Miracle-dz/UniFAR-FTUs huggingface dataset:
The forgotten woman's cancer: vulvar squamous cell carcinoma (VSCC) and a targeted approach to therapy.

BACKGROUND The incidence of vulvar squamous cell carcinoma (VSCC) has been on the rise since the 1990s. There has been no new treatment for advanced and recurrent disease in decades, with most women succumbing to the disease. Despite two distinct etiologies of VSCC, human papillomavirus (HPV)-associated and HPV-independent disease, there is no difference in therapeutic options. METHODS A literature review was carried out by searching EMBASE and Medline databases between January 1990 and March 2016 by pairing the keywords of vulvar carcinoma, vulva cancer, vulvar and vulva with molecular markers involved in the cell cycle, apoptosis and angiogenesis. Molecular targets of prognostic significance were identified and targeted agents of therapeutic relevance to both HPV-independent and HPV-associated VSCC were then reviewed. RESULTS Recent advances in our understanding of the molecular biology of VSCC provide insight into the future management of VSCC with molecular targeted therapies. Aberrant cell cycle activity is common in both HPV-associated and HPV-independent VSCC and is characterized by overexpression of p53, Rb and cyclin D1, supporting targeting of these protein products and their downstream pathways. Extracellular regulators of cellular activity, such as EGFR, as well as inhibitors of angiogenesis are being clinically evaluated in VSCC. HPV-independent VSCC is characterized by actionable mutations, including PI3K, CDKN2A and PTEN. In HPV-associated disease, therapeutic vaccines targeting the E6 and E7 HPV oncogenes and immune-based therapies are under investigation. CONCLUSION There has been a paucity of clinical trials in recent years in this neglected women's cancer. Directed therapy against cell cycle regulatory molecules and extracellular proteins and the inhibition of angiogenesis are of broad therapeutic relevance in VSCC. Therapeutic strategies that target actionable mutations should be explored. In HPV-associated VSCC, novel treatments that exploit the virology of HPV and/or enhance the host immune response merit further study.
Some Matching Problems for Bipartite Graphs

Certam apphcatlons require finding a perfect matching in a bipartite graph that satisfies some additional properties For one such type of restncUon the problem is proven to be NP-complete. If for a single subset of edges no more than r edges may be included m the matching then an O(ne) algorithm is given An efficient algorithm for finding all perfect matchmgs is presented It requires O(e) time per matching and a total of O(e) space This algorithm may be used to calculate the permanent of a matrix Finally, the algorithm ts generahzed to find all maximum matchmgs
The Prevalence of Disease Clusters in Older Adults with Multiple Chronic Diseases – A Systematic Literature Review

Background Since most clinical guidelines address single diseases, treatment of patients with multimorbidity, the co-occurrence of multiple (chronic) diseases within one person, can become complicated. Information on highly prevalent combinations of diseases can set the agenda for guideline development on multimorbidity. With this systematic review we aim to describe the prevalence of disease combinations (i.e. disease clusters) in older patients with multimorbidity, as assessed in available studies. In addition, we intend to acquire information that can be supportive in the process of multimorbidity guideline development. Methods We searched MEDLINE, Embase and the Cochrane Library for all types of studies published between January 2000 and September 2012. We included empirical studies focused on multimorbidity or comorbidity that reported prevalence rates of combinations of two or more diseases. Results Our search yielded 3070 potentially eligible articles, of which 19 articles, representing 23 observational studies, turned out to meet all our quality and inclusion criteria after full text review. These studies provided prevalence rates of 165 combinations of two diseases (i.e. disease pairs). Twenty disease pairs, concerning 12 different diseases, were described in at least 3 studies. Depression was found to be the disease that was most commonly clustered, and was paired with 8 different diseases, in the available studies. Hypertension and diabetes mellitus were found to be the second most clustered diseases, both with 6 different diseases. Prevalence rates for each disease combination varied considerably per study, but were highest for the pairs that included hypertension, coronary artery disease, and diabetes mellitus. Conclusions Twenty disease pairs were assessed most frequently in patients with multimorbidity. These disease combinations could serve as a first priority setting towards the development of multimorbidity guidelines, starting with the diseases with the highest observed prevalence rates and those with potential interacting treatment plans.
Xylem Surfactants Introduce a New Element to the Cohesion-Tension Theory1[OPEN]

