Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemodialysis as a Risk Factor for Lower Right Internal Jugular Stenosis in Cardiac Surgery Patients: A Retrospective Single-Center Study

Lower right internal jugular vein (RIJ) stenosis has been reported as a common cause of RIJ catheterization failure. However, the risk factors for lower RIJ stenosis in patients undergoing cardiac surgery is unclear. We reviewed the electronic medical records of all adult patients who had undergone cardiac operations in a single tertiary university hospital from January 2014 to January 2016. Patients were excluded if they were lack of preoperative contrast-enhanced chest computed tomography (CT) studies. Lower RIJ stenosis was defined as a ratio of cross-sectional area at the smallest level to cross-sectional area at the largest level less than 25%. Multivariable logistic regression analyses were used to investigate the risk factors for lower RIJ stenosis. A sensitivity analysis was also conducted using a cross-sectional area ratio of under 20%. The analysis included 889 patients, and the incidence of lower RIJ stenosis was 3.9%. The multivariable logistic regression analyses revealed that hemodialysis was an independent risk factor for lower RIJ stenosis (OR, 3.54; 95% CI, 1.472–8.514). Sensitivity analysis provided that hemodialysis (OR, 10.842; 95% CI, 3.589–32.75) was a significant predictor of cross-sectional area ratio <20%. Preoperative hemodialysis are significantly associated with an increased risk of lower RIJ stenosis in patients undergoing cardiac surgery. Extra care is needed during central venous catheterization in hemodialysis patients undergoing cardiac surgery.
A Novel Bispecific Antibody Targeting EGFR and VEGFR2 Is Effective against Triple Negative Breast Cancer via Multiple Mechanisms of Action

Simple Summary Triple-negative breast cancer (TNBC) accounts for approximately 10–20% of all diagnosed breast cancers and is often associated with a poor prognosis. There is therefore an urgent need to develop novel and targeted therapeutic approaches against TNBC. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are prominent therapeutic protein targets that are frequently overexpressed in TNBC. In this investigation, we developed a novel bispecific antibody (BsAb) targeting EGFR and VEGFR2 (designated as anti-EGFR/VEGFR2 BsAb) and investigate its anti-tumor activity using TNBC cellular and xenograft mouse models. Data from these studies indicate that anti-EGFR/VEGFR2 BsAb elicited more comprehensive anti-tumor activity via multiple mechanisms of action, including direct inhibition of EGFR and VEGFR2 in TNBC cells, and disruption of autocrine and paracrine pathways in TNBC and endothelial cells, compared to the individual parental mAbs. Our data suggest that this novel BsAb warrants further investigation as a targeted antibody therapeutic to treat TNBC. Abstract Both EGFR and VEGFR2 frequently overexpress in TNBC and cooperate with each other in autocrine and paracrine manner to enhance tumor growth and angiogenesis. Therapeutic mAbs targeting EGFR (cetuximab) and VEGFR2 (ramucirumab) are approved by FDA for numerous cancer indications, but none of them are approved to treat breast cancers. TNBC cells secrete VEGF-A, which mediates angiogenesis on endothelial cells in a paracrine fashion, as well as promotes cancer cell growth in autocrine manner. To disrupt autocrine/paracrine loop in TNBC models in addition to mediating anti-EGFR tumor growth signaling and anti-VEGFR2 angiogenic pathway, we generated a BsAb co-targeting EGFR and VEGFR2 (designated as anti-EGFR/VEGFR2 BsAb), using publicly available sequences in which cetuximab IgG backbone is connected to the single chain variable fragment (scFv) of ramucirumab via a glycine linker. Physiochemical characterization data shows that anti-EGFR/VEGFR2 BsAb binds to both EGFR and VEGFR2 in a similar binding affinity comparable to parental antibodies. Anti-EGFR/VEGFR2 BsAb demonstrates in vitro and in vivo anti-tumor activity in TNBC models. Mechanistically, anti-EGFR/VEGFR2 BsAb not only directly inhibits both EGFR and VEGFR2 in TNBC cells but also disrupts autocrine mechanism in TNBC xenograft mouse model. Furthermore, anti-EGFR/VEGFR2 BsAb inhibits ligand-induced activation of VEGFR2 and blocks paracrine pathway mediated by VEGF secreted from TNBC cells in endothelial cells. Collectively, our novel findings demonstrate that anti-EGFR/VEGFR2 BsAb inhibits tumor growth via multiple mechanisms of action and warrants further investigation as a targeted antibody therapeutic for the treatment of TNBC.
When Should We Think of Myelodysplasia or Bone Marrow Failure in a Thrombocytopenic Patient? A Practical Approach to Diagnosis

