Qualitative evaluation of artificial intelligence-generated weight management diet plans.

Importance: The transformative potential of artificial intelligence (AI), particularly via large language models, is increasingly being manifested in healthcare. Dietary interventions are foundational to weight management efforts, but whether AI techniques are presently capable of generating clinically applicable diet plans has not been evaluated. Objective: Our study sought to evaluate the potential of personalized AI-generated weight-loss diet plans for clinical applications by employing a survey-based assessment conducted by experts in the fields of obesity medicine and clinical nutrition. Design setting and participants: We utilized ChatGPT (4.0) to create weight-loss diet plans and selected two control diet plans from tertiary medical centers for comparison. Dietitians, physicians, and nurse practitioners specializing in obesity medicine or nutrition were invited to provide feedback on the AI-generated plans. Each plan was assessed blindly based on its effectiveness, balanced-ness, comprehensiveness, flexibility, and applicability. Personalized plans for hypothetical patients with specific health conditions were also evaluated. Main outcomes and measures: The primary outcomes measured included the indistinguishability of the AI diet plan from human-created plans, and the potential of personalized AI-generated diet plans for real-world clinical applications. Results: Of 95 participants, 67 completed the survey and were included in the final analysis. No significant differences were found among the three weight-loss diet plans in any evaluation category. Among the 14 experts who believed that they could identify the AI plan, only five did so correctly. In an evaluation involving 57 experts, the AI-generated personalized weight-loss diet plan was assessed, with scores above neutral for all evaluation variables. Several limitations, of the AI-generated plans were highlighted, including conflicting dietary considerations, lack of affordability, and insufficient specificity in recommendations, such as exact portion sizes. These limitations suggest that refining inputs could enhance the quality and applicability of AI-generated diet plans. Conclusion: Despite certain limitations, our study highlights the potential of AI-generated diet plans for clinical applications. AI-generated dietary plans were frequently indistinguishable from diet plans widely used at major tertiary medical centers. Although further refinement and prospective studies are needed, these findings illustrate the potential of AI in advancing personalized weight-centric care.

Alternative Treatments to Pharmacological Therapy in Pediatric Populations With Attention-Deficit/Hyperactivity Disorder (ADHD): A Scoping Review.

In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms "children with ADHD," "alternative treatment," and "cognitive behavioral therapy," articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

Ethanolic extract from fruiting bodies of Cordyceps militaris HL8 exhibits cytotoxic activities against cancer cells, skin pathogenic yeasts, and postharvest pathogen Penicillium digitatum.

Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43 mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15 mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51 µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.

Molecular mechanisms underlying phenotypic degeneration in Cordyceps militaris: insights from transcriptome reanalysis and osmotic stress studies.

Phenotypic degeneration in Cordyceps militaris poses a significant concern for producers, yet the mechanisms underlying this phenomenon remain elusive. To address this concern, we isolated two strains that differ in their abilities to form fruiting bodies. Our observations revealed that the degenerated strain lost the capacity to develop fruiting bodies, exhibited limited radial expansion, increased spore density, and elevated intracellular glycerol levels. Transcriptome reanalysis uncovered dysregulation of genes involved in the MAPK signaling pathway in the degenerate strain. Our RT-qPCR results demonstrated reduced expression of sexual development genes, along with upregulation of genes involved in asexual sporulation, glycerol synthesis, and MAPK regulation, when compared to the wild-type strain. Additionally, we discovered that osmotic stress reduced radial growth but increased conidia sporulation and glycerol accumulation in all strains. Furthermore, hyperosmotic stress inhibited fruiting body formation in all neutralized strains. These findings indicate dysregulation of the MAPK signaling pathway, the possibility of the activation of the high-osmolarity glycerol and spore formation modules, as well as the downregulation of the pheromone response and filamentous growth cascades in the degenerate strain. Overall, our study sheds light on the mechanisms underlying Cordyceps militaris degeneration and identifies potential targets for improving cultivation practices.