Lipid-based xylem surfactants affect water transport under negative pressure by coating hydrophobic surfaces and nanobubbles and are hypothesized to reduce embolism under normal pressure conditions. Vascular plants transport water under negative pressure without constantly creating gas bubbles that would disable their hydraulic systems. Attempts to replicate this feat in artificial systems almost invariably result in bubble formation, except under highly controlled conditions with pure water and only hydrophilic surfaces present. In theory, conditions in the xylem should favor bubble nucleation even more: there are millions of conduits with at least some hydrophobic surfaces, and xylem sap is saturated or sometimes supersaturated with atmospheric gas and may contain surface-active molecules that can lower surface tension. So how do plants transport water under negative pressure? Here, we show that angiosperm xylem contains abundant hydrophobic surfaces as well as insoluble lipid surfactants, including phospholipids, and proteins, a composition similar to pulmonary surfactants. Lipid surfactants were found in xylem sap and as nanoparticles under transmission electron microscopy in pores of intervessel pit membranes and deposited on vessel wall surfaces. Nanoparticles observed in xylem sap via nanoparticle-tracking analysis included surfactant-coated nanobubbles when examined by freeze-fracture electron microscopy. Based on their fracture behavior, this technique is able to distinguish between dense-core particles, liquid-filled, bilayer-coated vesicles/liposomes, and gas-filled bubbles. Xylem surfactants showed strong surface activity that reduces surface tension to low values when concentrated as they are in pit membrane pores. We hypothesize that xylem surfactants support water transport under negative pressure as explained by the cohesion-tension theory by coating hydrophobic surfaces and nanobubbles, thereby keeping the latter below the critical size at which bubbles would expand to form embolisms.
Static and dynamic buckling of FGM plates under compressive loading

Summary The static and dynamic buckling analysis is conducted for functionally graded composite plates under edgewise compression. The rectangular FGM plates with simply supported edges are studied. In the applied model the material properties vary continuously in the thickness direction according to a simple power law distribution in terms of constituents - it is the ceramic and metal volume fractions. The analyzed plate is composed of ceramic (zirconia or TiC) and metal (steel or aluminum, respectively) phases. Different through-thickness mechanical material properties have been modeled by the volume fraction exponent of value in the range of 0.1A. 10. The mechanical material properties are assumed as temperatureindependent. The static bifurcationial buckling as well as the dynamic buckling are considered, whereas the later due to rectangular and sine shape pulse loadings of finite duration. The dynamic pulse duration is close to the period T of fundamental natural vibrations (the values of 0.5T and 1T are assumed). The analytical static bifurcation load as well as nonlinear buckling in sense of von Karman has been determined. The application of Ritz method and Galerkin procedure have resulted in the postbuckling load-deflection curves creation. In the finite element static and dynamic analyses multilayered shell element has been employed and the graded material properties in twenty isotropic layers have been defined. The analytical and finite element solutions are compared in scope of the influence of: loading type application, imperfection sensitivity and pulse type and duration. The force control and displacement control type loadings in static and finite element dynamic analyses are applied and compared. The results of numerical calculations of static behavior (obtained analytically and by finite element method) and dynamic response (finite element analysis) are presented and compared in graphs.
Assessing the quality of institutions’ rankings obtained through multilevel linear regression models

The aim of this paper is to assess the quality of the ranking of institutions obtained with multilevel techniques in presence of different model misspecifications and data structures. Through a Monte Carlo simulation study, we find that it is quite hard to obtain a reliable ranking of the whole effectiveness distribution while, under various experimental conditions, it is possible to identify institutions with extreme performances. Ranking quality increases with increasing intra class correlation coefficient and/or overall sample size. Furthermore, multilevel models where the between and within cluster components of first-level covariates are distinguished perform significantly better than both multilevel models where the two effects are set to be equal and the fixed effect models.
TITLE : Cerebrospinal Fluid Rhinorrhea and Otorrhea

"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion. "
A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells

The bioactive phospholipids, lysophosphatidic acid (LPA) and phosphatidic acid (PA), regulate pivotal processes related to the pathogenesis of cancer. Here, we report characterization of a novel lipid kinase, designated acylglycerol kinase (AGK), that phosphorylates monoacylglycerol and diacylglycerol to form LPA and PA, respectively. Confocal microscopy and subcellular fractionation suggest that AGK is localized to the mitochondria. AGK expression was up-regulated in prostate cancers compared with normal prostate tissues from the same patient. Expression of AGK in PC-3 prostate cancer cells markedly increased formation and secretion of LPA. This increase resulted in concomitant transactivation of the EGF receptor and sustained activation of extracellular signal related kinase (ERK) 1/2, culminating in enhanced cell proliferation. AGK expression also increased migratory responses. Conversely, down-regulating expression of endogenous AGK inhibited EGF- but not LPA-induced ERK1/2 activation and progression through the S phase of the cell cycle. Hence, AGK can amplify EGF signaling pathways and may play an important role in the pathophysiology of prostate cancer.
Determining the land valuation model for peri-urban areas in Central Vietnam

