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Background: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes. Objectives: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy. Methods: Breast cancer patients with a CMR from 2013–2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed. Results: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229–0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease. Conclusions: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity. [ABSTRACT FROM AUTHOR]

With further characterization of patient phenotypes, disease outcomes, and response to therapy, clinicians will be able to better recognize COPA syndrome, allowing for more timely diagnosis and earlier intervention. In some cases, treatment can be guided by mechanism-related factors; for example, the Janus kinase inhibitors baricitinib and ruxolitinib have been utilized in some COPA syndrome patients. An unprecedented COPA gene mutation in two patients in the same family: comparative clinical analysis of newly reported patients with other known COPA gene mutations. [Extracted from the article]

Multiple studies have reported a doubling in risk of Coronavirus Disease-2019 (COVID-19) among cancer patients. Here, we examine the potential biological rationale behind this recurrent epidemiological observation. By leveraging large-scale genome-wide transcriptional data of normal and malignant tissues from adults and children, we found evidence of increased expression of SARS-CoV-2 viral entry genes in the cancer state, particularly in respiratory, gastrointestinal, and genitourinary tract tissues, with decreased expression in pediatric vs. adult samples. Additionally, by interrogating the temporal effects of radiotherapy on human peripheral blood mononuclear and mucosal cells, we observed important treatment-related alterations in host innate immunity, specifically type I interferon responses. Overall, cancers enhance expression of critical viral entry genes, and innate viral defenses can be dysregulated transiently during radiation treatments. These factors may contribute to the observed increased susceptibility to SARS-CoV-2 entry and severity of COVID-19 in cancer patients. [ABSTRACT FROM AUTHOR]

Choroideremia is an X‐linked recessive retinal degeneration predominantly affecting hemizygous males. It is caused by mutations in the CHM gene that encodes the Rab escort protein‐1. Characteristic features include early nyctalopia followed by progressive constriction of peripheral visual fields and sparing of the central vision until late in life with a distinct fundoscopic appearance. We present the case of a 17‐year‐old male with a c.282delT in exon 4 of CHM that has not previously been reported. Phenotypically this patient presented with an atypical choroideremia phenotype of early central macular degeneration in addition to the classic peripheral fundus characteristic findings. [ABSTRACT FROM AUTHOR]

Purpose Distant metastasis (DM) is the main cause of death for patients with human papillomavirus (HPV)–related oropharyngeal cancers (OPCs); yet, there are few reliable predictors of DM in this disease. The role of quantitative imaging (ie, radiomic) analysis was examined to determine whether there are primary tumor features discernible on imaging studies that are associated with a higher risk of DM developing. Methods and Materials Radiation therapy planning computed tomography scans were retrieved for all nonmetastatic p16-positive OPC patients treated with radiation therapy or chemoradiation therapy at a single institution between 2005 and 2010. Radiomic biomarkers were derived from each gross tumor volume. The biomarkers included 4 representative radiomic features from tumor first-order statistics, shape, texture, and wavelet groups, as well as a combined 4-feature signature. Univariable Cox proportional hazards models for DM risk were identified. The discriminative performance of prognostic univariable and multivariable models was compared using the concordance index (C-index). Subgroup analyses were performed. Results There were 300 HPV-related OPC patients who were eligible for the analysis. A total of 36 DM events occurred within a median follow-up period of 5 years. On univariable analysis, top results included the 4 representative radiomic features (C-index, 0.670-0.686; P <.001), the radiomic signature (C-index, 0.670; P <.001), tumor stage (C-index, 0.633; P <.001), tumor diameter (C-index, 0.653; P <.001), and tumor volume (C-index, 0.674; P <.001), which demonstrated moderate discrimination of DM risk. Combined clinical-radiomic models yielded significantly improved performance (C-index, 0.701-0.714; P <.05). In subgroup analyses, the radiomic biomarkers consistently stratified patients for DM risk, particularly for those cohorts with greater risks (C-index, 0.663-0.796), such as patients with stage III disease. Conclusions Radiomic biomarkers appear to classify DM risk for patients with nonmetastatic HPV-related OPC. Radiomic biomarkers could be used either alone or with other clinical characteristics in the assignment of DM risk in future HPV-related OPC clinical trials. [ABSTRACT FROM AUTHOR]

