Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between Serum Vascular Endothelial Growth Factor Levels and Stages of Diabetic Retinopathy and Other Biomarkers

Aim This study aims to measure serum vascular endothelial growth factor (VEGF) levels in a sample of Jordanian patients and to determine their relationship with the different stages of diabetic retinopathy. It also explores the correlation between VEGF concentrations and different biochemical and demographic findings. Materials and Methods A total of 167 adults participated in the study. Participants were divided into two main categories: patients with diabetes mellitus (DM) type 2 without diabetic retinopathy (DR) (N = 62) and patients with DM type 2 affected by DR (N = 105). DR patients were further subclassified into nonproliferative (N = 41) and proliferative (N = 64). Basic laboratory tests were measured to correlate with VEGF levels. Irisin, a hormone linked to diabetic retinopathy was also measured and correlated with VEGF. Results Serum VEGF was found to positively correlate with the severity of diabetic retinopathy. The means of VEGF serum concentrations were 60 pg/mL for controls, 133 pg/mL for nonproliferative DR patients, and 229 pg/mL for proliferative DR patients. We found a significant positive correlation with glycosylated hemoglobin (HbA1c), and a significant negative correlation with high-density lipoprotein (HDL) levels, age, and irisin. Conclusion In this cohort of Jordanian diabetics, serum VEGF concentrations strongly correlated with the presence and stages of diabetic retinopathy, suggesting it as an appropriate indicator for diabetic retinopathy early detection and management in this society. VEGF levels also significantly correlated with HbA1c, HDL, and irisin levels. Further studies are encouraged to explore these relationships in other ethnic groups and with different diabetic complications.
A Glass Fiber-Reinforced Resin Composite Splint to Stabilize and Replace Teeth in a Periodontally Compromised Patient

Combined periodontal and prosthodontic treatment demands of patients require a structured coordination of pretreatments and an adequate choice of restorations. This is especially true if multiple teeth are missing and insufficient crown-root ratios are obvious. A 40-year-old patient with a severe periodontitis (Stage IV, Grade C) was treated with active, nonsurgical periodontal therapy. Afterwards, a supportive periodontal therapy was provided with a recall interval of three to four months. Due to a high tooth mobility of the anterior teeth in the upper jaw and a missing left canine, a combination of a resin composite (Signum composite, Kulzer, Hanau, Germany) and a unidirectional glass prepreg fiber (Tender Fiber Quattro, MICERIUM, Avegno, Italy) was utilized to fabricate a splint in a labside approach to stabilize the remaining teeth. Moreover, an artificial denture tooth was adhesively luted to the splint. A temporary polymer-based material (Vita CAD-Temp, VITA Zahnfabrik, Bad Säckingen, Germany) was selected to supply the posterior teeth of the patient with a 3-unit fixed dental prosthesis (FDP), and both restorations were adhesively cemented. 19 months after insertion, a fracture of the fiber-reinforced resin composite splint occurred that was intraorally repaired. In spite of the fracture of the splint, all materials were functionally and esthetically stable over the follow-up period of 22 months.
The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases

Oxidative stress (OS) has the ability to damage different molecules and cellular structures, altering the correct function of organs and systems. OS accumulates in the body by endogenous and exogenous mechanisms. Increasing evidence points to the involvement of OS in the physiopathology of various chronic diseases that require prolonged periods of pharmacological treatment. Long-term treatments may contribute to changes in systemic OS. In this review, we discuss the involvement of OS in the pathological mechanisms of some chronic diseases, the pro- or antioxidant effects of their pharmacological treatments, and possible adjuvant antioxidant alternatives. Diseases such as high blood pressure, arteriosclerosis, and diabetes mellitus contribute to the increased risk of cardiovascular disease. Antihypertensive, lipid-lowering, and hypoglycemic treatments help reduce the risk with an additional antioxidant benefit. Treatment with methotrexate in autoimmune systemic inflammatory diseases, such as rheumatoid arthritis, has a dual role in stimulating the production of OS and producing mitochondrial dysfunction. However, it can also help indirectly decrease the systemic OS induced by inflammation. Medicaments used to treat neurodegenerative diseases tend to decrease the mechanisms related to the production of reactive oxygen species (ROS) and balance OS. On the other hand, immunosuppressive treatments used in cancer or human immunodeficiency virus infection increase the production of ROS, causing significant oxidative damage in different organs and systems without widely documented exogenous antioxidant administration alternatives.
Hyperoside Alleviates High Glucose-Induced Proliferation of Mesangial Cells through the Inhibition of the ERK/CREB/miRNA-34a Signaling Pathway

