.

Background

AF prevalence is rising over time and management is evolving. However, there has been no contemporary national assessment of expenditures of AF.

Methods

Using Medical Expenditure Panel Survey (MEPS) 2016-2021 data, we identified individuals with AF or AFL using International Classification of Disease (ICD)-10 codes and reported total and categorized expenditures. Using two-part and gamma regression models, respectively, we estimated the incremental expenditures with AF for the entire population and for individuals with common coexisting comorbidities. Among individuals with AF, we identified characteristics associated with higher expenditures.

Results

Of a weighted surveyed population of 248,067,064 adults, 3,564,763 (1.4%) had AF. Mean age was 71.9 ± 10.6 years and 45.7% were female. Mean unadjusted annual total healthcare expenditure for individuals with AF was $25,451 ± $1,100 compared with $9,254 ± $82 for individuals without AF. The highest spending categories were inpatient visits ($7,975 ± $733) and prescriptions ($6,505 ± $372). AF expenditures increased over the study period by 11.1%. After adjustment, the incremental annual expenditure attributable to AF was $6,188 per person. Incremental expenditures with AF were highest for those with cancer ($11,967, 95% CI $4,410 - $19,525), while AF did not significantly increase expenditures in HF (-$2,756, 95% CI -$10,048 - $4,535). Modified Charlson Comorbidity Index of 1 or ≥2, uninsured status, cancer, poor income level, ASCVD, COPD, and later survey year were associated with higher expenditures.

Conclusion

AF is associated with substantial healthcare expenditures which are increasing over time. With changes in screening and management, expenditures need periodic reassessments.

CONDENSED ABSTRACT

Introduction

AF prevalence is rising, but contemporary national expenditure assessments are lacking.

Methods

Two-part and gamma regression models of MEPS 2016-2021 data (all-payer cross-sectional US survey) estimated AF effect on healthcare expenditures.

Results

Of 248,067,064 adults, 1.4% had AF, with mean age 72.1 years and 45.7% female. Mean unadjusted annual expenditure was $25,451 ± $1,100 ($9,254 ± $82 without AF). Incremental adjusted annual expenditure attributable to AF was $6,188. Modified CCI of 1 or ≥2, uninsured status, cancer, poor income level, ASCVD, COPD, and later survey year were associated with higher expenditure.

Discussion

AF expenditures are substantial and increasing.
Integrating post-validation surveillance of lymphatic filariasis with the WHO STEPwise approach to non-communicable disease risk factor surveillance in Niue, a study protocol
Authors: Craig Adam T , Lawford Harriet , Mokoia Grizelda , Ikimau Minerva , Fetaui Peter , Marqardt Tonia , Lau Colleen L
Published: November 2024

Background

Lymphatic filariasis (LF),a mosquito-borne parasitic disease caused by three species of filarial worms, was first detected in Niue, a small Pacific Island nation of approximately 1,600 people, in 1954. After extensive efforts involving multiple rounds of Mass Drug Administration, Niue was validated by the World Health Organization (WHO) as having eliminated LF as a public health problem in 2016. However, no surveillance has been conducted since validation to confirm infection rates have remained below WHO’s elimination threshold. WHO has encouraged an integrated approach to disease surveillance; integrating LF post-validation surveillance (PVS) with existing surveys is an anticipated recommendation of the upcoming WHO LF-PVS guidelines. This paper describes a protocol for the implementation of an integrated approach to LF-PVS in Niue. We hypothesise that the approach describe here will offer a cost-efficient and operationally feasible means of monitoring the disease in the population.

Methods

The LF-PVS will be implemented as part of a planned national population-based WHO STEPwise approach to non-communicable disease (NCD) risk factor surveillance (STEPS) in Niue. Integration between the LF-PVS and STEPS will occur at multiple points, including during pre-survey community awareness raising and engagement, when obtaining informed consent, during the collection of demographics, risk factor, and location data, and when collecting finger-prick blood samples (for glucose as part of the STEPS survey and LF as part of the LF-PVS). The primary outcome measure for LF transmission will be antigen positivity. Microfilaria slides will be prepared for any antigen-positive cases. Dried blood spots will be prepared for all participants for Multiplex Bead Assays-based analysis to detect anti-filarial antibodies. We estimate a total sample size of 1,062 participants aged 15-69, representing approximately 66% of the population.

