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Background People living with HIV and non-communicable diseases (NCDs) are reported to experience challenges in accessing affordable and high-quality NCD care services. Consequently, the World Health Organization (WHO) recommends care integration of NCDs within the HIV services in resource-limited regions. The available opportunities and challenges need to be understood and addressed for an effective integration process. This study explored opportunities and challenges for integrating NCDs within HIV care and treatment services in Tanzania. Methods An exploratory qualitative case study was conducted in Tanzania between April and July 2022. A total of 22 key informants working at the ministerial level, supervising the provision of healthcare services in Tanzania, were recruited purposefully for in-depth interviews. Thematic analysis was employed during the study. Results Several opportunities were identified in the study for HIV/NCD services integration including the existence of an integration policy, the availability of regulations and guidelines, the existence of donor support, the presence of physical space and reliable information and communication systems, human resources adequacy, and political will to support the process. However, participants voiced concerns over the costs related to service integration, difficulties in reallocating donor funds, and hesitance of the healthcare providers as likely challenges to effective integration. Conclusion The findings of this study underscore that the effective and sustainable care integration of NCDs within HIV services relies on the availability of policy, funds, infrastructures, human resources, and stakeholders’ willingness to support the process.

Introduction Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use.Methods and analysis In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org.Ethics and dissemination The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings.Trial registration number NCT06445946.

PURPOSEThis study sought to delineate the clinical, laboratory, and imaging characteristics during multiple myeloma (MM) diagnosis, outline the treatment modalities administered, and ascertain the survival rates among patients with MM over a comprehensive 5-year span in Tanzania.METHODSThis retrospective cohort study investigated patients diagnosed with MM at the Cancer Care Clinic, Kilimanjaro Christian Medical Centre, between January 2017 and June 2022. Demographic data, clinical profiles, and survival outcomes were collected. The study employed the Kaplan-Meier method to determine overall survival (OS) and survival rates, supported by univariate analysis and a multivariate Cox regression model with significance of P < .05.RESULTSIn this study of 76 patients with MM, bone pain was the most common complaint (76.3%), and patients were age typically older than 50 years (82.5%). Laboratory tests showed frequent abnormalities, such as anemia (51.3%) and hypercalcemia (23.9%). Most patients were at stage III according to Durie Salmon Staging (82.7%), with imaging revealing various bone abnormalities. The median OS was 18.0 months, with 46.1% of patients passing away during the study period. Factors linked to shorter survival included anemia, renal failure, and bone involvement. Infection was the primary cause of death among these patients. The presenting complaint of bone pain significantly affected survival outcomes.CONCLUSIONThis study provides a comprehensive understanding of MM within the Sub-Saharan African context, highlighting age-related disparities in diagnosis, predominant presenting symptoms like bone pain, factors contributing to delayed diagnoses, and the impact on survival rates. The findings underscore the critical need for early recognition, improved diagnostics, and tailored interventions to enhance outcomes for patients with MM in this region.

This paper presents a groove gap waveguide structure designed to serve as a feeding network for dual circularly polarized antenna arrays in the millimeter wave spectrum (28-32 GHz). The proposed structure comprises four groove gap waveguide elements arranged in a cross-shaped configuration. A turnstile integrated into the middle position of the structure divides the incoming RF signal into these four waveguide elements. Four matching posts are incorporated at the end of the various groove gap waveguide elements to route each corresponding RF signal to four WR-28 waveguide sections. These four sections form the output ports of the feeding network. The appropriate design of the pin distributions along the four groove gap elements allows the entire feeding network to achieve a specific phase shift between the output ports. As a proof of concept, the proposed feeding network is connected to a dual circularly polarized antenna array composed of four sub-arrays. Two of these sub-arrays emit right-handed circularly polarized waves, while the other two are designed to provide left-handed circularly polarized waves. A prototype of the feeding network demonstrates its ability to produce the needed circularly polarized radiation for a given distribution of the pins along the various groove gap elements. The results show that the feeding network can achieve an insertion loss as low as 0.55 dB with a good impedance matching across the entire operational bandwidth. In addition, when the fabricated feeding network is connected to the dual-circularly polarized antenna prototype, a maximum realized gain of 15.14 dBic is obtained.

