Bilberry metabolomic and proteomic profiling during fruit ripening reveals key dynamics affecting fruit quality.

Bilberry (Vaccinium myrtillus L.) is a wild berry species that is prevalent in northern Europe. It is renowned and well-documented for its nutritional and bioactive properties, especially due to its anthocyanin content. However, an overview of biological systems governing changes in other crucial quality traits, such as size, firmness, and flavours, has received less attention. In the present study, we investigated detailed metabolomic and proteomic profiles at four different ripening stages of bilberry to provide a comprehensive understanding of overall quality during fruit ripening. By integrating omics datasets, we revealed a novel global regulatory network of plant hormones and physiological processes occurring during bilberry ripening. Key physiological processes, such as energy and primary metabolism, strongly correlate with elevated levels of gibberellic acids, jasmonic acid, and salicylic acid in unripe fruits. In contrast, as the fruit ripened, processes including flavour formation, cell wall modification, seed storage, and secondary metabolism became more prominent, and these were associated with increased abscisic acid levels. An indication of the increase in ethylene biosynthesis was detected during bilberry development, raising questions about the classification of non-climacteric and climacteric fruits. Our findings extend the current knowledge on the physiological and biochemical processes occurring during fruit ripening, which can serve as a baseline for studies on both wild and commercially grown berry species. Furthermore, our data may facilitate the optimization of storage conditions and breeding programs, as well as the future exploration of beneficial compounds in berries for new applications in food, cosmetics, and medicines.

Different Biocompatibility and Radioprotective Activity of Squid Melanin Nanoparticles on Human Stromal Cells.

Squid ink melanin nanoparticles (NPs) have recently been demonstrated to have a number of bioactivities; however, their biocompatibility has been poorly investigated. In this study, we aimed to evaluate the effects of this NP on stromal cells, including human fibroblasts (hFBs), human umbilical vein endothelial cells (hUVECs), and human umbilical cord-derived mesenchymal stem cells (UCMSCs), and on the development of zebrafish embryos under normal X-ray irradiation conditions. The NPs showed high biocompatibility with low cytotoxicity, no cell senescence induction, and no effect on cell migration in hFBs or cell differentiation in UCMSCs. Nonetheless, this compound prevented cell movement in UCMSCs and significantly suppressed tube formation in hUVECs at a dose of 25 µg/mL. The NPs successfully penetrated the hUVECs but not the other two stromal cell types. The expression levels of functional genes involved in angiogenesis, apoptosis, antioxidant activity, and radiation sensitivity were altered in NPs subjected to hUVECs but were not affected in hFBs and UCMSCs. Melanin NPs significantly rescued cell viability and gene expression in irradiated hFBs and UCMSCs but not in hUVECs. In vivo treatments of zebrafish embryos showed that melanin NPs were nontoxic whether alone or under X-ray irradiation. These findings suggested that nanosized squid ink melanin had biocompatibility with selective stromal cells and was safe for early development.

Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells.

A series of 14 conjugates of 2α,3ß,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, ß-alanine, or 11-aminoundecanoic acid) at position C-3. The conjugates were tested in vitro for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound 8, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile versus madecassic acid alone.

Effectiveness of a Smartphone-Based Stress Management Program for Depression in Hospital Nurses During COVID-19 in Vietnam and Thailand: 2-Arm Parallel-Group Randomized Controlled Trial.