Thrombocytopenia can arise from various conditions, including myelodysplastic syndromes (MDS) and bone marrow failure (BMF) syndromes. Meticulous assessment of the peripheral blood smear, identification of accompanying clinical conditions, and characterization of the clinical course are important for initial assessment of unexplained thrombocytopenia. Increased awareness is required to identify patients with suspected MDS or BMF, who are in need of further investigations by a step-wise approach. Bone marrow cytomorphology, histopathology, and cytogenetics are complemented by myeloid next-generation sequencing (NGS) panels. Such panels are helpful to distinguish reactive cytopenia from clonal conditions. MDS are caused by mutations in the hematopoietic stem/progenitor cells, characterized by cytopenia and dysplasia, and an inherent risk of leukemic progression. Aplastic anemia (AA), the most frequent acquired BMF, is immunologically driven and characterized by an empty bone marrow. Diagnosis remains challenging due to overlaps with other hematological disorders. Congenital BMF, certainly rare in adulthood, can present atypically with thrombocytopenia and can be misdiagnosed. Analyses for chromosome fragility, telomere length, and germline gene sequencing are needed. Interdisciplinary expert teams contribute to diagnosis, prognostication, and choice of therapy for patients with suspected MDS and BMF. With this review we aim to increase the awareness and provide practical approaches for diagnosis of these conditions in suspicious cases presenting with thrombocytopenia.
Effectiveness of Non-Presential Individualized Exercise Training PrOgram (NIETO) in Lower Limb Physical Performance in Advanced COPD

Muscle training, a component of pulmonary rehabilitation (PR), improves the physical performance of patients with chronic obstructive pulmonary disease (COPD). Despite the existing evidence, the traditional center-based PR model is applied to a small percentage of patients and presents numerous problems of accessibility, adherence, and costs. This study presents a home model of simple muscle training, non-presential, monitored by telephone and individualized, according to the severity of the COPD. In addition, to evaluate the results, simple tests associated with the physical performance of the lower limbs, previously validated in COPD, have been used, such as the four-meter walk, speed test (4MGS) and the five-repetition test sitting and standing (5STS). The objective was to evaluate whether the Individualized Non-Presential Exercise Training PrOgram (NIETO) induces improvements in the 4MGS, 5STS and quadriceps muscle strength (QMS) tests in outpatients with advanced COPD (FEV1 ≤ 50%). After one year, the QMS was significantly higher in the intervention group (IG) than in the control group (CG) (2.44 ± 4.07 vs. 0.05 ± 4.26 kg; p = 0.009). The 4MGS and 5STS tests were significantly shorter in IG than in CG (−0.39 ± 0.86 vs. 0.37 ± 0.96 s; p = 0.001) and (−1.55 ± 2.83 vs. 0.60 ± 2.06 s; p = 0.001), respectively. A home model of simple muscle training monitored by telephone such as NIETO, can improve 4MGS, 5STS, and quadriceps strength tests in outpatients with advanced COPD.
The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

Liver disease due to metabolic dysfunction constitute a worldwide growing health issue. Severe obesity is a particularly strong risk factor for non-alcoholic fatty liver disease, which affects up to 93% of these patients. Current diagnostic markers focus on the detection of advanced fibrosis as the major predictor of liver-related morbidity and mortality. The most accurate diagnostic tools use elastography to measure liver stiffness, with diagnostic accuracies similar in normal-weight and severely obese patients. The effectiveness of elastography tools are however hampered by limitations to equipment and measurement quality in patients with very large abdominal circumference and subcutaneous fat. Blood-based biomarkers are therefore attractive, but those available to date have only moderate diagnostic accuracy. Ongoing technological advances in omics technologies such as genomics, transcriptomics, and proteomics hold great promise for discovery of biomarkers and increased pathophysiological understanding of non-alcoholic liver disease and steatohepatitis. Very recent developments have allowed for single-cell sequencing and cell-type resolution of gene expression and function. In the near future, we will therefore likely see a multitude of breakthrough biomarkers, developed from a deepened understanding of the biological function of individual cell types in the healthy and injured liver.
Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA–ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.
Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain

The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.
Subcritical Water Extraction of Nutraceutical Compounds from Citrus Pomaces

