Miracle-dz/UniFAR-FTUs huggingface dataset:
Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis

Simple Summary Female breast cancer continues to be the leading cause of cancer deaths worldwide, and type 2 diabetes mellitus (T2DM) is one of the contributors to the poor prognosis of breast cancer. This raises the issue that T2DM might be associated with aggressive clinicopathological characteristics, which indicate pivotal prognostic values. This study aimed to clarify the differences in breast cancer characteristics at diagnosis between patients with and without pre-existing T2DM. Our meta-analyses showed an increased risk of being diagnosed with a late-stage tumor, large tumor size, and invasive lymph nodes in patients with T2DM. No significant results were observed for grade, estrogen/progesterone receptor, and human epidermal growth factor receptor. These findings indicate an association between T2DM and advanced breast cancer at diagnosis, and suggest that the more active role of breast cancer screening should be further explored for women with T2DM. Abstract Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04–1.36, p = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04–1.35, p = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05–1.51, p = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.
Deletion of Neuronal CuZnSOD Accelerates Age-Associated Muscle Mitochondria and Calcium Handling Dysfunction That Is Independent of Denervation and Precedes Sarcopenia

Skeletal muscle suffers atrophy and weakness with aging. Denervation, oxidative stress, and mitochondrial dysfunction are all proposed as contributors to age-associated muscle loss, but connections between these factors have not been established. We examined contractility, mitochondrial function, and intracellular calcium transients (ICTs) in muscles of mice throughout the life span to define their sequential relationships. We performed these same measures and analyzed neuromuscular junction (NMJ) morphology in mice with postnatal deletion of neuronal Sod1 (i-mn-Sod1-/- mice), previously shown to display accelerated age-associated muscle loss and exacerbation of denervation in old age, to test relationships between neuronal redox homeostasis, NMJ degeneration and mitochondrial function. In control mice, the amount and rate of the decrease in mitochondrial NADH during contraction was greater in middle than young age although force was not reduced, suggesting decreased efficiency of NADH utilization prior to the onset of weakness. Declines in both the peak of the ICT and force were observed in old age. Muscles of i-mn-Sod1-/- mice showed degeneration of mitochondrial and calcium handling functions in middle-age and a decline in force generation to a level not different from the old control mice, with maintenance of NMJ morphology. Together, the findings support the conclusion that muscle mitochondrial function decreases during aging and in response to altered neuronal redox status prior to NMJ deterioration or loss of mass and force suggesting mitochondrial defects contribute to sarcopenia independent of denervation.
Single-Tear Proteomics: A Feasible Approach to Precision Medicine

Lacrimal fluid is an attractive source of noninvasive biomarkers, the main limitation being the small sample amounts typically collected. Advanced analytical methods to allow for proteomics profiling from a few microliters are needed to develop innovative biomarkers, with attractive perspectives of applications to precision medicine. This work describes an effective, analytical pipeline for single-tear analysis by ultrahigh-resolution, shotgun proteomics from 23 healthy human volunteers, leading to high-confidence identification of a total of 890 proteins. Highly reproducible quantification was achieved by either peak intensity, peak area, or spectral counting. Hierarchical clustering revealed a stratification of females vs. males that did not emerge from previous studies on pooled samples. Two subjects were monitored weekly over 3 weeks. The samples clustered by withdrawal time of day (morning vs. afternoon) but not by follow-up week, with elevated levels of components of the immune system in the morning samples. This study demonstrates feasibility of single-tear quantitative proteomics, envisaging contributions of this unconventional body fluid to individualized approaches in biomedicine.
Modeling Energy Expenditure Estimation in Occupational Context by Actigraphy: A Multi Regression Mixed-Effects Model

The accurate prediction of energy requirements for healthy individuals has many useful applications. The occupational perspective has also been proven to be of great utility for improving workers’ ergonomics, safety, and health. This work proposes a statistical regression model based on actigraphy and personal characteristics to estimate energy expenditure and cross-validate the results with reference standardized methods. The model was developed by hierarchical mixed-effects regression modeling based on the multitask protocol data. Measurements combined actigraphy, indirect calorimetry, and other personal and lifestyle information from healthy individuals (n = 50) within the age of 29.8 ± 5 years old. Results showed a significant influence of the variables related to movements, heart rate and anthropometric variables of body composition for energy expenditure estimation. Overall, the proposed model showed good agreement with energy expenditure measured by indirect calorimetry and evidenced a better performance than the methods presented in the international guidelines for metabolic rate assessment proving to be a reliable alternative to normative guidelines. Furthermore, a statistically significant relationship was found between daily activity and energy expenditure, which raised the possibility of further studies including other variables, namely those related to the subject’s lifestyle.
Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review

Background: The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking. Methods: A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data. Results: Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine. Conclusions: The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes.
Printing of Zirconia Parts via Fused Filament Fabrication

