Data quality and timeliness analysis for post-vaccination adverse event cases reported through healthcare data exchange to FDA BEST pilot platform.

Introduction: This study is part of the U.S. Food and Drug Administration (FDA)'s Biologics Effectiveness and Safety (BEST) initiative, which aims to improve the FDA's postmarket surveillance capabilities by using real-world data (RWD). In the United States, using RWD for postmarket surveillance has been hindered by the inability to exchange clinical data between healthcare providers and public health organizations in an interoperable format. However, the Office of the National Coordinator for Health Information Technology (ONC) has recently enacted regulation requiring all healthcare providers to support seamless access, exchange, and use of electronic health information through the interoperable HL7 Fast Healthcare Interoperability Resources (FHIR) standard. To leverage the recent ONC changes, BEST designed a pilot platform to query and receive the clinical information necessary to analyze suspected AEs. This study assessed the feasibility of using the RWD received through the data exchange of FHIR resources to study post-vaccination AE cases by evaluating the data volume, query response time, and data quality. Materials and methods: The study used RWD from 283 post-vaccination AE cases, which were received through the platform. We used descriptive statistics to report results and apply 322 data quality tests based on a data quality framework for EHR. Results: The volume analysis indicated the average clinical resources for a post-vaccination AE case was 983.9 for the median partner. The query response time analysis indicated that cases could be received by the platform at a median of 3 min and 30 s. The quality analysis indicated that most of the data elements and conformance requirements useful for postmarket surveillance were met. Discussion: This study describes the platform's data volume, data query response time, and data quality results from the queried postvaccination adverse event cases and identified updates to current standards to close data quality gaps.

Intralobar bronchopulmonary sequestration in an adult: a case report.

Introduction: Bronchopulmonary sequestration (BPS) is typically a rare congenital disorder characterized by the presence of non-functioning lung tissue. There are two types of BPS: intralobar and extralobar sequestration, where extralobar sequestration can either be intrathoracic or sub-diaphragmatic. Case presentation: In this case report, we present the case of a 70-year-old male with intralobar BPS who presented with recurrent chest infections, and a diagnosis of intralobar pulmonary sequestration was made based on a computed tomography (CT) scan. Discussion: The diagnosis of intralobar pulmonary sequestration can be delayed as the intralobar type can present with varying imaging findings. A diagnosis can be made based on CT or MRI findings. A CT scan or MRI can show mass or consolidation with or without a cyst. Both CT and MRI can be reliable modalities to identify the arterial supply of the sequestered lung tissue, which is commonly a branch of the descending aorta. Conclusion: Sequestration should be suspected when a posterobasal lung abnormality is supplied by an abnormal artery from the aorta or another systemic artery.

Hirayama disease successfully treated by posterior fixation: a case report.

Introduction and importance: Hirayama disease is a rare form of motor neuron amyotrophy that usually presents with weakness and atrophy of the distal upper extremities in young males. It is believed that it is caused by spinal cord compression during neck flexion because of the widening of the posterior extradural space. This case has been brought to attention due to its extraordinary rarity, serving as an educational tool for medical professionals and to advocate for surgical intervention when deemed necessary. Case presentation: The authors present a case of a young male in his 20s who was diagnosed with Hirayama disease, had weakness and atrophy in both of his upper limbs, and has been successfully treated by posterior fixation at C4, C5, and C6 with lateral mass screws. Clinical discussion: The majority of cases stabilize after 2-3 years of progression; therefore, cervical collars are generally sufficient for therapy. However, in certain serious cases with progression even after that time, surgical intervention is an option. Because this is such an uncommon incidence, surgical therapy has not been explored and is controversial. Conclusion: The use of posterior fixation at C4, C5, and C6 with lateral mass screws as a therapy for Hirayama disease may be regarded as a successful approach.

Multi-GWAS reveals significant genomic regions for Mungbean yellow mosaic India virus resistance in urdbean (Vigna mungo (L.) across multiple environments.