BACKGROUND: During the COVID-19 pandemic, health care professionals experienced high levels of depression. However, extant research has not highlighted effective internet-based psychological interventions to improve the mental health in this population during the pandemic. It remains unclear whether self-guided, internet-based cognitive behavioral therapy (iCBT) programs are effective in improving the mental health of health care workers during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a smartphone-based iCBT stress management program for reducing the depression experienced by nurses in Vietnam and Thailand. METHODS: From March to April 2022, a 2-arm, parallel-group randomized controlled trial was implemented. One arm offered a 7-week self-guided iCBT program, and the other offered treatment as usual as a control arm. Full-time nurses were recruited from 6 hospitals: 2 hospitals in Vietnam and 4 hospitals in Thailand. The primary outcome of this program was the severity of depression measured by the Depression Anxiety Stress Scale-21 items. Follow-up surveys were conducted to measure the change in depression severity at 3 months (July-August 2022) and at 6 months (October-November 2022) after baseline. Mixed modeling for repeated measures was used to test the effects of the intervention compared with the control for the follow-up. RESULTS: A total of 1203 nurses were included in this study: 602 in the intervention group and 601 in the control group. The follow-up rate at 3 and 6 months ranged from 85.7% (515/601) to 87.5% (527/602). The completion rate for the program was 68.1% (410/602). The group difference in depression was significant at the 3-month follow-up (coefficient=-0.92, 95% CI -1.66 to -0.18; P=.02) and nonsignificant at the 6-month follow-up (coefficient=-0.33, 95% CI -1.11 to 0.45; P=.41). The estimated effect sizes were -0.15 and -0.06 at the 3- and 6-month follow-ups, respectively. CONCLUSIONS: Our study shows that the smartphone-based iCBT program was effective in reducing depression at the 3-month follow-up among hospital nurses in Vietnam and Thailand during the COVID-19 pandemic. However, the effect size was small, and therefore, these results may not be clinically meaningful. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000044145; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050128. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.20944/preprints202303.0450.v1.

Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.

Hypertension affects one billion people worldwide and is the most common risk factor for cardiovascular disease, yet a comprehensive picture of its underlying genetic factors is incomplete. Amongst regulators of blood pressure is the renal outer medullary potassium (ROMK) channel. While select ROMK mutants are prone to premature degradation and lead to disease, heterozygous carriers of some of these same alleles are protected from hypertension. Therefore, we hypothesized that gain-of-function (GoF) ROMK variants which increase potassium flux may predispose people to hypertension. To begin to test this hypothesis, we employed genetic screens and a candidate-based approach to identify six GoF variants in yeast. Subsequent functional assays in higher cells revealed two variant classes. The first group exhibited greater stability in the endoplasmic reticulum, enhanced channel assembly, and/or increased protein at the cell surface. The second group of variants resided in the PIP2-binding pocket, and computational modeling coupled with patch-clamp studies demonstrated lower free energy for channel opening and slowed current rundown, consistent with an acquired PIP2-activated state. Together, these findings advance our understanding of ROMK structure-function, suggest the existence of hyperactive ROMK alleles in humans, and establish a system to facilitate the development of ROMK-targeted antihypertensives.

Multi-organ immune-related adverse events from immune checkpoint inhibitors and their downstream implications: a retrospective multicohort study.

