Miracle-dz/UniFAR-FTUs huggingface dataset:
ID1 and ID4 Are Biomarkers of Tumor Aggressiveness and Poor Outcome in Immunophenotypes of Breast Cancer

Simple Summary Inhibitor of differentiation (ID) proteins are essential to promote proliferation during embryonic development, but they are silenced in most adult tissues. Evidence to date shows ID1 expression in many tumor types, including breast cancer. However, the role of the remaining ID family members, especially ID4, in breast cancer remains unclear. In this work, we aimed to assess the four ID genes expression in breast cancer cell lines and a long series of breast cancer samples and correlate them with clinicopathological features and patients’ survival. We observed a significantly higher expression of ID4 in tumor cell lines than the healthy breast epithelium cell line. We confirmed that the overexpression of ID1 and ID4 correlated with more aggressive phenotypes and poor survival in breast cancer patients’ samples. Our results support the importance of ID proteins as targets for the development of anti-cancer drugs. Abstract Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients’ outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.
Surface Properties of 1DTiO2 Microrods Modified with Copper (Cu) and Nanocavities

This work deals with Cu-modified 1DTiO2 microrods (MRs) and their surface properties. The pristine lyophilized precursor Cu_1DTiO2, prepared by an environmentally friendly cryo-lyophilization method, was further annealed in the temperature interval from 500 to 950 °C. The microstructure of all samples was characterized by electron microscopy (SEM/EDS and HRTEM/SAED), X-ray powder diffraction (XRD), infrared spectroscopy, simultaneous DTA/TGA thermoanalytical measurement, and mass spectroscopy (MS). Special attention was paid to the surface structure and porosity. The 1D morphology of all annealed samples was preserved, but their surface roughness varied due to anatase-rutile phase transformation and the change of the nanocrystals habits due to nanocavities formation after releasing of confined ice-water. The introduction of 2 wt. % Cu as electronically active second species significantly reduced the direct bandgap of 1DTiO2 in comparison with undoped TiO2 and the standard Degussa TiO2_P25. All samples were tested for their UV absorption properties and H2 generation by PEC water splitting. We presented a detailed study on the surface characteristics of Cu doped 1DTiO2 MRs due to gain a better idea of their photocatalytic activity.
The N terminus of myosin-binding protein C extends toward actin filaments in intact cardiac muscle

Using super-resolution fluorescence microscopy and in silico simulations, Rahmanseresht et al. demonstrate that the N terminus of myosin-binding protein C (MyBP-C) tends to bind to actin filaments in both active and relaxed muscle. Binding to the myosin head also appears possible but only when the myosin head is near the actin filament.
Detection and Characterization of Viral Pathogens Associated with Reproductive Failure in Wild Boars in Central Italy

Simple Summary Suid herpesvirus 1, porcine circovirus 2 and porcine parvovirus are causative agents of reproductive failures in swine and are widely diffused in the wild boar population. No data describing the impact of those viruses on the reproductive performance of wild boar are so far available. We aimed to investigate the ability of the above viruses to infect foetuses of free-ranging pregnant wild boar sows living in a highly-populated area. Molecular investigation revealed that although all investigated viruses were detected in pregnant sows, only herpesvirus and circovirus were detected in the foetuses. Phylogenetic analysis revealed a close relationship between the strains circulating in wild boar and those already described in domestic swine. This study highlights the importance of monitoring the circulation of pathogens that are shared between domestic and wild pigs. This information is essential for the pig industry to avoid possible economic losses. Abstract Wild boar and domestic swine share several pathogens, including viruses responsible for reproductive failures, representing an important sanitary and economic risk for the swine industry. Among them, suid herpesvirus 1 (SuHV-1), porcine circovirus 2 (PCV2) and porcine parvovirus 1 (PPV1) are widely diffused in the wild boar population. Unfortunately, little is known about their pathogenetic mechanisms and impact on the reproductive parameters of wild animals. This study aims to investigate the presence of viruses responsible for reproductive failure in pregnant wild boar sows and their foetuses. The investigation was conducted on 46 pregnant wild boar and their foetuses by molecular analysis; a phylogenetic study was performed on the positive samples. All of the investigated pathogens were identified in sows, while only herpesvirus and circovirus were detected in the tissues of their foetuses. Phylogenetic analysis revealed that the viral sequences obtained from the positive wild boars were closely related to those previously identified in domestic swine belonging to the same study areas. The results suggest that SuHV-1 and PCV2 can infect wild boar foetuses, with a possible impact on wild boar reproductive performance. Moreover, our data highlight the importance of continuous monitoring of swine pathogens circulating in wild environments, so as to carry out adequate sanitary actions.
Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7