Conclusions

The results of this study will provide insight into the status of LF in Niue and evaluate the advantages, challenges, and opportunities offered by integrated approaches to disease surveillance.
Revolutionizing large-scale DNA synthesis with microchip-based massive in parallel synthesis system
Authors: Zhang Xiandi , Jiang Xianger , Wang Yun , Chen Qinzhen , Zhang Ruihong , Jiang Hao , Zhang Hu , Beltran Antoni , Yang Weiya , Liang Chenglong , Chen Ning , Huang Yun , Ding Guqiao , Xie Chengwang , Gao Nanfeng , Zheng Kaijing , Liu Juntao , Xu Wei , Huang Jinlei , Cai Dong , Zhu Lihao , Mo Songjin , Shen Mengzhe , Zhang Wenwei , Lehner Ben , Ni Ming , Wang Jian , Xu Xun , Shen Yue
Published: November 2024

DNA synthesis serves as the fundamental enabling technology of engineering biology, aiming to provide DNA molecules of designed composition, length, and complexity at scale and low cost. Current high-throughput DNA synthesis technologies rely on intricate chip manufacturing and microfluidic systems to provide large-scale synthetic oligonucleotides, at the expense of low concentration and limited compatibility in the processing of longer DNA constructs assembly. Here, we report a microchip-based massive in parallel synthesis (mMPS), pioneering an “identification-sorting-synthesis-recycling” iteration mechanism to microchips for high throughput DNA synthesis. In comparison to microarray-based methods, we demonstrate that our method can increase the DNA product concentration by 4 magnitudes (to picomole-scale per sequence) and greatly simplifies the downstream processes for large-scale gene synthesis construction. By the construction of 1.97 million-diversity variant libraries that cover 1,254 human protein domains, we demonstrated the uniformity of the constructed variant libraries using mMPS-derived oligos is greatly improved, with amino acid distribution highly consistent as designed. In addition, by synthesizing 285 1kb-to-3kb genes with varying degrees of sequence complexity from previously reported strains A501 and 3DAC, potential ancestor of early archaea and bacteria, our result shows that the overall gene assembly success rate using mMPS-derived oligos is increased by 10-fold in comparison to other methods. Our mMPS technology holds the potential to close the gap between the quality and cost of writing DNA in increasing demand across many sectors of research and industrial activities.
The mitochondrial-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age
Authors: Mitchell Wayne , Pharaoh Gavin , Tyshkovskiy Alexander , Campbell Matthew , Marcinek David J. , Gladyshev Vadim N.
Published: November 2024

Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondrial-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. ELAM is proposed to restore mitochondrial bioenergetic function by stabilizing inner membrane structure and increasing oxidative phosphorylation coupling and efficiency. Although ELAM treatment effectively attenuates physiological declines in multiple tissues in rodent aging models, it remains unclear whether these functional improvements correlate with favorable changes in molecular biomarkers of aging. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function, coupled with post-treatment assessments of biological age and affected molecular pathways. We found that health status, as measured by frailty index, cardiac strain, diastolic function, and skeletal muscle force are significantly diminished with age, with skeletal muscle force changing in a sex-dependent manner. Conversely, ELAM mitigated frailty accumulation and was able to partially reverse these declines, as evidenced by treatment-induced increases in cardiac strain and muscle fatigue resistance. Despite these improvements, we did not detect statistically significant changes in gene expression or DNA methylation profiles indicative of molecular reorganization or reduced biological age in most ELAM-treated groups. However, pathway analyses revealed that ELAM treatment showed pro-longevity shifts in gene expression such as upregulation of genes involved in fatty acid metabolism, mitochondrial translation and oxidative phosphorylation, and downregulation of inflammation. Together, these results indicate that ELAM treatment is effective at mitigating signs of sarcopenia and heart failure in an aging mouse model, but that these functional improvements occur independently of detectable changes in epigenetic and transcriptomic age. Thus, some age-related changes in function may be uncoupled from changes in molecular biological age.