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Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Students struggle to regulate their learning during independent study sessions. In this study, we ask whether an online behavioral intervention helped introductory students decrease distraction while studying. The intervention consisted of exam 1 reflection, exam 2 planning, and exam 2 reflection exercises. During planning, students formed a goal, mentally contrasted (MC) a positive outcome of their goal to their present reality, identified an obstacle, and formed an implementation intention (II) to overcome that obstacle. During reflection, students self-reported their distraction while studying. Distraction was the most frequently reported study obstacle, and decreasing distraction was the second most frequently reported study goal. While students who aimed to decrease distraction as a goal did not follow through, students who planned for distraction obstacles did follow through on decreasing distraction levels. Only about half of students generated an II that aligned with their study goal, which may provide one reason for the opposing follow-through of distraction framed as a goal versus as an obstacle. Lastly, we examined the specificity of students' II's and found no relationship with follow-through. Overall, MC with II holds promise as a self-regulatory technique to help introductory biology students change their behaviors while studying.

Digitalization of (higher) education has been an increasingly important subject in the recent years, spiking especially due to pandemic lockdowns. While many scholars and third parties consider this process to be an improvement or even an inevitability, I argue that there is much to understand about it beyond 'attending to the materialities of digital education'. This paper aims to do two things: 1) to argue why digital materialities approach ('attending to the materialities of digital education') is not enough to grasp the digitalization of the University (and thus, its stakes) and 2) to discuss how combining general organology and an educational-phenomenological outlook offers a more robust way of understanding digitalization of the University and its stakes. I conclude by pointing to the issue of place and placefulness that seems to be one of the most directly affected characteristics of the University and studying, which calls on to be reflected further upon.

Abstract Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p

Abstract Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor‐related factors in an effort to optimize patient outcomes.

Abstract Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Abstract Chest computed tomography is one of the most common diagnostic tests, with 15 million scans performed annually in the United States. Coronary calcium can be visualized on these scans, but other measures of cardiac risk such as atrial and ventricular volumes have classically required administration of contrast. Here we show that a fully automated pipeline, incorporating two artificial intelligence models, automatically quantifies coronary calcium, left atrial volume, left ventricular mass, and other cardiac chamber volumes in 29,687 patients from three cohorts. The model processes chamber volumes and coronary artery calcium with an end-to-end time of ~18 s, while failing to segment only 0.1% of cases. Coronary calcium, left atrial volume, and left ventricular mass index are independently associated with all-cause and cardiovascular mortality and significantly improve risk classification compared to identification of abnormalities by a radiologist. This automated approach can be integrated into clinical workflows to improve identification of abnormalities and risk stratification, allowing physicians to improve clinical decision-making.

BACKGROUND: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortiums (PIDTCs) prospective and retrospective studies of SCID. OBJECTIVE: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. METHODS: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. RESULTS: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (

Augmented Reality (AR) is a technology that overlays virtual objects on a physical environment. The illusion afforded by AR is that these virtual artifacts can be treated like physical ones, allowing people to view them from different perspectives and point at them knowing that others see them in the same place. Despite extensive research in AR, there has been surprisingly little research into how people embrace this AR illusion, and in what ways the illusion breaks down. In this paper, we report the results of an exploratory, mixed methods study with six pairs of participants playing the novel Sightline AR game. The study showed that participants changed physical position and pose to view virtual artifacts from different perspectives and engaged in conversations around the artifacts. Being able to see the real environment allowed participants to maintain awareness of other participants’ actions and locus of attention. Players largely entered the illusion of interacting with a shared physical/virtual artifact, but some interactions broke the illusion, such as pointing into space. Some participants reported fatigue around holding their tablet devices and taking on uncomfortable poses.

BackgroundDepressive disorder is common among haemodialysis patients. The purpose of this study was to explore approaches to diagnosing depression in the context of a real-life setting, with the view of creating practical recommendations. It also aimed to evaluate the prevalence of depression and dementia.MethodsWe conducted a cross-sectional study in two Dialysis Centres in Poland. Cognitive functions were evaluated using Mini–Mental State Examination (MMSE). The screening for depressive symptoms was assessed using Beck Depression Inventory II (BDI-II). The diagnosis of major depressive disorder was confirmed by a psychiatrist using Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). Sociodemographic and clinical data were also collected.ResultsInitially, 136 patients agreed to participate in the study. Dementia was found in 13% of the study group. Sixty-two patients did not agree to perform all the proposed tests and were not included in the analysis, which eventually consisted of 70 patients. According to BDI-II, depressive symptoms were present in 35.7% of patients, while the diagnosis of major depressive disorder (MDD) was confirmed by the psychiatrist in 25.7%. According to the ROC analysis the optimal cut-off score for diagnosing MDD using BDI-II was ≥13 points.ConclusionsThis study suggests that the regular screening for depressive symptoms, followed by a psychiatric consultation in selected patients, might improve diagnosing depression with the goal of achieving a higher quality of life and a lower mortality rate. It may also be a cost-effective model for the management of depression among the haemodialysis population.