KEY MESSAGE: Unraveling genetic markers for MYMIV resistance in urdbean, with 8 high-confidence marker-trait associations identified across diverse environments, provides crucial insights for combating MYMIV disease, informing future breeding strategies. Globally, yellow mosaic disease (YMD) causes significant yield losses, reaching up to 100% in favorable environments within major urdbean cultivating regions. The introgression of genomic regions conferring resistance into urdbean cultivars is crucial for combating YMD, including resistance against mungbean yellow mosaic India virus (MYMIV). To uncover the genetic basis of MYMIV resistance, we conducted a genome-wide association study (GWAS) using three multi-locus models in 100 diverse urdbean genotypes cultivated across six individual and two combined environments. Leveraging 4538 high-quality single nucleotide polymorphism (SNP) markers, we identified 28 unique significant marker-trait associations (MTAs) for MYMIV resistance, with 8 MTAs considered of high confidence due to detection across multiple GWAS models and/or environments. Notably, 4 out of 28 MTAs were found in proximity to previously reported genomic regions associated with MYMIV resistance in urdbean and mungbean, strengthening our findings and indicating consistent genomic regions for MYMIV resistance. Among the eight highly significant MTAs, one localized on chromosome 6 adjacent to previously identified quantitative trait loci for MYMIV resistance, while the remaining seven were novel. These MTAs contain several genes implicated in disease resistance, including four common ones consistently found across all eight MTAs: receptor-like serine-threonine kinases, E3 ubiquitin-protein ligase, pentatricopeptide repeat, and ankyrin repeats. Previous studies have linked these genes to defense against viral infections across different crops, suggesting their potential for further basic research involving cloning and utilization in breeding programs. This study represents the first GWAS investigation aimed at identifying resistance against MYMIV in urdbean germplasm.

Time-in-Range With Insulin Versus Metformin in Gestational Diabetes Mellitus Using Continuous Glucose Monitoring: A Randomized Control Study at a Tertiary Care Centre in South India.

Background The prevalence of gestational diabetes mellitus (GDM) is increasing globally. When diet and lifestyle modifications are inadequate for control, managing GDM often involves insulin or metformin. Metformin's oral administration option improves patient compliance and acceptance, but concerns about its use persist, necessitating careful evaluation. Comparative studies between insulin and metformin in GDM are scarce. In pregnancies complicated by diabetes, precise glucose control is crucial for maternal-fetal well-being, and continuous glucose monitoring (CGM) plays a valuable role in achieving recommended targets. CGM provides comprehensive glucose profiles, including postprandial glucose excursions and details about time spent in hypoglycemia, euglycemia, and hyperglycemia. The time-in-range (TIR) metric, when used alongside A1C, offers more actionable information than A1C alone. To the best of our knowledge, no published trials compare TIR in GDM with metformin or insulin aspart/detemir, specifically focusing on CGM metrics. This randomized controlled trial (RCT) aims to assess TIR in women with GDM treated with either metformin or insulin. Materials and methods This study was a non-inferiority randomized control trial evaluating TIR in GDM using continuous glucose monitoring with metformin or insulin. Forty-four women with GDM were enrolled. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. CGM readings were collected for 14 days after sensor activation. Results In our study, 44 women with GDM completed the protocol, with 22 in the Metformin group and 22 in the Insulin group. Baseline characteristics did not differ between the groups. Age, BMI pre-gravid, BMI at 28 weeks, parity, family history of diabetes mellitus, previous history of GDM, glycated hemoglobin (HbA1c), oral glucose tolerance tests (OGTT) at zero hours, one hour, and two hours, as well as gestational weeks, did not significantly differ between the two groups. The metformin and insulin groups did not differ significantly in CGM metrics, including TIR, time above range, time below range, mean glucose, and glucose management indicator. Conclusion Based on our findings, the metformin and insulin groups did not differ in CGM metrics, including TIR, time above range, time below range, mean glucose, and glucose management indicator. In clinical practice, CGM metrics complement fasting blood glucose, postprandial glucose, and HbA1c as appropriate and useful clinical targets and outcome measurements. Metformin's oral administration option offers advantages such as improved patient compliance and acceptance in women with GDM.

