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From 2014–2019, invasive pulmonary aspergillosis complicated 7.2% (0–23.1% in different influenza seasons) of cases of influenza-associated respiratory failure in Edmonton, Alberta. Disease outcomes ranged from survival without therapy to death despite antifungals. Clinician vigilance, longitudinal local surveillance, and refined criteria to identify patients requiring therapy are needed.

The low prevalence levels associated with lymphatic filariasis elimination pose a challenge for effective disease surveillance. As more countries achieve the World Health Organization criteria for halting mass treatment and move on to surveillance, there is increasing reliance on the utility of transmission assessment surveys (TAS) to measure success. However, the long-term disease outcomes after passing TAS are largely untested. Using 3 well-established mathematical models, we show that low-level prevalence can be maintained for a long period after halting mass treatment and that true elimination (0% prevalence) is usually slow to achieve. The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (

Biofilms are arguably the root cause of most human infections, imposing a high level of public health concern. Biofilm growth is a lifestyle characterized by co-aggregation of organisms and secretion of an extracellular matrix (ECM) that facilitates attachment to a surface. They are responsible for up to 80% of all healthcare-acquired infections (National Institutes of Health) with the majority being diagnosed as device associated. They are multi-compositional structures that are influenced by surrounding biological, mechanical and chemical variation in their microenvironment. Within the confines of biofilms, microorganisms are capable of promoting increased rates of antimicrobial resistance. When observing biofilm physiology in the presence of a biomaterial, the attachment process and intermolecular activity, contribute to significant genotypic responses. When utilized as part of medical devices, antimicrobial biomaterials seek to prevent biofilm infections, however, the complexity of biofilms make it difficult to extract useful results necessary to improve material properties without consideration of bacterial molecular processes. This interdisciplinary article emphasizes molecular mechanisms as a pertinent consideration in evaluating biofilm growth on biomaterials. It also advocates for standardizing in vitro biofilm models as opposed to animal models. Such models include microfluidic systems, that can be engineered to scale and mimic infection-relevant microenvironments. The connection of advances in antibiofilm surface modifications and high-throughput sequencing make way for new and important biomaterial assessments. We endeavor to establish a gold standard model for in vitro biomaterials testing that incorporates the complexity of healthcare-associated infections in order to guide medical device design and improve disease outcomes.

Pediatric diffuse intrinsic pontine glioma (DIPG) represents approximately 20% of all pediatric CNS tumors. However, disease outcomes are dismal with a median survival of less than 1 year and a 2-year overall survival rate of less than 10%. Despite extensive efforts to improve survival outcomes, progress towards clinical improvement has been largely stagnant throughout the last 4 decades. Focal radiotherapy remains the standard of care with no promising single-agent alternatives and no evidence for improvement with the addition of a long list of systemic therapies. A better understanding of the biology of DIPG, though not easy due to obstacles in obtaining pathological material to study, is promising for the development of specific individualized treatment for this fatal disease. Recent studies have found epigenetic mutations to be successful predictors and prognostic factors for developing future management policies. The aim of this review is to give a global overview about the epidemiology, diagnosis, and treatment of DIPG. We further examine the controversial biopsy and autopsy issue that is unique to DIPG and assess the subsequent impact this issue has on the research efforts and clinical management of DIPG.

Background: The incidence of breast cancer (BC) continues to rise, with the latest record being 2.08 million globally. It also remains the most common female malignancy worldwide. Increasing awareness and screening have been suggested as contributory factors. Objective: To determine the relationship between disease laterality in breast cancer and disease outcome in terms of bone metastasis. Methods: The study is a hospital-based six-year retrospective review of all breast cancer patients who had bone scans done between 2011 and 2016. Results: A total of 992 bone scans (BS) were analysed for 500 (50.4%) patients with left-sided breast cancer and 492 (49.6%) with right-sided breast cancer. While 638 bone scans were abnormal, 354 were benign and 242 (24.39%) were equivocal. There was no association between primary tumour laterality and BS outcome (p = 0.544). Furthermore, Chi-Square for trend assessed the association between patients’ age and BC laterality but yielded no significance (p = 0.67). Conclusion: The laterality of breast cancer did not affect the stage of breast cancer as shown by bone scan outcomes in this study.

Introduction: To study the dose-response relationship between smoking and axial Spondyloarthritis (axSpA) disease outcome. Method: One hundred and sixty participants with axSpA were recruited from a single rheumatology center. All of them fulfilled the classification criteria for axSpA by the Assessment of SpondyloArthritis International Society (ASAS). Clinical, demographic and biochemical data was collected. Participants were asked for detailed smoking histories including past and current smoking, smoking duration and quantity. Radiographs of cervical and lumbar spine were performed for modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and modified New York (MNY) criteria for radiological sacroiliitis. Ankylosing Spondylitis Disease Activity Score (ASDAS) was calculated based on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Univariate and multivariate regression models were performed to determine the associations between pack-year smoking and different disease outcomes. Results: Among the participants, 62 (38.7%) were either current (N [Formula: see text] 39) or former smokers (N [Formula: see text] 23). Ex-smokers quit smoking by 18.8 ± 12.4 years. The mean pack-year for patients who had ever smoked was 19.4 ± 23.1. In univariate analyses, pack-year smoking was associated with BASFI (p Conclusion: In Chinese axSpA patients, pack-year smoking was independently associated with poorer functional status, worsened spinal mobility and more radiological damages. Smoking cessation should be encouraged in patients with axSpA.

