Inherent stochasticity during insulator-metal transition in VO2.

Vanadium dioxide (VO2), which exhibits a near-room-temperature insulator-metal transition, has great potential in applications of neuromorphic computing devices. Although its volatile switching property, which could emulate neuron spiking, has been studied widely, nanoscale studies of the structural stochasticity across the phase transition are still lacking. In this study, using in situ transmission electron microscopy and ex situ resistive switching measurement, we successfully characterized the structural phase transition between monoclinic and rutile VO2 at local areas in planar VO2/TiO2 device configuration under external biasing. After each resistive switching, different VO2 monoclinic crystal orientations are observed, forming different equilibrium states. We have evaluated a statistical cycle-to-cycle variation, demonstrated a stochastic nature of the volatile resistive switching, and presented an approach to study in-plane structural anisotropy. Our microscopic studies move a big step forward toward understanding the volatile switching mechanisms and the related applications of VO2 as the key material of neuromorphic computing.

Identifying miRNA biomarkers for breast cancer and ovarian cancer: a text mining perspective.

BACKGROUND: microRNA (miRNAs) are small, non-coding RNAs that mediate post-transcriptional gene silencing. Numerous studies have demonstrated the critical role of miRNAs in the development of breast cancer and ovarian cancer. To reduce potential bias from individual studies, a more comprehensive approach of exploring miRNAs in cancer research is essential. This study aims to explore the role of miRNAs in the development of breast cancer and ovarian cancer. METHODS: Abstracts of the publications were tokenized and the biomedical terms (miRNA, gene, disease, species) were identified and extracted for vectorization. Predictive analyses were conducted with four machine learning models: K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Random Forest (RF), and Naïve Bayes. Both holdout validation and cross-validation were utilized. Feature importance will be identified for miRNA-cancer networks construction. RESULTS: We found that miR-182 is highly specific to female cancers. miR-182 targets different genes in regulating breast cancer and ovarian cancer. Naïve Bayes provided a promising prediction model for breast cancer and ovarian cancer with miRNAs and genes combination, with an accuracy score greater than 60%. Feature importance identified miR-155 and miR-199 are critical for breast cancer and ovarian cancer prediction, with miR-155 being highly related to breast cancer, whereas miR-199 being more associated with ovarian cancer. CONCLUSION: Our approach effectively identified potential miRNA biomarkers associated with breast cancer and ovarian cancer, providing a solid foundation for generating novel research hypotheses and guiding future experimental studies.

Development of Biodegradable Osteopromotive Citrate-Based Bone Putty.

The burden of bone fractures demands development of effective biomaterial solutions, while additional acute events such as noncompressible bleeding further motivate the search for multi-functional implants to avoid complications including osseous hemorrhage, infection, and nonunion. Bone wax has been widely used in orthopedic bleeding control due to its simplicity of use and conformation to irregular defects; however, its nondegradability results in impaired bone healing, risk of infection, and significant inflammatory responses. Herein, a class of intrinsically fluorescent, osteopromotive citrate-based polymer/hydroxyapatite (HA) composites (BPLP-Ser/HA) as a highly malleable press-fit putty is designed. BPLP-Ser/HA putty displays mechanics replicating early nonmineralized bone (initial moduli from ≈2-500 kPa), hydration induced mechanical strengthening in physiological conditions, tunable degradation rates (over 2 months), low swelling ratios (<10%), clotting and hemostatic sealing potential (resistant to blood pressure for >24 h) and significant adhesion to bone (≈350-550 kPa). Simultaneously, citrate's bioactive properties result in antimicrobial (≈100% and 55% inhibition of S. aureus and E. coli) and osteopromotive effects. Finally, BPLP-Ser/HA putty demonstrates in vivo regeneration in a critical-sized rat calvaria model equivalent to gold standard autograft. BPLP-Ser/HA putty represents a simple, off-the-shelf solution to the combined challenges of acute wound management and subsequent bone regeneration.

Screening of bimetallic electrocatalysts for water purification with machine learning.