Incorporating Synthetic Accessibility in Drug Design: Predicting Reaction Yields of Suzuki Cross-Couplings by Leveraging AbbVie's 15-Year Parallel Library Data Set.

Despite the increased use of computational tools to supplement medicinal chemists' expertise and intuition in drug design, predicting synthetic yields in medicinal chemistry endeavors remains an unsolved challenge. Existing design workflows could profoundly benefit from reaction yield prediction, as precious material waste could be reduced, and a greater number of relevant compounds could be delivered to advance the design, make, test, analyze (DMTA) cycle. In this work, we detail the evaluation of AbbVie's medicinal chemistry library data set to build machine learning models for the prediction of Suzuki coupling reaction yields. The combination of density functional theory (DFT)-derived features and Morgan fingerprints was identified to perform better than one-hot encoded baseline modeling, furnishing encouraging results. Overall, we observe modest generalization to unseen reactant structures within the 15-year retrospective library data set. Additionally, we compare predictions made by the model to those made by expert medicinal chemists, finding that the model can often predict both reaction success and reaction yields with greater accuracy. Finally, we demonstrate the application of this approach to suggest structurally and electronically similar building blocks to replace those predicted or observed to be unsuccessful prior to or after synthesis, respectively. The yield prediction model was used to select similar monomers predicted to have higher yields, resulting in greater synthesis efficiency of relevant drug-like molecules.

Mortality and morbidity ramifications of proposed retractions in healthcare coverage for the United States.

In the absence of universal healthcare in the United States, federal programs of Medicaid and Medicare are vital to providing healthcare coverage for low-income households and elderly individuals, respectively. However, both programs are under threat, with either enacted or proposed retractions. Specifically, raising Medicare age eligibility and the addition of work requirements for Medicaid qualification have been proposed, while termination of continuous enrollment for Medicaid was recently effectuated. Here, we assess the potential impact on mortality and morbidity resulting from these policy changes. Our findings indicate that the policy change to Medicare would lead to over 17,000 additional deaths among individuals aged 65 to 67 and those to Medicaid would lead to more than 8,000 deaths among those under the age of 65. To illustrate the implications for morbidity, we further consider a case study among those people with diabetes who would be likely to lose their health insurance under the policy changes. We project that these insurance retractions would lead to the loss of coverage for over 700,000 individuals with diabetes, including more than 200,000 who rely on insulin.

Evaluation of Strategies for Transitioning to Annual SARS-CoV-2 Vaccination Campaigns in the United States.

BACKGROUND: The U.S. Food and Drug Administration has proposed administering annual SARS-CoV-2 vaccines. OBJECTIVE: To evaluate the effectiveness of an annual SARS-CoV-2 vaccination campaign, quantify the health and economic benefits of a second dose provided to children younger than 2 years and adults aged 50 years or older, and optimize the timing of a second dose. DESIGN: An age-structured dynamic transmission model. SETTING: United States. PARTICIPANTS: A synthetic population reflecting demographics and contact patterns in the United States. INTERVENTION: Vaccination against SARS-CoV-2 with age-specific uptake similar to that of influenza vaccination. MEASUREMENTS: Incidence, hospitalizations, deaths, and direct health care cost. RESULTS: The optimal timing between the first and second dose delivered to children younger than 2 years and adults aged 50 years or older in an annual vaccination campaign was estimated to be 5 months. In direct comparison with a single-dose campaign, a second booster dose results in 123 869 fewer hospitalizations (95% uncertainty interval [UI], 121 994 to 125 742 fewer hospitalizations) and 5524 fewer deaths (95% UI, 5434 to 5613 fewer deaths), averting $3.63 billion (95% UI, $3.57 billion to $3.69 billion) in costs over a single year. LIMITATIONS: Population immunity is subject to degrees of immune evasion for emerging SARS-CoV-2 variants. The model was implemented in the absence of nonpharmaceutical interventions and preexisting vaccine-acquired immunity. CONCLUSION: The direct health care costs of SARS-CoV-2, particularly among adults aged 50 years or older, would be substantially reduced by administering a second dose 5 months after the initial dose. PRIMARY FUNDING SOURCE: Natural Sciences and Engineering Research Council of Canada, Notsew Orm Sands Foundation, National Institutes of Health, Centers for Disease Control and Prevention, and National Science Foundation.