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of severe malaria are unknown. We used the remaining serum samples from a large cohort study in Muheza, Tanzania to describe vector-borne filarial sero-reactivity among young children and to identify associations between exposure to filarial parasites and subsequent severe malaria infections. We identified positive filarial antibody responses (as well as positive antibody responses to Strongyloides stercoralis) among infants as young as six months. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria. Specifically, infants who developed severe malaria by one year of age were 3.9 times more likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial antigen at six months of age compared with infants who did not develop severe malaria. [ABSTRACT FROM AUTHOR]

Background: Obesity is a growing epidemic in most developed countries including the United States resulting in an increased number of obese patients with end-stage renal disease. A previous study has shown that obese patients with end-stage renal disease have a survival benefit with transplantation compared with dialysis. However, due to serious comorbidities, many centers place restrictions on the selection of obese patients for transplantation. Further, due to obese patients having an increased risk of diabetes, it is unclear whether obesity can be an independent risk, independent of diabetes for increasing adverse renal transplant outcomes. Methods: To investigate the role of obesity in kidney transplantation, we used the Scientific Registry of Transplant Recipients database. After filtering for subjects that had the full set of covariates including age, gender, graft type, ethnicity, diabetes, peripheral vascular disease, dialysis time and time period of transplantation for our analysis, 191,091 subjects were included in the analyses. Using multivariate logistic regression analyses adjusted for covariates we determined whether obesity is an independent risk factor for adverse outcomes such as delayed graft function, acute rejection, urine protein and graft failure. Cox regression modeling was used to determine hazard ratios of graft failure. Results: Using multivariate model analyses, we found that obese patients have significantly increased risk of adverse transplant outcomes, including delayed graft function, graft failure, urine protein and acute rejection. Cox regression modeling hazard ratios showed that obesity also increased risk of graft failure. Life-table survival curves showed that obesity may be a risk factor independent of diabetes mellitus for a shorter time to graft failure. Conclusions: A key observation in our study is that the risks for adverse outcome of obesity are progressive with increasing body mass index. Furthermore, pre-obese overweight recipients compared with normal weight recipients also had increased risks of adverse outcomes related to kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of non-pharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions. Methods: We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors. Results: In the initial survey, individuals reporting a chronic disease had both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls. Conclusions: It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized. [ABSTRACT FROM AUTHOR]

Purpose To evaluate ( 1 ) the quantity and quality of current undergraduate oncology teaching at a major Canadian medical school; and ( 2 ) curricular changes over the past decade, to enhance local oncology education and provide insight for other educators. Methods and Materials Relevant 2011-2012 undergraduate curricular sessions were extracted from the University of Toronto curriculum mapping database using keywords and database identifiers. Educational sessions were analyzed according to Medical Council of Canada objectives, discussion topics, instructor qualifications, teaching format, program year, and course subject. Course-related oncology research projects performed by students during 2000 to 2012 were extracted from another internal database. Elective choices of clerks during 2008-2014 were retrieved from the institution. The 2011-2012 and 2000-2001 curricula were compared using common criteria. Results The 2011-2012 curriculum covers 5 major themes (public health, cancer biology, diagnosis, principles of care, and therapy), which highlight 286 oncology teaching topics within 80 sessions. Genitourinary (10, 12.5%), gynecologic (8, 10.0%), and gastrointestinal cancers (7.9, 9.8%) were the most commonly taught cancers. A minority of sessions were taught by surgical oncologists (6.5, 8.1%), medical oncologists (2.5, 3.1%), and radiation oncologists (1, 1.2%). During 2000-2012, 9.0% of students (233 of 2578) opted to complete an oncology research project. During 2008-2014, oncology electives constituted 2.2% of all clerkship elective choices (209 of 9596). Compared with pre-2001 curricula, the 2012 oncology curriculum shows notable expansion in the coverage of epidemiology (6:1 increase), prevention (4:1), screening (3:1), and molecular biology (6:1). Conclusions The scope of the oncology curriculum has grown over the past decade. Nevertheless, further work is needed to improve medical student knowledge of cancers, particularly those relevant to public health needs. Defining minimum curricular content, emphasizing content based on population needs, and ensuring educational delivery with the support and expertise of oncologists and non-oncologists will be essential next steps. [ABSTRACT FROM AUTHOR]