This paper introduces a dual band-pass and dual band-stop filter that is designed along its flexible back-end circuitry to sense and monitor muscle contractions. The filter and its back-end circuit are proposed to be wearable, flexible, and stretchable. The presented design is composed of several logarithmically scaled spiral-shaped defected ground structures (DGS) located along the ground plane of a co-planar waveguide transmission line. In addition, U-shaped slots are integrated within the transmission line to maintain the sensing operation of the filter when its structure is stretched. The entire structure is fabricated on a multi-part flexible Polyethylene Terephthalate (PET) substrate and its stretchable configuration is enabled through the integration of a Room-Temperature-Vulcanizing (RTV) silicon substrate. Such stretchable ability is obtained through the movement of the multiple parts that compose the filter and is exhibited by the tuning of its band-pass and band-stop frequencies of operation between 1 GHz and 4 GHz. Correspondingly, the stretchable ability of the filter is also indicated by the change in magnitudes of its reflection and transmission coefficients. As a result, for the band-pass operation, the insertion loss of the flexible wearable filter, placed above the human arm, at the first frequency (1.39 GHz) is −1.95 dB with a tuning range of 590 MHz, and at the second frequency (2.68 GHz) −1.94 dB with a tuning range of 330 MHz. The change in the response of the presented system is proportional to the intensity of the muscle contraction. To capture this change, a custom-designed integrated flexible back-end circuit interrogates the sensor, collects the magnitudes of the reflection and transmission coefficients, and outputs corresponding voltages. As a result, monitoring the output voltage of the back-end circuit indicates the muscle contraction level, which is sensed from the stretching movement of the filter's structure. The back-end circuit and the sensor are fabricated and tested over multiple measurement cycles where the ability of the sensor to track muscle contraction is demonstrated.

Abstract This study proposes a highly sensitive portable device that utilizes electromagnetic waves and data analytics for instantaneous Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS‐CoV‐2) detection. The device consists of a Radio Frequency (RF) circuit that interprets reflected and transmitted electromagnetic waves to identify virus signatures in physiologically significant matrices, including human saliva and diluted nasopharyngeal swabs. The sensor's accuracy is validated in both pre‐clinical and clinical settings, where clinical measurements demonstrate an instantaneous detection accuracy of 94%, sensitivity of 95%, and specificity of 97.5% between the sensor's physical parameters and SARS‐CoV‐2 detection. The sensor's accurate real‐time response is due to its unique design and precise modeling techniques. In addition, the same sensing system is tested across different viruses and its ability to differentiate between influenza A, respiratory syncytial, and SARS‐CoV‐2 viruses is proven. Hence this work presents a holistic system that can predict the viral concentration of SARS‐CoV‐2, as well as differentiate between different viruses instantaneously and without adding any amplifying agent.

Abstract In disaster-prone areas, damaged infrastructure requires impromptu communications leveraging lightweight and adaptive antennas. Accordingly, we introduce a bi-stable deployable quadrifilar helix antenna that passively reconfigures its radiation characteristics in terms of pattern and polarization. The proposed structure is composed of counter-rotating helical strips, connected by rotational joints to allow a simultaneous change in the helix height and radius. Each helical strip is composed of a fiber-reinforced composite material to achieve two stable deployed states that are self-locking. The reconfiguration between an almost omnidirectional pattern and a circularly polarized directive pattern enables the antenna to be suitable for both terrestrial and satellite communication within the L-band. More specifically, the presented design in infrastructure-less areas achieves satellite localization with directive circularly polarized waves and point-to-point terrestrial connectivity with an almost omnidirectional state. Hence, we present a portable, agile, and passively reconfigured antenna solution for low-infrastructure areas.

BackgroundAfrica has consistently had the highest prevalence (70.1%) of H. pylori, and this has led to significant cases of dyspepsia, gastric cancers, and upper gastrointestinal bleeding. However, most studies have used sero-prevalence, which might not give the current state of the infection. Among the tests, the stool antigen test is simple, quick, and effective. The study aimed to determine the feco-prevalence, endoscopic pattern, and associated factors of H. pylori infection among symptomatic adult patients in Northern Tanzania.Materials and methodsA hospital-based, cross-sectional study was conducted from October 2022 to April 2023 among adults attending the gastroenterology clinic at Kilimanjaro Chistian Medical Centre. A systematic random sampling was used to select the participants with indications of undergoing esophagogastroduodenoscopy. Questionnaires, stool and blood samples, and endoscopy were used to collect variable data. Numerical and categorical variables were summarized into narrations and tables. Logistic regression was used to assess the factors associated with H. pylori.ResultsThe feco-prevalence of H. pylori was 43.4%. Chronic gastritis (51.1%) was the most common endoscopic pattern, whereas duodenal ulcers and gastric ulcers were significantly associated with H. pylori infection. Increasing in age (p ConclusionThe feco-prevalence of H. pylori is high in this setting. H. pylori stool antigen can be used as the initial workup for symptomatic patients before the initiation of proton pump inhibitors. Additionally, due to other causes of dyspepsia, it is advised that H. pylori stool antigen testing be part of the initial evaluation and esophagogastroduodenoscopy be considered in the absence of other alarm symptoms if symptoms persist despite an appropriate trial of medical therapy.

