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Abstract Background While there is increasing recognition of the morbidity of cardiovascular disease in cancer survivors, including accelerated atherosclerosis following thoracic radiotherapy, patients are frequently under-optimized for cardiovascular risk. Methods In this prospective single-arm cohort pilot study, patients were treated with high-dose thoracic radiotherapy and had early consultation with cardio-oncology. Twenty patients were enrolled. The primary endpoint was adherence to cardio-oncology consultation. Secondary endpoints were cardiovascular medication intervention rate and patient-reported intervention perspectives. Clonal hematopoiesis of indeterminate potential, a major cardiovascular risk marker enriched in patients with cancer and induced by radiation exposure, was measured as an exploratory endpoint. Results The cohort median age is 71 years. Most patients are female (13/20), have primary lung or esophageal carcinoma (16/20), and 7/20 have pre-existing cardiovascular disease. We show that cardio-oncology consultation adherence is high (19/20) and results in cardiovascular medication optimization changes in most patients (12/19), most commonly to initiate or intensify statin therapy (8/12). 8/12 patients with a primary cardiologist prior to enrollment have medication changes recommended. Most (12/17) participants are glad to learn about their heart health during cancer treatment. Clonal hematopoiesis is detectable prior to treatment in 8/20 patients and three develop new variants after treatment (1/3 de novo). Conclusions We observe that early cardio-oncology consultation is feasible, leads to cardiovascular medication optimization in the majority (>60%) of participants, most commonly to initiate or intensify statin therapy. New clonal hematopoiesis variants are detectable early after radiotherapy and the impact on post-treatment cardiovascular risk is worthy of further study.

JWST has now revealed a population of broad-line active galactic nuclei (AGN) at z ≳ 4 characterized by a distinctive spectral energy distribution shape, with a very red rest-frame optical and very blue rest-frame UV continuum. While the optical continuum is thought to originate from the accretion disk, the origin of the UV continuum has been largely unclear. We report the detection of the strong rest-frame UV emission lines of C iii ] λλ 1907, 1909 and C iv λλ 1549, 1551 in a “little red dot” AGN, COS-66964. Spectroscopically confirmed at z = 7.0371, COS-66964 exhibits broad H α emission (FWHM ∼ 2000 km s ^−1 ) and weak broad H β , implying significant dust attenuation to the broad-line region ( ${A}_{V}=3.{9}_{-0.9}^{+1.7}$ ). The H α line width implies a central supermassive black hole (SMBH) mass of ${M}_{{\rm{BH}}}=\left(1.{9}_{-0.7}^{+1.6}\right)\times 1{0}^{7}$ M _⊙ and an Eddington ratio λ ∼ 0.3–0.5. While marginal He ii λ 4687 and [Fe x ] λ 6376 detections further indicate that the AGN dominates in the rest-frame optical, the nondetection of He ii λ 1640 in the UV despite high EW C iii ] and C iv (∼35 Å) is more consistent with photoionization by massive stars. The nondetection of Mg ii λλ 2800 is similarly inconsistent with an AGN scattered light interpretation. Assuming the rest-frame UV is dominated by stellar light, we derive a stellar mass of $\mathrm{log}{M}_{\star }/{M}_{\odot }\sim 8.5$ , implying an elevated M _BH / M _⋆ ratio ∼2 orders of magnitude above the local relation, but consistent with other high- z AGN discovered by JWST. The source is unresolved in all bands, implying a very compact size ≲200 pc in the UV. This suggests that the simultaneous buildup of compact stellar populations (i.e., galaxy bulges) and the central SMBH is ongoing even at z ≳ 7.