Mutations in structural subunits and assembly factors of complex I of the oxidative phosphorylation system constitute the most common cause of mitochondrial respiratory chain defects. Such mutations can present a wide range of clinical manifestations, varying from mild deficiencies to severe, lethal disorders. We describe a patient presenting intrauterine growth restriction and anemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with fatal outcome. Whole genome sequencing revealed an intronic biallelic mutation in the NDUFB7 gene (c.113‐10C>G) and splicing pattern alterations in NDUFB7 messenger RNA were confirmed by RNA Sequencing. The detected variant resulted in a significant reduction of the NDUFB7 protein and reduced complex I activity. Complementation studies with expression of wild‐type NDUFB7 in patient fibroblasts normalized complex I function. Here we report a case with a primary complex I defect due to a homozygous mutation in an intron region of the NDUFB7 gene.
Oxidative Pentose Phosphate Pathway Enzyme 6-Phosphogluconate Dehydrogenase Plays a Key Role in Breast Cancer Metabolism

Simple Summary Cancer cells alter their metabolism to maintain their high need for energy, produce enough macromolecules for biosynthesis, and preserve their redox status. The investigation of cancer cell-specific metabolic alterations has vital importance to identify targets to be exploited for therapeutic development. The pentose phosphate pathway (PPP) is often highly activated in tumor cells to maintain redox level, as this pathway takes an important role in reactive oxygen species detoxification. PPP also yields ribose-5-phosphate, a five-carbon sugar essential for synthesizing nucleotides necessary for DNA replication and cell proliferation. In this study, we inhibited one of the key enzymes of this biochemical pathway and observed the main functions of this enzyme in breast cancer cells. We have demonstrated that inhibition of this enzyme reduces cell proliferation and leads to cell cycle arrest and apoptosis. Besides that, we showed that the inhibition of this enzyme causes an alteration in cellular metabolism. All these findings indicate that targeting this enzyme with specific pharmacological inhibitors is an effective strategy in fighting cancer. Abstract The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer.
Home quality and child health: Analysis of the Survey of Income and Program Participation

Housing is considered a core social determinant of health (SDH) through mechanisms such as the quality, affordability, and location of the home. However, few nationally representative studies examine these mechanisms simultaneously with child health and healthcare use. To determine the associations between home quality and child health, a series of logistic regression analyses was employed using the Survey of Income and Program Participation (SIPP). The 2014 SIPP sample is a multistage, stratified sample of 53,070 housing units from 820 sample areas designed to represent the civilian, noninstitutionalized population of the United States. The analytic sample included 12,964 children aged 2–14 years. Poor housing quality was defined as whether the home had holes in the floor, cracks in the ceiling, plumbing issues, and/or pest problems. Outcome measures included child health status, number of medical visits, and hospitalizations. The results indicated that poor housing quality was associated with poorer health (OR = 1.16, 95% CI = 1.05–1.27) and a greater number of medical visits (OR = 1.11, 95% CI = 1.03, 1.20) after controlling for number of persons per household, neighborhood safety, nonmetropolitan status, parent’s ability to afford housing-related expenses, and other SDH. Future work investigating and intervening on the SDH in children could specifically include the quality and contexts in which homes are situated.
The impact of COVID-19 prevention measures on epidemiology of orthopedic injuries: the outbreak ages fractures!