This paper presents a diplexer design that generates a pair of fundamental and harmonic frequencies. The diplexer is based on a capacitively loaded resonator that is able to reconfigure its frequency pair with respect to capacitive loading. The system shows a fundamental and harmonic frequency pair of 5 GHz and 10 GHz without any capacitive loading and 2.5 GHz and 5 GHz when loaded with a 1pF/0.5 pF capacitor pair. The complete system is fabricated and tested where good agreement is obtained between the measured and computed results. The testing is performed for the two states of the diplexer, when the diplexer is unloaded and after loading it with the capacitor pairs. For both unloaded and loaded scenarios, the proposed design produces a maximum insertion loss of 0.6 dB with an isolation of at least 35 dB at the corresponding operational frequencies. The structure is also able to provide a minimum return loss of 25 dB at each port. The proposed diplexer is then integrated with a frequency doubler chip and the full system maintains an acceptable efficiency along with a high conversion gain of approximately 15 dB.

This paper presents a compact ultra-high frequency (UHF) folded antenna design that relies on a single radio frequency micro-electro-mechanical switch (RF-MEMS) to reconfigure its frequency of operation between 575 MHz and 760 MHz. The reconfigurable multi-layered antenna design has a volumetric folded topology with total dimensions of 40×40mm2; equivalent to 0.11λx0.11λ at 575 MHz. The antenna is fabricated and tested where the measurements agree well with the simulation results. The antenna exhibits a radiation efficiency of 40% at 575 MHz and 62% at 760 MHz. Furthermore, the proposed antenna is tested in a cognitive radio environment to validate its ability to adapt to cognitive input and tune its performance across white space within the UHF band. This is achieved by relying on a trained classifier model that is embedded within a microcontroller to autonomously control the state of the integrated switch based on which channel is idle.

Abstract Background The emergency of antimicrobial resistance due to irrational antimicrobial use has put public health under threat. Accredited Drug Dispensing Outlets (ADDOs) play an important role in enhancing availability and accessibility of antimicrobials, however, there is a scarcity of studies assessing antimicrobial dispensing practices in these outlets, focusing on children in Tanzania. Objective This study was conducted to assess the antimicrobial dispensing practices among ADDO dispensers and explore the factors influencing the use of antimicrobials for children in Tanzania. Methods A community-based cross-sectional study utilizing both qualitative (interviews) and quantitative (simulated clients) methods was conducted between June and September 2020 in seven zones and 14 regions in Tanzania. Results The study found inappropriate dispensing and use of antimicrobials for children, influenced by multiple factors such as patient’s and dispenser’s knowledge and attitude, financial constraints, and product-related factors. Only 8% (62/773) of dispensers asked for prescriptions, while the majority (90%) were willing to dispense without prescriptions. Most dispensers, 83% (426/513), supplied incomplete doses of antimicrobials and only 60.5% (345/570) of the dispensers gave proper instructions for antimicrobial use to clients. Over 75% of ADDO dispensers displayed poor practice in taking patient history. Conclusion ADDO dispensers demonstrated poor practices in dispensing and promoting rational antimicrobial use for children. Training, support, and regulatory interventions are required to improve antimicrobial dispensing practices in community drug outlets.

Abstract This work introduces novel body-matched, vasculature-inspired, quasi-antenna-arrays that act as electromagnetic sensors to instantaneously, continuously, and wirelessly sense glucose variations in the bloodstream. The proposed sensors are personalized, leverage electromagnetic waves, and are coupled with a custom machine-learning-based signal-processing module. These sensors are flexible, and embedded in wearable garments such as socks, which provide conformity to curved skin surfaces and movement resilience. The entire wearable system is calibrated against temperature, humidity, and movement resulting in high accuracy in glucose variations tracking. In-Vivo experiments on diabetic rats and pigs exhibit a 100% diagnostic accuracy over a wide range of glucose variations. Human trials on patients with diabetes and healthy individuals reveal a clinical accuracy of continuous glucose monitoring of 99.01% in twenty-eight subjects who underwent Oral Glucose Tolerance Tests. Hence, our approach ensures the continuous tracking of glucose variations from hypo-to-hyper glycemic levels with great fidelity.

