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BackgroundEvidence-based decision-making is essential to improve public health benefits and resources, especially in low- and middle-income countries (LMICs), but the mechanisms of its implementation remain less straightforward. The availability of high-quality, reliable, and sufficient data in LMICs can be challenging due to issues such as a lack of human resource capacity and weak digital infrastructure, among others. Health information systems (HISs) have been critical for aggregating and integrating health-related data from different sources to support evidence-based decision-making. Nutrition information systems (NISs), which are nutrition-focused HISs, collect and report on nutrition-related indicators to improve issues related to malnutrition and food security—and can assist in improving populations’ nutritional statuses and the integration of nutrition programming into routine health services. Data visualization tools (DVTs) such as dashboards have been recommended to support evidence-based decision-making, leveraging data from HISs or NISs. The use of such DVTs to support decision-making has largely been unexplored within LMIC contexts. In Bangladesh, the Mukto dashboard was developed to display and visualize nutrition-related performance indicators at the national and subnational levels. However, despite this effort, the current use of nutrition data to guide priorities and decisions remains relatively nascent and underused. ObjectiveThe goal of this study is to better understand how Bangladesh’s NIS, including the Mukto dashboard, has been used and areas for improvement to facilitate its use for evidence-based decision-making toward ameliorating nutrition-related service delivery and the health status of communities in Bangladesh. MethodsPrimary data collection was conducted through qualitative semistructured interviews with key policy-level stakeholders (n=24). Key informants were identified through purposive sampling and were asked questions about the experiences and challenges with the NIS and related nutrition dashboards. ResultsMain themes such as trust, data usability, personal power, and data use for decision-making emerged from the data. Trust in both data collection and quality was lacking among many stakeholders. Poor data usability stemmed from unstandardized indicators, irregular data collection, and differences between rural and urban data. Insufficient personal power and staff training coupled with infrastructural challenges can negatively affect data at the input stage. While stakeholders understood and expressed the importance of evidence-based decision-making, ultimately, they noted that the data were not being used to their maximum potential. ConclusionsLeveraging DVTs can improve the use of data for evidence-based decision-making, but decision makers must trust that the data are believable, credible, timely, and responsive. The results support the significance of a tailored data ecosystem, which has not reached its full potential in Bangladesh. Recommendations to reach this potential include ensuring a clear intended user base and accountable stakeholders are present. Systems should also have the capacity to ensure data credibility and support ongoing personal power requirements.

BackgroundHighly effective COVID-19 vaccines are available and free of charge in the United States. With adequate coverage, their use may help return life back to normal and reduce COVID-19–related hospitalization and death. Many barriers to widespread inoculation have prevented herd immunity, including vaccine hesitancy, lack of vaccine knowledge, and misinformation. The Ad Council and COVID Collaborative have been conducting one of the largest nationwide targeted campaigns (“It’s Up to You”) to communicate vaccine information and encourage timely vaccination across the United States. More than 300 major brands, digital and print media companies, and community-based organizations support the campaigns to reach distinct audiences. ObjectiveThe goal of this study was to use aggregated mobility data to assess the effectiveness of the campaign on COVID-19 vaccine uptake. MethodsCampaign exposure data were collected from the Cuebiq advertising impact measurement platform consisting of about 17 million opted-in and deidentified mobile devices across the country. A Bayesian spatiotemporal hierarchical model was developed to assess campaign effectiveness through estimating the association between county-level campaign exposure and vaccination rates reported by the Centers for Disease Control and Prevention. To minimize potential bias in exposure to the campaign, the model included several control variables (eg, age, race or ethnicity, income, and political affiliation). We also incorporated conditional autoregressive residual models to account for apparent spatiotemporal autocorrelation. ResultsThe data set covers a panel of 3104 counties from 48 states and the District of Columbia during a period of 22 weeks (March 29 to August 29, 2021). Officially launched in February 2021, the campaign reached about 3% of the anonymous devices on the Cuebiq platform by the end of March, which was the start of the study period. That exposure rate gradually declined to slightly above 1% in August 2021, effectively ending the study period. Results from the Bayesian hierarchical model indicate a statistically significant positive association between campaign exposure and vaccine uptake at the county level. A campaign that reaches everyone would boost the vaccination rate by 2.2% (95% uncertainty interval: 2.0%-2.4%) on a weekly basis, compared to the baseline case of no campaign. ConclusionsThe “It’s Up to You” campaign is effective in promoting COVID-19 vaccine uptake, suggesting that a nationwide targeted mass media campaign with multisectoral collaborations could be an impactful health communication strategy to improve progress against this and future pandemics. Methodologically, the results also show that location intelligence and mobile phone–based monitoring platforms can be effective in measuring impact of large-scale digital campaigns in near real time.