Introduction and purpose: The article focuses on the analysis of young people's awareness of the consumption of energy drinks, especially those containing caffeine. The aim of the study is to understand the level of knowledge about the awareness and consumption of energy drinks among students aged 18-25. This study was conducted using surveys and involving 202 participants. Material and Methods: The study was conducted using online anonymous surveys, involving 202 participants. The participants were students aged 18-25 both women and men. The results were analyzed according to the age and gender. Moreover, based on the available literature examining aspects related to the consumption of energy drinks. Results: The study shows that the vast majority of respondents (94.06%) are aware of the impact of energy substances on the body. The charts also illustrate that caffeine, as the main ingredient in energy drinks, is well understood in terms of cardiovascular effects. Moreover, the student community is aware of the link between excessive sugar consumption and the risk of cancer development. Discussion: The study shows that young people are aware of the negative impact of energy drinks on health. Nevertheless, not all areas of knowledge are clear to them. The continuous increase in the level of education can undoubtedly contribute to the introduction of healthy eating habits among students. Most respondents declare to drink energy drinks again, it should draw our special attention. Conclusions: It is worth noting the need for further education, especially in the field of metabolic syndrome. It also highlights the role of research and education in shaping public health awareness. Finally, the article suggests that further research and targeted educational programs are critical to improving public health, especially in the context of energy drink consumption.

Metabolic dysfunction-associated steatotic liver disease is the most common form of liver disease and poses significant health risks to patients who progress to metabolic dysfunction-associated steatohepatitis. Fatty acid overload alters endoplasmic reticulum (ER) calcium stores and induces mitochondrial oxidative stress in hepatocytes, leading to hepatocellular inflammation and apoptosis. Obese mice have impaired liver sarco/ER Ca2+-ATPase (SERCA) function, which normally maintains intracellular calcium homeostasis by transporting Ca2+ ions from the cytoplasm to the ER. We hypothesized that restoration of SERCA activity would improve diet-induced steatohepatitis in mice by limiting ER stress and mitochondrial dysfunction. WT and melanocortin-4 receptor KO (Mc4r−/−) mice were placed on either chow or Western diet (WD) for 8 weeks. Half of the WD-fed mice were administered CDN1163 to activate SERCA, which reduced liver fibrosis and inflammation. SERCA activation also restored glucose tolerance and insulin sensitivity, improved histological markers of metabolic dysfunction-associated steatohepatitis, increased expression of antioxidant enzymes, and decreased expression of oxidative stress and ER stress genes. CDN1163 decreased hepatic citric acid cycle flux and liver pyruvate cycling, enhanced expression of mitochondrial respiratory genes, and shifted hepatocellular [NADH]/[NAD+] and [NADPH]/[NADP+] ratios to a less oxidized state, which was associated with elevated PUFA content of liver lipids. In sum, the data demonstrate that pharmacological SERCA activation limits metabolic dysfunction-associated steatotic liver disease progression and prevents metabolic dysfunction induced by WD feeding in mice.

Abstract Epicardial adipose tissue (EAT) volume and attenuation are associated with cardiovascular risk, but manual annotation is time-consuming. We evaluated whether automated deep learning-based EAT measurements from ungated computed tomography (CT) are associated with death or myocardial infarction (MI). We included 8781 patients from 4 sites without known coronary artery disease who underwent hybrid myocardial perfusion imaging. Of those, 500 patients from one site were used for model training and validation, with the remaining patients held out for testing (n = 3511 internal testing, n = 4770 external testing). We modified an existing deep learning model to first identify the cardiac silhouette, then automatically segment EAT based on attenuation thresholds. Deep learning EAT measurements were obtained in

Abstract The results of studies on the influence of zinc oxide nanoparticles (ZnO-NPs) on the structural, thermal and optical properties of thin films of mixtures of phenyl-C71-butyric acid methyl ester (PCBM) with poly[3-hexylthiophene] (P3HT) of various molecular weights are described in this article. The structural properties of the layers of: polymers, mixtures of polymers with fullerenes and their composites with ZnO-NPs were investigated using X-ray diffraction. Whereas their glass transition temperature and optical parameters have been determined by temperature-dependent spectroscopic ellipsometry. The presence of ZnO-NPs was also visible in the images of the surface of the composite layers obtained using scanning electron microscopy. These blends and composite films have also been used as the active layer in bulk heterojunction photovoltaic structures. The molecular weight of P3HT (Mw = 65.2; 54.2 and 34.1 kDa) and the addition of nanoparticles affected the power conversion efficiency (PCE) of the obtained solar cells. The determined PCE was the highest for the device prepared from the blend of P3HT:PCBM with the polymer of the lowest molecular weight. However, solar cells with ZnO-NPs present in their active layer had lower efficiency, although the open-circuit voltage and fill factor of almost all devices had the same values whether they contained ZnO-NPs or not. It is worth noting that thermal studies carried out using temperature-dependent ellipsometry showed a significant effect of the presence of ZnO-NPs on the value of the glass transition temperature, which was higher for composite films than for films made of a polymer-fullerene blend alone.