Background: The application of stringent prevention measures for contrasting COVID-19 spread generated changes not only in the outbreak course, but also in epidemiology of traumatic fractures. The aim of this study was to report the epidemiologic characteristics of surgically-treated fractures during the COVID-19 outbreak over a six-month period, and to describe the variation in volumes and types of injuries, by comparing them with fractures which occurred during the same period in 2019. Methods: We retrospectively analyzed all surgically-treated fractures which were admitted from the January 1st 2020 to June 30th 2020, and compared these data to those of the corresponding timeframe in 2019. The collected data of interest included demographics, such as age and gender, fracture location, time lapse between presentation at Emergency Department and admission in the ward, length of stay. Results: A total of 117 patients were admitted with a diagnosis of facture and surgically treated, with no cases of COVID-19 positive patients. In the corresponding period of 2019, the number of patients admitted for the same reasons was 129. This decrease was more significant in the period between March and April (-30.6%), during which time prevention measures were more stringent. The only statistically significant discrepancy between the two study groups was the mean age, which was significantly higher in 2020. The location of examined injuries were similar in the two study groups, with proximal femur fractures representing the most frequent injuries. Conclusions: This study demonstrated significant changes of epidemiologic patterns of fractures during COVID-19 outbreak. These data should provide support for clinicians and government to evaluate the management and prevention strategies of traumatic not only during outbreak but also in non-outbreak period. (www.actabiomedica.it)
The Role and Activities of Board-Certified Chaplains in Advance Care Planning

Background: Healthcare chaplains have key roles in providing palliative support to patients and families, and they are well-suited to facilitate advance care planning (ACP). However, empirical data on the roles and responsibilities of chaplains in facilitating ACP are limited. Objectives: To examine the roles of board-certified healthcare chaplains in ACP in various healthcare settings. Methods: A cross-sectional, web-based self-report survey was conducted with 585 board-certified chaplains recruited from 3 major professional chaplains’ organizations in the U.S. The survey data included chaplains’ demographic and professional characteristics, their roles and responsibilities, and responses regarding communication and participation with other healthcare team members in facilitating ACP, including experienced barriers. Results: More participants worked in community hospital settings (42%) and academic medical centers (19.6%) than in any other setting. Over 90% viewed ACP as an important part of their work, 70% helped patients complete advance directives, and 90% helped patients discuss their preferences about end-of-life treatments. Many chaplains were not consistently included in team discussions regarding decision-making, although most chaplains reported that they could always find ways to communicate with their teams. Conclusion: Professional board-certified chaplains regularly engage in facilitating ACP discussions with patients and families in various healthcare settings. There is a need to recognize and provide systematic support for the role of chaplains in facilitating ACP conversations and to integrate chaplains into routine interdisciplinary team and family meetings.
False positive Influenza rapid tests using newly EUA cleared multiplex assay in a low prevalence setting

To the Editor, We report a cluster of false positive Influenza A and B rapid antigen tests from a point of care testing laboratories within a large healthcare system in central Texas. In the backdrop of current coronavirus disease 2019 pandemic and due to heightened epidemiological interventions by governments and public health authorities there has been a significant reduction in the cases of respiratory viruses including Influenza viruses. Given the very low prevalence of respiratory viruses and in the context of emerging infectious diseases diagnostic kits being approved under Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration, it is becoming incumbent upon the local CLIA certified laboratories to establish assay performance characteristics. Between November 15, 2020 and mid‐December 2020, six BSW Healthcare clinics in central Texas reported 22 (11.1%) positive rapid antigen test results of the 197 total tests performed. The rapid antigen test is a newly EUA cleared test that detects Influenza A, Influenza B and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Of the 22 Influenza‐positive tests, 2 (9%) were Influenza A and 20 (90.9%) were Influenza B. Considering the very low prevalence of Influenza in the region, we decided to confirm all 22 rapid antigen positive tests by a molecular reference method. All 22‐specimens tested negative on Influenza molecular test indicating 100% of the Influenza results were false positive on the new EUA cleared rapid antigen test. To assess the performance characteristics of the rapid antigen test, specifically the SARS‐CoV‐2 target, all negative SARS‐CoV‐2 specimens were reflexed to an EUA molecular test for confirmation. Of the 139 SARS‐CoV‐2 antigen negative specimens, 14 (10%) were confirmed to be positive by molecular test indicating 10% of the antigen tests were false negative. Influenza activity in the United States between September 2020 and mid‐December 2020 was relatively low with laboratory‐ confirmed influenza test positivity rate at 0.2%. It is very well‐ known in the clinical laboratory community that rapid antigen tests lack sensitivity. Studies have shown that the sensitivity of these tests can be less than 60% in a normal Influenza season. It can be speculated that due to very low prevalence of Influenza viruses, rapid antigen tests might be experiencing some assay interference, producing false positive results. When the prevalence of the disease is low, the positive predictive value of the test is low, and false‐ positive test results are more likely. The false‐positive influenza results reported here may have resulted in increased health care costs and potential inappropriate use of antiviral medications. While a negative rapid test may not be useful for categorically ruling out SARS‐CoV‐2, it may be useful in certain clinical context. A technical inquiry with the manufacturer has yielded no response citing further investigation is warranted at their end.
DPP4 Inhibitor Sitagliptin Enhances Lymphocyte Recruitment and Prolongs Survival in a Syngeneic Ovarian Cancer Mouse Model