The research objective is to build a land valuation model for peri-urban areas in central Vietnam. This was achieved by conducting 200 surveys that examined other factors that influence land prices using a 5-level Likert scale. Then, the Hedonic regression provide novelty in research model was built using SPSS 26.0 software. The research results have given a land pricing model that explains 72.8% of land price fluctuations. This model identifies the main factor causing these fluctuations. These factors include distance to the main road (30.92%), ability to generate cash flow (23.13%), area of the land (16.14%), feng shui (8.14%), location of the land plot (8.00%), width of road attached to the land plot (7.25%), and education level in the area around the land plot (6.44%). This study will illuminate the suitability of the regression model for land valuation in peri-urban regions of Central Vietnam, providing valuable guidance for policymakers, real estate professionals, researchers and the local residents in this field.
An Integrated Framework for Enablers in Supply Chain Resilience: Model Development and Analysis

Supply chain resilience (SCRE) has emerged as a critical capability for mitigating the challenges posed by supply chain risks and vulnerabilities. To address the question of how businesses can enhance SCRE via the integration of organizational, technological, and environmental factors, this paper aims to develop a hierarchical model based on the Technology–Organization–Environment (TOE) framework. The model utilizes Interpretive Structural Modeling (ISM) to analyze the hierarchical relationships among these enablers. By assessing the driving power and dependence power of these enablers, a classification is derived using the Matrix of Cross Impact Multiplications Applied to Classification (MICMAC) method. This study focuses on five selected enablers and presents a streamlined framework along with six propositions to validate their impact on SCRE. The findings of this developed framework offer valuable insights into the critical strategies that practitioners can employ to enhance SCRE, ensuring uninterrupted operations even in dynamic and complex environments. This research contributes to the growing body of knowledge on SCRE, providing a structured framework for organizations to navigate the challenges of an ever-changing business landscape.
Genetic Variation in Volunteerism

Research has shown that prosocial behaviors of various kinds are passed from generation to generation, but the role played by genetics in the transmission of volunteerism has been unexplored. Data from the Midlife in the United States (MIDUS) Twins and Siblings samples are used to estimate genetic heritability of hours volunteered per month. Although unique environmental factors of the kind sociologists have traditionally focused upon account for most of the variance, women do owe some of their disposition to perform volunteer work to their genes. There is no genetic effect for men.
Grouped L0 least squares penalised Magnetoencephalography

The distributed source inverse problem for Magnetoencephalography (MEG) requires regularisation in order to calculate a stable and accurate solution. Recently there has been interest in source reconstruction via the l1 penalised least squares problem. Although this gives some sparseness the ideal measure for sparsity is the l0 norm. Here we develop a cyclic descent algorithm to solve the grouped-variable l0 penalised least squares problem for an underdetermined linear system. We demonstrate the utility of this method on real MEG data and show an increase in sparsity achieved using the l0 instead of the l1 penalty.
Characterization of Regional Left Ventricular Function in Nonhuman Primates Using Magnetic Resonance Imaging Biomarkers: A Test-Retest Repeatability and Inter-Subject Variability Study

Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.
Laparoscopic replacement of urinary tract segments using biodegradable materials in a large-animal model.