In Los Angeles, California, USA, 2 epidemics of West Nile virus (WNV) disease have occurred since WNV was recognized in 2003. To assess which measure of risk was most predictive of human cases, we compared 3 measures: the California Mosquito-Borne Virus Surveillance and Response Plan Assessment, the vector index, and the Dynamic Continuous-Area Space-Time system. A case-crossover study was performed by using symptom onset dates from 384 persons with WNV infection to determine their relative environmental exposure to high-risk conditions as measured by each method. Receiver-operating characteristic plots determined thresholds for each model, and the area under the curve was used to compare methods. We found that the best risk assessment model for human WNV cases included surveillance data from avian, mosquito, and climate sources. [ABSTRACT FROM AUTHOR]

Background: West Nile virus (WNV) is a mosquito-borne flavivirus maintained and amplified among birds and tangentially transmitted to humans and horses which may develop terminal neuroinvasive disease. Outbreaks typically have a three-year pattern of silent introduction, rapid amplification and subsidence, followed by intermittent recrudescence. Our hypothesis that amplification to outbreak levels is contingent upon antecedent seroprevalence within maintenance host populations was tested by tracking WNV transmission in Los Angeles, California from 2003 through 2011. Methods: Prevalence of antibodies against WNV was monitored weekly in House Finches and House Sparrows. Tangential or spillover transmission was measured by seroconversions in sentinel chickens and by the number of West Nile neuroinvasive disease (WNND) cases reported to the Los Angeles County Department of Public Health. Results: Elevated seroprevalence in these avian populations was associated with the subsidence of outbreaks and in the antecedent dampening of amplification during succeeding years. Dilution of seroprevalence by recruitment resulted in the progressive loss of herd immunity following the 2004 outbreak, leading to recrudescence during 2008 and 2011. WNV appeared to be a significant cause of death in these avian species, because the survivorship of antibody positive birds significantly exceeded that of antibody negative birds. Cross-correlation analysis showed that seroprevalence was negatively correlated prior to the onset of human cases and then positively correlated, peaking at 4-6 weeks after the onset of tangential transmission. Antecedent seroprevalence during winter (Jan-Mar) was negatively correlated with the number of WNND cases during the succeeding summer (Jul-Sep). Conclusions: Herd immunity levels within after hatching year avian maintenance host populations <10% during the antecedent late winter and spring period were followed on three occasions by outbreaks of WNND cases during the succeeding summer. Because mosquitoes feed almost exclusively on these avian species, amplification was directly related to the availability of receptive non-immune hosts. [ABSTRACT FROM AUTHOR]

Abstract: Azurin and Laz are bacterial proteins that have been shown to exert anticancer effects against a variety of solid tumors. Their effects on liquid cancers have never been studied. We now show that they are also effective against liquid-borne cancers such as leukemia. Azurin and Laz can each enter in two leukemia cell lines but Laz exerts a greater cytotoxic effect on both K562 and HL60 cells, while having little effect on peripheral blood mononuclear cells, where they have very limited entry. In addition to Azurin and Laz, we have recently identified another protein, Pa-CARD, from Pseudomonas aeruginosa that carries a caspase recruiment domain (CARD)-like domain. This CARD domain polypeptide, called Pa-CARD, demonstrates cytotoxic activity against leukemia cells. In the leukemia cell lines, HL60 and K562, the anticancer activity of Laz and Pa-CARD is mediated through cell cycle arrest at the G2/M phase involving the Wee1 protein stabilization and the depletion of phosphorylated AKT-Ser-473, the active form of a serine/threonine kinase that is often dysregulated in many cancer types. [Copyright &y& Elsevier]

Previous treatments of systemic isotretinoin, antibiotics and surgical excision without adjuvant radiotherapy were unsuccessful, and he was ineligible for re-excision given the size of the lesion. A 27-year-old man of African descent presented to our radiotherapy clinic with a 5-year history of a recurrent 15 × 8 × 4 cm keloidal tumour (i.e., acne keloidalis nuchae) on his posterior neck (Figure 1A). [Extracted from the article]

Deals with a study which characterized the presence of nuclear matrix metalloproteinase-2 (MMP-2) activity and hypothesize that its role may include degradation of the nuclear matrix protein poly (ADP-ribose) polymerase (PARP). Determination of the subcellular localization of MMP-2; Comparison of the amino acid sequence of bovine PARP with various MMP-2 cleavage recognition sequences.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury—an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause. [ABSTRACT FROM AUTHOR]

Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old female with a history of left breast lumpectomy and diagnosed with desmoid fibromatosis or aggressive fibromatosis after ultrasound-guided core biopsy. Topics discussed include her clinical examination identifies swelling in right iliac fossa close to the right iliac crest, without any regional lymphadenopathy, her Immunohistochemistry detected smooth muscle actin and cytoplasmic expression of b-catenin, and treatment with radiotherapy.

Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18–50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)—all co-administered with normal saline for blinding—or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov , NCT02334462. Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9–106·3], 146·4 [108·3–198·0], and 410·2 [301·6–558·0]; Pfs25 geometric mean 177·7 [130·3–242·4] and 315·7 [209·9–474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6–82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3–79·8]), after the third dose and after the fourth dose (88·9% [81·7–96·2] for Pfs230D1 and 85·0% [78·4–91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1–67·3] after the third dose and 58·2% [48·5–67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1–83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [–0·013 to 0·014], Pfs230D1 22 [2%] of 954 [–0·005 to 0·027], and combination 11 [1%] of 940 [–0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (–0·024 to 0·001). Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness. Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Purpose: Distant metastasis (DM) is the main cause of death for patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs); yet, there are few reliable predictors of DM in this disease. The role of quantitative imaging (ie, radiomic) analysis was examined to determine whether there are primary tumor features discernible on imaging studies that are associated with a higher risk of DM developing.Methods and Materials: Radiation therapy planning computed tomography scans were retrieved for all nonmetastatic p16-positive OPC patients treated with radiation therapy or chemoradiation therapy at a single institution between 2005 and 2010. Radiomic biomarkers were derived from each gross tumor volume. The biomarkers included 4 representative radiomic features from tumor first-order statistics, shape, texture, and wavelet groups, as well as a combined 4-feature signature. Univariable Cox proportional hazards models for DM risk were identified. The discriminative performance of prognostic univariable and multivariable models was compared using the concordance index (C-index). Subgroup analyses were performed.Results: There were 300 HPV-related OPC patients who were eligible for the analysis. A total of 36 DM events occurred within a median follow-up period of 5 years. On univariable analysis, top results included the 4 representative radiomic features (C-index, 0.670-0.686; P < .001), the radiomic signature (C-index, 0.670; P < .001), tumor stage (C-index, 0.633; P < .001), tumor diameter (C-index, 0.653; P < .001), and tumor volume (C-index, 0.674; P < .001), which demonstrated moderate discrimination of DM risk. Combined clinical-radiomic models yielded significantly improved performance (C-index, 0.701-0.714; P < .05). In subgroup analyses, the radiomic biomarkers consistently stratified patients for DM risk, particularly for those cohorts with greater risks (C-index, 0.663-0.796), such as patients with stage III disease.Conclusions: Radiomic biomarkers appear to classify DM risk for patients with nonmetastatic HPV-related OPC. Radiomic biomarkers could be used either alone or with other clinical characteristics in the assignment of DM risk in future HPV-related OPC clinical trials. [ABSTRACT FROM AUTHOR]

Background: Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells.Methods: In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry.Results: Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC.Conclusions: These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction.Clinical Trials Registration: NCT02504918. [ABSTRACT FROM AUTHOR]

A paradigm shift in cancer treatment occurred with the advent of immune checkpoint inhibitors (ICI). ICI therapy has improved tumor response and increased overall survival in patients with solid tumors and hematologic malignancies. While ICI therapy has improved overall patient outcomes in oncology, it has also introduced novel adverse effects called immune-related adverse effects (irAEs). Studies have shown that the development of irAEs is associated with improved overall survival, but certain irAEs like pneumonitis and myocarditis are life threatening, and could result in death if not identified and treated early. Therefore, it is important for radiologists to be aware of complications arising from ICI administration, especially those related to the heart and lungs as they are associated with greater mortality. This paper will review the imaging features of cardiothoracic toxicities, recurrent and chronic irAEs, and atypical tumor responses associated with irAEs. • Imaging plays a key role in identifying the cardiothoracic complications of immunotherapy. • Some cardiothoracic complications are associated with high mortality and imaging plays a crucial role in their diagnosis. • Early detection of complications can prompt early initiation of treatment, allowing patients to continue immunotherapy. [ABSTRACT FROM AUTHOR]

How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease‐19 (COVID‐19) has been a global pursuit over the past years. Here, a microfluidic high‐plex immuno‐serolomic assay is developed to simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti‐spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibilityand accuracy. It is applied to the measurement of 1012 blood samples including in‐depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein analysis reveals distinct immune mediator modules that exhibit a reduced degree of diversity in protein‐protein cooperation in patients with hematologic malignancies or receiving B cell depletion therapy. Serological analysis identifies that COVID‐infected patients with hematologic malignancies display impaired anti‐RBD antibody response despite high level of anti‐spike IgG, which can be associated with limited clonotype diversity and functional deficiency in B cells. These findings underscore the importance to individualize immunization strategies for these high‐risk patients and provide an informative tool to monitor their responses at the systems level. [ABSTRACT FROM AUTHOR]