Purpose Hyperoside, a flavonoid isolated from conventional medicinal herbs, has been demonstrated to exert a significant protective effect in diabetic nephropathy. This study aimed to determine the underlying mechanisms, by which hyperoside inhibits high glucose-(HG-) induced proliferation in mouse renal mesangial cells. Methods Mouse glomerular mesangial cells line (SV40-MES13) was used to study the inhibitory effect of hyperoside on cell proliferation induced by 30 mM glucose, which was used to simulate a diabetic condition. Viable cell count was assessed using the Cell Counting Kit-8 and by the 5-ethynyl-20-deoxyuridine incorporation assay. The underlying mechanism involving miRNA-34a was further investigated by quantitative RT-PCR and transfection with miRNA-34a agomir. The phosphorylation levels of extracellular signal-regulated kinases (ERKs) and cAMP-response element-binding protein (CREB) were measured by Western blotting. The binding region and the critical binding sites of CREB in the miRNA-34a promoter were investigated by the chromatin immunoprecipitation assay and luciferase reporter assay, respectively. Results We found that hyperoside could significantly decrease HG-induced proliferation of SV40-MES13 cells in a dose-dependent manner, without causing obvious cell death. In addition, hyperoside inhibited the activation of ERK pathway and phosphorylation of its downstream transcriptional factor CREB, as well as the miRNA-34a expression. We further confirmed that CREB-mediated regulation of miRNA-34a is dependent on the direct binding to specific sites in the promoter region of miRNA-34a. Conclusion Our cumulative results suggested that hyperoside inhibits the proliferation of SV40-MES13 cells through the suppression of the ERK/CREB/miRNA-34a signaling pathway, which provides new insight to the current investigation on therapeutic strategies for diabetic nephropathy.
Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.
Combined Acetabulum Fracture and Hip Dislocation in an 18-Year-Old Female at 35-Week Gestation: A Case Report and Review of the Literature

Caring for an injured, pregnant patient can be a management challenge. We report the case of an 18-year-old female who sustained a left acetabulum fracture with a concurrent hip dislocation at 35 weeks' gestation following a motor vehicle accident. Through an interdisciplinary, team-based approach, the patient was guided through obstetric delivery and orthopedic surgical fracture fixation without complication. By being familiar with the unique challenges in management posed by pregnant patients, orthopedic surgeons can be better equipped to minimize morbidity and mortality in this patient population while maximizing clinical outcomes.
Men with Latent Autoimmune Diabetes and Type 2 Diabetes May Have Different Change Patterns in Free Testosterone

Objective Type 2 diabetic (T2D) male patients with low total testosterone (TT) levels are at an increasing risk of all-cause mortality. However, the levels of TT in male patients with latent autoimmune diabetes in adults (LADA) remain largely unknown. Research Design and Methods. This was a single-center, open, observational study. The inclusion criteria were male patients who were diagnosed with LADA, and sex, body mass index, C-peptide, and glycated hemoglobin (HbA1c) levels matched with those of T2D patients. Islet function/sensitivity and sex hormone concentrations were determined at baseline and 1-year follow-up. The primary endpoint was the changes in androgen levels from baseline to 1-year follow-up in patients with LADA. Results Our data showed that TT and Bio-T levels remained unchanged, while FT levels significantly decreased from baseline to 1-year follow-up in patients with T2D. However, TT, Bio-T, and FT concentrations dramatically increased in the LADA group from baseline to 1-year follow-up. Furthermore, a Spearman analysis showed that changes of TT, FT, and Bio-T levels from baseline to endpoint were significantly negatively correlated with Δ homeostasis model assessment-2 IR (ΔHOMA2-IR), respectively. Conclusions The FT change patterns in patients with LADA may differ from those in patients with T2D. Our data also indicated the significant negative correlation between insulin sensitivity and changes of TT, FT, and Bio-T levels along with the diabetic duration in patients with T2D and LADA.
Botanical Composition and Diet Quality of the Vicuñas (Vicugna vicugna Mol.) in Highland Range of Parinacota, Chile