Osimertinib is first-line treatment for epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC) and has been associated with cardiotoxicity. However, the nature of cardiac remodeling and associated risk factors remains incompletely understood. Retrospective analysis of NSCLC patients with ≥1 echocardiogram post-osimertinib between 2007 and 2022 was performed. The cumulative incidence of grade ≥2 cardiac common terminology criteria for adverse events (CTCAE) was estimated and Fine and Gray regressions performed (non-cardiac death as competing risk). Eighty-five patients [mean [interquartile range, IQR], 68 [60–75] years; 67% female; 12% with pre-existing heart conditions] met inclusion criteria. With a median follow up of 34.7 months, the 2-year cumulative incidence of grade ≥2 and grade ≥3 cardiac events were 19.2% and 8.5%, respectively. There was an increased risk of grade ≥2 cardiac CTCAE with pre-existing arrhythmia [hazard ratio(HR) 3.90, 95%CI, 1.11–13.72; p = 0.034] and higher body mass index (HR 1.07, 95%CI, 1.00–1.14; p = 0.04). Following osimertinib (vs. baseline), the median QTc was prolonged (451 vs. 437 ms; p

Chronic diseases are the leading cause of death and disability in the United States, and much of this burden can be attributed to lifestyle and behavioral risk factors. Lifestyle medicine is an approach to preventing and treating lifestyle-related chronic disease using evidence-based lifestyle modification as a primary modality. NYC Health + Hospitals, the largest municipal public health care system in the United States, is a national pioneer in incorporating lifestyle medicine systemwide. In 2019, a pilot lifestyle medicine program was launched at NYC Health + Hospitals/Bellevue to improve cardiometabolic health in high-risk patients through intensive support for evidence-based lifestyle changes. Analyses of program data collected from January 29, 2019 to February 26, 2020 demonstrated feasibility, high demand for services, high patient satisfaction, and clinically and statistically significant improvements in cardiometabolic risk factors. This pilot is being expanded to 6 new NYC Health + Hospitals sites spanning all 5 NYC boroughs. As part of the expansion, many changes have been implemented to enhance the original pilot model, scale services effectively, and generate more interest and incentives in lifestyle medicine for staff and patients across the health care system, including a plant-based default meal program for inpatients. This narrative review describes the pilot model and outcomes, the expansion process, and lessons learned to serve as a guide for other health systems.

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.

Abstract Background and purpose Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. Materials and methods A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. Results Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. Conclusion There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection. Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan–Meier overall survival and progression-free survival estimates were calculated. Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression. Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation.

Objective Patients now have direct access to their radiology reports, which can include complex terminology and be difficult to understand. We assessed ChatGPT's ability to generate summarized MRI reports for patients with prostate cancer and evaluated physician satisfaction with the artificial intelligence (AI)-summarized report. Methods We used ChatGPT to summarize five full MRI reports for patients with prostate cancer performed at a single institution from 2021 to 2022. Three summarized reports were generated for each full MRI report. Full MRI and summarized reports were assessed for readability using Flesch-Kincaid Grade Level (FK) score. Radiation oncologists were asked to evaluate the AI-summarized reports via an anonymous questionnaire. Qualitative responses were given on a 1–5 Likert-type scale. Fifty newly diagnosed prostate cancer patient MRIs performed at a single institution were additionally assessed for physician online portal response rates. Results Fifteen summarized reports were generated from five full MRI reports using ChatGPT. The median FK score for the full MRI reports and summarized reports was 9.6 vs. 5.0, ( p

Abstract Several symptoms have been connected to increased healthcare resource utilization (HRU) in the context of inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and ulcerative colitis (UC). This study was designed to investigate the prevalence of IBD-associated symptoms and to determine whether any are independently associated with HRU. We undertook a retrospective analysis of data related to consecutive IBD patient encounters from a tertiary care referral center between 1/1/2015 and 8/31/2019. Demographics, clinical activity, endoscopic severity, IBD-related symptom scores, anxiety and depression scores, and other key clinical data were abstracted. Four hundred sixty-seven IBD patients [247f.: 220 m; 315 CD, 142 UC and 11 indeterminate colitis] were included in this study. The most common symptoms were fatigue (83.6%), fecal urgency (68.2%) and abdominal pain (63.5%). Fatigue, abdominal pain, anxiety or depression, corticosteroids, and opioids were each positively associated with HRU, while NSAID and mesalamine use were inversely associated on bivariate analysis. The only factor that demonstrated a statistically significant association with HRU in the whole cohort on multivariable analysis was abdominal pain. Abdominal pain is independently associated with HRU and should be specifically screened for in IBD patients to identify individuals at risk of undergoing expensive interventions. This study also reinforces the importance of optimizing diagnostic and therapeutic management of abdominal pain in IBD.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