Abstract Subcritical water (SCW) extraction of citrus pomaces (CPs) was carried out, and antioxidant activity and nutraceutical compound levels of the SCW extracts were evaluated in detail. At first, CP samples were subjected to the SCW extraction under various conditions focusing on the extraction temperature and time. Consequently, the highest total phenol contents, radical scavenging activity, and reducing power were found when extraction was carried at 200°C and 1.4 MPa for 60 min. Furthermore, the amounts of three kinds of polymethoxylated flavones (sinensetin, nobiletin, and tangeretin) in the SCW extracts also showed the highest values under this condition. These results indicate that SCW is an effective medium for the fast and highly efficient extraction of the antioxidants and nutraceutical compounds from CPs.
The Relationship between Cardiovascular Risk Scores and Several Markers of Subclinical Atherosclerosis in an Asymptomatic Population

Background: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic individuals. Methods: A cross-sectional, single-center study included 120 asymptomatic CVD subjects. Four CVD risk scores were computed: SCORE, Framingham, QRISK, and PROCAM. Subclinical atherosclerosis has been determined by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), aortic and brachial augmentation indexes (AIXAo, respectively AIXbr), aortic systolic blood pressure (SBPao), and ankle-brachial index (ABI). Results: The mean age was 52.01 ± 10.73 years. For cIMT—SCORE was more sensitive; for PWV—Framingham score was more sensitive; for AIXbr—QRISK and PROCAM were more sensitive while for AIXao—QRISK presented better results. As for SBPao—SCORE presented more sensitive results. However, ABI did not correlate with any CVD risk score. Conclusions: All four CV risk scores are associated with markers of subclinical atherosclerosis in asymptomatic population, except for ABI, with specific particularities for each CVD risk score. Moreover, we propose specific cut-off values of CV risk scores that may indicate the need for subclinical atherosclerosis assessment.
Characteristics of Periodontal Tissues in Prosthetic Treatment with Fixed Dental Prostheses

The objective of the present study was to investigate the effects of various types of fixed prostheses on periodontal tissues and explore the association of gingival biotype and gum recession in relation to prosthesis types. The study participants (N = 95) were divided into three groups based on the type of dental prosthesis: Group-I: cobalt-chrome (Co-Cr) ceramic prosthesis fabricated by the conventional method (n = 35); Group-II: consisted of patients with Co-Cr ceramic prostheses fabricated by a computer-aided design and computer aided manufacturing (CAD/CAM) technique (n = 30); and Group-III: zirconia-based prostheses fabricated by the CAD/CAM technique (n = 30). Following the use of prostheses, periodontal examinations were performed using the Community Periodontal Index (CPI) and Modified Approximal Plaque Index (MAPI). In addition, the gingival biotype was examined using a probe transparency method. The Statistical Package for the Social Sciences (SPSS), Version 20 (IBM Company, Chicago, IL, USA), was used to analyze the results, and the significance level was set at p = 0.05. It showed the MAPI results after the use of prosthetic rehabilitation for 12 months of periodontitis in 87.9% ± 15.4 of patients in Group-I, in 80.6% ± 17.97 in those in Group-II, and in 62.5% ± 21.4 in those in Group-III (p < 0.01). The CPI index results indicated a high prevalence of periodontal disease in all groups. The number of people with healthy periodontium constituted 17.1% of patients in Group-I, 24.2% in Group-II, and 37.1% in Group-III. Our study concluded that prosthetic treatment with periodontal diseases showed better outcomes while using dental prostheses fabricated by the CAD/CAM technique compared to the conventionally fabricated dental prostheses. The thin gingival biotype is more often associated with gingival recession than the thick biotype.
Competitive Sorption of Dissolved Organic Matter Fractions to Soils and Related Mineral Phases

Experiments with soils, Al(OH) 3 gel, and goethite were conducted to investigate the competitive sorption of hydrophilic and hydrophobic dissolved organic matter (DOM) fractions and inorganic anions such as SO 4 2- and H 2 PO 4 - . The DOM for the experiments was extracted from a mor layer. The ratio of hydrophilic to hydrophobic dissolved organic carbon was 37/63. The sorption of the hydrophobic DOM fraction was strongly favored over the binding of the hydrophilic fractions on soils and hydrous oxides. Under conditions of a limited number of available binding sites, the preferential sorption of hydrophobic DOM suppressed the binding of hydrophilic DOM or even resulted in a displacement of indigenous hydrophilic organic substances. Favorable chemical properties were assumed to be responsible for the strong sorption of hydrophobic DOM. The SO 4 2- induced little reduction of the DOM sorption, whereas H 2 PO 4 - caused a strong decrease. The effects of both inorganic anions were more pronounced for the hydrophilic than for the hydrophobic DOM fraction. As the sorption of hydrophilic DOM was strongly affected by inorganic anions and hydrophobic DOM, hydrophilic DOM seems to be the most mobile organic component in soil solutions. The results give evidence that competitive interactions among the chemically heterogeneous DOM constituents need to be considered in DOM transport process in soils.
Glioma biopsies Classification Using Raman Spectroscopy and Machine Learning Models on Fresh Tissue Samples