BACKGROUND: Understanding co-occurrence patterns and prognostic implications of immune-related adverse events is crucial for immunotherapy management. However, previous studies have been limited by sample size and generalisability. In this study, we leveraged a multi-institutional cohort and a population-level database to investigate co-occurrence patterns of and survival outcomes after multi-organ immune-related adverse events among recipients of immune checkpoint inhibitors. METHODS: In this retrospective study, we identified individuals who received immune checkpoint inhibitors between May 31, 2015, and June 29, 2022, from the Massachusetts General Hospital, Brigham and Women's Hospital, and Dana-Farber Cancer Institute (Boston, MA, USA; MGBD cohort), and between April 30, 2010, and Oct 11, 2021, from the independent US population-based TriNetX network. We identified recipients from all datasets using medication codes and names of seven common immune checkpoint inhibitors, and patients were excluded from our analysis if they had incomplete information (eg, diagnosis and medication records) or if they initiated immune checkpoint inhibitor therapy after Oct 11, 2021. Eligible patients from the MGBD cohort were then propensity score matched with recipients of immune checkpoint inhibitors from the TriNetX database (1:2) based on demographic, cancer, and immune checkpoint inhibitor characteristics to facilitate cohort comparability. We applied immune-related adverse event identification rules to identify patients who did and did not have immune-related adverse events in the matched cohorts. To reduce the likelihood of false positives, patients diagnosed with suspected immune-related adverse events within 3 months after chemotherapy were excluded. We performed pairwise correlation analyses, non-negative matrix factorisation, and hierarchical clustering to identify co-occurrence patterns in the MGBD cohort. We conducted landmark overall survival analyses for patient clusters based on predominant immune-related adverse event factors and calculated accompanying hazard ratios (HRs) and 95% CIs, focusing on the 6-month landmark time for primary analyses. We validated our findings using the TriNetX cohort. FINDINGS: We identified 15 246 recipients of immune checkpoint inhibitors from MGBD and 50 503 from TriNetX, of whom 13 086 from MGBD and 26 172 from TriNetX were included in our propensity score-matched cohort. Median follow-up durations were 317 days (IQR 113-712) in patients from MGBD and 249 days (91-616) in patients from TriNetX. After applying immune-related adverse event identification rules, 8704 recipients of immune checkpoint inhibitors were retained from MGBD, of whom 3284 (37·7%) had and 5420 (62·3%) did not have immune-related adverse events, and 18 162 recipients were retained from TriNetX, of whom 5538 (30·5%) had and 12 624 (69·5%) did not have immune-related adverse events. In both cohorts, positive pairwise correlations of immune-related adverse events were commonly observed. Co-occurring immune-related adverse events were decomposed into seven factors across organs, revealing seven distinct patient clusters (endocrine, cutaneous, respiratory, gastrointestinal, hepatic, musculoskeletal, and neurological). In the MGBD cohort, the patient clusters that predominantly had endocrine (HR 0·53 [95% CI 0·40-0·70], p<0·0001) and cutaneous (0·61 [0·46-0·81], p=0·0007) immune-related adverse events had favourable overall survival outcomes at the 6-month landmark timepoint, while the other clusters either had unfavourable (respiratory: 1·60 [1·25-2·03], p=0·0001) or neutral survival outcomes (gastrointestinal: 0·86 [0·67-1·10], p=0·23; musculoskeletal: 0·97 [0·78-1·21], p=0·78; hepatic: 1·20 [0·91-1·59], p=0·19; and neurological: 1·30 [0·97-1·74], p=0·074). Similar results were found in the TriNetX cohort (endocrine: HR 0·75 [95% CI 0·60-0·93], p=0·0078; cutaneous: 0·62 [0·48-0·82], p=0·0007; respiratory: 1·21 [1·00-1·46], p=0·044), except for the neurological cluster having unfavourable (rather than neutral) survival outcomes (1·30 [1·06-1·59], p=0·013). INTERPRETATION: Reliably identifying the immune-related adverse event cluster to which a patient belongs can provide valuable clinical information for prognosticating outcomes of immunotherapy. These insights can be leveraged to counsel patients on the clinical impact of their individual constellation of immune-related adverse events and ultimately develop more personalised surveillance and mitigation strategies. FUNDING: US National Institutes of Health.

Pediatric Erythroid Sarcoma Diagnostically Confirmed by Identification of a Recurrent NFIA::CBFA2T3 Fusion.

Erythroid sarcoma (ES) is exceedingly rare in the pediatric population with only a handful of reports of de novo cases, mostly occurring in the central nervous system (CNS) or orbit. It is clinically and pathologically challenging and can masquerade as a nonhematopoietic small round blue cell tumor. Clinical presentation of ES without bone marrow involvement makes diagnosis particularly difficult. We describe a 22-month-old female with ES who presented with a 2-cm mass involving the left parotid region and CNS. The presence of crush/fixation artifact from the initial biopsy made definitive classification of this highly proliferative and malignant neoplasm challenging despite an extensive immunohistochemical workup. Molecular studies including RNA-sequencing revealed a NFIA::CBFA2T3 fusion. This fusion has been identified in several cases of de novo acute erythroid leukemia (AEL) and gene expression analysis comparing this case to other AELs revealed a similar transcriptional profile. Given the diagnostically challenging nature of this tumor, clinical RNA-sequencing was essential for establishing a diagnosis.

Celecoxib and sulindac sulfide elicit anticancer effects on PIK3CA-mutated head and neck cancer cells through endoplasmic reticulum stress, reactive oxygen species, and mitochondrial dysfunction.

Gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Patients with HNC harboring PIK3CA mutations receive therapeutic benefits from the use of non-steroidal anti-inflammatory drugs (NSAIDs). However, the molecular mechanisms underlying these effects remain unknown. Here, we examined the Detroit562 and FaDu cell lines as HNC models with and without a hyperactive PIK3CA mutation (H1047R), respectively, regarding their possible distinct responses to the NSAIDs celecoxib and sulindac sulfide (SUS). Detroit562 cells exhibited relatively high PI3K/Akt pathway-dependent cyclooxygenase-2 (COX-2) expression, associated with cell proliferation. Celecoxib treatment restricted cell proliferation and upregulated endoplasmic reticulum (ER) stress-related markers, including GRP78, C/EBP-homologous protein, activating transcription factor 4, death receptor 5, and reactive oxygen species (ROS). These effects were much stronger in Detroit562 cells than in FaDu cells and were largely COX-2-independent. SUS treatment yielded similar results. Salubrinal (an ER stress inhibitor) and N-acetyl-L-cysteine (a ROS scavenger) prevented NSAID-induced ROS generation and ER stress, respectively, indicating crosstalk between ER and oxidative stress. In addition, celecoxib and/or SUS elevated cleaved caspase-3 levels, Bcl-2-associated X protein/Bcl-2-interacting mediator of cell death expression, and mitochondrial damage, which was more pronounced in Detroit562 than in FaDu cells. Salubrinal and N-acetyl-L-cysteine attenuated celecoxib-induced mitochondrial dysfunction. Collectively, our results suggest that celecoxib and SUS efficiently suppress activating PIK3CA mutation-harboring HNC progression by inducing ER and oxidative stress and mitochondrial dysfunction, leading to apoptotic cell death, further supporting NSAID treatment as a useful strategy for oncogenic PIK3CA-mutated HNC therapy.

The p21+ perinecrotic hepatocytes produce the chemokine CXCL14 after a severe acetaminophen overdose promoting hepatocyte injury and delaying regeneration.

Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available single-nuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as CXCL14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, CXCL14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or CXCL14 with a neutralizing antibody. We found that targeting CXCL14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting senescent hepatocytes had no effect. These data support the conclusion that the sustained induction of p21 in hepatocytes with persistent CXCL14 secretion are critical mechanistic events leading to ALF in mice and human patients.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Risk Factors for Severe Seafood Allergy Among Adults in an Urban City in Vietnam.

Purpose: Increasing seafood consumption is associated with more frequent reports of food allergy. Little is known about seafood allergy (SFA) among adults in Vietnam. We investigated the characteristics of individuals with SFA and the risk factors for severe SFA. Patients and methods: A cross-sectional, web-based survey was conducted among individuals aged ≥ 18 years from universities in Ho Chi Minh City (Vietnam) between December 2021 and July 2022. The survey was based on a structured, validated questionnaire related to FA. Strict definitions of "convincing allergy" were used. Multivariate analysis was used to estimate the risk factors for severe SFA after adjusting for covariates. Data were analyzed using JASP (v.0.16.3) and SPSS (v.22.0). Results: Totally, 1038 out of 2137 (48.57%) individuals completed the questionnaire, of whom 285 (27.46%) had reported SFA. Convincing SFA accounted for 20.13% (209/1038) of the cases, with convincing shellfish allergy being more common than fish allergy. Participants with comorbid shellfish and fish allergy had higher prevalence of atopic dermatitis, peanut/nut allergy, other food allergy, and cutaneous and upper airway symptoms compared to participants with shellfish allergy (p < 0.05). The spectrum of reactive seafood was diverse and characterized by local species. The age of symptom onset was most commonly during late childhood and adolescence, with most reactions persisting into adulthood. A history of anaphylaxis, comorbid peanut, and tree nut allergy, and ≥3 allergens were associated with severe SFA. Conclusion: Features of causative, coexisting seafood allergy, and risk factors for severe SFA were demonstrated, which can provide a reference for future studies.

Outcomes and Costs of the Transition From a Paper-Based Immunization System to a Digital Immunization System in Vietnam: Mixed Methods Study.