The internal medicine in-training examination (IM-ITE) has been traditionally used as a measuring tool to evaluate the base of knowledge of the residents in internal medicine residency programs across the US. Multiple interventions has been applied and studied to increase the first-time passing rate of ABIM, as it is an indicator of each residency program’s performance and ranking. Additionally, studies have demonstrated that different learning styles and preferences are a predictor of exam results; however, it is not well known whether certain preferred learning styles are correlated with certain IM-ITE results. Primary objective of our study was to find a correlation between residents’ preferred learning style, based on Kolb learning style inventory, and their PGY1 and PGY2 IM-ITE performance score difference. Secondary objective was to find the correlation between PGY2s’ IM-ITE score and their preferred learning styles based on the Kolb learning style inventory. Mean scores of PGY1 and PGY2 IM-ITE were compared in each learning style group. Additionally, the mean difference between the PGY1 and PGY2 IM-ITE scores for each learning group was compared as well. The analysis of the mean IM-ITE score from PGY1 to PGY2 between groups revealed a statistically significant improvement in IM-ITE score from PGY1 to PGY2 in all groups, however, with a larger difference in one of the groups.

The presence of lymph node positivity (LN+) guides adjuvant treatment for endometrial adenocarcinoma (EAC) patients, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Sociodemographic factors in addition to pathologic tumor characteristics may more accurately predict risk of LN+ in EAC patients. Patients diagnosed between 2004 and 2016 with pathologic T1-T2 EAC who had at least one lymph node sampled at the time of surgery in the National Cancer Data Base were included. Pathologic primary tumor predictors of LN+ were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN+, nomograms were generated. Among the 35,170 EAC patients included, 2864 were node positive. Using multivariable analysis, younger patient age (OR 0.98, 95% CI 0.98–0.99, p < 0.001), black versus white race (OR 1.19, 95% CI 1.01–1.40, p = 0.04), increasing pathologic tumor stage and grade, increase in tumor size, and presence of lymphovascular invasion were predictive of regional LN+. Both black versus white (OR 1.64, 95% CI 1.27–2.09, p < 0.001) and other versus white race (OR 1.54, 95% CI 1.12–2.07, p = 0.006) strongly predicted paraaortic LN+ in the multivariable analysis. Independent subset analyses of black and white women revealed that tumor grade was a stronger predictor of LN+ among black women. In addition to standard pathologic tumor features, patient age and race were associated with a higher risk of regional LN+ generally and paraaortic LN+ specifically. This information may inform adjuvant treatment decisions and guide future studies.

Abstract Background Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. Methods From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15–27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24–25.5) over 2–3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan–Meier method. Results Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57–62.8). Median follow-up was 19 months (range 3–48). Two–year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications resolved within 24 h from treatment. Acute grade 1–2 toxicity was identified in 4 patients, whereas none developed late toxicity beyond 90 days of follow-up. Conclusion Percutaneous HDR brachyablation is a safe and promising treatment option for centrally located primary and metastatic lung tumors. Future comparisons with stereotactic body radiotherapy and other ablative techniques are warranted to expand multi-disciplinary management options.

Abstract Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P

Purpose: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein. Methods and Materials: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed. Results: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], −0.83 to 1.59 cm), −3.22 cm (IQR, −5.12 to −1.84 cm), and 0.9 cm (IQR, −1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of −3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively. Conclusions: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted.

We apply the color–magnitude intercept calibration method (CMAGIC) to the Nearby Supernova Factory SNe Ia spectrophotometric data set. The currently existing CMAGIC parameters are the slope and intercept of a straight line fit to the linear region in the color–magnitude diagram, which occurs over a span of approximately 30 days after maximum brightness. We define a new parameter, ω _XY , the size of the “bump” feature near maximum brightness for arbitrary filters X and Y . We find a significant correlation between the slope of the linear region, β _XY , in the CMAGIC diagram and ω _XY . These results may be used to our advantage, as they are less affected by extinction than parameters defined as a function of time. Additionally, ω _XY is computed independently of templates. We find that current empirical templates are successful at reproducing the features described in this work, particularly SALT3, which correctly exhibits the negative correlation between slope and “bump” size seen in our data. In 1D simulations, we show that the correlation between the size of the “bump” feature and β _XY can be understood as a result of chemical mixing due to large-scale Rayleigh–Taylor instabilities.