Simple Summary The role of immunity in the development and progression of epithelial ovarian cancer (EOC) is well established. Poor T-cell infiltration is associated with mortality in EOC patients, and recent evidence has suggested that the enzyme DPP4 plays a role in this process. The aim of our study was to evaluate the potential of the clinically-approved DPP4-inhibitor sitagliptin to improve immune responses in mice with EOC. We showed that sitagliptin improved CD8+ T-cell responses in an EOC mouse model, consequently reducing metastatic burden and prolonging survival. These data provide a rationale for the use of DPP4-inhibitors as a second-line treatment for EOC. Abstract Immunity plays a key role in epithelial ovarian cancer (EOC) progression with a well-documented correlation between patient survival and high intratumoral CD8+ to T regulatory cell (Treg) ratios. We previously identified dysregulated DPP4 activity in EOCs as a potentially immune-disruptive influence contributing to a reduction in CXCR3-mediated T-cell infiltration in solid tumours. We therefore hypothesized that inhibition of DPP4 activity by sitagliptin, an FDA-approved inhibitor, would improve T-cell infiltration and function in a syngeneic ID8 mouse model of EOC. Daily oral sitagliptin at 50 mg/kg was provided to mice with established primary EOCs. Sitagliptin treatment decreased metastatic tumour burden and significantly increased overall survival and was associated with significant changes to the immune landscape. Sitagliptin increased overall CXCR3-mediated CD8+ T-cell trafficking to the tumour and enhanced the activation and proliferation of CD8+ T-cells in tumour tissue and the peritoneal cavity. Substantial reductions in suppressive cytokines, including CCL2, CCL17, CCL22 and IL-10, were also noted and were associated with reduced CD4+ CD25+ Foxp3+ Treg recruitment in the tumour. Combination therapy with paclitaxel, however, typical of standard-of-care for patients in palliative care, abolished CXCR3-specific T-cell recruitment stimulated by sitagliptin. Our data suggest that sitagliptin may be suitable as an adjunct therapy for patients between chemotherapy cycles as a novel approach to enhance immunity, optimise T-cell-mediated function and improve overall survival.
Decision aids to prepare patients for shared decision making: Two randomized controlled experiments on the impact of awareness of preference‐sensitivity and personal motives

To participate in shared decision making (SDM), patients need to understand their options and develop trust in their own decision‐making abilities. Two experiments investigated the potential of decision aids (DAs) in preparing patients for SDM by raising awareness of preference‐sensitivity (Study 1) and showing possible personal motives for decision making (Study 2) in addition to providing information about the treatment options.
Genetics and Epigenetics of Nasal Polyposis: a Systematic Review.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses that is often associated with nasal polyposis (CRSwNP) in the most severe cases. As in other complex diseases, genetic factors are thought to play an important role in the risk and development of the disease. Environment may also modulate the epigenetic signature in affected patients. In the present systematic review, we aimed to compile all published data on genetic and epigenetic variations in CRSwNP since 2000. We found 104 articles, 24 of which were related to epigenetic studies. We identified more than 150 genetic variants in 99 genes involved in the pathogenesis of nasal polyposis. These were clustered into 8 main networks, linking genes involved in inflammation and immune response (eg, MHC), cytokine genes (eg, TNF), leukotriene metabolism, and the extracellular matrix. A total of 89 miRNAs were also identified; these are associated mainly with biological functions such as the cell cycle, inflammation, and the immune response. We propose a potential relationship between genes and the miRNAs identified that may open new lines of investigation. An in-depth knowledge of gene variants and epigenetic traits could help us to design more tailored treatment for patients with CRSwNP.