Simple Summary For the proper management of grazing wild ungulates, it is very important to know the botanical composition and quality of their selected diets. In the case of the vicuña, a wild camelid that lives in the Chilean highlands, there is little information related to these aspects. Therefore, in this work, the variations in the botanical composition and quality of their diets throughout the year were studied, which were estimated by analyzing the plant fragments found in the feces and the concentration of nitrogen within them. The vicuña mainly selects grasses from dry and wet grassland but is also capable of selecting other species, such as graminoids and dicotyledonous herbs. These plants contribute to obtaining a diverse and high-quality diet, this being an efficient foraging strategy to be able to consume a good quality diet, mainly in the months of high nutritional demand, which coincides with the summer rainy season. Abstract Understanding the botanical composition of herbivores’ diets and their nutritional quality is an important question in the development of sustainable strategies for the management of natural resources. In Chilean highland vicuña-grazed grasslands, there is little information in this regard and, therefore, this study aimed to determine the year-round profile of the diet’s botanical composition and quality. In highland grasslands, on an area of 21.9 ha, continuously grazed for 3.06 VU/ha/year (18°03′ S, 69°13′ W; 4425 m.o.s.l), twelve feces piles were sampled monthly and were analyzed through microhistology, and the nitrogen concentration [NF, OM basis] was determined. The botanical composition, diversity (J) and selectivity index (Ei) of the main species were estimated. Diets were composed of dry–grassland grasses (37.7%), wet–grassland grasses (36.6%), graminoids (14.3%) and forbs (10.2%). The diet diversity ranged from 0.79 (dry–winter) to 0.87 (wet–summer). The main dominant grassland species obtained negative Ei values. The annual mean value of [NF] was estimated as 1.82%, with a higher value in summer months (2.21%), which coincides with the physiological states of higher nutritional demand. The vicuñas behave like generalist ungulates, having a high degree of selectivity towards grass species, which mostly fulfill a nutritional role in subsistence and a functional role in survival, applying foraging strategies that allow them to obtain a better quality diet during the season of greatest nutritional demand.
Mass Production of the Black Soldier Fly, Hermetia illucens (L.), (Diptera: Stratiomyidae) Reared on Three Manure Types

Simple Summary The black soldier fly (BSF) has gained a considerable amount of attention globally for its ability to convert organic material into valuable biomass for waste management and food and feed purposes. As the industry of producing BSF expands, connecting research and application is necessary to optimize mass-production facilities. Historically, research on the BSF has been conducted at a benchtop scale. Expanding these results to industrial practices is challenging, as results typically are not scalable. This study investigates the production of BSF fed animal manure (swine, dairy, and poultry) at a larger scale (thousands of larvae fed kg of diet) than what has been previously published (small-scale studies with hundreds of larvae fed g of diet). Abstract Recent interest in the mass production of black soldier fly (BSF) larvae has resulted in many studies being generated. However, a majority of the studies are benchtop, or small-scale, experiments. Results generated from such studies may not translate to large-scale/industrial production. The current study was conducted at a conventional large-scale (10,000 larvae/treatment fed seven kg) to determine the impact on selected life-history traits when BSF were fed seven kg of manure (swine, dairy, or poultry) or a control diet (Gainesville diet: 50% wheat bran, 30% alfalfa meal, and 20% corn). Results showed larvae fed dairy manure took one to two days longer to develop to prepupation, with lower survivorship (45%) compared to those fed poultry or swine manure (>70%). Furthermore, the maximum larval weight was reached on day six for those fed swine manure, while other treatments achieved the maximum weight on day seven. However, larvae fed swine manure averaged 150 mg, while those fed the other diets ranged between 175 and 200 mg. Data from this study may be valuable for the industrialization of BSF. Companies using a scale varying from previously published work, including this study, should conduct pilot studies to optimize their system prior to implementation.
Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

Diabetes and Alzheimer’s disease (AD) place a significant burden on health care systems in the world and its aging populations. These diseases have long been regarded as separate entities; however, advanced glycation end products (AGEs) and the receptors for AGEs (RAGE) may be a link between diabetes and AD. In our study, mice injected with AGEs through stereotaxic surgery showed significant AD-like features: behavior showed decreased memory; immunofluorescence showed increased phosphorylated tau and APP. These results suggest links between diabetes and AD. Patients with diabetes are at a higher risk of developing AD, and the possible underlying molecular components of this association are now beginning to emerge.
Snakes from the lower Miocene locality of Dolnice (Czechoslovakia)

ABSTRACT The Lower Miocene (MN 4) locality of Dolnice (West Czechoslovakia) has yielded remains of about 12 ophidian taxa: Scolecophidia indet. , Bransateryx septentrionalis, n.sp. , cf. Gongylophis sp. (Boidae), Palaeonatrix lehmani, Neonatrix nova, n.sp. , Texasophis bohemiacus, n.sp. , Coluber dolnicensis, n.sp. , three different unidentified colubrine snakes (Colubridae), Vipera platys-pondyla, n.sp. , and Vipera antiqua, n.sp. (Viperidae). Several of the above snake genera are well known from other Miocene sites in West Europe and North America (Bransateryx, Neonatrix, Texasophis), while others represent recent genera of more isolated occurrence (Gongylophis, Vipera of the “Oriental vipers” group).
Life span extension by glucose restriction is abrogated by methionine supplementation: Cross-talk between glucose and methionine and implication of methionine as a key regulator of life span