An agent-based framework to study forced migration: A case study of Ukraine.

The ongoing Russian aggression against Ukraine has forced over eight million people to migrate out of Ukraine. Understanding the dynamics of forced migration is essential for policy-making and for delivering humanitarian assistance. Existing work is hindered by a reliance on observational data which is only available well after the fact. In this work, we study the efficacy of a data-driven agent-based framework motivated by social and behavioral theory in predicting outflow of migrants as a result of conflict events during the initial phase of the Ukraine war. We discuss policy use cases for the proposed framework by demonstrating how it can leverage refugee demographic details to answer pressing policy questions. We also show how to incorporate conflict forecast scenarios to predict future conflict-induced migration flows. Detailed future migration estimates across various conflict scenarios can both help to reduce policymaker uncertainty and improve allocation and staging of limited humanitarian resources in crisis settings.

A rare case report of coexisting rheumatic heart disease and systemic lupus erythematous.

This case report discusses the rare coexistence of Systemic Lupus Erythematosus (SLE) and Rheumatic Heart Disease (RHD) in a 46-year-old female patient, challenging the conventional understanding of their distinct presentations. The patient exhibited migratory joint pains, palpitations, and shortness of breath. Diagnostic investigations confirmed SLE based on EULAR/ACR criteria, with positive anti-nuclear and anti-dsDNA antibodies. Concurrently, transthoracic echocardiography revealed severe mitral stenosis and regurgitation, leading to the diagnosis of RHD. The patient underwent successful open-heart surgery with mitral valve replacement. The discussion explores the rarity of this coexistence, emphasizing the need for cautious consideration and further research into potential immunological overlaps between SLE and RHD. The report concludes with a call for comprehensive studies to enhance our understanding of the pathophysiology connecting these two conditions.

Pelvic lymph node dissection before or after laparoscopic radical cystectomy: An ambispective study comparing ease of surgery and operative outcomes.

Introduction: It is unclear when pelvic lymph node dissection (PLND) should be performed during laparoscopic radical cystectomy. Proponents of PLND performed before cystectomy claim that early PLND skeletonizes the urinary bladder's vascular pedicles, making cystectomy easy. Others contend that an early cystectomy provides space and flexibility during subsequent PLND. This first-of-its-kind study compared PLND before and after cystectomy for the ease of performing surgery (total operative time, cystectomy time, and PLND time) and the operative outcomes (number of lymph nodes removed, blood loss, and complication rates). Methods: This ambispective cohort study included a predetermined sample size of 44 patients. The first 22 patients underwent PLND after cystectomy (Group 1), and the following 22 underwent PLND before cystectomy (Group 2). The primary outcome was total operative time. Secondary outcomes included cystectomy time, PLND time, number of lymph nodes removed, blood loss, and complication rates. Results: The baseline characteristics were similar in both groups. The total operative time (344.23 ± 41.58 min vs. 326.95 ± 43.63 min, P = 0.19), cystectomy time (119.36 ± 34.44 min vs. 120.91 ± 35.16 min, P = 0.53), PLND time (126.82 ± 18.75 min vs. 119.36 ± 23.34 min, 0.25), number of dissected lymph nodes (13.27 ± 4.86 vs. 14.5 ± 4.76, P = 0.40), and blood loss (620.45 ± 96.23 ml vs. 642.27 ± 131.8 ml, P = 0.20) were similar in the two groups. The complication rates categorized by Clavien-Dindo grading were identical in the two groups. Conclusions: PLND done after cystectomy was comparable to PLND done before cystectomy regarding the ease of surgery and the operative outcomes.

Laparoscopic Radical Nephrectomy in the Current Era: Technical Difficulties, Troubleshoots, a Guide to the Apprentice, and the Current Learning Curve.