Ambient particulate matter (PM) pollution in China continues to be a major public health challenge. With the release of the new WHO air quality guidelines in 2021, there is an urgent need for China to contemplate a revision of air quality standards (AQS). In the recent decade, there has been an increase in epidemiological studies on PM in China. A comprehensive evaluation of such epidemiological evidence among the Chinese population is central for revision of the AQS in China and in other developing countries with similar air pollution problems. We thus conducted a systematic review on the epidemiological literature of PM published in the recent decade. In summary, we identified the following: (1) short-term and long-term PM exposure increase mortality and morbidity risk without a discernible threshold, suggesting the necessity for continuous improvement in air quality; (2) the magnitude of long-term associations with mortality observed in China are comparable with those in developed countries, whereas the magnitude of short-term associations are appreciably smaller; (3) governmental clean air policies and personalized mitigation measures are potentially effective in protecting public and individual health, but need to be validated using mortality or morbidity outcomes; (4) particles of smaller size range and those originating from fossil fuel combustion appear to show larger relative health risks; and (5) molecular epidemiological studies provide evidence for the biological plausibility and mechanisms underlying the hazardous effects of PM. This updated review may serve as an epidemiological basis for China’s AQS revision and proposes several perspectives in designing future health studies.

Objectives: Exposure to air pollutants has been linked to preterm birth (PTB) after natural conception. However, few studies have explored the effects of air pollution on PTB in patients who underwent in vitro fertilization (IVF). We aimed to investigate the association between ambient air pollutants exposure and PTB risk in IVF patients.Methods: This retrospective cohort study included 2,195 infertile women who underwent IVF treatment from January 2017 and September 2020 in Hangzhou Women's Hospital. Totally 1,005 subjects who underwent a first fresh embryo(s) transfer cycle were analyzed in this study. Residential exposure to ambient six air pollutants (PM2.5, PM10, SO2, NO2, CO, O3) during various periods of the IVF timeline were estimated by satellite remote-sensing and ground measurement. Cox proportional hazards models for discrete time were used to explore the association between pollutants exposure and incident PTB, with adjustment for confounders. Stratified analyses were employed to explore the effect modifiers.Results: The clinical pregnancy and PTB rates were 61.2 and 9.3%, respectively. We found that PM2.5 exposure was significantly associated with an increased risk of PTB during 85 days before oocyte retrieval [period A, adjusted hazard ratio, HR=1.09, 95%CI: 1.02–1.21], gonadotropin start to oocyte retrieval [period B, 1.07 (1.01–1.19)], first trimester of pregnancy [period F, 1.06 (1.01–1.14)], and the entire IVF pregnancy [period I, 1.07 (1.01–1.14)], respectively. An interquartile range increment in PM10 during periods A and B was significantly associated with PTB at 1.15 (1.04–1.36), 1.12 (1.03–1.28), and 1.14 (1.01–1.32) for NO2 during period A. The stratified analysis showed that the associations were stronger for women aged

Digital health is having a profound effect on health systems, changing the balance of power between provider and patient, enabling new models of care, and shifting the focus of health systems toward client-centered health care within low- and middle-income countries. Though many of these changes are just being felt due to resistance by organizations and individuals reluctant to change the status quo, the explosive growth of digital technology globally means that these changes are inevitable. We can expect to see increasing use of telemedicine for remote diagnostics and treatment, protocol-driven health care to improve quality of care, and better access to goods and services through changes in the organization of transportation and delivery services. Data will become central to health systems, whether big data and artificial intelligence tools for surveillance, planning, and management or “personalized data” in the form of universal electronic record systems and customized treatment protocols. As with any disruptive innovation, the growth of digital health will also bring challenges, including who owns, controls, and manages the data being collected and how to maintain privacy and confidentiality in this data-rich world.

Abstract Background Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation. Methods Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques. Discussion The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae. Trial registration Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023).