Objective Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum. Methods This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow‐up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7‐item, and the Patient‐Reported Outcomes Measurement Information System Global Health measure. A semi‐parametric, group‐based mixture model (trajectory analysis) was applied. Results Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms. Conclusions Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women.

Objective This study aimed to develop a prediction model that estimates the probability that a pregnant person who has had asymptomatic or mild coronavirus disease 2019 (COVID-19) prior to delivery admission will progress in severity to moderate, severe, or critical COVID-19. Study Design This was a secondary analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients who delivered from March through December 2020 at hospitals across the United States. Those eligible for this analysis presented for delivery with a current or previous asymptomatic or mild SARS-CoV-2 infection. The primary outcome was moderate, severe, or critical COVID-19 during the delivery admission through 42 days postpartum. The prediction model was developed and internally validated using stratified cross-validation with stepwise backward elimination, incorporating only variables that were known on the day of hospital admission. Results Of the 2,818 patients included, 26 (0.9%; 95% confidence interval [CI], 0.6–1.3%) developed moderate–severe–critical COVID-19 during the study period. Variables in the prediction model were gestational age at delivery admission (adjusted odds ratio [aOR], 1.15; 95% CI, 1.08–1.22 per 1-week decrease), a hypertensive disorder in a prior pregnancy (aOR 3.05; 95% CI, 1.25–7.46), and systolic blood pressure at admission (aOR, 1.04; 95% CI, 1.02–1.05 per mm Hg increase). This model yielded an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.72–0.91). Conclusion Among individuals presenting for delivery who had asymptomatic–mild COVID-19, gestational age at delivery admission, a hypertensive disorder in a prior pregnancy, and systolic blood pressure at admission were predictive of delivering with moderate, severe, or critical COVID-19. This prediction model may be a useful tool to optimize resources for SARS-CoV-2-infected pregnant individuals admitted for delivery. Key Points Three factors were associated with delivery with more severe COVID-19. The developed model yielded an area under the receiver operating characteristic curve of 0.82 and model fit was good. The model may be useful tool for SARS-CoV-2 infected pregnancies admitted for delivery. [ABSTRACT FROM AUTHOR]

Daucus carota L., a member of the Apiaceae family, comprises 13 subspecies, with one being cultivated (D. carota L. ssp. sativus (Hoffm.) Arcang.) and the remaining being wild. Traditionally, the wild carrot has been recognized for its antilithic, diuretic, carminative, antiseptic, and anti-inflammatory properties and has been employed in the treatment of urinary calculus, cystitis, gout, prostatitis, and cancer. While extensive literature is available on the phytochemical, pharmacological, and therapeutic evaluations of the cultivated carrot, limited information has been published on the wild carrot. A thorough search was conducted on the phytochemical composition, folk-medicine uses, and pharmacological properties of wild carrot subspecies (Daucus carota L. ssp. carota). Various electronic databases were consulted, and the literature spanning from 1927 to early 2023 was reviewed. Thirteen wild Daucus carota subspecies were analyzed, revealing over 310 compounds, including terpenoids, phenylpropenoids, flavonoids, and phenolic acids, with 40 constituting more than 3% of the composition. This review also highlights the antioxidant, anticancer, antipyretic, analgesic, antibacterial, antifungal, hypolipidemic, and hepato- and gastroprotective properties of wild carrot subspecies. Existing in vitro and in vivo studies support their traditional uses in treating infections, inflammation, and cancer. However, further research on other subspecies is required to confirm additional applications. Well-designed preclinical and clinical trials are still necessary to establish the safety and efficacy of wild Daucus carota for human use.

[Ru(bipy)2(dpphen)]Cl2 (where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) (complex 1) is a sterically strained compound that exhibits promising in vitro photocytotoxicity on an array of cell lines. Since lung adenocarcinoma cancer remains the most common lung cancer and the leading cause of cancer deaths, the current study aims to evaluate the plausible effect and uptake of complex 1 on human alveolar carcinoma cells (A549) and mesenchymal stem cells (MSC), and assess its cytotoxicity in vitro while considering its effect on cell morphology, membrane integrity and DNA damage. MSC and A549 cells showed similar rates of complex 1 uptake with a plateau at 12 h. Upon photoactivation, complex 1 exhibited selective, potent anticancer activity against A549 cells with phototoxicity index (PI) values of 16, 25 and 39 at 24, 48 and 72 h, respectively. This effect was accompanied by a significant increase in A549-cell rounding and detachment, loss of membrane integrity and DNA damage. Flow cytometry experiments confirmed that A549 cells undergo apoptosis when treated with complex 1 followed by photoactivation. In conclusion, this present study suggests that complex 1 might be a promising candidate for photochemotherapy with photoproducts that possess selective anticancer effects in vitro. These results are encouraging to probe the potential activity of this complex in vivo.