Electrocatalysis provides a potential solution to NO3 - pollution in wastewater by converting it to innocuous N2 gas. However, materials with excellent catalytic activity are typically limited to expensive precious metals, hindering their commercial viability. In response to this challenge, we have conducted the most extensive computational search to date for electrocatalysts that can facilitate NO3 - reduction reaction, starting with 59 390 candidate bimetallic alloys from the Materials Project and Automatic-Flow databases. Using a joint machine learning- and computation-based screening strategy, we evaluated our candidates based on corrosion resistance, catalytic activity, N2 selectivity, cost, and the ability to synthesize. We found that only 20 materials will satisfy all criteria in our screening strategy, all of which contain varying amounts of Cu. Our proposed list of candidates is consistent with previous materials investigated in the literature, with the exception of Cu-Co and Cu-Ag based compounds that merit further investigation.

Insight into purification of monoclonal antibodies in industrial columns via studies of Protein A binding capacity by in situ ATR-FTIR spectroscopy.

Therapeutic monoclonal antibodies (mAbs) are effective treatments for a range of cancers and other serious diseases, however mAb treatments cost on average ∼$100 000 per year per patient, limiting their use. Currently, industry favours Protein A affinity chromatography (PrAc) as the key step in downstream processing of mAbs. This step, although highly efficient, represents a significant mAb production cost. Fouling of the Protein A column and Protein A ligand leaching contribute to the cost of mAb production by shortening the life span of the resin. In this study, we assessed the performance of used PrAc resin recovered from the middle inlet, center and outlet as well as the side inlet of a pilot-scale industrial column. We used a combination of static binding capacity (SBC) analysis and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy to explore the used resin samples. SBC analysis demonstrated that resin from the inlet of the column had lower binding capacity than resin from the column outlet. ATR-FTIR spectroscopy with PLS (partial least square) analysis confirmed the results obtained from SBC analysis. Importantly, in situ ATR-FTIR spectroscopy also allowed both measurement of the concentration and assessment of the conformational state of the bound Protein A. Our results reveal that PrAc resin degradation after use is dependent on column location and that neither Protein A ligand leaching nor denaturation are responsible for binding capacity loss.

The Effect of Cyclic Strain on Human Fibroblasts With Lamin A/C Mutations and Its Relation to Heart Disease.

Although mutations in the Lamin A/C gene (LMNA) cause a variety of devastating diseases, the pathological mechanism is often unknown. Lamin A/C proteins play a crucial role in forming a meshwork under the nuclear membrane, providing the nucleus with mechanical integrity and interacting with other proteins for gene regulation. Most LMNA mutations result in heart diseases, including some types that primarily have heart disease as the main pathology. In this study, we used cells from patients with different LMNA mutations that primarily lead to heart disease. Indeed, it is a mystery why a mutation to the protein in every nucleus of the body manifests as a disease of primarily the heart in these patients. Here, we aimed to investigate if strains mimicking those within the myocardial environment are sufficient to cause differences in cells with and without the LMNA mutation. To test this, a stretcher device was used to induce cyclic strain upon cells, and viability/proliferation, cytoskeleton and extracellular matrix organization, and nuclear morphology were quantified. The properties of cells with Hutchinson-Gilford progeria syndrome (HGPS) were found to be significantly different from all other cell lines and were mostly in line with previous findings. However, the properties of cells from patients who primarily had heart diseases were not drastically different when compared to individuals without the LMNA mutation. Our results indicated that cyclic strain alone was insufficient to cause any significant differences that could explain the mechanisms that lead to heart diseases in these patients with LMNA mutations.

Evaluation of Treatment-Dose Enoxaparin in Acutely Ill Morbidly Obese Patients at an Academic Medical Center: A Randomized Clinical Trial.