Simple Summary Raman Spectroscopy (RS) is an optical technique able to determine biochemical differences within a biological tissue, yet there are few reports of its application in fresh tissue. This potential could be relevant to detect glioma infiltration and to guide surgery to achieve a total resection. We deployed RS with machine learning algorithms in a surgical scenario to probe the diagnostic accuracy ex-vivo in discriminating between normal-appearing and fresh neoplastic tissue in patients undergoing glioma resection. Analyzing 3450 spectra from 63 samples, we identified 19 novel RS shifts. These 19 novel shifts of known biological relevance were included in the analytical workflow, leading to 83% and 82% accuracy and precision, respectively, in discriminating between normal-appearing and neoplastic tissue. This study further supported the translational development of real-time tissue analysis with RS in oncological brain surgery and yielded novel findings in the biochemical features of the brain tissue affected by glioma. Abstract Identifying tumor cells infiltrating normal-appearing brain tissue is critical to achieve a total glioma resection. Raman spectroscopy (RS) is an optical technique with potential for real-time glioma detection. Most RS reports are based on formalin-fixed or frozen samples, with only a few studies deployed on fresh untreated tissue. We aimed to probe RS on untreated brain biopsies exploring novel Raman bands useful in distinguishing glioma and normal brain tissue. Sixty-three fresh tissue biopsies were analyzed within few minutes after resection. A total of 3450 spectra were collected, with 1377 labelled as Healthy and 2073 as Tumor. Machine learning methods were used to classify spectra compared to the histo-pathological standard. The algorithms extracted information from 60 different Raman peaks identified as the most representative among 135 peaks screened. We were able to distinguish between tumor and healthy brain tissue with accuracy and precision of 83% and 82%, respectively. We identified 19 new Raman shifts with known biological significance. Raman spectroscopy was effective and accurate in discriminating glioma tissue from healthy brain ex-vivo in fresh samples. This study added new spectroscopic data that can contribute to further develop Raman Spectroscopy as an intraoperative tool for in-vivo glioma detection.
The Impact of Antiosteoporotic Drugs on Glucose Metabolism and Fracture Risk in Diabetes: Good or Bad News?

Osteoporosis and diabetes mellitus represent global health problems due to their high, and increasing with aging, prevalence in the general population. Osteoporosis can be successfully treated with both antiresorptive and anabolic drugs. While these drugs are clearly effective in reducing the risk of fracture in patients with postmenopausal and male osteoporosis, it is still unclear whether they may have the same efficacy in patients with diabetic osteopathy. Furthermore, as bone-derived cytokines (osteokines) are able to influence glucose metabolism, it is conceivable that antiosteoporotic drugs may have an effect on glycemic control through their modulation of bone turnover that affects the osteokines’ release. These aspects are addressed in this narrative review by means of an unrestricted computerized literature search in the PubMed database. Our findings indicate a balance between good and bad news. Active bone therapies and their modulation of bone turnover do not appear to play a clinically significant role in glucose metabolism in humans. Moreover, there are insufficient data to clarify whether there are any differences in the efficacy of antiosteoporotic drugs on fracture incidence between diabetic and nondiabetic patients with osteoporosis. Although more studies are required for stronger recommendations to be issued, bisphosphonates appear to be the first-line drug for treatment of osteoporosis in diabetic patients, while denosumab seems preferable for older patients, particularly for those with impaired renal function, and osteoanabolic agents should be reserved for patients with more severe forms of osteoporosis.
Interface Strength and Fiber Content Influence on Corn Stover Fibers Reinforced Bio-Polyethylene Composites Stiffness

Stiffness of material is a key parameter that allows the use of material for structural or semi-structural purposes. Besides, lightweight materials are increasingly calling the attention of the industry. Environmental impact is also increasing in its importance. Bio-based materials produced from renewable sources can be good candidates for structural purposes combining lightweight and low environmental impact. Nonetheless, similar mechanical properties of commodities have to be reached with such materials. In this work, composite materials from corn stover fibers as a bio-polyethylene reinforcement were produced and tested. The effect of coupling agents to improve the fiber–matrix interface has been evaluated. It has been found that coupling agent content influenced the stiffness of the materials, increasing the Young’s modulus and the material processability. The best performance was achieved for a 6% of coupling agent, corresponding to 4.61 GPa for 50 w/w% of corn stover fibers. Micromechanics showed the impact of the semi-random orientation of the fibers and the lesser impact of its morphology. It was possible to determine a triangular packing of the composites as a hypothesis for future research.