Background and Objectives: Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting mainly elderly patients. Still, little is known about the pathogenesis of pruritus in BP or the factors that affect the clinical course of the disease. This study aimed to evaluate the factors influencing the clinical course of BP among older patients. Materials and Methods: A retrospective analysis of medical records of 55 patients with BP hospitalized in the dermatology department in 2015–2021 was conducted. The study focused on preliminary diagnosis, medical history, clinical examination (characteristics and location of cutaneous changes), laboratory investigation, and direct and indirect immunofluorescence. Results: Analysis of laboratory results in combination with the clinical course of BP showed that red blood cell count, hemoglobin, and hematocrit values were negatively associated with a risk of erosions and erythema, while MCHC values were positively correlated with a risk of associated pruritus. A correlation was found between neurological diseases and an increased risk of erosions. Conclusions: We have shown that age and neurological conditions, including stroke, affect the clinical course of BP. Further studies on a larger group of patients should be conducted to investigate the different factors affecting the clinical aspect of BP and to understand the relationship between them.

Introduction and aim: Adenoma pleomorphum (multiform adenoma) is the most popular bening tumor, that originates from the salivary glands. Neoplasm develops mainly from large salivary glands and its occurrence in the nasal cavity is rare and falls mainly in the 3-6 decade of life. Only 1% of all pleomorphic adenomas develop in the nasal and sinus cavities. Despite being a benign tumor, malignant transformation can occur in 2-10% of cases. Description of the case: We report a case of a 21-year-old female ethnically Polish patient with nasal multiform adenoma with initial diagnosis, which indicated a polyp. The final diagnosis was based on the histopathological examination of the resected lesion. The tumor was removed by an endoscopic method with no tissue margins, which may increase the risk of recurrence. Conclusions: Our case demonstrates that despite pleomorphic adenomas typically occurs in the 3rd to 6th decade of life, clinical symptoms are nondistinctive with a polyp and nasal cavity is a very rare location there should be always be increased vigilance leading to choosing best diagnostic measures to form right diagnosis.

Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research. Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management. Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice.

Introduction and purpose: Breast cancer poses a significant global health challenge, especially in Poland, where it is the most prevalent cancer among women. Despite advancements in medical technology, individual awareness and proactive health practices, such as Breast Self-Examination (BSE), are crucial for early detection. This study focuses on BSE practices in the Tarnów district of Poland, a small city facing unique healthcare challenges, to understand the prevalence, knowledge, and attitudes toward BSE. The aim of study was to comprehensively investigate BSE practices among women in the Tarnów district, considering socio-demographic factors. Material and Methods: Anonymous questionnaires assessed socio-demographic characteristics, attitudes toward BSE, frequency of BSE performance, knowledge on BSE, and sources of information. The survey involved 100 Polish women in gynecologist and general practitioner offices in Tarnów County. Results were analyzed in relation to age, education, and place of residence. Results: While 90% of women were familiar with BSE, 10% had never heard of it. While 29% performed BSE monthly, 18% never conducted the examination. Knowledge gaps were identified, particularly regarding optimal BSE practices. Information sources included the Internet (44%) and gynecologists (28%). Notably, 65% expressed a willingness to participate in BSE training. Conclusions: In conclusion, the study provides valuable insights into BSE practices among women in the Tarnów district, emphasizing the need for targeted interventions to encourage regular BSE. Knowledge gaps and the willingness of women to participate in training present opportunities for healthcare initiatives. The study also highlights the need for broader health education campaigns to dispel myths and enhance awareness, particularly regarding breast cancer affecting both genders. Limitations include a small sample size and geographic specificity to Tarnów district.

Introduction: Diabetes poses a significant global health challenge, impacting patient well-being and longevity. Despite advances in diagnosis and treatment, the prevalence of diabetes continues to rise, with projections indicating a substantial increase in affected individuals in the coming years. The complications of diabetes, including cardiovascular disease, retinopathy, nephropathy, and neuropathy, underscore the importance of early detection and management. In this context, artificial intelligence (AI) offers promising opportunities to revolutionize diabetes care, enabling faster diagnostics, more effective treatment strategies. Description of the State of Knowledge: Artificial intelligence (AI) has emerged as a transformative force in healthcare, leveraging machine learning and deep learning algorithms to analyze vast amounts of medical data. These algorithms enable more accurate diagnosis, prediction of disease onset, and early detection of complications associated with diabetes. Machine learning models, including support vector machines and neural networks, have shown promise in identifying diabetes risk factors and predicting disease progression. Deep learning techniques, with their ability to analyze complex data patterns, offer further insights into diabetes diagnosis. Additionally, fuzzy cognitive maps provide a framework for decision-making based on patient data, enhancing early detection efforts. Summary: Artificial intelligence holds immense potential to transform diabetes care, offering solutions for early detection, personalized treatment, and improved patient outcomes. By harnessing the power of AI algorithms, healthcare providers can enhance diagnostic accuracy, predict disease progression, and implement targeted interventions.