BACKGROUND: Enoxaparin dosing recommendations for morbidly obese patients are lacking. Retrospective and observational studies reported goal anti-Xa levels with a median dose of 0.8 mg/kg using total body weight. Further studies are needed to determine if a more conservative dosing strategy is warranted. OBJECTIVE: To determine if reduced dose enoxaparin was more effective than standard dose at achieving goal anti-Xa levels in morbidly obese patients. METHODS: A prospective, randomized, controlled study was conducted in patients with a body mass index (BMI) ≥40 kg/m2. Patients were randomized to standard (1 mg/kg) or reduced dose (0.8 mg/kg) enoxaparin every 12 hours. The primary outcome was the proportion of patients with an initial anti-Xa at goal (0.5-1.1 IU/mL). RESULTS: A total of 62 patients were enrolled and randomized to 1 mg/kg (n = 32) or 0.8 mg/kg (n = 30), and 54 patients completed the study. The study did not meet accrual for 80% power. Goal anti-Xa levels were achieved in a similar proportion for the reduced-dose (n = 25/28) and standard dose arms (n = 20/26; 89.3% vs 76.9%; P = 0.29). Overall, 9 patients required dose adjustments, of which 6 were in the 1-mg/kg arm, and all were above goal. No documented bleeding or thrombotic events were reported. CONCLUSIONS AND RELEVANCE: This was the first randomized, controlled trial of enoxaparin dosing in patients with a BMI ≥40 kg/m2. Overall, 89% of patients had a goal anti-Xa when initiated on 0.8 mg/kg. Based on the results, reduced dose enoxaparin may be a reasonable dosing strategy in morbidly obese patients.

Isotype dependent on-column non-reversible aggregation of monoclonal antibodies.

Monoclonal antibodies of the IgG2 and IgG4 isotype were found to exhibit an increased propensity for displaying two-peak elution profiles during cation exchange chromatography. In some cases, this two-peak elution profile also resulted in the formation of non-reversible mAb aggregates. Comparison of IgG1, IgG2, and IgG4 molecules with the same variable region reveals that the two-peak behaviour is predominantly mediated by the constant region and most likely the lower CH1, hinge and upper CH2 regions of the mAb. Furthermore, comparison of the behaviour of two different IgG4 molecules, reveals that the degree of non-reversible aggregate formation, whilst facilitated by the isotype format, is mediated primarily by the variable region of the molecule. As well as the properties of the mAb molecule itself, the chemistry and structure of the cation exchange resin was also found to have an effect, with the two-peak elution profile being more pronounced with polymer-grafted resins such as Capto S Impact and Eshmuno CPX. These results combined support the theory that binding of IgG2 and IgG4 mAbs to cation exchange resins usually occurs through at least two mechanisms mediated by the structural features of the constant region of IgG2s and IgG4s. One of these mechanisms is not only stronger than the other, but also can lead to a conformational change in the molecule. This conformational change can occur in both variable and constant domains of the antibody. This transitory unfolded state can in turn lead to non-reversible aggregation of some mAb molecules.

A case-control study of the risk factors for developing aspergillosis following cardiac transplant.

BACKGROUND: Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following cardiac transplantation; however, data regarding the predictors of IA in this patient population are limited. METHODS: We conducted a case-control study to identify the risk factors for IA in patients who underwent cardiac transplantation at a single center from 1986 to 2008 (Cohort 1) and 2009 to 2015 (Cohort 2). Cases of IA were matched to two controls from the same year of transplantation, and data were collected from the date of cardiac transplantation to the date of documented Aspergillus infection for each case, or for an equivalent number of days for each control. Univariate and multivariate logistic regressions were used to identify independent predictors of IA in Cohort 1. After 2009, targeted antifungal prophylaxis with oral voriconazole was initiated in patients with risk factors for IA. The incidence of IA was compared pre- and postintervention. RESULTS: IA was identified in 23 of 189 (8.0%) patients within Cohort 1. Significant risk factors for IA on multivariate analysis included an increased number of pretransplant hospitalizations (OR 1.81, 95% CI 1.19-2.76) and posttransplant acute cellular allograft rejection (ACR) (OR 1.99, 95% 1.06-3.75). Following the implementation of targeted antifungal prophylaxis in 2009, IA was identified in 2 of 107 (2.0%) patients in Cohort 2. CONCLUSIONS: Increased pretransplant hospitalizations and posttransplant ACR episodes represent significant risk factors for IA following cardiac transplant. Targeted antifungal prophylaxis in at-risk patients reduces the incidence of IA.

A Comparison of Self-reported Medication Adherence to Concordance Between Part D Claims and Medication Possession.