BACKGROUND: The electronic National Immunization Information System (NIIS) was introduced nationwide in Vietnam in 2017. Health workers were expected to use the NIIS alongside the legacy paper-based system. Starting in 2018, Hanoi and Son La provinces transitioned to paperless reporting. Interventions to support this transition included data guidelines and training, internet-based data review meetings, and additional supportive supervision visits. OBJECTIVE: This study aims to assess (1) changes in NIIS data quality and use, (2) changes in immunization program outcomes, and (3) the economic costs of using the NIIS versus the traditional paper system. METHODS: This mixed methods study took place in Hanoi and Son La provinces. It aimed to analyses pre- and postintervention data from various sources including the NIIS; household and health facility surveys; and interviews to measure NIIS data quality, data use, and immunization program outcomes. Financial data were collected at the national, provincial, district, and health facility levels through record review and interviews. An activity-based costing approach was conducted from a health system perspective. RESULTS: NIIS data timeliness significantly improved from pre- to postintervention in both provinces. For example, the mean number of days from birth date to NIIS registration before and after intervention dropped from 18.6 (SD 65.5) to 5.7 (SD 31.4) days in Hanoi (P<.001) and from 36.1 (SD 94.2) to 11.7 (40.1) days in Son La (P<.001). Data from Son La showed that the completeness and accuracy improved, while Hanoi exhibited mixed results, possibly influenced by the COVID-19 pandemic. Data use improved; at postintervention, 100% (667/667) of facilities in both provinces used NIIS data for activities beyond monthly reporting compared with 34.8% (202/580) in Hanoi and 29.4% (55/187) in Son La at preintervention. Across nearly all antigens, the percentage of children who received the vaccine on time was higher in the postintervention cohort compared with the preintervention cohort. Up-front costs associated with developing and deploying the NIIS were estimated at US $0.48 per child in the study provinces. The commune health center level showed cost savings from changing from the paper system to the NIIS, mainly driven by human resource time savings. At the administrative level, incremental costs resulted from changing from the paper system to the NIIS, as some costs increased, such as labor costs for supportive supervision and additional capital costs for equipment associated with the NIIS. CONCLUSIONS: The Hanoi and Son La provinces successfully transitioned to paperless reporting while maintaining or improving NIIS data quality and data use. However, improvements in data quality were not associated with improvements in the immunization program outcomes in both provinces. The COVID-19 pandemic likely had a negative influence on immunization program outcomes, particularly in Hanoi. These improvements entail up-front financial costs.

Research on optimization of spray drying conditions, characteristics of anthocyanins extracted from Hibiscus sabdariffa L. flower, and application to marshmallows.

Anthocyanin, a main-colored bioactive compound found in Hibiscus sabdariffa L., is well-known for a varied range of applications as food additives in foodstuff, and natural colorants in food, pharmaceutical, and printing industries. The study aimed to find out the suitable conditions for the spray-drying process to obtain anthocyanin powder from the extract as well as characterized the powder. In addition, the obtained powder was applied to marshmallows and determined the acceptability of appearance, quality, and scavenging capacity of the candy. The carrier of maltodextrin and gum arabic was selected for spray-drying, which had optimal conditions at 144°C and 7 mL/min, resulting in 100.22 mg/g anthocyanin content with an encapsulation efficiency of 93.87%. The obtained anthocyanin has appropriate moisture of 5.14%, quite appropriate bulk density, and tapped density, it also was high solubility, and poor flowability but easy compression. The shape of the particle by SEM analysis was low particle size (2-10 µm), wrinkled, unequal spherical size, rough surfaces with indentations, and slight cracks. The X-ray diffraction (XRD) spectrum of the sample had very low crystallinity and diffuse wide peaks revealing that anthocyanin still exists inside maltodextrin particles. The FT-IR spectrum had oscillations of characteristic groups of anthocyanin structure. Marshmallow samples added 5% anthocyanin powder gained high acceptability of appearance and maintained the scavenging capacity (DPPH) with an IC50 value of 7368.31 ppm after a month of storage.

Cancer type and histology influence cutaneous immunotherapy toxicities: a multi-institutional cohort study.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in the setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. OBJECTIVES: To investigate the influence of cancer type and histology on the development of cirAEs in the setting of ICI therapy and survival outcomes. METHODS: This retrospective cohort study included patients recruited between 1 December 2011 and 30 October 2020. They received ICI from 2011 to 2020 with follow-up of outcomes through October 2021. We identified 3668 recipients of ICI therapy who were seen at Massachusetts General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were used to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modelling was used to examine the impact of cirAE development on mortality. RESULTS: Compared with other nonepithelial cancers (neuroendocrine, leukaemia, lymphoma, myeloma, sarcoma and central nervous system malignancies), cutaneous squamous cell carcinoma [cSCC; hazard ratio (HR) 3.57, P < 0.001], melanoma (HR 2.09, P < 0.001), head and neck adenocarcinoma (HR 2.13, P = 0.009), genitourinary transitional cell carcinoma (HR 2.15, P < 0.001) and genitourinary adenocarcinoma (HR 1.53, P = 0.037) were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma (HR 0.37, P < 0.001) and cSCC (HR 0.51, P = 0.011). CONCLUSIONS: The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICI therapies. This study improves our understanding of patients who are at highest risk of developing cirAEs and would, therefore, benefit from appropriate counselling and closer monitoring by their oncologists and dermatologists throughout their ICI therapy. Limitations include its retrospective nature and cohort from one geography.

