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Objective Individuals who work on health data systems and services are uniquely positioned to understand the risks of health data collection and use. We designed and conducted a survey assessing the perceptions of those who work with health data around health data consent, sharing, and privacy practices in healthcare and clinical research. Methods A 43-item online survey was distributed via a market research firm to individuals (18+) who work with health data in the United States from March to April 2023. Descriptive statistics were calculated for all variables. Associations with demographic variables were assessed using Pearson's X 2 tests and ordinal logistic regression. Results Most of our respondents (61.7%) reported that they would trust people to use their health data across various sectors, but more respondents trusted those working in academic medical research (86.5%) and healthcare offices (89.9%) compared to those working in industry (68.2%). Despite this reported trust, a strong majority believed that individuals should have complete control over their health data (97.3%), specific consent should be obtained for each use of their health data (92.0%), and that there should be higher standards of consent and privacy for health records data than other types of data (93.7%). Conclusions Based on our findings, we might infer that people who work with health data generally trust institutions across sectors to protect their health data. However, many would prefer to have complete control over who has access to their health data and how it is used. These insights should be explored further through qualitative studies.

Abstract Background Fructans are water-soluble carbohydrates that accumulate in wheat and are thought to contribute to a pool of stored carbon reserves used in grain filling and tolerance to abiotic stress. Results In this study, transgenic wheat plants were engineered to overexpress a fusion of two fructan biosynthesis pathway genes, wheat sucrose: sucrose 1-fructosyltransferase (Ta1SST) and wheat sucrose: fructan 6-fructosyltransferase (Ta6SFT), regulated by a wheat ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (TaRbcS) gene promoter. We have shown that T4 generation transgene-homozygous single-copy events accumulated more fructan polymers in leaf, stem and grain when compared in the same tissues from transgene null lines. Under water-deficit (WD) conditions, transgenic wheat plants showed an increased accumulation of fructan polymers with a high degree of polymerisation (DP) when compared to non-transgenic plants. In wheat grain of a transgenic event, increased deposition of particular fructan polymers such as, DP4 was observed. Conclusions This study demonstrated that the tissue-regulated expression of a gene fusion between Ta1SST and Ta6SFT resulted in modified fructan accumulation in transgenic wheat plants and was influenced by water-deficit stress conditions.

BackgroundParasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome.MethodsA matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community.ResultsIn simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia.ConclusionThe findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.

# Background Limitations exist with current ACLR functional testing assessments that may be mitigated by including single-leg multi-directional testing. # Hypothesis/Purpose To compare Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI) scores, limb symmetry index (LSI) of the single-leg vertical jump (SLVJ), single-leg medial rotation hop (SLMRH), single-leg lateral hop (SLLH), and isokinetic quadriceps strength between participants with an ACLR and healthy controls and assess predictors of quadriceps strength asymmetry. It was hypothesized that ACL-RSI scores and LSIs for all tests would differ between ACLR and healthy control groups and within the ACLR group a strong correlation would exist between all outcome measures and quadriceps strength. # Study Design Cross-Sectional Study # Methods Twenty-six participants with an ACLR (median 13 months after surgery) and twenty-six matched healthy controls were recruited to participate in this study. Performance was assessed via SLVJ, SLMRH, SLLH, and isokinetic quadriceps strength. Between-group comparisons were made with independent t-tests and Mann-Whitney U test. Within the ACLR group, bivariate correlation and multivariate regression analysis were performed to assess the relationship between the outcome measures and quadriceps strength asymmetry. # Results Significant between-limb differences were only identified in the ACLR group (p< 0.05): SLVJ LSI: 88.5%, SLMRH LSI: 93.6%, SLLH LSI: 92.7%, quadriceps strength LSI 80.9% - 83.9%, which were significantly lower (p 0.05) correlation with quadriceps strength (r= 0.12-0.30). # Conclusion Single-leg multidirectional test LSIs were less in ACLR participants than matched healthy controls and all were directly related to quadriceps strength. Psychological readiness to return to sport was not related to quadriceps strength.