الملخص: أهداف البحث: لقد تم تسجيل ارتفاع في نسبة انتشار الإصابة بمرض الخلايا المنجلية في المملكة العربية السعودية. ويعتبر أكثر المضاعفات شيوعا لدى الأطفال الذين يعانين من مرض الخلايا المنجلية هو الآلام الناجمة عن أزمات انسداد الأوعية الدموية، التي تحدث عندما تتجمع خلايا الدم الحمراء المصابة وتسبب احتشاءات في الاوعية الدموية الصغيرة. تهدف هذه الدراسة إلى تقييم مستوى الوعي حول أزمة انسداد الأوعية الدموية بين آباء مرضى الأنيميا المنجلية في منطقة المدينة المنورة وتأثير ذلك على أعراض المرض. طرق البحث: دراسة مقطعية، أجريت باستخدام استبانة منظمة ومحققة. شملت العينة ١٢٣ مشاركا، من آباء أطفال مصابين بالأنيميا المنجلية تتراوح أعمارهم بين ٢ إلى ١٨ عاما يعيشون في منطقة المدينة المنورة. النتائج: متوسط درجة المعرفة الكلية كان ٣٠ ±٤. حيث يتمتع غالبية الآباء (٧٤٪) بمستوى جيد من المعرفة. كان هناك ارتباط كبير بين مجموع نقاط المعرفة ونتائج المرض خلال العام الماضي للدراسة كما أظهر التحليل الإحصائي نتائج غير معتبرة بعد ربط المعرفة الكلية بتعليم الأب والأم وكذلك دخل الأسرة. يعتقد أولياء الأمور أن أفضل طريقة لزيادة الوعي بأزمة انسداد الأوعية الدموية هي اجتماعات التثقيف الصحي المباشرة بنسبة ٦٠.٩٧٪، بينما يعتقد ٣٠.٨٩٪ أن المعلومات المكتوبة أفضل، ويعتقد ٢١.١٣٪ أن الإنترنت سيكون خيارا جيدا لزيادة الوعي. الاستنتاجات: أظهرت الدراسة وجود وعي جيد عند آباء مرضى الانيميا المنجلية عن أزمات انسداد الأوعية الدموية. ولقد أثرت معرفة الآباء بطبيعة المرض على نتائج أزمة انسداد الأوعية الدموية في أطفالهم بشكل إيجابي. Abstract: Objectives: KSA has been reported to have a high prevalence of sickle cell disease (SCD). The most common complication of SCD in children is pain due to vaso-occlusion crises (VOCs) that ensue when sickle-shaped red blood cells are entrapped in small vessels, leading to infarcts. This study aimed to determine the level of awareness about VOCs among parents of patients with SCD and its correlation with the disease outcomes. Methods: A cross-sectional study was conducted including 123 parents of children with SCD, aged 2–18 years old. All recruited participants were residents of Almadinah Almunawwarah. A structured and validated questionnaire was used for data collection. Results: The mean total knowledge score was 30 ± 4. The majority of parents (74%) had a good level of knowledge about SCD. There was a significant association between the total knowledge score and the outcome of VOCs during the year prior (p

Knowledge of patients with type 2 diabetes (T2D) may affect the disease outcome and reduce complications. Diabetes health education can improve the prognosis, cut the financial burden, and prevent ...

Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups.This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: 40, 40‒49, 50‒65 and 65 years. Physical functioning, disease activity, remission rates and disease impact were compared.Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40-49 years, 26.4% (n = 60) were 50-65 years and 33.0% (n = 75) were patients 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged 40 years, 13.1% of patients aged 40-49 years and 26.7% of patients aged 50-65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged 40 years, more patients 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p 0.05).Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.

Older people living with HIV (PLWH) may have delayed diagnosis and access to care and therefore have poorer disease outcomes. Little is known about HIV care and disease outcomes among older PLWH in China. This retrospective cohort study used data from all adult HIV/AIDS cases during 1988–2017 in Chongqing, China from two national databases. We compared demographic and behavioral profiles, HIV care, virologic suppression, and mortality between two age groups of 18–49 and ≥50 years. Multivariate logistic and cox regression analyses were used to calculate adjusted odds ratio (AOR) and adjusted hazard ratio (AHR) among older versus younger PLWH. Of 46,580 adult HIV/AIDS cases, 76.1% were men and 38.2% were 50 years of age or older. The proportion of older cases in men increased from 2.4% in 2002 to 51.8% in 2017, and in women from 3.3% to 57.9%. Older PLWH had a lower CD4 count than their younger counterparts at HIV diagnosis (median 323 vs. 391 cells/μL; p

Heart failure (HF) has been associated with poor morbidity and survival despite advancement in its medical therapy. Poor knowledge, self-care practice and adherence to therapies which lead to poor disease outcomes have been previously reported. However, knowledge, attitude, self-care practice and HRQoL of Malaysian HF population have yet been described. This baseline information is crucial in designing educational programs aimed at improving adherence to therapies hence optimizing clinical outcomes. This single-centred, cross-sectional study utilizing self-administered, validated questionnaire involving 125 randomly selected HF patients found that most study subjects have moderate knowledge, attitude and self-care practice with good HRQoL. Weak and inverse correlations were found between age and knowledge and attitude scores. Subjects with NYHA Class I had significantly poorer knowledge level compared to those in other classes and female subjects had significantly better attitude compared to male subjects. Knowledge score was also found to be weakly but significantly correlated to attitude and self-care practice scores suggesting that improving knowledge among these patients can improve attitude and self-care practice. This study supports the need for continuous and individualized educational programs to improve knowledge hence attitude and self-care practice among these patients.