ObjectiveTo evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.MethodsPatients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3-6 and as maintenance monotherapy in cycles 7-34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival.ResultsAn interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual.ConclusionsThe addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.

Purpose: In response to the COVID-19 pandemic, there has been a rapid growth in the use of telehealth/telemedicine that will likely be sustained in the postpandemic setting. Mobile health applications (apps) can be used as part of the telehealth encounter to monitor patient-reported outcomes (PROs) and enhance patient-provider communication. Methods and Materials: A systematic review was performed of mobile health apps with symptom trackers. We searched the iOS App Store and Android Google Play using the words cancer, oncology, and symptom tracker. Apps were included if they incorporated a symptom tracking function that could allow patients with cancer to record symptoms and PROs. Apps were evaluated using the mobile apps rating scale, which includes engagement, functionality, aesthetics, information, and app subjective quality. Results: The initial search yielded 1189 apps, with 101 apps eligible after title and description screening. A total of 41 apps met eligibility criteria and were included in this study. The majority of apps (73%, n = 30) were general health/pain symptom trackers, and 27% (n = 11) were cancer-specific. The app quality mean scores assessed using the mobile apps rating scale ranged from 2.43 to 4.23 (out of 5.00). Only 1 app has been trialed for usability among patients with cancer. Conclusions: Although various symptom tracking apps are available, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients to optimize PRO assessment and integration with telehealth/telemedicine encounters to increase symptom recognition and enhance patient-provider communication is urgently needed.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide affecting upwards of one third the global population. For reasons not fully understood, individuals with NAFLD and its more severe variant, nonalcoholic steatohepatitis (NASH), are at increased risk for venous thromboembolism which significantly increases morbidity and mortality. Lifestyle changes centering around exercise training are the mainstay of treatment for NAFLD/NASH. While exercise training can lessen venous thromboembolic risk in healthy persons and those with cardiovascular disease, whether or not this benefit is seen in patients with NAFLD/NASH remains unknown. In order to better understand how exercise training impacts thrombosis risk in NAFLD, we present the design of a thirty-two week randomized controlled clinical trial of 42 sedentary subjects age 18–69 with biopsy proven NASH. The main aim is to determine the impact of an aerobic exercise training program on the abnormal hemostatic system unique to NAFLD/NASH. The main outcome is change in plasminogen activator inhibitor one level, an established marker for venous thromboembolism. Secondary outcomes include body composition, cardiorespiratory fitness, control of comorbid metabolic conditions (e.g., obesity, hypertension, hyperlipidemia, diabetes), dietary composition, health related quality of life, liver enzymes and histology, NAFLD/NASH disease activity (e.g., biomarkers, clinical decision aids), microbiome, other markers of hemostasis, and PNPLA3 gene expression. The study represents the first clinical trial of an exercise training program to reduce elevated clotting risk in subjects with NAFLD/NASH.

Age-related source memory deficits result, in part, because young and older adults attend to different information. We asked whether focusing young and older adults‘ attention on specific features at encoding would result in similar subjective experiences of the vividness of the features and how this might affect source memory. Ratings of the vividness of visual detail, emotion, and associations were similar for young and older adults both when they were perceiving pictures and when they were thinking about them after a brief delay. Although young adults had better source memory than older adults, source accuracy did not differ depending on feature attended, and correlations between ratings and source memory showed that focus on the different types of information was equally predictive of source memory accuracy for young and older adults. Although preliminary, the results suggest that when attention is focused on specific information at encoding, young and older adults later use the various categories of source-specifying information similarly in making source attributions. Nevertheless, older adults did worse on the source test, suggesting they had less discriminable source information overall, this information was not well bound, and/or they experienced difficulty in strategic retrieval and monitoring processes.

While numerous studies have examined gamification from the students' perspectives, few studies focus on the faculty's experience in detail. This article analyzes the experiences and self-reflections of five university instructors who designed and implemented gamification for their online or hybrid courses. It uses a design research approach to inform the gamification design and implementation decisions and draws on data collected from weekly meetings recorded over Google Hangout, as well as meeting minutes, design documents, emails, and informal reflections that retrospectively examine the process of designing and implementing the gamified courses. It also discusses the data gathered from students on their perspectives and experiences in class. While students' feedback on gamification were largely positive, many faculty members acknowledge that creating a coherent gamified course was difficult and time-consuming. However, the process of designing itself may be worth going through because it made faculty more conscious of how their teaching values were being reflected in the gamified system. The article ends with reflections on the institutional and technological constraints that were encountered, and offers recommendations on how to support educators new to gamifying learning in their courses.