(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the current study, we used VESGEN for the assessment of individuals with early-stage NPDR imaged by FA (Cohort 1) and by optical coherence tomography angiography (OCTA; Cohort 2). (2) Methods: Cohort 1 included type 2 diabetics (T2D), represented 21 eyes (ranging from no DR to moderate DR), and also included nondiabetic controls (NDC; n = 15 eyes). Cohort 2 consisted of 23 eyes from T2D subjects (including no DR subjects and moderate DR subjects) and NDC (n = 18 eyes). (3) Results: In the FA-VESGEN study, total tortuosity (Tv) of microvessels (G ≥ 6) increased in T2D with mild DR compared to the controls. In contrast, the VESGEN analysis of OCTA images showed that vessel length (characterized as density) was lower in T2D subjects before the diagnosis of DR and following the diagnosis of DR when compared to the controls. Additionally, T2D showed a significant decrease in vessel area (density). (4) Conclusions: FA elucidated the vessel morphology of small-generation microvessels to a greater degree than OCTA; however, OCTA identified changes in vessel density better than FA. VESGEN analysis can be used with both standard FA and OCTA to facilitate our understanding of early events in DR, including before the clinical diagnosis of DR.

Abstract Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.

Totally endoscopic robotic mitral valve repair is the least invasive surgical therapy for mitral valve disease. Robotic mitral valve surgery demonstrates faster recovery with shorter hospital stays, less morbidity, and equivalent mortality and mid-term durability compared to sternotomy. In this review, we will explore the advantages and disadvantages of robotic mitral valve surgery and consider important technical details of both operative set-up and mitral valve repair techniques. The number of robotic cardiac surgical procedures being performed globally is expected to continue to rise as experience grows with robotic techniques and increasing numbers of cardiac surgeons become proficient with this innovative technology. This will be facilitated by the introduction of newer robotic systems and increasing patient demand.

Summary: Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

Patients with inflammatory bowel disease (IBD) are exposed to chronic systemic inflammation and are at risk for secondary malignancies. Here we review the literature on the risk of myeloid neoplasms (MN) in IBD and present the disease profiles of patients at a single institution with IBD who later developed MN, comparing them to those in the literature. No IBD characteristic was found to associate with MN disease severity, including the previously-identified association between MNs and thiopurine exposure. Of the somatic mutations identified in out cohort's MN, mutations in TET2 were most prevalent, followed by FLT3-ITD, BCR-ABL, and NPM1 mutations.

An approach to gauge theory in the context of locally conformally flat space–time is described. It is discussed how there are a number of natural principal bundles associated with any given locally conformally flat space–time X. The simplest of these principal bundles is the bundle PX(G) with structure group G = U(2, 2). An 11-dimensional bundle Q with structure group a certain seven-dimensional group K is constructed by a method involving a reduction of structure group for the bundle PX(G). It is shown how the gauge groups U(1), SU(2), and SU(3) can be derived from the geometry of locally conformally flat space–time. Fock spaces of multiparticle states for the fields of the standard model are constructed in the context of bundles with these groups as structure groups. Scattering and other particle interaction processes are defined in terms of linear maps between multiparticle state spaces. A technique for computing analytically and/or computationally the masses of the elementary particles is described. This method involves the computation of a certain quantity called the integral mass spectrum for a given family of particles and then the masses of the particles in the family are determined to be the locations of the peaks of the integral mass spectrum. The method is applied successfully in the electroweak sector to the cases of the charged leptons, μ and τ, and the Z0 particle.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract Anthropogenic climate change causes more frequent and intense fluctuations in the El Niño Southern Oscillation (ENSO). Understanding the effects of ENSO on agricultural systems is crucial for predicting and ameliorating impacts on lives and livelihoods, particularly in perennial tree crops, which may show both instantaneous and delayed responses. Using cocoa production in Ghana as a model system, we analyse the impact of ENSO on annual production and climate over the last 70 years. We report that in recent decades, El Niño years experience reductions in cocoa production followed by several years of increased production, and that this pattern has significantly shifted compared with prior to the 1980s. ENSO phase appears to affect the climate in Ghana, and over the same time period, we see corresponding significant shifts in the climatic conditions resulting from ENSO extremes, with increasing temperature and water stress. We attribute these changes to anthropogenic climate change, and our results illustrate the big data analyses necessary to improve understanding of perennial crop responses to climate change in general, and climate extremes in particular.

Weight gain is a known adverse effect of ruxolitinib, a JAK1/2 inhibitor that is the mainstay of treatment for many patients with myelofibrosis. The mechanisms behind weight increase with ruxolitinib is incompletely understood, although decreased adipose tissue lipolysis and increased appetite due to blocking the effects of leptin in the hypothalamus have been proposed. In order to explore the metabolic changes in ruxolitinib-treated patients with myelofibrosis, we performed a pilot study to assess the feasibility of using a portable indirect calorimeter to quantify energy expenditure before and during ruxolitinib treatment and report the results of two patients. Waist circumference increased during ruxolitinib treatment in both patients. Energy expenditure initially increased followed by a decrease and then increase again, but to levels below baseline. These results suggest that weight gain secondary to ruxolitinib may be related to changes in whole body energy expenditure.