Antibody Response after a Booster COVID-19 Vaccine Mixing in Vietnam.

BACKGROUND: The booster vaccine is essential for maintaining the antibody against the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus. This study sought to evaluate the antibody response after booster coronavirus disease 2019 (COVID-19) vaccines and compare the immunogenic by different vaccine combination strategies. METHODS: A cross-sectional study in Hanoi, Vietnam was conducted on 679 adult participants who received two doses of vaccines with any combination of AstraZeneca, Pfizer, and Moderna during the COVID-19 vaccination campaign in 2021. The SARS-CoV-2 S1/S2 Immunoglobulin G (IgG) antibody concentrations were measured by the LIAISON SARS-CoV-2 S1/S2 IgG and presented as arbitrary units. RESULTS: We found that the median (interquartile range (IQR)) of IgG level among those who completed two doses of Moderna and Pfizer was 484.55 (284.80) AU/mL and 349.00 (362.50) AU/mL, respectively. Meanwhile, the counterpart of AstraZeneca was 110.00 (128.10) AU/mL. Mixing two doses of AstraZeneca-Pfizer has higher odds of having high IgG level than two doses of Pfizer (Odds Ratios (OR) = 2.94, 95% Confidence Intervals (CI): 1.57-5.51), AstraZeneca (OR = 28.50, 95% CI: 15.00-54.14). CONCLUSIONS: We found that the matching two doses of mRNA vaccines are more immunogenic as compared to the DNA vector vaccines. Furthermore, mixing AstraZeneca-Pfizer has higher antibody quantities as compared to matching vaccines, while lower the rate of advert events.

Injecting drug use increases the risk of death in HIV patients on antiretroviral therapy in Vietnam.

The Human Immunodeficiency Virus (HIV) epidemic remains a major public health issue worldwide. In Vietnam, the HIV epidemic is essentially driven by people who inject drugs (PWID). This study aims to compare mortality and loss to follow-up (LTFU) between PWID and other patients. From June 2017 to April 2018, HIV-infected adults were enrolled in a prospective cohort from time of ART initiation in six provinces of North Vietnam. The end date was July 2020. Mortality and LTFU were described using competing-risk survival models. Factors associated with mortality and with LTFU were identified using Cox models with a competing-risk approach. Of the 578 participants, 261 (45.2%) were PWID and almost exclusively male. 49 patients died, corresponding to a mortality rate (95% confidence interval (CI)) of 3.7 (2.8-4.9) per 100 person-months, and 79 were lost to follow-up, corresponding to a rate (95% CI) of 6.0 (4.8-7.4) per 100 person-months. PWID were at higher risk of death but not of LTFU. Overall, LTFU was high in both groups. Latecomers to clinical visits were more at risk of both death and LTFU. Therefore, this should be a warning to clinical teams and preventive actions taken in these patients.Trial registration: ClinicalTrials.gov identifier: NCT03249493..

Effects of MAT1-2 Spore Ratios on Fruiting Body Formation and Degeneration in the Heterothallic Fungus Cordyceps militaris.

The medicinal mushroom Cordyceps militaris is widely exploited in traditional medicine and nutraceuticals in Asian countries. However, fruiting body production in C. militaris is facing degeneration through cultivation batches, and the molecular mechanism of this phenomenon remains unclear. This study showed that fruiting body formation in three different C. militaris strains, namely G12, B12, and HQ1, severely declined after three successive culturing generations using the spore isolation method. PCR analyses revealed that these strains exist as heterokaryons and possess both the mating-type loci, MAT1-1 and MAT1-2. Further, monokaryotic isolates carrying MAT1-1 or MAT1-2 were successfully separated from the fruiting bodies of all three heterokaryotic strains. A spore combination of the MAT1-1 monokaryotic isolate and the MAT1-2 monokaryotic isolate promoted fruiting body formation, while the single monokaryotic isolates could not do that themselves. Notably, we found that changes in ratios of the MAT1-2 spores strongly influenced fruiting body formation in these strains. When the ratios of the MAT1-2 spores increased to more than 15 times compared to the MAT1-1 spores, the fruiting body formation decreased sharply. In contrast, when MAT1-1 spores were increased proportionally, fruiting body formation was only slightly reduced. Our study also proposes a new solution to mitigate the degeneration in the heterokaryotic C. militaris strains caused by successive culturing generations.