In this work, a process chain for the fabrication of dense zirconia parts will be presented covering the individual steps feedstock compounding, 3D printing via Fused Filament Fabrication (FFF) and thermal postprocessing including debinding and sintering. A special focus was set on the comprehensive rheological characterization of the feedstock systems applying high-pressure capillary and oscillation rheometry. The latter allowed the representation of the flow situation especially in the nozzle of the print head with the occurring low-shear stress. Oscillation rheometry enabled the clarification of the surfactant’s concentration, here stearic acid, or more general, the feedstocks composition influence on the resulting feedstock flow behavior. Finally, dense ceramic parts (best values around 99 % of theory) were realized with structural details smaller than 100 µm.
Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract

Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous. We investigated HCC that segregates in three inbred families (LUCC03, LUCC16, and LUCC24). Ophthalmological examinations revealed cataracts with variability related to the age of onset segregating in a recessive manner in these families. Exome sequencing of probands identified a novel homozygous c.2710delG;p.(Val904Cysfs*36) EPHA2 variant in LUCC03 and a known homozygous c.2353G>A;p.(Ala785Thr) EPHA2 variant in the other two recessive families. EPHA2 encodes a transmembrane tyrosine kinase receptor, which is primarily involved in membrane-transport, cell-cell adhesion, and repulsion signaling processes. Computational structural modeling predicts that substitution of a threonine for an alanine p.(Ala785Thr) results in the formation of three new hydrogen bonds with the neighboring residues, which causes misfolding of EPHA2 in both scenarios. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of EPHA2-related HCC.
Telepsychiatry to Provide Mental Health Support to Healthcare Professionals during the COVID-19 Crisis: A Cross-Sectional Survey among 321 Healthcare Professionals in France

Pandemics are difficult times for the mental health of healthcare professionals, who are more likely to present with PTSD-like symptoms. In the context of a highly contagious communicable disease, telemedicine is a useful alternative to usual care, and should be considered as a means to support healthcare professionals’ mental health. This is a multicenter (n = 19), cross-sectional study, based on a 27-item questionnaire, aiming to investigate the acceptability to healthcare workers of a telepsychiatry service as a means of providing mental health support during the COVID-19 pandemic. Between October and December 2020, 321 responses were received, showing that women, caregiving staff, and those directly involved in the care of COVID-19 patients are less favorable to the idea of receiving remote support. In our population, barriers were related to the clinical setting or ethics, and most of the respondents would not accept a drug prescription by telepsychiatry. Although telepsychiatry should be a part of the armamentarium of mental health management, it is not suitable as a stand-alone approach, and should be combined with conventional face-to-face consultations.
Unraveling the plant diversity of the Amazonian canga through DNA barcoding

Abstract The canga of the Serra dos Carajás, in Eastern Amazon, is home to a unique open plant community, harboring several endemic and rare species. Although a complete flora survey has been recently published, scarce to no genetic information is available for most plant species of the ironstone outcrops of the Serra dos Carajás. In this scenario, DNA barcoding appears as a fast and effective approach to assess the genetic diversity of the Serra dos Carajás flora, considering the growing need for robust biodiversity conservation planning in such an area with industrial mining activities. Thus, after testing eight different DNA barcode markers (matK, rbcL, rpoB, rpoC1, atpF‐atpH, psbK‐psbI, trnH‐psbA, and ITS2), we chose rbcL and ITS2 as the most suitable markers for a broad application in the regional flora. Here we describe DNA barcodes for 1,130 specimens of 538 species, 323 genera, and 115 families of vascular plants from a highly diverse flora in the Amazon basin, with a total of 344 species being barcoded for the first time. In addition, we assessed the potential of using DNA metabarcoding of bulk samples for surveying plant diversity in the canga. Upon achieving the first comprehensive DNA barcoding effort directed to a complete flora in the Brazilian Amazon, we discuss the relevance of our results to guide future conservation measures in the Serra dos Carajás.
Genome-Wide Identification and Characterization of Polygalacturonase Gene Family in Maize (Zea mays L.)

Polygalacturonase (PG, EC 3.2.1.15) is a crucial enzyme for pectin degradation and is involved in various developmental processes such as fruit ripening, pollen development, cell expansion, and organ abscission. However, information on the PG gene family in the maize (Zea mays L.) genome and the specific members involved in maize anther development are still lacking. In this study, we identified 55 PG family genes from the maize genome and further characterized their evolutionary relationship and expression patterns. Phylogenetic analysis revealed that ZmPGs are grouped into six Clades, and gene structures of the same Clade are highly conserved, suggesting their functional conservation. The ZmPGs are randomly distributed across maize chromosomes, and collinearity analysis showed that many ZmPGs might be derived from tandem duplications and segmental duplications, and these genes are under purifying selection. Furthermore, gene expression analysis provided insights into possible functional divergence among ZmPGs. Based on the RNA-seq data analysis, we found that many ZmPGs are expressed in various tissues while 18 ZmPGs are highly expressed in maize anther, and their detailed expression profiles in different anther developmental stages were further investigated by using RT-qPCR analysis. These results provide valuable information for further functional characterization and application of the ZmPGs in maize.
Clinical and Radiological Outcomes After Isolated Anterior Horn Repair of Medial and Lateral Meniscus at 24 Months’ Follow-up, With the Outside-In Technique