Reem Al Argan,1 Dania Alkhafaji,1 Abdulmohsen Al Elq,1 Waleed Albaker,1 Safi Alqatari,1 Alaa Alzaki,1 Abrar Alwaheed,1 Abir Al Said,1 Huda Bukhari,1 Sara Al Warthan,1 Mohammad Zeeshan,2 Fatimah AlRubaish,1 Zainab AlElq,1 Ahmed Alsahlawi,1 Mohannad Alalwan,1 Amani AlHwiesh,1 Fatimah I Alabdrabalnabi1 1Department of Internal Medicine, College of Medicine-Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi Arabia; 2Department of Medical Education, College of Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi ArabiaCorrespondence: Reem Al ArganDepartment of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi ArabiaTel +966 138957999 Extension 1842Email Rjalarqan@iau.edu.saPurpose: Diabetes mellitus (DM) has been reported to be associated with a worse outcome of COVID-19 infection. The evidence is scarce in the Middle East and Saudi Arabia. We aimed to evaluate the impact of diabetes mellitus and hyperglycemia in non-diabetic individuals on the severity and outcome of COVID-19 infection.Methods: This is a retrospective observational study, which included patients with confirmed COVID-19 infection [RT-PCR positive for SARS-CoV2] who were admitted to King Fahd Hospital of the University-Khobar-Eastern Province-Saudi Arabia from March to September 2020. Baseline demographic data, laboratory investigations, and markers of the severity of COVID-19 were analyzed. The collected data were categorized according to the Saudi Arabian Ministry of Health COVID-19 infection severity criteria. Patients were divided into three groups as follows: patients in Group 1 had pre-existing DM, patients in Group 2 did not have DM but were documented to have hyperglycemia at presentation, and patients in Group 3 were neither diabetics nor hyperglycemics at presentation and served as the control group. The severity and outcome of the control group were compared with the other two groups. The effect of risk factors on the severity and outcome of COVID-19 infection was studied in the DM group.Results: A total of 414 patients were included (70.5% males and 29.5% females). The mean age (SD) of patients was 52.3 (± 15.5) years. Compared to the control group, pre-existing DM was found to be significantly associated with severe (OR 3.61), critical disease (OR 4.32), intensive care unit (ICU) admission (OR 2.0), and death (OR 2.0) from COVID-19 infection. Hyperglycemia without known DM was also found to be associated with critical COVID-19 pneumonia (P 0.001), and had longer duration of hospitalization (P 0.014), higher ICU admission, mechanical ventilation, and death from COVID-19 infection (P < 0.0001).Conclusion: Diabetes mellitus and hyperglycemia at presentation, even in the absence of pre-existing DM, are independent risk factors for disease severity and worse outcome of COVID-19 infection. These patients should be identified and managed accordingly. The COVID-19 vaccination program should also target those populations to improve their outcomes.Keywords: COVID-19 infection, diabetes mellitus, hyperglycemia, disease severity, disease outcome, mortality

Processing-in-memory (PIM) architecture has been considered as a promising solution for the “memory-wall” issue in many data-intensive applications, especially in bioinformatics. Recent works of developing PIM for genome alignment and assembling have achieved tremendous improvement, while another important genome analysis - mRNA quantification has not been explored. Efficient and accurate mRNA quantification is a crucial step for molecular signature identification, disease outcome prediction and drug development. In this paper, for the first time, we propose a SOT-MRAM based PIM platform, named PIM-Quantifier, for efficient mRNA quantification. A PIM-friendly alignment-free quantification algorithm is first proposed. Then, we present the optimized PIM architecture/circuit designs and mapping method to efficiently accelerate mRNA quantification. Extensive experiments show that PIM-Quantifier significantly improves mRNA quantification performance than CPU and recent other PIM platforms in efficiency defined as throughput/power.

Background: The clinical spectrum and disease course of Crohn’s disease (CD) are heterogeneous and difficult to predict based on initial presentation. Aim: To analyze the long-term disease course and factors leading to poor prognosis of the disease.Methods: In total, 112 patients with CD who were initially diagnosed or treated at our institution were included. We analyzed their clinical data, disease characteristics according to Montreal classification, endoscopic and computed tomography (CT) examinations at initial visit, and 2-year, 5-year, and last follow-ups. We categorized the long-term disease course into four categories: remission, stable, chronic refractory, and chronic relapsing. Significant factors associated with a poorer prognosis were analyzed.Results: The median follow-up period was 107 (range, 61-139) months. Complicated disease behavior increased slightly (20.5% to 26.2%). Chronic refractory (19.6%) and relapsing (16.1%) courses were defined as unfavorable disease course. Two-year disease characteristics were significant factors for unfavorable disease course, and the combination of 2-year perianal disease and 2-year moderate-to-severe CT activity could predict unfavorable disease course with the highest accuracy (0.722, area under the curve 0.768, p