Wearable Augmented Reality: Research Trends and Future Directions from Three Major Venues.

Wearable Augmented Reality (AR) has attracted considerable attention in recent years, as evidenced by the growing number of research publications and industry investments. With swift advancements and a multitude of interdisciplinary research areas within wearable AR, a comprehensive review is crucial for integrating the current state of the field. In this paper, we present a review of 389 research papers on wearable AR, published between 2018 and 2022 in three major venues: ISMAR, TVCG, and CHI. Drawing inspiration from previous works by Zhou et al. and Kim et al., which summarized AR research at ISMAR over the past two decades (1998-2017), we categorize the papers into different topics and identify prevailing trends. One notable finding is that wearable AR research is increasingly geared towards enabling broader consumer adoption. From our analysis, we highlight key observations related to potential future research areas essential for capitalizing on this trend and achieving widespread adoption. These include addressing challenges in Display, Tracking, Interaction, and Applications, and exploring emerging frontiers in Ethics, Accessibility, Avatar and Embodiment, and Intelligent Virtual Agents.

Evaluating the Compliance, Efficacy, and Cost of Formulated Vitamins Versus Separate Supplements in Post-bariatric Surgery Patients.

OBJECTIVE: Micronutrient deficiencies are common complications after bariatric surgery as alterations to the gastrointestinal tract change absorption. Patients are recommended to take supplements including multivitamins, B complex, calcium, vitamin D, and iron after bariatric surgery, and can take these as specifically formulated vitamins for post-bariatric patients or separate vitamin supplements. We investigated the compliance, efficacy, and cost of specifically formulated vitamins for post-bariatric patients in comparison to separate vitamin supplements. METHODS: We surveyed 126 post-bariatric adult patients between February 1, 2022, and August 31, 2022, who had undergone bariatric surgery between 2014 and 2021 to assess the type of supplements taken, compliance, and cost. Demographics, type of bariatric surgery, and serum micronutrient levels were evaluated for all patients. RESULTS: There were 51 patients taking formulated vitamins and 75 patients taking separate vitamins. The formulated vitamin group demonstrated greater adherence to optimal vitamin dosage (formulated vitamin group, 76.5% vs. separate supplement group, 30.7%; p < 0.001) and higher compliance (formulated vitamin group, 90.2% vs. separate supplement group, 66.7%; p = 0.002). The costs associated with both groups were comparable. No significant difference was observed in the incidence of micronutrient deficiency between the groups. CONCLUSIONS: Our study shows that formulated vitamins do not offer significant difference in micronutrient levels or cost compared to separate standard vitamin supplements. However, formulated bariatric vitamins have improved compliance compared to separate vitamin supplements.

A Case of Abnormal Liver Function Tests in a Patient Receiving Total Parenteral Nutrition.

Hepatic dysfunction is prevalent in patients receiving total parenteral nutrition (TPN), resulting from steatosis, cholestasis, and cholecystitis. Regular assessments and monitoring of TPN patients are essential, even for clinically stable patients on long-term TPN. Furthermore, it is crucial to establish a differential diagnosis for hepatic dysfunction and investigate for other possible causes of elevated liver enzymes and underlying liver conditions. We present the case of a 56-year-old female patient with severe protein-calorie malnutrition on TPN, who exhibited significantly elevated liver enzymes during the routine periodic assessment. Subsequent investigation revealed that the patient had been taking traditional Chinese herbal medications concurrently with TPN. After discontinuing the herbal medications, the patient's liver enzymes returned to normal levels within 3 weeks.