Background The effects of repair of isolated anterior horn meniscus lesions have not been thoroughly described in the literature. We aimed to evaluate outcomes with subjective clinical scores and imaging modalities after repair of isolated anterior horn tears, at 24 months’ follow-up. Methods Records of all patients that opted for surgical repair of isolated, anterior horn tears of the medial and lateral meniscus were retrospectively reviewed, between 2016 and 2018. All patients were treated with arthroscopic outside-in technique by the same surgeon. Preoperative and postoperative clinical files were accessed to recover records of preoperative symptomatology, patient-reported scores [International Knee Documentation Committee (IKDC) rating, Lysholm score and Tegner activity level], preoperative and postoperative MRI data and time from injury to surgery. Results Mean age of eight patients was 25.25 years (range 18-37 years). Diagnostic preoperative MRI revealed isolated anterior horn tear of the lateral meniscus and medial meniscus in five patients and an isolated anterior horn tear of the medial meniscus in three patients. Mean time from injury to surgical repair was 23.75 days (range 7-43). We considered seven out of eight repairs to be successfully healed. At 24 months’ follow-up: Mean Lysholm score was 92.25 (range 89-95), Tegner activity scale score was 6.5 (range 5-8) and IKDC score was 91.78 (range 87.8-94.4). All scores significantly improved compared to preoperative values (p<0.001). Conclusions Outside-in is a reliable technique to repair meniscal anterior horn tears, both medially and laterally, with high healing rates and patient satisfaction in young, active patients.
Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs

Simple Summary Immunotherapy is increasingly being used to treat solid tumors and lymphoproliferative diseases. The main classes of drugs are: HER-2-targeted therapies, CTLA-blockers, PD/PDL-1 inhibitors, CAR-T therapy. All these drugs are associated with meaningful cardiac toxicity, ranging from a transient decline of left ventricular function with complete reversibility to myocarditis with a high fatality rate. Abstract Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.
Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas

Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of RANKL, together with BCATN1, LEF1, and FOSL1 genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas
Sleep Quality and Eating Disorder-Related Psychopathologies in Patients with Night Eating Syndrome and Binge Eating Disorders

Night eating syndrome (NES) is an eating disorder (ED) characterized by nocturnal ingestion (NI), evening hyperphagia, morning anorexia, as well as mood and sleep disturbances. This study compared subjective and objective sleep quality and ED-related psychopathologies in patients seeking treatment for ED. Method: The sample was composed of 170 women, aged 18–68, who were referred for an ED assessment from 2011 to 2020. The participants were divided into three subgroups: NES-NI only (n = 30), NES+ binge eating (BE) (including binge eating disorders or bulimia nervosa (n = 52), and BE-only (n = 88). The measures consisted of a psychiatric evaluation, objective sleep monitoring measured by an actigraph for 1 week, a subjective sleep self-report, and ED-related psychopathology questionnaires. Results: Objective sleep monitoring revealed significant group differences, with higher sleep efficiency in participants with BE-only and longer sleep durations for the NES-NI only group. Subjectively, the BE-only group described a significantly lower sleep quality than either the NES-NI only or the NES+BE groups. ED-related psychopathology was lower in the NES-NI-only group. A stepwise linear regression revealed that general psychopathology (the brief symptom inventory total score) was a significant predictor of subjective sleep quality. Conclusion: NES-NI-only was correlated with less psychopathology, but with more subjective and objective sleep disturbances. These results lend weight to the supposition that NES lies on a continuum of ED psychopathologies, and that NES-NI-only appears to be a separate entity from NES+BE and BE-only in terms of its psychopathology.
Effect of Microwave Treatment in a High Pressure Microwave Reactor on Graphene Oxide Reduction Process—TEM, XRD, Raman, IR and Surface Electron Spectroscopic Studies

Reduced graphene oxide (rGO) was prepared by chemical reduction of graphene oxide (GO) (with a modified Hummers method) in aqueous solutions of hydrazine (N2H4), formaldehyde (CH2O), formic acid (HCO2H) accompanied by a microwave treatment at 250 °C (MWT) by a high pressure microwave reactor (HPMWR) at 55 bar. The substrates and received products were investigated by TEM, XRD, Raman and IR spectroscopies, XPS, XAES and REELS. MWT assisted reduction using different agents resulted in rGOs of a large number of vacancy defects, smaller than at GO surface C sp3 defects, oxygen groups and interstitial water, interlayer distance and diameter of stacking nanostructures (flakes). The average number of flake layers obtained from XRD and REELS was consistent, being the smallest for CH2O and then increasing for HCO2H and N2H4. The number of layers in rGOs increases with decreasing content of vacancy, C sp3 defects, oxygen groups, water and flake diameter. MWT conditions facilitate formation of vacancies and additional hydroxyl, carbonyl and carboxyl groups at these vacancies, provide no remarkable modification of flake diameter, what results in more competitive penetration of reducing agent between the interstitial sites than via vacancies. MWT reduction of GO using a weak reducing agent (CH2O) provided rGO of 8 layers thickness.