We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

Agrobacterium tumefaciens growing in liquid attaches to the surface of tomato and Arabidopsis thaliana roots, forming a biofilm. The bacteria also colonize roots grown in sterile quartz sand. Attachment, root colonization, and biofilm formation all were markedly reduced in celA and chvB mutants, deficient in production of cellulose and cyclic β-(1,2)-D-glucans, respectively. We have identified two genes (celG and celI) in which mutations result in the overproduction of cellulose as judged by chemical fractionation and methylation analysis. Wild-type and chvB mutant strains carrying a cDNA clone of a cellulose synthase gene from the marine urochordate Ciona savignyi also overproduced cellulose. The overproduction in a wild-type strain resulted in increased biofilm formation on roots, as evaluated by light microscopy, and levels of root colonization intermediate between those of cellulose-minus mutants and the wild type. Overproduction of cellulose by a nonattaching chvB mutant restored biofilm formation and bacterial attachment in microscopic and viable cell count assays and partially restored root colonization. Although attachment to plant surfaces was restored, overproduction of cellulose did not restore virulence in the chvB mutant strain, suggesting that simple bacterial binding to plant surfaces is not sufficient for pathogenesis.

Red yeast rice (RYR), produced by the fermentation of the Monascus purpureus mold, has been used for a long time in Asian cuisine and traditional medicine. It consists of multiple bioactive substances, including monacolins, which potentially can be used as a nutraceutical. Monacolin K, which is chemically identical to lovastatin, has been recognized as responsible for the cholesterolreducing effect of this compound. While the European Food Safety Authority maintains that the use of monacolin K from RYR preparations of at least 10 mg can produce a normal blood cholesterol level, the United States Food and Drug Administration considers monacolin K, due to its similarity with lovastatin, an unapproved drug, and therefore marketing of products that label the monacolin content is prohibited. This mini-review summarizes the benefit of RYR in hyperlipidemia, maintains RYR use as a food, and addresses the importance of regulation regarding RYR and the need for clinical data and clear label information for consumers with reference to a toxin-free, nonaugmented, standardized amount of monacolins.

Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied. Methods: Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67. Results: Interprostatic Ki-67 mean ± standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ± 3.8%, 7.4 ± 6.8%, and 12.0 ± 12.4% (ANOVA P=0.013). Intraprostatic mean ± SD Ki-67 ranges in L, I, and H risk patients were 2.6 ± 3.6%, 5.3 ± 6.8%, and 10.9 ± 12.3% (ANOVA P=0.027). Intralesion mean ± SD Ki-67 ranges in L, I, and H risk patients were 1.1 ± 0.9%, 5.2 ± 7.9%, and 8.1 ± 10.8% (ANOVA P=0.22). ADC values at Ki-67 > and

Abstract Background Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. Methods we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. Results We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. Conclusion The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

Abstract Introduction Though animal-related injuries and fatalities have been documented throughout the world, the variety of attacks by wild animals native to rural East Africa are less commonly described. Given the proximity of our northwestern Tanzania hospital to Lake Victoria, Lake Tanganyika, and the Serengeti National Park, and presentation of several patients attacked by bush animals and suffering a variety of complex injuries, we sought to report the pattern of attacks and surgical management in a resource-limited setting. Materials and methods Four patients who were admitted to the northwestern Tanzania tertiary referral hospital, Bugando Medical Centre (BMC), in 2010-2011 suffered attacks by different bush animals: hyena, elephant, crocodile, and vervet monkey. These patients were triaged as trauma patients in the Casualty Ward, then admitted for inpatient monitoring and treatment. Their outcomes were followed to discharge. Results The age and gender of the patients attacked was variable, though all but the pediatric patient were participating in food gathering or guarding activities in rural locations at the time of the attacks. All patients required surgical management of their injuries, which included debridement and closure of wounds, chest tube insertion, amputation, and external fixation of an extremity fracture. All patients survived and were discharged home. Discussion Though human injuries secondary to encounters with undomesticated animals such as cows, moose, and camel are reported, they often are indirect traumas resulting from road traffic collisions. Snake attacks are well documented and common. However, this series of unique bush animal attacks describes the initial and surgical management of human injuries in the resource-limited setting of the developing world. Conclusion Animal attacks are common throughout the world, but their pattern may vary in Africa throughout jungle and bush environmental settings. It is important to understand the management of these attacks in resource-limited health care environment. Further, the growing population and human encroachment on previously wild habitats such as the northwestern Tanzania bush argues for increased community awareness to assist in prevention of human injuries by animals.