Efficient control of the fungal pathogens Colletotrichum gloeosporioides and Penicillium digitatum infecting citrus fruits by native soilborne Bacillus velezensis strains.

Destruction of citrus fruits by fungal pathogens during preharvest and postharvest stages can result in severe losses for the citrus industry. Antagonistic microorganisms used as biological agents to control citrus pathogens are considered alternatives to synthetic fungicides. In this study, we aimed to identify fungal pathogens causing dominant diseases on citrus fruits in a specialized citrus cultivation region of Vietnam and inspect soilborne Bacillus isolates with antifungal activity against these pathogens. Two fungal pathogens were characterized as Colletotrichum gloeosporioides and Penicillium digitatum based on morphological characteristics and ribosomal DNA internal transcribed spacer sequence analyses. Reinfection assays of orange fruits confirmed that C. gloeosporioides causes stem-end rot, and P. digitatum triggers green mold disease. By the heterologous expression of the green fluorescent protein (GFP) in C. gloeosporioides using Agrobacterium tumefaciens-mediated transformation, we could observe the fungal infection process of the citrus fruit stem-end rot caused by C. gloeosporioides for the first time. Furthermore, we isolated and selected two soilborne Bacillus strains with strong antagonistic activity for preventing the decay of citrus fruits by these pathogens. Molecular analyses of 16 S rRNA and gyrB genes showed that both isolates belong to B. velezensis. Antifungal activity assays indicated that bacterial culture suspensions could strongly inhibit C. gloeosporioides and P. digitatum, and shield orange fruits from the invasion of the pathogens. Our work provides a highly effective Bacillus-based preservative solution for combating the fungal pathogens C. gloeosporioides and P. digitatum to protect citrus fruits at the postharvest stages.

Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.

INTRODUCTION: Increasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID. METHODS: Prospective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART. RESULTS: Overall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (p<0.001). In multivariate analysis, PWID were more at risk of failure (p = 0.001), as were patients who were late to clinical visits (p<0.001) and not fully adherent (p<0.001). CONCLUSIONS: Despite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care. TRIAL REGISTRATION: Clinical Trial Number: NCT03249493.

Therapeutic targeting of histone lysine demethylase KDM4B blocks the growth of castration-resistant prostate cancer.

Epigenetics is an emerging mechanism for tumorigenesis. Treatment that targets epigenetic regulators is becoming an attractive strategy for cancer therapy. The role of epigenetic therapy in prostate cancer (PCa) remains elusive. Previously we demonstrated that upregulation of histone lysine demethylase KDM4B correlated with the appearance of castration resistant prostate cancer (CRPC) and identified a small molecular inhibitor of KDM4B, B3. In this study, we further investigated the role of KDM4B in promoting PCa progression and tested the efficacy of B3 using clinically relevant PCa models including PCa cell line LNCaP and 22Rv1 and xenografts derived from these cell lines. In loss and gain-functional studies of KDM4B in PCa cells, we found that overexpression of KDM4B in LNCaP cells enhanced its tumorigenicity whereas knockdown of KDM4B in 22Rv1 cells reduced tumor growth in castrated mice. B3 suppressed the growth of 22Rv1 xenografts and sensitized tumor to anti-androgen receptor (AR) antagonist enzalutamide inhibition. B3 also inhibited 22Rv1 tumor growth synergistically with rapamycin, leading to cell apoptosis. Comparative transcriptomic analysis performed on KDM4B knockdown and B3-treated 22Rv1 cells revealed that B3 inhibited both H3K9me3 and H3K27me3 demethylase activities. Our studies establish KDM4B as a target for CRPC and B3 as a potential therapeutic agent. B3 as monotherapy or in combination with other anti-PCa therapeutics offers proof of principle for the clinical translation of epigenetic therapy targeting KDMs for CRPC patients.

Reliability of Current Classification Systems for Periprosthetic Fractures of the Humerus.