Cutaneous immune-related adverse events (cirAEs) are the most common complications to occur for oncology patients treated with immune checkpoint inhibitors (ICIs). cirAEs can lead to increased use of healthcare resources and significant morbidity. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. In this study, we aimed to investigate the influence of cancer organ system and histology on the development of cirAEs and survival outcomes. To do this, we included a cohort of patients retrospectively between 1 December 2011 and 30 October 2020. We identified 3668 ICI recipients who were seen at Massachusetts General Brigham and Dana-Farber in Boston, Massachusetts. Of these, 669 people developed cirAEs. Multivariate Cox proportional hazards models were used to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI start, and year of ICI initiation. Time-varying Cox proportional hazards modelling was used to examine the impact of cirAE development on mortality. We found that, compared with other nonepithelial cancers, patients with cutaneous squamous cell carcinoma (cSCC) and melanoma were at significantly higher risk of cirAEs. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma and cSCC. This study improves our understanding of patients who are at highest risk of developing cirAEs ­ those with melanoma and cSCC. Therefore, many patients could benefit from appropriate counselling and close monitoring by their oncologists and dermatologists throughout ICI therapy.

COVID-19 Knowledge, Beliefs, and Intention to Get Vaccinated: A Brief Educational Intervention Among Black and Hispanic Populations.

We aimed to determine the effect of a brief educational intervention on COVID-19 vaccine knowledge, beliefs, and vaccination intention in Black and Hispanic communities in Houston, Texas. As part of the Community Engagement Alliance (CEAL) Against COVID-19 Disparities study (2020-2022), 1606 Black and Hispanic adults completed Web-based surveys before and after viewing COVID-19 educational materials. The intervention significantly improved health beliefs and vaccination intention. Disseminating short and ethnically appropriate educational materials is an effective strategy to decrease vaccine hesitancy in minority populations. (Am J Public Health. 2024;114(S1):S82-S86. https://doi.org/10.2105/AJPH.2023.307501).

Ensuring Continuity of Tuberculosis Care during Social Distancing through Integrated Active Case Finding at COVID-19 Vaccination Events in Vietnam: A Cohort Study.

COVID-19 significantly disrupted tuberculosis (TB) services in Vietnam. In response, the National TB Program (NTP) integrated TB screening using mobile chest X-rays into COVID-19 vaccination events. This prospective cohort study evaluated the integrated model's yield, treatment outcomes, and costs. We further fitted regressions to identify risk factors and conduct interrupted time-series analyses in the study area, Vietnam's eight economic regions, and at the national level. At 115 events, we conducted 48,758 X-ray screens and detected 174 individuals with TB. We linked 89.7% to care, while 92.9% successfully completed treatment. The mean costs per person diagnosed with TB was $547. TB risk factors included male sex (aOR = 6.44, p < 0.001), age of 45-59 years (aOR = 1.81, p = 0.006) and ≥60 years (aOR = 1.99, p = 0.002), a history of TB (aOR = 7.96, p < 0.001), prior exposure to TB (aOR = 3.90, p = 0.001), and symptomatic presentation (aOR = 2.75, p < 0.001). There was a significant decline in TB notifications during the Delta wave and significant increases immediately after lockdowns were lifted (IRR(γ1) = 5.00; 95%CI: (2.86, 8.73); p < 0.001) with a continuous upward trend thereafter (IRR(γ2) = 1.39; 95%CI: (1.22, 1.38); p < 0.001). Similar patterns were observed at the national level and in all regions but the northeast region. The NTP's swift actions and policy decisions ensured continuity of care and led to the rapid recovery of TB notifications, which may serve as blueprint for future pandemics.