Abhishek Pandey, MSObjectives The main aim of this study is to present our experience with laparoscopic radical nephrectomy (LRN) and share practical solutions to various surgical challenges and the learning curve we realized. Materials and Methods We retrospectively analyzed our LRN database for relevant demographic, clinical, imaging, operative, and postoperative data, including operative videos. We described various complications, vascular anomalies, intraoperative difficulties, and our improvisations to improve safety and outcomes. Statistical Analysis We evaluated the learning curve, comparing the initial half cases (group 1) against the latter half (group 2), using the chi-squared test for categorical variables and Student's t -test for continuous variables. Results Of the 106 patients included, LRN was successful in 95% ( n = 101), and five cases converted to open surgical approach. The mean tumor size was 7.4 cm, 42% incidentally detected. The cumulative complication rate was 15%, including five main renal vein injuries. Intraoperative difficulties included ureter identification ( n = 6), venous bleed during hilar dissection ( n = 11), double renal arteries ( n = 23), and venous anomalies ( n = 20). Arterial anatomy had 95% concordance with the imaging findings. We describe various trade tricks to perform hilar dissection, identify and control anomalous vasculature, handle venous bleed, confirm arterial control, and improve decisions using imaging, technology, and guidance of a mentor. No statistically significant difference in the learning curve was observed between the study groups. Conclusion With LRN already established as the current standard of care, our description intends to share the trade tricks and inspire novice urologists, who can assimilate training and reproduce good results under proper guidance. The steep learning curve described in the past may not be apparent in the current era of training and technological advancement.

Sacral agenesis without maternal diabetes: a case report.

Introduction: Sacral agenesis is a rare congenital condition that is characterized by sacrococcygeal bone agenesis. It is associated with spinal cord anomalies as well as problems with the genitourinary system, large bowel, and lower extremities. Fetal ultrasound allows for diagnosis even before birth. Case presentation: The authors present the case of a 1-year-old girl with sacral agenesis type III and bilateral congenital talipes equinovarus with spina bifida who was born to a nondiabetic mother and had a normal anomaly scan. Clinical discussion: People with less severe forms of sacral agenesis can live a normal life, and it is not connected with cognitive impairment; however, concomitant bladder, colon, and lower limb disorders cause considerable morbidity. The majority of treatment is supportive, frequently requiring orthopedic, urological, gastroenterological, pediatric, and physiotherapy support. Conclusion: Genetic and prepregnancy counseling, as well as early screening of high-risk mothers, remain the only options for prevention of the disease since treatment is mostly supportive.

Lipoma of the middle finger in an elderly male: A case report.

INTRODUCTION AND IMPORTANCE: Lipomas are common benign tumors originating from adipocytes, often found in adipose-rich regions of the body. Lipomas in the fingers are rare, and their occurrence in acral areas is even more exceptional. We present a case of an elderly male with a lipoma on the middle finger of his left hand, highlighting the rarity of this presentation and the importance of surgical management. CASE PRESENTATION: A 70-year-old male presented with a painless swelling on the palmar aspect of his left middle finger. The mass had gradually enlarged over two years, without associated symptoms. Physical examination revealed a soft, painless mass between the proximal and distal interphalangeal joints, with intact finger function. Surgical excision was performed successfully, and histopathological examination confirmed the diagnosis of a benign lipoma. CLINICAL DISCUSSION: Lipomas are most commonly found in adipose-rich areas but rarely manifest in the fingers. Surgical intervention is considered when symptoms arise or for cosmetic reasons. In this case, the patient's desire for symptom relief and the potential for compression-related issues justified surgical excision. Surgical management of finger lipomas has shown positive outcomes with minimal complications and low recurrence rates. CONCLUSION: This case emphasizes the importance of considering lipomas in the differential diagnosis of painless finger swellings, even in atypical locations. Surgical intervention can provide effective symptom relief and prevent potential complications. While this case contributes to our understanding of finger lipomas, further research and long-term follow-up are needed to enhance our knowledge of these rare occurrences and their management.

Intergenic spacer (IGS-1) region sequence-based identification, genotypic analysis, and antifungal susceptibility of clinical Trichosporon species.