OBJECTIVE: Numerous classification systems exist to evaluate periprosthetic humerus fractures, although most are based on limited patient numbers. The Wright and Cofield system is the most widely used classification system. We sought to evaluate the interobserver and intraobserver reliabilities of this system compared with the Unified Classification System (UCS) using the largest patient sample to date. METHODS: This retrospective study identified patients between December 2011 and January 2021 with a periprosthetic fracture of the humerus around the stem of a shoulder arthroplasty component. Three upper extremity fellowship-trained surgeons evaluated all radiographs for stem stability, evidence of preinjury stem loosening, Wright and Cofield classification, UCS classification, and recommended treatment for each case at 2 timepoints separated by 2 months. The kappa statistic for interobserver and intraobserver reliability was calculated. RESULTS: Seventy-six patients were included. There was moderate interobserver (kappa 0.53) and substantial intraobserver (kappa 0.69) agreement when classifying stem stability after fracture. There was moderate interobserver (kappa 0.48) and intraobserver (kappa 0.60) agreement when evaluating for stem loosening before fracture. There was fair interobserver (kappa 0.29) and moderate intraobserver (kappa 0.51) agreement regarding the UCS class. There was moderate interobserver (kappa 0.41) and intraobserver (kappa 0.57) agreement regarding the proposed treatment. There was slight interobserver (kappa 0.04) and moderate intraobserver (kappa 0.44) agreement regarding the Wright and Cofield classification. CONCLUSION: The Wright and Cofield system is less reliable than the UCS classification. A more reliable and clinically relevant classification system is needed to standardize discussion of periprosthetic proximal humerus fractures.

Accuracy of Noninvasive Diagnostic Tests for the Detection of Significant and Advanced Fibrosis Stages in Nonalcoholic Fatty Liver Disease: A Systematic Literature Review of the US Studies.

BACKGROUND: The purpose of this systematic literature review (SLR) was to evaluate the accuracy of noninvasive diagnostic tools in detecting significant or advanced (F2/F3) fibrosis among patients with nonalcoholic fatty liver (NAFL) in the US healthcare context. METHODS: The SLR was conducted in PubMed and Web of Science, with an additional hand search of public domains and citations, in line with the PRISMA statement. The study included US-based original research on diagnostic test sensitivity, specificity and accuracy. RESULTS: Twenty studies were included in qualitative evidence synthesis. Imaging techniques with the highest diagnostic accuracy in F2/F3 detection and differentiation were magnetic resonance elastography and vibration-controlled transient elastography. The most promising standard blood biomarkers were NAFLD fibrosis score and FIB-4. The novel diagnostic tools showed good overall accuracy, particularly a score composed of body mass index, GGT, 25-OH-vitamin D, and platelet count. The novel approaches in liver fibrosis detection successfully combine imaging techniques and blood biomarkers. CONCLUSIONS: While noninvasive techniques could overcome some limitations of liver biopsy, a tool that would provide a sufficiently sensitive and reliable estimate of changes in fibrosis development and regression is still missing.

Chromosome Numbers and Genome Sizes of All 36 Duckweed Species (Lemnaceae).

Usually, chromosome sets (karyotypes) and genome sizes are rather stable for distinct species and therefore of diagnostic value for taxonomy. In combination with (cyto)genomics, both features provide essential cues for genome evolution and phylogenetic relationship studies within and between taxa above the species level. We present for the first time a survey on chromosome counts and genome size measurement for one or more accessions from all 36 duckweed species and discuss the evolutionary impact and peculiarities of both parameters in duckweeds.

Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival.