Pentraxin 2 (PTX-2; serum amyloid P component), a circulating endogenous regulator of the inflammatory response to tissue injury and fibrosis, is reduced in patients with myelofibrosis (MF). Zinpentraxin alfa (RO7490677, PRM-151) is a recombinant form of PTX-2 that has shown preclinical antifibrotic activity and no dose-limiting toxicities in phase I trials. We report results from stage 1 of a phase II trial of zinpentraxin alfa in patients with intermediate-1/2 or high-risk MF. Patients (n=27) received intravenous zinpentraxin α weekly (QW) or every 4 weeks (Q4W), as monotherapy or an additional therapy for patients on stable-dose ruxolitinib. The primary endpoint was overall response rate (ORR; investigatorassessed) adapted from International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria. Secondary endpoints included modified Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) change, bone marrow (BM) MF grade reduction, pharmacokinetics, and safety. ORR at week 24 was 33% (n=9/27) and varied across individual cohorts (QW: 38% [3/8]; Q4W: 14% [1/7]; QW+ruxolitinib: 33% [2/6]; Q4W+ruxolitinib: 50% [3/6]). Five of 18 evaluable patients (28%) experienced a ≥50% reduction in MPN-SAF TSS, and six of 17 evaluable patients (35%) had a ≥1 grade improvement from baseline in BM fibrosis at week 24. Most treatment-emergent adverse events (AE) were grade 1–2, most commonly fatigue. Among others, anemia and thrombocytopenia were infrequent (n=3 and n=1, respectively). Treatment-related serious AE occurred in four patients (15%). Overall, zinpentraxin alfa showed evidence of clinical activity and tolerable safety as monotherapy and in combination with ruxolitinib in this open-label, non-randomized trial (clinicaltrials gov. Identifier: NCT01981850).

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicentre UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. Mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR vs 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including IABP support (p=0.02), early re-operation (p

Abstract Background Understanding the cost and/or cost-effectiveness of implementation strategies is crucial for organizations to make informed decisions about the resources needed to implement and sustain evidence-based interventions (EBIs). This economic evaluation protocol describes the methods and processes that will be used to assess costs and cost-effectiveness across implementation strategies used to improve the reach, adoption, implementation, and organizational maintenance of an evidence-based pediatric weight management intervention- Building Health Families (BHF). Methods A within-trial cost and cost-effectiveness analysis (CEA) will be completed as part of a hybrid type III effectiveness-implementation trial (HEI) designed to examine the impact of an action Learning Collaborative (LC) strategy consisting of network weaving, consultee-centered training, goal-setting and feedback, and sustainability action planning to improve the adoption, implementation, organizational maintenance, and program reach of BHF in micropolitan and surrounding rural communities in the USA, over a 12-month period. We discuss key features of implementation strategy components and the associated cost collection and outcome measures and present brief examples on what will be included in the CEA for each discrete implementation strategy and how the results will be interpreted. The cost data will be collected by identifying implementation activities associated with each strategy and using a digital-based time tracking tool to capture the time associated with each activity. Costs will be assessed relative to the BHF program implementation and the multicomponent implementation strategy, included within and external to a LC designed to improve reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of BHF. The CEA results will be reported by RE-AIM outcomes, using the average cost-effectiveness ratio or incremental cost-effectiveness ratio. All the CEAs will be performed from the community perspective. Discussion The proposed costing approach and economic evaluation framework for dissemination and implementation strategies and EBI implementation will contribute to the evolving but still scant literature on economic evaluation of implementation and strategies used and facilitate the comparative economic analysis. Trial registration ClinicalTrials.gov NCT04719442 . Registered on January 22, 2021.