Estimating tumor purity is especially important in the age of precision medicine. Purity estimates have been shown to be critical for correction of tumor sequencing results, and higher purity samples allow for more accurate interpretations from next-generation sequencing results. In addition, tumor purity has been shown to be correlated with survival outcomes for several diseases. Molecular-based purity estimates using computational approaches require sequencing of tumors, which is both time-consuming and expensive. Here we propose an approach, weakly-supervised purity (wsPurity), which can accurately quantify tumor purity within a slide, using multiple and different types of cancer. This approach allows for a flexible analysis of tumors from whole slide imaging (WSI) of histology hematoxylin and eosin (H&E) slides. Our model predicts tumor type with high accuracy (greater than 80% on an independent test cohort), and tumor purity at a higher accuracy compared to a comparable fully-supervised approach (0.1335 MAE on an independent test cohort). In addition to tumor purity prediction, our approach can identify high resolution tumor regions within a slide, to enrich tumor cell selection for downstream analyses. This model could also be used in a clinical setting, to stratify tumors into high and low tumor purity, using different thresholds, in a cancer-dependent manner, depending on what purity levels correlate with worse disease outcomes. In addition, this approach could be used in clinical practice to select the best tissue block for sequencing. Overall, this approach can be used in several different ways to analyze WSIs of tumor H&E sections.

In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for other cardiovascular risk factors, such as hypertension or hypercholesterolemia. Mechanisms of legacy were particularly deciphered in diabetes, leading to the concept of metabolic memory. In a more discreet manner, other memory phenomena were also described in preclinical studies that demonstrated long-lasting deleterious effects of lipids or angiotensin II on vascular wall components. Interestingly, epigenetic changes and reactive oxygen species (ROS) appear to be common features of “memory” of the vascular wall.

Domestic pigs share many similarities with humans in their pulmonary anatomy, physiology, and immunology. Accordingly, pigs have been shown to be valuable models to study human tuberculosis (TB). Here we examined the outcome of disease in domestic pigs challenged via two different routes with either the human-adapted TB bacillus Mycobacterium tuberculosis or the zoonotic bovine TB bacillus M. bovis in head-to-head comparisons. We found that pigs challenged intravenously with M. bovis AF2122/97 exhibited severe morbidity and rapid onset of mortality, accompanied by higher tissue bacterial burden and necrosis compared to pigs challenged similarly with M. tb Erdman. Concordantly, pigs challenged with aerosolized M. bovis AF2122/97 exhibited reduced weight gain and more severe pathology than pigs challenged similarly with M. tb Erdman. Moreover, pigs aerosol-challenged with M. bovis AF2122/97 exhibited a spectrum of granulomatous lesions ranging from small well-contained granulomas to caseous-necrotic lesions mimicking active TB disease in humans. In contrast, pigs aerosol-challenged with M. tb Erdman exhibited arrested granuloma development. Irrespective of challenge dose and pathological outcome however, peripheral IFN-γ responses were similar in both M. bovis AF2122/97 and M. tb Erdman challenged pigs. This study demonstrates domestic pigs can support infections with M. bovis and M. tb and develop pathology similar to what is observed in humans. And although M. bovis AF2122/97 appears to be more virulent than M. tb Erdman, both strains can be used to model TB in domestic pigs, depending on whether one wishes to recapitulate either acute and active TB or latent TB infections.

For most diseases, building large databases of labeled genetic data is an expensive and time-demanding task. To address this, we introduce genetic Generative Adversarial Networks (gGAN), a semi-supervised approach based on an innovative GAN architecture to create large synthetic genetic data sets starting with a small amount of labeled data and a large amount of unlabeled data. Our goal is to create a mechanism able to increase the sample size of the labeled data and generalize learning over different populations while keeping awareness of the quality of its own predictions. The proposed model achieved satisfactory results using real genetic data from different datasets and populations, in which the test populations may not have the same genetic profiles. The proposed model is self-aware and capable of determining whether a new genetic profile has enough compatibility with the data on which the network was trained and is thus suitable for prediction. The code and datasets used can be found at https://github.com/caio-davi/gGAN

IntroductionDespite the high COVID-19 vaccination coverage among adults, there is concern over a peak in SARS-CoV-2 infections in the coming months. To help ensure that healthcare systems are not overwhelmed in the event of a new wave of SARS-CoV-2 infections, many countries have extended vaccination to adolescents (those aged 12-17 years) and may consider further extending to children aged 5-11 years. However, there is considerable debate about whether or not to vaccinate healthy adolescents and children against SARS-CoV-2 because, while vaccination of children and adolescents may limit transmission from these groups to other, more vulnerable groups, adolescents and children themselves have limited risk of severe disease if infected and may experience adverse events from vaccination. To quantify the benefits of extending COVID-19 vaccination beyond adults we compare daily cases, hospital admissions, and intensive care (IC) admissions for vaccination in adults only, those 12 years and above, and those 5 years and above.Methods and FindingsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model to simulate disease outcomes (e.g., cases, hospital admissions, IC admissions) under different vaccination scenarios. The model is partitioned into 10-year age bands (0-9, 10-19, …, 70-79, 80+) and accounts for differences in susceptibility and infectiousness by age group, seasonality in transmission rate, modes of vaccine protection (e.g., infection, transmission), and vaccine characteristics (e.g., vaccine effectiveness). Model parameters are estimated by fitting the model piecewise to daily cases from the Dutch notification database Osiris from 01 January 2020 to 22 June 2021. Forward simulations are performed from 22 June 2021 to 31 March 2022. We performed sensitivity analyses in which vaccine-induced immunity waned.We found that upon relaxation of all non-pharmaceutical control measures a large wave occurred regardless of vaccination strategy. We found overall reductions of 5.7% (4.4%, 6.9%) of cases, 2.0% (0.7%, 3.2%) of hospital admissions, and 1.7% (0.6%, 2.8%) of IC admissions when those 12 years and above were vaccinated compared to vaccinating only adults. When those 5 years and above were vaccinated we observed reductions of 8.7% (7.5%, 9.9%) of cases, 3.2% (2.0%, 4.5%) of hospital admissions, and 2.4% (1.2%, 3.5%) of IC admissions compared to vaccination in adults only. Benefits of extending vaccination were larger within the age groups included in the vaccination program extension than in other age groups. The benefits of vaccinating adolescents and children were smaller if vaccine protection against infection, hospitalization, and transmission (once infected) wanes.DiscussionOur results highlight the benefits of extending COVID-19 vaccination programs beyond adults to reduce infections and severe outcomes in adolescents and children and in the wider population. A reduction of infections in school-aged children/adolescents may have the added benefit of reducing the need for school closures during a new wave. Additional control measures may be required in future to prevent a large wave despite vaccination program extensions. While the results presented here are based on population characteristics and the COVID-19 vaccination program in The Netherlands, they may provide valuable insights for other countries who are considering COVID-19 vaccination program extensions.