Hypertrophic/dilated cardiomyopathy, often a prequel to heart failure, is accompanied by maladaptive transcriptional changes that contribute to arrythmias and contractile misfunction. Transgenic mice constitutively expressing high levels of calcineurin are known to develop extreme heart hypertrophy, which progresses to dilated cardiomyopathy, and to die several weeks after birth. Here, we characterized aberrant transcriptional and epigenetic pathways in this mouse model and established a pharmacological approach to treat established cardiomyopathy. We found that H3K4me3 (trimethyl histone 3 lysine 4) and H3K9me3 (trimethyl histone 3 lysine 9) Jumonji histone demethylases are markedly increased at the protein level and show enhanced enzymatic activity in diseased hearts. These epigenetic regulators continued to increase with time, further affecting cardiac gene expression. Our findings parallel the lower H3K4me3 and H3K9me3 levels seen in human patients. Inhibition of Jumonji demethylase activities in vivo results in lower histone demethylase enzymatic function in the heart and higher histone methylation levels and leads to partial reduction of heart size, reversal of maladaptive transcriptional programs, improved heart function, and prolonged survival. At the molecular level, target genes of transcription factor myocyte enhancer factor 2 are specifically regulated in response to pharmacological or genetic inhibition of Jumonji demethylases. Similar transcriptional reversal of disease-associated genes is seen in a second disease model based on cardiac mechanical overload. Our findings validate pharmacological inhibitors of Jumonji demethylases as potential therapeutics for the treatment of cardiomyopathies across disease models and provide evidence of the reversal of maladaptive transcriptional reprogramming leading to partial restoration of cardiac function. In addition, this study defines pathways of therapeutic resistance upregulated with disease progression.

Shoulder Synovial Chondromatosis in an Adolescent Athlete: A Case Report.

Introduction: Synovial chondromatosis refers to a benign proliferative disease of the synovium. Reports in children are rare and reports involving the pediatric shoulder are even more rare. In this review of the literature and case report, we provide a summary of all published cases in children and a report of a case of shoulder synovial chondromatosis in an adolescent female athlete. Case Presentation: A 15-year-old female cheerleader presented to the clinic with gradual onset right shoulder pain with a severity of 5/10. On physician examination, the patient had tenderness over the proximal humerus, limited abduction to 160°, limited forward flexion, and a total arc of motion of <180°. Radiograph of the shoulder demonstrated multiple calcific intra-articular loose bodies consistent with synovial chondromatosis. Arthroscopic removal resulted in resolution of symptoms at the 36-week follow-up. Conclusions: Our literature search revealed only eight case reports on shoulder synovial chondromatosis in children. The location of the chondromatosis within the shoulder joint can be intra-articular, extra-articular, within the biceps sheath, or combined. In general, for chondomatoses confined to the glenohumeral joint space, open surgery is not required. Bony erosions can occur in the setting of chondromatosis though may not need to be addressed surgically. Although rare, this diagnosis should be considered when confronted with shoulder pain that is exacerbated during long athletic events with limited range of motion on physical examination in the adolescent athlete. Arthroscopic treatment in conjunction with physical therapy and early mobilization can lead to a successful outcome.

Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells.

BACKGROUND: Nasopharyngeal carcinoma (NPC) in endemic regions and younger patients is characterized by a prominent lymphomononuclear infiltration. Radiation is the principal therapeutic modality for patients with NPC. Recent data suggest that the efficacy of radiotherapy in various cancers can be augmented when combined with immune checkpoint blockade. Here, we investigate the effect of radiotherapy on the killing of NPC cells by Natural Killer (NK) cells. METHODS: NPC cell lines and a patient-derived xenograft were exposed to NK cells in the context of radiotherapy. Cytotoxicity was measured using the calcein-release assay. The contribution of the PD-L1/PD-1 checkpoint and signaling pathways to killing were analyzed using specific inhibitors. RESULTS: Radiotherapy sensitized NPC cells to NK cell killing and upregulated expression of PD-1 ligand (PD-L1) in NPC cells and PD-1 receptor (PD-1) in NK cells. Blocking of the PD-L1/PD-1 checkpoint further increased the killing of NPC cells by NK cells in the context of radiotherapy. CONCLUSION: Radiation boosts the killing of NPC cells by NK cells. Killing can be further augmented by blockade of the PD-L1/PD-1 checkpoint. The combination of radiotherapy with PD-L1/PD-1 checkpoint blockade could therefore increase the efficacy of radiotherapy in NPC tumors.