Interactions between the medical community, government, and the wider public during the COVID-19 pandemic have been an important consideration throughout the pandemic response. Attitudes towards vaccinations, in particular, have been especially complex. From the discordance of political and healthcare interests to vaccine hesitancy, there are an array of perspectives on both the delivery and administration of the vaccine. However, in a time of crisis, coherent voices need to prevail. Clinicians need to be encouraged to vocalize their expertise and lived experiences beyond the bedside. Gaps in clinician involvement with decision-making bodies have led to an erosion of trust between the public and healthcare authorities. In this commentary, we argue that it is important that medical professionals are supported in their advocacy, to act as a bridge between reliable and unbiased healthcare information and the wider community, to promote public trust, and to combat medical misinformation. [ABSTRACT FROM AUTHOR]

This research presents three new numerical representations for classifying short exon and intron sequences using discrete Fourier transform period-3 value. Based on the human genome, results indicate that the Complex Twin- Pair representation is attractive compared with other numerical representations and the approach has potential applications in genome annotation and read mapping. [ABSTRACT FROM AUTHOR]

The article discusses a dual-setting mentoring program for female medical students at Queen's University School of Medicine in Kingston, Ontario. It describes how the mentoring program was designed to address the increasing numbers of female medical trainees and the limited number of female physician mentors using the dual-setting, or large- and small-group model.

BACKGROUND AND OBJECTIVES: In 2000, the US Congress authorized the National Institutes of Health to conduct a prospective national longitudinal study of environmental influences on children's health and development from birth through 21 years. Several recruitment methodologies were piloted to determine the optimal strategy for a main National Children's Study. METHODS: After an initial pilot recruitment that used a household enumeration strategy performed poorly, the National Children's Study Vanguard Study developed and evaluated the feasibility, acceptability, and cost of 4 alternate strategies to recruit a large prospective national probability sample of pregnant women and their newborn children. We compare household-based recruitment, provider-based recruitment, direct outreach, and provider-based sampling (PBS) strategies with respect to overall recruitment success, efficiency, cost, and fulfillment of scientific requirements. RESULTS: Although all 5 strategies achieved similar enrollment rates (63%-81%) among eligible women, PBS achieved the highest recruitment success as measured by the ratio of observed-to-expected newborn enrollees per year of 0.99, exceeding those of the other strategies (range: 0.35-0.48). Because PBS could reach the enrollment target through sampling of high volume obstetric provider offices and birth hospitals, it achieved the lowest ratio of women screened to women enrolled and was also the least costly strategy. With the exception of direct outreach, all strategies enrolled a cohort of women whose demographics were similar to county natality data. CONCLUSIONS: PBS demonstrated the optimal combination of recruitment success, efficiency, cost, and population representativeness and serves as a model for the assembly of future prospective probability-based birth cohorts. [ABSTRACT FROM AUTHOR]

Background The extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and transmission in Mali and the surrounding region is not well understood. We aimed to estimate the cumulative incidence of SARS-CoV-2 in 3 communities and understand factors associated with infection. Methods Between July 2020 and January 2021, we collected blood samples and demographic, social, medical, and self-reported symptoms information from residents aged 6 months and older over 2 study visits. SARS-CoV-2 antibodies were measured using a highly specific 2-antigen enzyme-linked immunosorbent assay optimized for use in Mali. We calculated cumulative adjusted seroprevalence for each community and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis. Results Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 31.3% (837/2672) were aged <10 years, 27.6% (737/2672) were aged 10–17 years, and 41.1% (1098/2572) were aged ≥18 years. The cumulative SARS-CoV-2 exposure rate was 58.5% (95% confidence interval, 47.5–69.4). This varied between sites and was 73.4% in the urban community of Sotuba, 53.2% in the rural town of Bancoumana, and 37.1% in the rural village of Donéguébougou. Study site and increased age were associated with serostatus at both study visits. There was minimal difference in reported symptoms based on serostatus. Conclusions The true extent of SARS-CoV-2 exposure in Mali is greater than previously reported and may now approach hypothetical "herd immunity" in urban areas. The epidemiology of the pandemic in the region may be primarily subclinical and within background illness rates. [ABSTRACT FROM AUTHOR]