Storage conditions influence the nutritive value and quality of many legumes. The aim of this study was to evaluate the quality of beans stored under hermetic conditions as a strategy for preserving the quality of beans post-harvest. Three bean varieties [Rosecoco, small red (Wairimu)], and red mottled (Nyayo)] were adjusted to three moisture levels (12%, 15% and 18%) and stored in hermetic bags and ordinary polypropylene bags and sampled after 0, 45, 90, 135,180, 225 and 270 days for chemical and anti-nutritional analysis. Total soluble sugars, in-vitro starch and protein digestibility, free amino nitrogen, tannin content and phytic acid content of the beans were determined using standard methods. Results showed that the beans in hermetic bags had 22%, 23% and 18% higher total soluble sugars, in-vitro starch and protein digestibility, respectively, than those in polypropylene bag during storage. On day 225 of storage, beans in hermetic bags had the optimal in-vitro starch and protein digestibility, and tannin content. Principal component analysis indicated that nutrient and anti-nutrient retention of the beans was achieved with lower storage moisture and duration in hermetic bags. The results of this study can be used to explain the superiority of the hermetic storage technology over ordinary methods of beans storage, and by extension other legumes, in nutrient retention during storage.

Abstract Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in late Rab7‐positive multivesicular endosomes, and also in recycling Rab11a‐positive endosomes, particularly under some forms of nutrient stress. The core proteins of the Endosomal Sorting Complex Required for Transport (ESCRT) participate in exosome biogenesis and ILV‐mediated destruction of ubiquitinylated cargos. Accessory ESCRT‐III components have reported roles in ESCRT‐III‐mediated vesicle scission, but their precise functions are poorly defined. They frequently only appear essential under stress. Comparative proteomics analysis of human small extracellular vesicles revealed that accessory ESCRT‐III proteins, CHMP1A, CHMP1B, CHMP5 and IST1, are increased in Rab11a‐enriched exosome preparations. We show that these proteins are required to form ILVs in Drosophila secondary cell recycling endosomes, but unlike core ESCRTs, they are not involved in degradation of ubiquitinylated proteins in late endosomes. Furthermore, CHMP5 knockdown in human HCT116 colorectal cancer cells selectively inhibits Rab11a‐exosome production. Accessory ESCRT‐III knockdown suppresses seminal fluid‐mediated reproductive signalling by secondary cells and the growth‐promoting activity of Rab11a‐exosome‐containing EVs from HCT116 cells. We conclude that accessory ESCRT‐III components have a specific, ubiquitin‐independent role in Rab11a‐exosome generation, a mechanism that might be targeted to selectively block pro‐tumorigenic activities of these vesicles in cancer.

BackgroundSARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age.MethodsWeekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination.ResultsThe percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older.ConclusionsThe decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

Ropeginterferon alfa-2b is a novel, long-acting mono-pegylated proline-IFN-alpha-2b approved for treatment of polycythemia vera in adults, regardless of thrombotic risk level or treatment history. Clinical trial data indicate the dose and titration of ropeginterferon alfa-2b is safe and effective. However, additional studies may provide rationale for an amended, higher initial dosage and rapid titration. This article is an overview of current and upcoming studies of ropeginterferon alfa-2b in myeloproliferative neoplasms that support the exploration of an amended dosing scheme in order to optimize patient tolerability and efficacy outcomes.

This study aimed to determine the effect of fermentation using an isolated Levilactobacillus brevis strain on the antinutrients and the protein quality of cassava leaves. Cassava leaves from tajirika and kibandameno variety which are considered bitter and sweet varieties, respectively, were fermented using the probiotic isolate and spontaneous fermentation was used as a control. The antinutrients of interest were cyanide and phytic acid whereas the protein quality of the leaves was analyzed in terms of the total crude protein and in-vitro digestibility. These were analyzed using standard procedures namely; picrate paper method for cyanide, spectrophotometry for phytic acid, Kjedahl method for the crude protein, and trypsin and pepsin enzymes simulation for the actual human digestion process for the in vitro protein digestibility. The data obtained was analyzed using the SPSS software and means separated at p 37% with the L. brevis isolate for both cassava varieties which was higher than 20–33% for the spontaneous fermentation (control). The crude protein in both the varieties ranged between 28% and 32% and improved up to 43% on fermentation. Upon digestion of the cassava leaves, the in vitro protein digestibility improved from 63% up to 94%. The findings of this study therefore indicates that the Levilactobacillus brevis isolate can reduce cyanide and phytic acid as well as improve the protein quality by increasing the crude protein content and enhancing the digestibility of protein in cassava leaves of kibandameno and tajirika varieties, hence can be used to detoxify cassava leaves and for food formulation.