Abstract The antibody conjugate gemtuzumab ozogamicin (GO; Mylotarg®) provides targeted therapy of acute myeloid leukemia (AML), with recent approvals for patients with CD33-positive disease at diagnosis or relapse, as monotherapy or combined with chemotherapeutics. While its clinical efficacy is well documented, the molecular routes by which GO induces AML cell death warrant further analyses. We have earlier reported that this process is initiated via mitochondria-mediated caspase activation. Here we provide additional data, focusing on the involvement of caspase-2 in this mechanism. We show that this enzyme plays an important role in triggering apoptotic death of human AML cells after exposure to GO or its active moiety calicheamicin. Accordingly, the caspase-2 inhibitor z-VDVAD-fmk reduced GO-induced caspase-3 activation. This finding was validated with shRNA and siRNA targeting caspase-2, resulting in reduced caspase-3 activation and cleavage of poly [ADP-ribose] polymerase 1 (PARP-1). We previously demonstrated that GO-induced apoptosis included a conformational change of Bax into a pro-apoptotic state. Present data reveal that GO-treatment also induced Bid cleavage, which was partially reduced by caspase-2 specific inhibition while the effect on GO-induced Bax conformational change remained unaltered. In mononuclear cells isolated from AML patients that responded to GO treatment in vitro, processing of caspase-2 was evident, whereas in cells from an AML patient refractory to treatment no such processing was seen. When assessing diagnostic samples from 22 AML patients, who all entered complete remission (CR) following anthracycline-based induction therapy, and comparing patients with long versus those with short CR duration no significant differences in baseline caspase-2 or caspase-3 full-length protein expression levels were found. In summary, we demonstrate that GO triggers caspase-2 cleavage in human AML cells and that the subsequent apoptosis of these cells in part relies on caspase-2. These findings may have future clinical implications.

Biomarker signatures identified through minimally invasive procedures already at diagnosis of non‐small‐cell lung cancer (NSCLC) could help to guide treatment with immune checkpoint inhibitors (ICI). Here, we performed multiplex profiling of immune‐related proteins in fine‐needle aspirate (FNA) samples of thoracic lesions from patients with NSCLC to assess PD‐L1 expression and identify related protein signatures. Transthoracic FNA samples from 14 patients were subjected to multiplex antibody‐based profiling by proximity extension assay (PEA). PEA profiling employed protein panels relevant to immune and tumor signaling and was followed by Qlucore® Omics Explorer analysis. All lesions analyzed were NSCLC adenocarcinomas, and PEA profiles could be used to monitor 163 proteins in all but one sample. Multiple key immune signaling components (including CD73, granzyme A, and chemokines CCL3 and CCL23) were identified and expression of several of these proteins (e.g., CCL3 and CCL23) correlated to PD‐L1 expression. We also found EphA2, a marker previously linked to inferior NSCLC prognosis, to correlate to PD‐L1 expression. Our identified protein signatures related to stage included, among others, CXCL10 and IL12RB1. We conclude that transthoracic FNA allows for extensive immune and tumor protein profiling with assessment of putative biomarkers of important for ICI treatment selection in NSCLC.

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow‐up of personalized cancer therapy, including immunotherapy. Fine‐needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL‐6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune‐related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.

ObjectivesThe aim was to analyse the tumor expression of Notch1, Hes1, Ascl1, and DLL3 in Small-Cell Lung Cancer (SCLC) and each such biomarker's potential association with clinical characteristics and prognosis after platinum-doublet chemotherapy (PDCT).Material and methodsThe protein expression of the biomarkers was evaluated using immunohistochemistry. Patients were categorized according to their sensitivity to first line PDCT: with a Progression-free survival (PFS) ≥ 3 months after completion of treatment considered "sensitive" and < 3 months after completion of treatment considered "refractory". PFS and overall survival were computed using Kaplan-Meier curves with 95% confidence interval.Results and conclusionThe study included 46 patients, with 21 and 25 of the patients having "sensitive" and "refractory" disease, respectively. The majority of patients had a high DLL3 expression (n = 38), while a minority had Notch 1-high expression (n = 10). The chi-square test showed that there was a statistically significant negative association between Notch1 and Ascl1 expression (p = 0.013). The overall survival for patients with Notch1- high vs. low expression was 8.1 vs. 12.4 months, respectively (p = 0.036). Notch1 expression was an independent prognostic factor in the multivariate analysis (p = 0.02). No other biomarker showed any prognostic impact in this highly selected SCLC cohort. DLL3 is highly expressed in the majority of advanced staged SCLC cases, as expected. In the same patient population, Notch1 expression might have a potential prognostic implication, by driving a non-neuroendocrine differentiation process. Given the small number of cases with Notch1 high expression, the results of this study needs to be confirmed on a larger cohort.

The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p