Background: Myocardial infarction in younger adults is an understudied research area. Objectives: This paper reports on characteristics, risk factors, and disease outcomes of young adults with St-elevation myocardial infarction (STEMI).Methods: This is a sub-analysis of data from the Kermanshah Acute Coronary Syndrome Registry, including all patients aged ≤45 with STEMI (n=247) registered in the registry from June 2017 to June 2019. Results: Patients aged ≤45 constituted 10.66% of all patients with STEM; the majority was male (91.8%), and the most common CVD risk factors included: smoking (56.7%), low high-density lipoprotein (55.5%), elevated triglyceride (44.4%), hypertension (38.2%), hypercholesterolemia (38.1%), elevated low-density lipoprotein (26.3%), and obesity (24.3%). Many patients (62.8%) received primary percutaneous coronary intervention (PCI), and in-hospital mortality was low at 0.8%. Conclusions: Younger adults should be screened for CVD risk factors, and are educated and supported to participate in programs that aim to reduce risk through risk factor modification.

Introduction: The COVID-19 has been associated with many problems for the general public and especially health care workers (HCWs). This study conducted to provide predictors of COVID-19 outcomes on HCWs in Rasht, Iran.Methods: In a retrospective cross-sectional study, 381 HCWs with positive RT-PCR or high-resolution lungs computed tomography for COVID-19 from February 21 to April 19, 2020 evaluated. The prevalence, demographic, clinical, laboratory, and radiological presentations and outcomes and their correlation were studied.Results: The prevalence of COVID-19 in HCWs was 5.62%, and the total mortality rate was 0.2%. The mortality rates were different between genders (P=0.002) and in general ward compared to intensive care unit (P=0.001). In the multivariate analysis, age (OR:1.12, 95%CI 1.02–1.23, P=0.014), diabetes mellitus (DM) (OR:10.73, 95%CI 1.91–60.3, P=0.007), blood group B (OR:19.2, 95%CI 1.8–199.984, P=0.013), the presence of peribronchovascular involvement (OR:1.1, 95% CI OR:1.02–1.2, P=0.019), dyspnea on admission (OR:1.05, 95%CI 1.01–1.09, P=0.013), higher neutrophil count (OR:1.09, 95%CI 1.04–1.14, PP=0.001), and longer prothrombin time (OR:1.027, 95%CI 1.008–1.046, P=0.005) increase the risk of mortality. The cutoff of 90% for oxygen saturation on admission (sensitivity=91.9%, specificity=88.9%) and 1004 for absolute lymphocyte count (sensitivity=81.8%, specificity=66.6%) were estimated as predictors of mortality.Conclusions: Old age, male sex, underlying disease of DM and hypertension, O2 saturation less than 90%, and absolute lymphocyte count less than 1004/mL in HCWs are prone to adverse outcomes such as the need for mechanical ventilation or death.

Over recent years, the long known class of small nucleolar RNAs (snoRNAs) have gained interest among the scientific community, especially in the clinical context. The main molecular role of this interesting family of non-coding RNAs is to serve as scaffolding RNAs to mediate site-specific RNA modification of ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). With the development of new sequencing techniques and sophisticated analysis pipelines, new members of the snoRNA family were identified and global expression patterns in disease backgrounds could be determined. We will herein shed light on the current research progress in snoRNA biology and their clinical role by influencing disease outcome in hematological diseases. Astonishingly, in recent studies snoRNAs emerged as potent biomarkers in a variety of these clinical setups, which is also highlighted by the frequent deregulation of snoRNA levels in the hema-oncological context. However, research is only starting to reveal how snoRNAs might influence cellular functions and the connected disease hallmarks in hematological malignancies.

Although most patients with differentiated thyroid cancer (DTC) and biochemical incomplete response (BIR) follow a good clinical outcome, progression to structural disease may occur in 8–17% of patients. We aimed to identify factors that could predict the long-term outcomes of BIR patients. To this end, we conducted a retrospective review study of 1049 charts from our Differential Thyroid Cancer registry of patients who were initially treated with total thyroidectomy between 1962 and 2019. BIR was defined as suppressed thyroglobulin (Tg) &gt, 1 ng/mL, stimulated Tg &gt, 10 ng/mL or rising anti-Tg antibodies, who did not have structural evidence of disease, and who were assessed 12–24 months after initial treatment. We found 83 patients (7.9%) matching the definition of BIR. During a mean follow-up of 12 ± 6.6 years, 49 (59%) patients remained in a state of BIR or reverted to no evidence of disease, while 34 (41%) progressed to structural disease. At the last follow-up, three cases (3.6%) were recorded as disease-related death. The American Thyroid Association (ATA) Initial Risk Stratification system and/or AJCC/TNM (8th ed.) staging system at diagnosis predicted the shift from BIR to structural disease, irrespective of their postoperative Tg levels. We conclude that albeit 41% of BIR patients may shift to structural disease, and most have a rather indolent disease. Specific new individual data enable the Response to Therapy reclassification to become a dynamic system to allow for the better management of BIR patients in the long term.