Abstract Background The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses. Methods Design Observational cohort study of progressive incremental exposure to EHH. Setting University human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m. Participants 198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest. Main outcome measures Exercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry. Results Of 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood flow velocity and microvascular blood flow at 7950 m and arterial blood gas measurement at 8400 m. Conclusions This study demonstrates the feasibility and safety of conducting a large healthy volunteer cohort study of human adaptation to hypoxia in this difficult environment. Systematic measurements of a large set of variables were achieved in 222 subjects and at altitudes up to 8400 m. The resulting dataset is a unique resource for the study of genotype:phenotype interactions in relation to hypoxic adaptation.

Abstract Background Prolonged exposure to war has severely impacted the provision of health services in the Democratic Republic of the Congo (DRC). Health infrastructure has been destroyed, health workers have fled and government support to health care services has been made difficult by ongoing conflict. Poor reproductive health (RH) indicators illustrate the effect that the prolonged crisis in DRC has had on the on the reproductive health (RH) of Congolese women. In 2007, with support from the RAISE Initiative, the International Rescue Committee (IRC) and CARE conducted baseline assessments of public hospitals to evaluate their capacities to meet the RH needs of the local populations and to determine availability, utilization and quality of RH services including emergency obstetric care (EmOC) and family planning (FP). Methods Data were collected from facility assessments at nine general referral hospitals in five provinces in the DRC during March, April and November 2007. Interviews, observation and clinical record review were used to assess the general infrastructure, EmOC and FP services provided, and the infection prevention environment in each of the facilities. Results None of the nine hospitals met the criteria for classification as an EmOC facility (either basic or comprehensive). Most facilities lacked any FP services. Shortage of trained staff, essential supplies and medicines and poor infection prevention practices were consistently documented. All facilities had poor systems for routine monitoring of RH services, especially with regard to EmOC. Conclusions Women's lives can be saved and their well-being improved with functioning RH services. As the DRC stabilizes, IRC and CARE in partnership with the local Ministry of Health and other service provision partners are improving RH services by: 1) providing necessary equipment and renovations to health facilities; 2) improving supply management systems; 3) providing comprehensive competency-based training for health providers in RH and infection prevention; 4) improving referral systems to the hospitals; 5) advocating for changes in national RH policies and protocols; and 6) providing technical assistance for monitoring and evaluation of key RH indicators. Together, these initiatives will improve the quality and accessibility of RH services in the DRC - services which are urgently needed and to which Congolese women are entitled by international human rights law.