OBJECTIVE: Medicare Part D claims indicate medication purchased, but people who are not fully adherent may extend prescription use beyond the interval prescribed. This study assessed concordance between Part D claims and medication possession at a study visit in relation to self-reported medication adherence. MATERIALS AND METHODS: We matched Part D claims for 6 common medications to medications brought to a study visit in 2011-2013 for the Atherosclerosis Risk in Communities study. The combined data consisted of 3027 medication events (claims, medications possessed, or both) for 2099 Atherosclerosis Risk in Communities study participants. Multinomial logistic regression estimated the association of concordance (visit only, Part D only, or both) with self-reported medication adherence while controlling for sociodemographic characteristics, veteran status, and availability under Generic Drug Discount Programs. RESULTS: Relative to participants with high adherence, medication events for participants with low adherence were approximately 25 percentage points less likely to match and more likely to be visit only (P<0.001). The results were similar but smaller in magnitude (approximately 2-3 percentage points) for participants with medium adherence. Compared with females, medication events for male veterans were approximately 11 percentage points less likely to match and more likely to be visit only. Events for medications available through Generic Drug Discount Programs were 3 percentage points more likely to be visit only. CONCLUSIONS: Part D claims were substantially less likely to be concordant with medications possessed at study visit for participants with low self-reported adherence. This result supports the construction of adherence proxies such as proportion days covered using Part D claims.

Tuberculosis care among refugees arriving in Europe: a ERS/WHO Europe Region survey of current practices.

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries.A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European Region.Out of 36 responding countries, 31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%) reporting outcomes of LTBI treatment. Screening for TB is based on algorithms including different combinations of symptom-based questionnaires, bacteriology and chest radiography and LTBI screening on different combinations of tuberculin skin test and interferon-γ release assays. In 22 (61.1%) countries, TB and LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB services are organised in collaboration with the private sector. 27 (75%) countries answered that screening for TB is performed as per national and international guidelines, while 19 (52.7%) gave the same answer with regards to LTBI screening. Infection control measures are inadequate in several of the countries surveyed.There is need for improved coordination of TB screening in Europe to implement the End TB Strategy and achieve TB elimination.

The barriers and facilitators to the design and delivery of sustainable healthcare across NHS Scotland: A forcefield analysis.

Healthcare systems around the world have set ambitious targets to design and deliver more environmentally sustainable healthcare. To achieve these targets, individuals, teams, organisations, and whole systems will have to change current attitudes, practices and processes. Change management theory advocates for early identification of the influencing forces to change, so that actions can be taken to overcome the barriers and strengthen the facilitators to increase the likelihood of success. This project undertook a forcefield analysis exercise to identify the barriers and facilitators to the design and delivery of sustainable healthcare in Scotland. The exercise identified 12 facilitators and 12 barriers to sustainable change and formulated ten recommendations to strengthen the former and overcome the latter. It is hoped that the results will raise awareness of the factors that influence the design and delivery of sustainable healthcare and will inform what actions can be taken to increase the likelihood of success.

The Association Between Well-Being and Empathy in Medical Residents: A Cross-Sectional Survey.

Objective: To evaluate the extent to which personal well-being may be associated with empathy, while controlling for potential confounders. Settings/Location: Residency programs throughout the United States. Subjects: A total of 407 medical residents from residencies including general medicine, surgery, specialized and diagnostic medicine participated in this study. Outcome Measures: Well-being was measured using the modified existential well-being subscale of the spiritual well-being scale. Empathy was measured using the Jefferson Scale of Empathy. Results: Well-being was found to be positively correlated with empathy when adjusted for possible confounders (p < 0.001). In addition to well-being, other factors noted to be statistically significant contributors to higher empathy scores while controlling for the others included age, gender, year in residency, specialty, and work-hours (p < 0.05 for each). After controlling for these factors, a resident's year in residency was not found to be a statistically significant contributor to empathy score. Conclusions: In this study, well-being was associated with empathy in medical and surgical residents. Empathy is a fundamental component of physician competency, and its development is an essential aspect of medical training. These findings suggest that efforts to increase well-being may promote empathy among medical residents.

Rational design of nanoscale stabilized oxide catalysts for OER with OC22.

The efficiency of H2 production via water electrolysis is limited by the sluggish oxygen evolution reaction (OER). As such, significant emphasis has been placed upon improving the rate of OER through the anode catalyst. More recently, the Open Catalyst 2022 (OC22) framework has provided a large dataset of density functional theory (DFT) calculations for OER intermediates on the surfaces of oxides. When coupled with state-of-the-art graph neural network models, total energy predictions can be achieved with a mean absolute error as low as 0.22 eV. In this work, we interpolated a database of the total energy predictions for all slabs and OER surface intermediates for 4119 oxide materials in the original OC22 dataset using pre-trained models from the OC22 framework. This database includes all terminations of all facets up to a maximum Miller index of 1. To demonstrate the full utility of this database, we constructed a flexible screening framework to identify viable candidate anode catalysts for OER under varying reaction conditions for bulk, surface, and nanoscale Pourbaix stability as well as material cost, overpotential, and metastability. From our assessment, we were able to identify 122 and 68 viable candidates for OER under the bulk and nanoscale regime, respectively.