Yeast cells lower their intracellular methionine level in response to glucose restriction to regulate metabolism and life span. Caloric restriction (CR) is known to extend life span across species; however, the molecular mechanisms are not well understood. We investigate the mechanism by which glucose restriction (GR) extends yeast replicative life span, by combining ribosome profiling and RNA-seq with microfluidic-based single-cell analysis. We discovered a cross-talk between glucose sensing and the regulation of intracellular methionine: GR down-regulated the transcription and translation of methionine biosynthetic enzymes and transporters, leading to a decreased intracellular methionine concentration; external supplementation of methionine cancels the life span extension by GR. Furthermore, genetic perturbations that decrease methionine synthesis/uptake extend life span. These observations suggest that intracellular methionine mediates the life span effects of various nutrient and genetic perturbations, and that the glucose-methionine cross-talk is a general mechanism for coordinating the nutrient status and the translation/growth of a cell. Our work also implicates proteasome as a downstream effector of the life span extension by GR.
When floods hit the road: Resilience to flood-related traffic disruption in the San Francisco Bay Area and beyond

Flood-related traffic disruption is not limited to the areas of inundation but has regional, spatially extended impacts. As sea level rises, urban traffic networks in low-lying coastal areas face increasing risks of flood disruptions. Closure of flooded roads causes employee absences and delays, creating cascading impacts to communities. We integrate a traffic model with flood maps that represent potential combinations of storm surges, tides, seasonal cycles, interannual anomalies driven by large-scale climate variability such as the El Niño Southern Oscillation, and sea level rise. When identifying inundated roads, we propose corrections for potential biases arising from model integration. Our results for the San Francisco Bay Area show that employee absences are limited to the homes and workplaces within the areas of inundation, while delays propagate far inland. Communities with limited availability of alternate roads experience long delays irrespective of their proximity to the areas of inundation. We show that metric reach, a measure of road network density, is a better proxy for delays than flood exposure.
Thrombin generation, tissue factor microvesicles and the endothelium in multiple myeloma and pancreatic cancer during treatment

Cancer and its anti-neoplastic treatment are frequently complicated by venous thromboembolism (VTE) occurrence. Multiple myeloma (MM), a haematological malignancy and Pancreatic cancer (PC), a solid tumour are two common malignancies with similarly high VTE incidence, which worsens during treatment. Thrombin production is a key step in the pathologic evolution of VTE and may play an important role in determining VTE risk in cancer patients. The calibrated automated thrombography (CAT) assay is emerging as a reliable tool for real time estimation of thrombin generation (TG) potential, and there is a clinical need for such knowledge on the dynamic pathways underlying the thrombotic phenotype of various malignancies. Hypothetically, TG measurement may also provide a view of the haemostatic variances that exist in MM and PC as cancers with high VTE incidences. Therefore, this thesis aimed to explore the TG changes that exist in both malignancies in patients before, during and after treatment. It also explores the interaction of Tissue Factor (TF) associated with Microvesicles (MVs) or TFMVs with tumour stroma especially the endothelium, or any procoagulant changes such as thrombin production due to this interaction; and thus, aimed to study TFMVs involvement through the disruption of endothelial haemostasis. The results presented in this thesis demonstrate that solid and haematological malignant cells have significantly differing TG kinetics that may correlate with TF expression levels, and that TG parameters identified changes in MM during treatment, specifically the Lag times and Times-to-Peak parameters were progressively elevated until the third chemotherapy cycle. In summary, procoagulant activity on the endothelium can be stimulated by TFMVs produced by cancer cells in vitro, and this study of thrombin as a procoagulant factor in MM and PC and its relationship to TFMVs may lead to future understanding of their important role in cancer VTE development, and thus merits further study.
FeFET-based low-power bitwise logic-in-memory with direct write-back and data-adaptive dynamic sensing interface

Compute-in-memory (CiM) is a promising method for mitigating the memory wall problem in data-intensive applications. The proposed bitwise logic-in-memory (BLiM) is targeted at data intensive applications, such as database, data encryption. This work proposes a low-power BLiM approach using the emerging nonvolatile ferroelectric FETs with direct write-back and data-adaptive dynamic sensing interface. Apart from general-purpose random-access memory, it also supports BLiM operations such as copy, not, nand, xor, and full adder (FA). The novel features of the proposed architecture include: (i) direct result-write-back based on the remnant bitline BLiM charge that avoids bitline sensing and charging operations; (ii) a fully dynamic sensing interface that needs no static reference current, but adopts data-adaptive voltage references for certain multi-operand operations, and (iii) selective bitline charging from wordline (instead of pre-charging all bitlines) to save power and also enable direct write-back. Detailed BLiM operations and benchmarking against conventional approaches show the promise of low-power computing with the FeFET-based circuit techniques.