OBJECTIVES: Molecular genotyping of Trichosporon species using intergenic spacer region (IGS-1) sequencing and antifungal drug susceptibility testing of T. asahii clinical isolates from Indian patients. MATERIALS AND METHODS: Fifty-five Trichosporon strains were characterized using IGS-1 sequencing from 2006 to 2018 and tested against 5 antifungals using CLSI M27-A3 guidelines. RESULTS: In this study, broad-spectrum antibiotics with steroids, catheters, and ICU stays were major underlying risk factors. These cases were most commonly associated with diabetes (type-2), chronic obstructive pulmonary disease, and hypertension. Out of fifty-five isolates, 47 (85%) were identified as T. asahii, and the remaining 6 were T. inkin (11%) and 2 were Cutaneotrichosporon dermatis (3.6%). The most common genotype of T. asahii was G3 (22; 49%) subsequently G4 (12; 23%), G1 (8; 17%), and G7 (2; 4%). One new genotype of T asahii was found in addition to the fifteen already known genotypes. Indian T. asahii isolates showed a low level of amphotericin B (range 0.06-4 â€‹mg/l) resistance but relatively higher in fluconazole (range 0.25-64 â€‹mg/l). Although, comparatively low MIC ranges were found in the case of voriconazole (0.03-1 â€‹mg/l), posaconazole (0.06-1 â€‹mg/l) and itraconazole (0.06-1 â€‹mg/l). Voriconazole appeared to be the most active drug in T. asahii isolates. The MICs for all the drugs were comparatively lower in the case of non-Trichosporon asahii strains. CONCLUSION: T. asahii was the most common Trichosporon isolate. Speciation is necessary for optimal antifungal therapy. Voriconazole-based treatment, Steroids, removal of catheters and control of underlying conditions results in positive outcomes.

Modelling the impact of a high-uptake bivalent booster scenario on the COVID-19 burden and healthcare costs in New York City.

Background: Uptake of the COVID-19 bivalent booster vaccine (targeting the original SARS-CoV-2 strain and subvariants BA.4 and BA.5 of the Omicron variant) among eligible residents of New York City (NYC) has been modest and declining. Assessing the impact of improved population-level booster coverage with bivalent vaccines in NYC can help inform investment towards vaccination and potential cost-savings. Methods: We calibrated an agent-based model of disease transmission to confirmed and probable cases of COVID-19 in NYC and simulated it to project outcomes under two scenarios. In the base case scenario, we assumed that vaccination continued with the average daily rate of 92 vaccine doses per 100,000 administered during December 2022. In the counterfactual scenario, we modeled a high-uptake scenario between January 1, 2023 and March 31, 2023, with an average daily rate of 296 vaccine doses per 100,000 population that increased bivalent coverage in NYC to match the age-specific influenza vaccine coverage of the 2020-2021 season. Vaccination rate outside the campaign duration remained the same as the base case scenario. Findings: Compared to the base case, the high-uptake scenario averted 88,274 (95% Confidence Interval [CI]: 77,097-100,342) cases, and prevented 2,917 (95% CI: 2,557-3,267) hospitalizations between January 1 through the end of June 2023. Averted outcomes resulted in net savings of $217.2 (95% CI: 190.0-242.2) million in direct healthcare costs. We estimated that the high-uptake scenario would avert 72,879 (95% CI: 63,894-82,228) days of student absenteeism from schools due to COVID-19 illness. Interpretation: Our results illustrate the continued benefits of COVID-19 vaccines in preventing severe health outcomes, averting healthcare costs, and maintaining educational continuity in NYC. Funding: The Canadian Institutes of Health Research, The Natural Sciences and Engineering Research Council of Canada, NIH, Centers for Disease Control and Prevention (CDC), NSF, The Commonwealth Fund, and The Notsew Orm Sands Foundation.

PINNED: identifying characteristics of druggable human proteins using an interpretable neural network.