Comparable safety and non-inferior immunogenicity of the SARS-CoV-2 mRNA vaccine candidate PTX-COVID19-B and BNT162b2 in a phase 2 randomized, observer-blinded study.

In the aftermath of the COVID-19 pandemic, the evolution of the SARS-CoV-2 into a seasonal pathogen along with the emergence of new variants, underscores the need for dynamic and adaptable responses, emphasizing the importance of sustained vaccination strategies. This observer-blind, double-dummy, randomized immunobridging phase 2 study (NCT05175742) aimed to compare the immunogenicity induced by two doses of 40 µg PTX-COVID19-B vaccine candidate administered 28 days apart, with the response induced by two doses of 30 µg Pfizer-BioNTech COVID-19 vaccine (BNT162b2), administered 21 days apart, in Nucleocapsid-protein seronegative adults 18-64 years of age. Both vaccines were administrated via intramuscular injection in the deltoid muscle. Two weeks after the second dose, the neutralizing antibody (NAb) geometric mean titer ratio and seroconversion rate met the non-inferiority criteria, successfully achieving the primary immunogenicity endpoints of the study. PTX-COVID19-B demonstrated similar safety and tolerability profile to BNT162b2 vaccine. The lowest NAb response was observed in subjects with low-to-undetectable NAb at baseline or no reported breakthrough infection. Conversely, participants who experienced breakthrough infections during the study exhibited higher NAb titers. This study also shows induction of cell-mediated immune (CMI) responses by PTX-COVID19-B. In conclusion, the vaccine candidate PTX-COVID19-B demonstrated favourable safety profile along with immunogenicity similar to the active comparator BNT162b2 vaccine.

CT imaging-derived phenotypes for abdominal muscle and their association with age and sex in a medical biobank.

The study of muscle mass as an imaging-derived phenotype (IDP) may yield new insights into determining the normal and pathologic variations in muscle mass in the population. This can be done by determining 3D abdominal muscle mass from 12 distinct abdominal muscle regions and groups using computed tomography (CT) in a racially diverse medical biobank. To develop a fully automatic technique for assessment of CT abdominal muscle IDPs and preliminarily determine abdominal muscle IDP variations with age and sex in a clinically and racially diverse medical biobank. This retrospective study was conducted using the Penn Medicine BioBank (PMBB), a research protocol that recruits adult participants during outpatient visits at hospitals in the Penn Medicine network. We developed a deep residual U-Net (ResUNet) to segment 12 abdominal muscle groups including the left and right psoas, quadratus lumborum, erector spinae, gluteus medius, rectus abdominis, and lateral abdominals. 110 CT studies were randomly selected for training, validation, and testing. 44 of the 110 CT studies were selected to enrich the dataset with representative cases of intra-abdominal and abdominal wall pathology. The studies were divided into non-overlapping training, validation and testing sets. Model performance was evaluated using the Sørensen-Dice coefficient. Volumes of individual muscle groups were plotted to distribution curves. To investigate associations between muscle IDPs, age, and sex, deep learning model segmentations were performed on a larger abdominal CT dataset from PMBB consisting of 295 studies. Multivariable models were used to determine relationships between muscle mass, age and sex. The model's performance (Dice scores) on the test data was the following: psoas: 0.85 ± 0.12, quadratus lumborum: 0.72 ± 0.14, erector spinae: 0.92 ± 0.07, gluteus medius: 0.90 ± 0.08, rectus abdominis: 0.85 ± 0.08, lateral abdominals: 0.85 ± 0.09. The average Dice score across all muscle groups was 0.86 ± 0.11. Average total muscle mass for females was 2041 ± 560.7 g with a high of 2256 ± 560.1 g (41-50 year old cohort) and a change of - 0.96 g/year, declining to an average mass of 1579 ± 408.8 g (81-100 year old cohort). Average total muscle mass for males was 3086 ± 769.1 g with a high of 3385 ± 819.3 g (51-60 year old cohort) and a change of - 1.73 g/year, declining to an average mass of 2629 ± 536.7 g (81-100 year old cohort). Quadratus lumborum was most highly correlated with age for both sexes (correlation coefficient of - 0.5). Gluteus medius mass in females was positively correlated with age with a coefficient of 0.22. These preliminary findings show that our CNN can automate detailed abdominal muscle volume measurement. Unlike prior efforts, this technique provides 3D muscle segmentations of individual muscles. This technique will dramatically impact sarcopenia diagnosis and research, elucidating its clinical and public health implications. Our results suggest a peak age range for muscle mass and an expected rate of decline, both of which vary between genders. Future goals are to investigate genetic variants for sarcopenia and malnutrition, while describing genotype-phenotype associations of muscle mass in healthy humans using imaging-derived phenotypes. It is feasible to obtain 3D abdominal muscle IDPs with high accuracy from patients in a medical biobank using fully automated machine learning methods. Abdominal muscle IDPs showed significant variations in lean mass by age and sex. In the future, this tool can be leveraged to perform a genome-wide association study across the medical biobank and determine genetic variants associated with early or accelerated muscle wasting.