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

Abstract Response to environmental thermomechanical inputs in applications that range from wearable electronics to aerospace structures necessitates agile communication systems driven by reconfigurable electromagnetic structures. Antennas in these systems must dynamically preserve acceptable radiation characteristics while enabling on‐demand performance reconfiguration. However, existing reconfiguration mechanisms through stretchable conductors rely on high‐strain behavior in soft substrates, which limits their applicability. Herein, this work demonstrates the use of mechanical metamaterials for stretchable conductors and dielectrics in antennas. Metamaterials allow conductor stretching up to 30% with substrate base material tensile moduli ranging from 26 MPa to 44 GPa. It is shown, through several antenna designs, that mechanical metamaterials enable similar frequency reduction upon stretching as monolithic conductors, while simultaneously providing a miniaturization effect. The conductor patterning, furthermore, provides control over coupling between mechanical stretching and electromagnetic reconfiguration. This approach enables designing reconfigurable antenna functionality through metamaterial geometry in response to arising needs in applications ranging from body‐adapted electronics to space vehicles.

ImportancePregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.MethodsRECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.DiscussionRECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.Clinical trials.gov identifierClinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a variety of vasoactive bioactive lipid metabolites during the inflammatory response and produce pro-resolving mediators (e.g., Lipoxin A4, LXA4) in cooperation with leukocytes and platelets to bring a halt to inflammation. Aspirin, used in a variety of cardiovascular and pro-thrombotic disorders (e.g., atherosclerosis, angina, preeclampsia), potently inhibits proinflammatory eicosanoid formation. Moreover, aspirin stimulates the synthesis of pro-resolving lipid mediators (SPM), so-called Aspirin-Triggered Lipoxins (ATL). We demonstrate that cytokines stimulated a time- and dose-dependent increase in PGI2 (6-ketoPGF1α) and PGE2 formation that is blocked by aspirin. Eicosanoid production was caused by cytokine-induced expression of cyclooxygenase-2 (COX-2). We also detected increased production of pro-resolving LXA4 in cytokine-stimulated endothelial cells. The R-enantiomer of LXA4, 15-epi-LXA4, was enhanced by aspirin, but only in the presence of cytokine challenge, indicating dependence on COX-2 expression. In contrast to previous reports, we detected arachidonate 5-lipoxygenase (ALOX5) mRNA expression and its cognate protein (5-lipoxygenase, 5-LOX), suggesting that endothelial cells possess the enzymatic machinery necessary to synthesize both pro-inflammatory and pro-resolving lipid mediators independent of added leukocytes or platelets. Finally, we observed that, endothelial cells produced LTB4 in the absence of leukocytes. These results indicate that endothelial cells produce both pro-inflammatory and pro-resolving lipid mediators in the absence of other cell types and aspirin exerts pleiotropic actions influencing both COX and LOX pathways.

Testicular germ cell tumours (TGCTs) respond well to cisplatin-based therapy. However, cisplatin resistance and poor outcomes do occur. It has been suggested that a shift towards DNA hypermethylation mediates cisplatin resistance in TGCT cells, although there is little direct evidence to support this claim. Here we utilized a series of isogenic cisplatin-resistant cell models and observed a strong association between cisplatin resistance in TGCT cells and a net increase in global CpG and non-CpG DNA methylation spanning regulatory, intergenic, genic and repeat elements. Hypermethylated loci were significantly enriched for repressive DNA segments, CTCF and RAD21 sites and lamina associated domains, suggesting that global nuclear reorganization of chromatin structure occurred in resistant cells. Hypomethylated CpG loci were significantly enriched for EZH2 and SUZ12 binding and H3K27me3 sites. Integrative transcriptome and methylome analyses showed a strong negative correlation between gene promoter and CpG island methylation and gene expression in resistant cells and a weaker positive correlation between gene body methylation and gene expression. A bidirectional shift between gene promoter and gene body DNA methylation occurred within multiple genes that was associated with upregulation of polycomb targets and downregulation of tumour suppressor genes. These data support the hypothesis that global remodelling of DNA methylation is a key factor in mediating cisplatin hypersensitivity and chemoresistance of TGCTs and furthers the rationale for hypomethylation therapy for refractory TGCT patients.