The identification of human proteins that are amenable to pharmacologic modulation without significant off-target effects remains an important unsolved challenge. Computational methods have been devised to identify features which distinguish between "druggable" and "undruggable" proteins, finding that protein sequence, tissue and cellular localization, biological role, and position in the protein-protein interaction network are all important discriminant factors. However, many prior efforts to automate the assessment of protein druggability suffer from low performance or poor interpretability. We developed a neural network-based machine learning model capable of generating druggability sub-scores based on each of four distinct categories, combining them to form an overall druggability score. The model achieves an excellent performance in separating drugged and undrugged proteins in the human proteome, with an area under the receiver operating characteristic (AUC) of 0.95. Our use of multiple sub-scores allows the assessment of potential protein targets of interest based on distinct contributors to druggability, leading to a more interpretable and holistic model to identify novel targets.

The Local Microbiome in Esophageal Cancer and Treatment Response: A Review of Emerging Data and Future Directions.

The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response. The advent of nucleic acid sequencing technologies has enabled more comprehensive, culture-independent bacterial identification. Across several tumor types, studies of tissue-specific microbiomes have shown associations between the overall microbiome composition, the relative abundance of specific bacteria, and tumorigenesis. Furthermore, in the era of cancer immunotherapy, several studies have demonstrated that the microbiome and specific bacteria may modify treatment responses and the risk of immune-related adverse events. DESIGN: peer-reviewed, published studies describing the role of local, gastrointestinal-specific microbiota or the role of the gut microbiome in treatment responses were reviewed. PubMed was searched from 1 September 2022 to 1 November 2022, using the following terms in combination: "microbiome", "tumor microbiome", "esophageal cancer", "cancer", "cancer treatment", and "immunotherapy". Original research articles were considered, and other reviews or editorials were discarded. In total, approximately 250 articles were considered. RESULTS: over 70 studies describing microbiome research in either gastrointestinal carcinogenesis or the systemic treatment response were identified and reviewed. CONCLUSIONS: a growing body of evidence supports the role of the esophageal microbiome in both esophageal tumorigenesis and the immune checkpoint inhibitor response. More well-designed, comprehensive studies are required to collect the appropriate clinical, microbial, and immunophenotype data that are needed to clarify the precise role of the microbiome in esophageal carcinogenesis and treatment.

Effect of Self-Healing by Dicyclopentadiene Microcapsules on Tensile and Fatigue Properties of Epoxy Composites.

Microcapsules of urea-formaldehyde (UF) containing dicyclopentadiene (DCPD) were synthesized by the in situ polymerization technique for self-healing of epoxy. The dispersion of microcapsules in the epoxy matrix was achieved using ultrasonication. Composites of epoxy, having 0.5, 1.0, 1.5, and 2.0 wt.% of microcapsules capable of self-healing, were prepared. The shape and size of the microcapsules were determined by field emission electron microscopy. Spherical capsules of DCPD, with an average diameter of 172 nm, were obtained. Investigation of tensile properties indicated a decrease in the tensile modulus with an increase in wt.% of microcapsules. There was a reduction of 22%, 27%, 39%, and 30% in the elastic modulus of composites for 0.5, 1.0, 1.5, and 2.0 wt.% of microcapsules, respectively. Tensile strength was found to increase with an increase in wt.% of microcapsules. The tensile strength of the composites increased by 33%, 20%, 8%, and 21% for 0.5, 1.0, 1.5, and 2.0 wt.% of microcapsules, respectively, in comparison with that of neat epoxy. The fatigue life of composites was investigated by conducting uniaxial tension-tension fatigue tests at constant stress amplitudes of 20, 25, 30, and 35 MPa, at a constant stress ratio (R = 0.1) and a frequency of 3 Hz. The fatigue life of composites increased with an increase in wt.% of microcapsules in comparison with that of neat epoxy. It was found that the fatigue life of the composites decreased with 1.5 and 2.0 wt.% of microcapsules in comparison with composites with 0.5 and 1.0 wt.% of microcapsules. The fracture surfaces of the tested samples were examined with the help of scanning electron microscopy (SEM) to understand the various mechanisms responsible for the change in modulus, strength, failure strain, and fatigue life of composites.