Adequacy and safety are the twin prerogatives of the blood transfusion service which in turn is an indispensable component of public health delivery; however, many Caribbean countries have inadequate blood supply for the current and projected demands of their health care systems. Understanding blood donor motivators and barriers is crucial to improving the rate of voluntary non-remunerated blood donation (VNRD) to meet World Health Organisation (WHO) targets. The objective of this study was to review current research on the landscape of blood donation practices and attitudes in the Caribbean. We undertook a systematic search of electronic databases through September 2023 to identify studies of blood donation practices, knowledge and attitudes, including motivators and barriers to donation in the English-speaking Caribbean. We identified eight (8) relevant studies of observational study design. VNRD remain relatively uncommon; family replacement or remunerated donations were most common. Barriers to blood donation included lack of a known recipient such as a family member who needed blood, never having been asked to donate, presumed ineligibility to donate, and fear of needles or adverse reactions. Study participants indicated willingness to donate blood if provided more information about the importance of blood donation. There is a paucity of published research regarding blood donor knowledge, motivators and barriers in the Caribbean context. Such research could indicate the necessary interventions for achieving the goals of an adequate and safe blood supply., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background and Objectives: Granulocyte transfusion supports patients with severe neutropenia. Maintaining a pool of eligible donors and optimizing donation frequency are essential for ensuring an adequate supply while safeguarding donor well-being. This study investigates the impact of donation frequency on erythrogram parameters, focusing on sex-specific differences., Study Design and Methods: We conducted a retrospective analysis of 343 successive granulocyte collections from 65 apheresis donors over 11 years (2012-2023). Donors were categorized by sex, and erythrogram parameters were analysed in relation to donation frequency and intervals., Results: Frequent donations within a short inter-donation interval (≥3 in 14 days) affected subsequent pre-donation haemoglobin levels. Each additional donation within 14 days led to a decrease of 0.81 g/dL in haemoglobin (p = 0.017). A significant interaction between sex and donations within 14 days (β = 0.76, p = 0.018) indicated that frequent donations had a more pronounced negative effect on haemoglobin levels in female donors. The proportion of donations meeting the pre-donation haemoglobin eligibility criteria declined with each successive donation within 14 days (100% at first, 85.8% at second, 25% at third). Female donors showed a significant haemoglobin reduction over three donations within 14 days (13.4-11.6 g/dL, p = 0.005) compared to males (14.4 -14 g/dL, p = 0.95)., Conclusion: Short inter-donation intervals have a more pronounced negative effect on pre-donation haemoglobin levels in female donors, underscoring the need for individualized donation guidelines to ensure donor safety., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Summary: DamID sequencing is a technique to map the genome-wide interaction of a protein with DNA. Damsel is the first Bioconductor package to provide an end to end analysis for DamID sequencing data within R. Damsel performs quantification and testing of significant binding sites along with exploratory and visual analysis. Damsel produces results consistent with previous analysis approaches., Availability and Implementation: The R package Damsel is available for install through the Bioconductor project https://bioconductor.org/packages/release/bioc/html/Damsel.html and the code is available on GitHub https://github.com/Oshlack/Damsel/., (© The Author(s) 2024. Published by Oxford University Press.)

Epithelial organs maintain their integrity and prevent tumor initiation by actively removing defective cells, such as those that have lost apicobasal polarity. Here, we identify how transcription factors of two key signaling pathways-Jun-N-terminal kinase (JNK) and Hippo-regulate epithelial integrity by controlling transcription of an overlapping set of target genes. Targeted DamID experiments reveal that, in proliferating cells of the Drosophila melanogaster eye, the AP-1 transcription factor Jun and the Hippo pathway transcription regulators Yorkie and Scalloped bind to a common suite of target genes that promote organ growth. In defective neoplastic cells, AP-1 transcription factors repress transcription of growth genes together with the C-terminal binding protein (CtBP) co-repressor. If gene repression by AP-1/CtBP fails, neoplastic tumor growth ensues, driven by Yorkie/Scalloped. Thus, AP-1/CtBP eliminates defective cells and prevents tumor initiation by acting in parallel to Yorkie/Scalloped to repress expression of a shared transcriptome. These findings shed new light on the maintenance of epithelial integrity and tumor suppression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We study the transport of rigid ellipsoidal swimmers in a periodic vortex array via numerical simulation and dynamical systems analysis. Via ensemble simulations, we show the counterintuitive result that slower swimming speeds can generate fast ballistic transport, while faster swimming speeds generate chaotic and diffusive transport, which is inherently slower in the long run. To explain this, we use the symmetry of the flow to construct a time-reversible Poincaré return map on a two-dimensional surface of section in phase space. For sufficiently small swimming speeds, we find stable periodic orbits on the surface of section surrounded by invariant tori, similar to Kolmogorov-Arnold-Moser curves. Trajectories within these tori are ballistic. As the swimming speed is increased, the periodic orbits undergo a sequence of period-doubling bifurcations that destroys the ballistic tori. These bifurcations exactly match the ballistic to diffusive transition from the ensemble simulations. Additional ensemble simulations are used to test the robustness of these results to noise. The ballistic behavior is destroyed as the strength of rotational diffusion increases. However, we estimate that the ballistic tori might still be seen in experiments.