OBJECTIVE We elected to evaluate laparoscopic segmental bladder and ureteral replacement with free biodegradable graft materials in a large-animal model. MATERIALS AND METHODS In 18 Yucatan minipigs, a 1.5- to 2.8-cm segment of the upper ureter was excised. In 15 study animals, the ureter was laparoscopically replaced: by a stinted (6F double-J stent) tube graft made of acellular matrix (AMX) prepared from minipig ureters (MUMX) in 6 animals, acellular matrix prepared from domestic pig ureters (DUMX) in 3, and small-intestinal submucosa (SIS) in 6. In 3 control animals, the ureteral gap was bridged only by an indwelling stent. The stent was removed at 6 weeks, and retrograde ureteropyelography was performed preoperatively and at 8 and 12 weeks postoperatively, when animals were sacrificed. In 18 Yucatan minipigs, 3 x 3-cm bladder dome segments were laparoscopically replaced: by acellular matrix prepared from minipig small bowel (MBMX) in 6 animals, and SIS in 6 animals. The bladder was closed primarily in 6 control animals. Bladder capacity was assessed preoperatively and at 6 and at 12 weeks, when the animals were sacrificed. RESULTS The average operating time for ureteral replacement was 187 (range 105-360) minutes. At 12 weeks, all animals had complete obstruction at the level of the replacement, with fibrosis +/- bone formation at the level of the stricture. For the bladder replacement groups, the average operating time was 147 (range 85-200) minutes. At 12 weeks, the bladder capacity was 60% of the preoperative capacity in the control group, 118% in the MBMX group, and 142% in the SIS group. Histologic examination showed regeneration of urothelium and some muscle with both MBMX and SIS. CONCLUSIONS We were able to develop a reliable laparoscopic technique for both segmental ureteral and partial bladder replacement in a porcine model. With AMX and SIS replacement, regeneration of urothelium occurred in both ureter and bladder. However, functional replacement was successful only in the bladder.
Ceramide 1-Phosphate Acts as a Positive Allosteric Activator of Group IVA Cytosolic Phospholipase A2α and Enhances the Interaction of the Enzyme with Phosphatidylcholine*

Previous findings from our laboratory have demonstrated that cPLA2α is directly activated by the emerging bioactive sphingolipid, ceramide 1-phosphate (C-1-P) (1). In this study, a Triton X-100/phosphatidylcholine (PC) mixed micelle assay was utilized to determine the kinetics and specificity of this lipid-enzyme interaction. Using this assay, the addition of C-1-P induced a dramatic increase in the activity of cPLA2α (>15-fold) with a Ka of 2.4 mol % C-1-P/Triton X-100 micelle. This activation was highly specific as the addition of other lipids had insignificant effects on cPLA2α activity. Studies using surface-dilution kinetics revealed that C-1-P had no effect on the Michaelis-Menten constant, KmB, but decreased the dissociation constant (K As) value by 87%. Thus, C-1-P not only increases the membrane affinity of cPLA2α but also may act as an allosteric activator of the enzyme. Surface plasmon resonance analysis of the C-1-P/cPLA2α interaction verified a decrease in the dissociation constant, demonstrating that cPLA2α bound PC vesicles containing C-1-P with increased affinity (5-fold) compared with PC vesicles alone. The effect on the dissociation rate of cPLA2α was also found to be lipid-specific with the exception of phosphatidylinositol 4,5-bisphosphate, which caused a modest increase in vesicle affinity (2-fold). Lastly, the binding site for C-1-P was determined to be within the C2-domain of cPLA2α, unlike phosphatidylinositol 4,5-bisphosphate. These data demonstrate a novel interaction site for C-1-P and suggest that C-1-P may function to recruit cPLA2α to intracellular membranes as well as allosterically activate the membrane-associated enzyme.
Cellular and Humoral Cross-Immunity against Two H3N2v Influenza Strains in Presumably Unexposed Healthy and HIV-Infected Subjects

Human cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States. Pre-existing humoral and cellular immunity has been recognized as one of the key factors in limiting the infection burden of an emerging influenza virus strain, contributing to restrict its circulation and to mitigate clinical presentation. Aim of this study was to assess humoral and cell-mediated cross immune responses to H3N2v in immuno-competent (healthy donors, n = 45) and immuno-compromised hosts (HIV-infected subjects, n = 46) never exposed to H3N2v influenza strain. Humoral response against i) H3N2v (A/H3N2/Ind/08/11), ii) animal vaccine H3N2 strain (A/H3N2/Min/11/10), and iii) pandemic H1N1 virus (A/H1N1/Cal/07/09) was analysed by hemagglutination inhibition assay; cell-mediated response against the same influenza strains was analysed by ELISpot assay. A large proportion of healthy and HIV subjects displayed cross-reacting humoral and cellular immune responses against two H3N2v strains, suggesting the presence of B- and T-cell clones able to recognize epitopes from emerging viral strains in both groups. Specifically, humoral response was lower in HIV subjects than in HD, and a specific age-related pattern of antibody response against different influenza strains was observed both in HD and in HIV. Cellular immune response was similar between HD and HIV groups and no relationship with age was reported. Finally, no correlation between humoral and cellular immune response was observed. Overall, a high prevalence of HD and HIV patients showing cross reactive immunity against two H3N2v strains was observed, with a slightly lower proportion in HIV persons. Other studies focused on HIV subjects at different stages of diseases are needed in order to define how cross immunity can be affected by advanced immunosuppression.