The advent of advances in machine learning (ML)-based techniques has popularized wide applications of artificial intelligence (AI) in various fields ranging from robotics to medicine. In recent years, there has been a surge in the application of AI to research in cardiovascular medicine, which is largely driven by the availability of large-scale clinical and multi-omics datasets. Such applications are providing a new perspective for a better understanding of cardiovascular disease (CVD), which could be used to develop novel diagnostic and therapeutic strategies. For example, studies have shown that ML has a substantial potential for early diagnosis of different types of CVD, prediction of adverse disease outcomes such as heart failure, and development of newer and personalized treatments. In this article, we provide an overview and discuss the current status of a wide range of AI applications, including machine learning, reinforcement learning, and deep learning, in cardiovascular medicine. © 2021 American Physiological Society. Compr Physiol 11:1-12, 2021.

The current literature still gives a little information about the relationships between the ABO blood group system and the immune response to the virus or the different disease outcomes. Hypothesizing the presence of a predisposition by some blood groups to COVID-19, we searched for differences between patients towards the different outcomes of disease.We enrolled 330 inpatients with a diagnosis of COVID-19, determining both their ABO blood group system and Rh factor, collecting demographic, clinical and laboratory data. We searched for relationships with COVID-19 outcomes within an observation period of 180 days (Intensification of Care-IoC, Inhospital death, 180-days mortality). The most frequent ABO blood group was A (45.8%); a minor part was represented by group O (38.8%), B (11.5%), AB (3.9%). As for the Rh factor, 86.7% of patients were Rh-positive. There were no significant differences between blood groups and Rh factors as for age, length of hospital stays (LoS), or Charlson Comorbidity Index (CCI), nor we found significant relationships between the ABO groups and COVID-19 outcomes. A significant relation was found between AB group and IoC (p = 0.03) while as for the Rh factor, the patients with Rh factor positive died with less frequency during the stay (p = 0.03). Cox regression analyses showed substantial differences in the survival functions concerning the Rh factors. The Rh factor seems to be involved in the 180-day prognosis. The survival functions of patients with Rh factor positive show, in fact, significantly better curves when compared to those with Rh factor negative.

The dynamics of host-parasite interactions are highly temperature-dependent and may be modified by increasing frequency and intensity of climate-driven heat events. Here, we show that altered patterns of temperature variance lead to an almost order-of-magnitude shift in thermal performance of host and pathogen life-history traits over and above the effects of mean temperature and, moreover, that different temperature regimes affect these traits differently. We found that diurnal fluctuations of ±3°C lowered infection rates and reduced spore burden compared to constant temperatures in our focal hostGlobal warming is increasing average temperatures and causing extreme temperature fluctuations and heatwaves. These changes may affect when, where, and how often infectious disease outbreaks occur. This could have profound impacts on agriculture, human health, and wildlife. Studying how extreme temperatures or temperature fluctuations alter infections in laboratory animals may help scientists to better understand the impact of climate change on disease. A small aquatic invertebrate, such as a water flea, is one good candidate for such studies. These tiny creatures can be grown in small glass jars in temperature-controlled aquariums. Kunze, Luijckx et al. show that temperature fluctuations and heat waves have complex effects on parasitic infections in water fleas. In the experiments, water fleas housed with a parasite that infects them were exposed to constant temperatures, fluctuating temperatures, or three-day heatwaves, while being kept at a broad range of mean water temperatures. Then, Kunze, Luijckx et al. measured how these conditions affected the water fleas’ longevity, reproduction, and parasite infections. This revealed that temperature variations had a unique effect on the life span, and reproduction and infection rates of the water fleas, depending on the average water temperature the animals were kept at. Heatwaves drastically increased the number of parasites in the water fleas at an average water temperature of 16 °C but had no effect at all or decreased the number of parasites at 19 °C and 22 °C, respectively. Similarly, at high average water temperatures (24 °C), temperature fluctuations reduced the number of water fleas infected with parasites and the number of parasites in each infected flea. Moreover, the maximum temperature at which parasites were able to cause infections was 5 °C lower under fluctuating temperatures than under constant temperatures. Kunze and Luijckx et al. show that consistent high temperatures, temperature changes, extreme weather events, and mean water temperature affect disease outcomes in water fleas. More studies are needed to assess how temperature variations change the course of diseases in other organisms and to understand the underlying mechanisms. Learning more about disease-temperature interactions will help scientists predict climate change-driven disease outbreaks.