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

Dihaloiodoarenes: α,α-dihalogenation of phenylacetate derivatives.

A hypervalent iodine reagent-based α-carbonyl dihalogenation reaction is reported. Treating diazoacetate derivatives with either iodobenzene dichloride or iodotoluene difluoride results in gem-dichlorination or gem-difluorination products, respectively. The reaction is catalyzed by either Lewis acid or Lewis base activation of the aryl-λ(3)-iodane (ArIX2) species and proceeds rapidly and chemoselectively to the desired gem-difunctionalized products in good to excellent yield.

Text mining-based identification of promising miRNA biomarkers for diabetes mellitus.

Introduction: MicroRNAs (miRNAs) are small, non-coding RNAs that play a critical role in diabetes development. While individual studies investigating the mechanisms of miRNA in diabetes provide valuable insights, their narrow focus limits their ability to provide a comprehensive understanding of miRNAs' role in diabetes pathogenesis and complications. Methods: To reduce potential bias from individual studies, we employed a text mining-based approach to identify the role of miRNAs in diabetes and their potential as biomarker candidates. Abstracts of publications were tokenized, and biomedical terms were extracted for topic modeling. Four machine learning algorithms, including Naïve Bayes, Decision Tree, Random Forest, and Support Vector Machines (SVM), were employed for diabetes classification. Feature importance was assessed to construct miRNA-diabetes networks. Results: Our analysis identified 13 distinct topics of miRNA studies in the context of diabetes, and miRNAs exhibited a topic-specific pattern. SVM achieved a promising prediction for diabetes with an accuracy score greater than 60%. Notably, miR-146 emerged as one of the critical biomarkers for diabetes prediction, targeting multiple genes and signal pathways implicated in diabetic inflammation and neuropathy. Conclusion: This comprehensive approach yields generalizable insights into the network miRNAs-diabetes network and supports miRNAs' potential as a biomarker for diabetes.

Longitudinal Cadaver-Based Training Curriculum for Musculoskeletal Ultrasound-Guided Procedures Among Physical Medicine and Rehabilitation Residents.

ABSTRACT: Musculoskeletal ultrasound has become a fundamental diagnostic and treatment tool in the field of physical medicine and rehabilitation. However, there is no standardized curriculum for teaching and practicing musculoskeletal ultrasound during physical medicine and rehabilitation residency. The objective of this study was to describe a longitudinal curriculum using unembalmed fresh frozen cadavers to teach physical medicine and rehabilitation residents ultrasound-guided procedures. This protocol can help guide residents to begin learning how to independently identify important musculoskeletal structures and perform some of the most common musculoskeletal procedures relevant to clinical practice. Residents performed a procedure on average 6.99 times per block, and residents' self-reported confidence in various aspects of ultrasound practice significantly improved after this curriculum ( P < 0.005). Hence, a cadaver-based training curriculum may be a worthwhile tool for preparing physical medicine and rehabilitation residents to perform musculoskeletal ultrasound-guided procedures in the clinical setting.