Abstract The coronavirus disease 2019 (COVID‐19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented international health crisis. COVID‐19 clinical presentations cover a wide range from asymptomatic to severe illness and death. Given the limited therapeutic resources and unexpected clinical features of the disease, readily accessible predictive biomarkers are urgently needed to improve patient care and management. We asked the degree to which anemia may influence the outcome of patients with COVID‐19. To this end, we identified 3777 patients who were positively diagnosed with COVID‐19 between March 1 and April 1 2020 in New York City. We evaluated 2,562 patients with available red blood cell, hemoglobin, and related laboratory values. Multivariable cox proportional hazards regression showed that anemia was a significant independent predictor of mortality (hazard ratio (HR): 1.26, 95% Confidence Interval [CI]: 1.06‐1.51), independent of age, sex, and comorbidities. There was a direct correlation between the degree of anemia and the risk of mortality when hemoglobin was treated as a continuous variable (HRadj 1.05; [CI]: 1.01‐1.09). The hemoglobin level that was maximally predictive of mortality, was 11.5 g/dL in males and 11.8 g/dL in females. These findings identify a routinely measured biomarker that is predictive of disease outcomes and will aid in refining clinical care algorithms and optimize resource allocation. Mechanisms of impacts of anemia on COVID‐19 outcome are likely to be multiple in nature and require further investigation.

The aim of this study was to assess the probiotic potential and safety profile of a Lactiplantibacillus plantarum EGER41 strain isolated from Kenyan spontaneously fermented milk, Amabere amaruranu. The L. plantarum EGER41 isolate was tested for temperature sensitivity (at 15 °C, 30 °C, 37 °C, and 45 °C), pH tolerance (at 2.0, 2.5, 3.0, 3.5, and 6.5 as control), and 0.4% phenol tolerance to observe its survival in the gastrointestinal tract of humans. For safety evaluation of the isolate, antagonistic activity was tested against pathogenic strains of Staphylococcus aureus, Escherichia coli, Salmonella enterica serovar Typhi, and Candida albicans, while antibiotic susceptibility pattern was examined using nalidixic acid, ampicillin, azithromycin, ciprofloxacin, tetracycline, gentamicin, and chloramphenicol antibiotic discs and haemolytic activity was done using lamb blood agar. The L. plantarum isolate had an optimal growth at 37 °C, it also demonstrated low pH tolerance (2.0–3.5). It was able to maintain its viability (∼100%) after exposure to 0.4% phenol. The selected isolate showed inhibition (antagonistic activity) against the pathogens with S. typhi having the largest (ZDI = 31.0 ± 1.73 mm) zone of diameter inhibition (ZDI) and Candida albicans having the least (ZDI = 18.0 ± 0.76 mm). L. plantarum isolate was sensitive to Azithromycin, tetracycline and chloramphenicol and was intermediately sensitive to gentamycin, while it was resistant to nalidixic acid, ampicillin, and ciprofloxacin. The isolate also exhibited γ-haemolytic activity hence safe for use as a starter culture and was identified as a Lactiplantibacillus plantarum EGER 41 strain based on 16S rRNA gene sequencing. The selected isolate can potentially be used as a starter culture and a probiotic since it had excellent probiotic properties.

Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (

Chronic myeloproliferative neoplasms (MPN) frequently evolve to a blast phase (BP) that is almost uniformly resistant to induction chemotherapy or hypomethylating agents. We explored the functional properties, genomic architecture, and cell of origin of MPN-BP initiating cells (IC) using a serial NSG mouse xenograft transplantation model. Transplantation of peripheral blood mononuclear cells (MNC) from 7 of 18 patients resulted in a high degree of leukemic cell chimerism and recreated clinical characteristics of human MPN-BP. The function of MPN-BP ICs was not dependent on the presence of JAK2V617F, a driver mutation associated with the initial underlying MPN. By contrast, multiple MPN-BP IC subclones coexisted within MPN-BP MNCs characterized by different myeloid malignancy gene mutations and cytogenetic abnormalities. MPN-BP ICs in 4 patients exhibited extensive proliferative and self-renewal capacity, as demonstrated by their ability to recapitulate human MPN-BP in serial recipients. These MPN-BP IC subclones underwent extensive continuous clonal competition within individual xenografts and across multiple generations, and their subclonal dynamics were consistent with functional evolution of MPN-BP IC. Finally, we show that MPN-BP ICs originate from not only phenotypically identified hematopoietic stem cells, but also lymphoid-myeloid progenitor cells, which were each characterized by differences in MPN-BP initiating activity and self-renewal capacity.