Background Atherosclerosis develops silently for decades before adult cardiovascular disease (aCVD) occurs. There is currently no evidence directly linking childhood risk factors to aCVD outcomes. Methods i3C is an international consortium of 7 cohorts involving 40,709 participants enrolled between 1970-95 in childhood (age 3-19) who underwent measurement for BMI, SBP, total cholesterol, and triglycerides, and smoking (the last mostly in adolescence). Participants were followed by direct contact and review of medical records or death registry ascertainment through adulthood in 2014-19. 20,560 participants were found and interviewed or had died in the approximately 40 years since enrollment; 738 had a CVD event, confirmed by medical record review (n = 449) or death certificate ICD code (n = 289). Results Estimated hazard ratios (HRs) for childhood risk factors and their confidence intervals are displayed in the table below. The CIs excluded 1.0 for all these variables in the univariable analysis and, although the HRs were reduced in multivariable analysis which included all of these risk factors, the CIs still excluded 1.0. Conclusion Exposure to CVD risk factors in youth predicts adult CVD with implications for primordial CVD prevention. Key messages Intervention to reduce CVD risk factors in childhood is likely to reduce risk of adult CVD

INTRODUCTION AND OBJECTIVE:Adherence to scheduled androgen deprivation therapy (ADT) has been shown to influence disease outcomes and overall survival. We evaluated ADT documentation and adherence ...

The COVID-19 pandemic has infected over 200 million people worldwide and killed more than 4 million as of August 2021. Many intervention strategies have been utilized by governments around the world, including masks, social distancing, and vaccinations. However, officials making decisions regarding interventions may have a limited time to act. Computer simulations can aid them by predicting future disease outcomes, but they also have limitations due to requirements on processing power or time. This paper examines whether a machine learning model can be trained on a small subset of simulation runs to inexpensively predict future disease trajectories very close to the original simulation results. Using four previously published agent-based models for COVID-19, this paper analyzes the predictions of decision tree regression machine learning models and compares them to the results of the original simulations. The results indicate that accurate machine learning meta-models can be generated from simulation models with no strong interventions (e.g., vaccines, lockdowns) using small amounts of simulation data. However, meta-models for simulation models that include strong interventions required much more training data to achieve a similar accuracy. This indicates that machine learning meta-models could be used in some scenarios to assist in faster decision making.

Inflammatory bowel disease (IBD) is a chronic, incurable disease involving the gastrointestinal tract. It is characterized by complex, unclear pathogenesis, increased prevalence worldwide, and a wide spectrum of extraintestinal manifestations and comorbidities. Recognition of IBD remains challenging and delays in disease diagnosis still poses a significant clinical problem as it negatively impacts disease outcome. The main diagnostic tool in IBD continues to be invasive endoscopy. We aimed to create an IBD machine learning prediction model based on routinely performed blood, urine, and fecal tests. Based on historical patients’ data (702 medical records: 319 records from 180 patients with ulcerative colitis (UC) and 383 records from 192 patients with Crohn’s disease (CD)), and using a few simple machine learning classificators, we optimized necessary hyperparameters in order to get reliable few-features prediction models separately for CD and UC. Most robust classificators belonging to the random forest family obtained 97% and 91% mean average precision for CD and UC, respectively. For comparison, the commonly used one-parameter approach based on the C-reactive protein (CRP) level demonstrated only 81% and 61% average precision for CD and UC, respectively. Results of our study suggest that machine learning prediction models based on basic blood, urine, and fecal markers may with high accuracy support the diagnosis of IBD. However, the test requires validation in a prospective cohort.

Rationale: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Objectives: Perfor...

The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the Boston University Amyloidosis Center. Outcomes were analyzed according to date of diagnosis: 1980-1989 (era 1), 1990-1999 (era 2), 2000-2009 (era 3), and 2010-2019 (era 4). Overall survival increased steadily with median values of 1.4, 2.6, 3.3, and 4.6 years for eras 1–4, respectively (P 10 years after diagnosis). Under changing standards of care, survival improved and early mortality declined over the last 40 years. These findings support a more optimistic outlook for patients with AL amyloidosis.

Background: Vitamin D deficiency may increase the risk of severe COVID-19 disease. Objectives: To determine if 25-hydroxyvitamin D [25(OH)D] levels in patients hospitalized for COVID-19 were associated with the clinical outcomes of days on oxygen, duration of hospitalization, ICU admission, need for assisted ventilation, or mortality. Methods: We conducted a retrospective study of 92 patients admitted to the hospital with SARS-CoV-2 infection between April 16, 2020 and October 17, 2020. Multivariable regression was performed to assess the independent relationship of 25(OH)D values on outcomes, adjusting for significant covariates and the hospitalization day the level was tested. Results: About 15 patients (16.3%) had 25(OH)D levels Conclusion: Vitamin D status was not related to any of the primary outcomes reflecting severity of COVID-19 in hospitalized patients. However, our sample size may have lacked sufficient power to demonstrate a small effect of vitamin D status on these outcomes.

Among approximately 4.6 million members of Kaiser Permanente Northern California, we examined associations of severe COVID‐19 with demographic factors and comorbidities. As of July 23, 2021, 16 182 had been hospitalized, 2416 admitted to an ICU, and 1525 died due to COVID‐19. Age was strongly associated with hospitalization, ICU admission, and death. Black persons and Hispanic ethnicity had higher risk of death compared with Whites. Among the comorbidities examined, Alzheimer's disease was associated with the highest risk for hospitalization (aHR 3.19, CI: 2.88–3.52) and death (aHR 4.04, CI: 3.32–4.91). Parkinson's disease had the second highest risk of death (aHR = 2.07, CI: 1.50–2.87).

Introduction/objectives To evaluate the journey to diagnosis, disease characteristics and burden of disease in male and female patients with axial spondyloarthritis (axSpA) across Europe. Method Data from 2846 unselected patients participating in the European Map of Axial Spondyloarthritis (EMAS) study through an online survey (2017–2018) across 13 countries were analysed. Sociodemographic characteristics, lifestyle, diagnosis, disease characteristics and patient-reported outcomes (PROs) [disease activity –BASDAI (0–10), spinal stiffness (3–12), functional limitations (0–54) and psychological distress (GHQ-12)] were compared between males and females using chi-square (for categorical variables) and student t (for continuous variables) tests. Results In total, 1100 (38.7%) males and 1746 (61.3%) females participated in the EMAS. Compared with males, females reported considerable longer diagnostic delay (6.1 ± 7.4 vs 8.2 ± 8.9 years; p p p p p Conclusion The patient journey to diagnosis of axSpA is much longer and arduous in females, which may be related to physician bias and lower frequency of HLA-B27 carriership. Regarding PROs, females experience higher disease activity and poorer psychological health compared with males. These results reflect specific unmet needs in females with axSpA needing particular attention. Key Points• Healthcare professionals’ perception of axSpA as a predominantly male disease may introduce some bias during the diagnosis and management of the disease. However, evidence about male-female differences in axSpA is scarce.• EMAS results highlight how female axSpA patients report longer diagnostic delay and higher burden of the disease in a large sample of 2846 participants of 13 European countries.• Results reflect unmet needs of European female patients. Healthcare professionals should pay close attention in order to accurately diagnose and efficiently manage axSpA cases while further research should be developed on the cause of reported gender differences.

The COVID-19 pandemic highlighted the lack of understanding around effective public health interventions to curtail the spread of an emerging respiratory virus. Here, we examined the public health approaches implemented by each state to limit the spread and burden of COVID-19. Our analysis revealed that stronger statewide interventions positively correlated with fewer COVID-19 deaths, but some neighboring states with distinct intervention strategies had similar SARS-CoV-2 case trajectories. Additionally, more than two weeks is needed to observe an impact on SARS-CoV-2 cases after an intervention is implemented. These data provide a critical framework to inform future interventions during emerging pandemics.

Cardiorespiratory fitness (CRF) is associated with mortality and cardiovascular disease, but assessing CRF in the population is challenging. Here we develop and validate a novel framework to estimate CRF (as maximal oxygen consumption, VO2max) from heart rate response to low-risk personalised exercise tests. We apply the method to examine associations between CRF and health outcomes in the UK Biobank study, one of the world’s largest and most inclusive studies of CRF, showing that risk of all-cause mortality is 8% lower (95%CI 5–11%, 2670 deaths among 79,981 participants) and cardiovascular mortality is 9% lower (95%CI 4–14%, 854 deaths) per 1-metabolic equivalent difference in CRF. Associations obtained with the novel validated CRF estimation method are stronger than those obtained using previous methodology, suggesting previous methods may have underestimated the importance of fitness for human health.

At the start of the COVID-19 pandemic, most US K-12 schools shutdown and millions of students began remote learning. By September 2020, little guidance had been provided to school districts to inform fall teaching. This indecision led to a variety of teaching postures within a given state. In this report we examine Ohio school districts in-depth, to address whether on-premises teaching impacted COVID-19 disease outcomes in that community. We observed that counties with on-premises teaching had more cumulative deaths at the end of fall semester than counties with predominantly online teaching. To provide a measure of disease progression, we developed an observational disease model and examined multiple possible confounders, such as population size, mobility, and demographics. Examination of micropolitan counties revealed that the progression of COVID-19 disease was faster during the fall semester in counties with predominantly on-premises teaching. The relationship between increased disease prevalence in counties with on-premises teaching was not related to deaths at the start of the fall semester, population size, or the mobility within that county. This research addresses the critical question whether on-premises schooling can impact the spread of epidemic and pandemic viruses and will help inform future public policy decisions on school openings.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dose, infection, and coronavirus disease 2019 (COVID-19) outcomes remains poorly understood. This review summarizes the existing literature regarding this issue, identifies gaps in current knowledge, and suggests opportunities for future research. In humans, host characteristics, including age, sex, comorbidities, smoking, and pregnancy, are associated with severe COVID-19. Similarly, in animals, host factors are strong determinants of disease severity, although most animal infection models manifest clinically with mild to moderate respiratory disease. The influence of variants of concern as it relates to infectious dose, consequence of overall pathogenicity, and disease outcome in dose–response remains unknown. Epidemiologic data suggest a dose–response relationship for infection contrasting with limited and inconsistent surrogate-based evidence between dose and disease severity. Recommendations include the design of future infection studies in animal models to investigate inoculating dose on outcomes and the use of better proxies for dose in human epidemiology studies.

Low-coverage or shallow whole genome sequencing (sWGS) approaches can efficiently detect somatic copy number aberrations (SCNAs) at low cost. This is clinically important for many cancers, in particular cancers with severe chromosomal instability (CIN) that frequently lack actionable point mutations and are characterised by poor disease outcome. Absolute copy number (ACN), measured in DNA copies per cancer cell, is required for meaningful comparisons between copy number states, but is challenging to estimate and in practice often requires manual curation. Using a total of 60 cancer cell lines, 148 patient-derived xenograft (PDX) and 142 clinical tissue samples, we evaluate the performance of available tools for obtaining ACN from sWGS. We provide a validated and refined tool called Rascal (relative to absolute copy number scaling) that provides improved fitting algorithms and enables interactive visualisation of copy number profiles. These approaches are highly applicable to both pre-clinical and translational research studies on SCNA-driven cancers and provide more robust ACN fits from sWGS data than currently available tools.