Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and prognostic significance of APAF‐1, caspase‐8 and caspase‐9 in stage II/III colon carcinoma: Caspase‐8 and caspase‐9 is associated with poor prognosis

Apoptosis protease activating factor‐1 (APAF‐1), caspase‐8 and caspase‐9 are important factors in the execution of death signals. To study their prognostic influence in colon carcinoma, expression of APAF‐1, caspase‐8 and caspase‐9 was determined by immunohistochemistry in normal colon mucosa (n = 8) and R0‐resected stage II/III colon carcinomas (n ≥ 124) using a semiquantitative score. Staining results were correlated with disease‐free survival by Kaplan–Meier estimates, and multivariate Cox analyses were performed. In normal colon, APAF‐1 and caspase‐8 are most strongly expressed in the luminal surface epithelium, whereas caspase‐9 is expressed all along the crypt axis. In colon carcinomas, there is considerable variability in the expression of these proapoptotic factors, although complete loss of caspase‐8 and caspase‐9 is rare. APAF‐1 expression did not correlate with disease‐free survival. Instead, both expression of caspase‐9 and high‐level expression of caspase‐8 in a majority of tumor cells were significantly associated with adverse prognosis (p = 0.004 and p = 0.029, respectively). The influence of caspase‐8 expression was mainly seen in patients with stage III colon carcinoma (p = 0.011), whereas the prognostic influence of caspase‐9 expression was significant in stage II cases (p = 0.037) and just failed to be significant in stage III tumors (p = 0.0581). After adjusting for confounding factors in a multivariate Cox analysis, the effect of caspase‐9 in predicting disease‐free survival was confirmed (p = 0.003). Our data suggest that, in colon carcinomas, expression of caspase‐8 and caspase‐9 is significantly associated with poor survival. Caspase‐9 may be an independent prognosticator in colon carcinoma.
Effect of Glucose Starvation on Glucose Transport in Neuronal Cells in Primary Culture from Rat Brain

Abstract: The regulation of glucose transport into cultured brain cells during glucose starvation was studied. On glucose deprivation for 40 h, 2‐deoxy‐d‐glucose (2‐DG) uptake was stimulated twofold in neuronal cells but was not changed significantly in astrocytes. On refeeding, the increased activity of neuronal cells rapidly returned to the basal level, an observation indicating that the effect of glucose starvation was reversible. The increase was due solely to change in the Vmax, a finding suggesting that the number of glucose transporters on the plasma membrane is increased in starved cells. Cycloheximide inhibited this increase. In the presence of cycloheximide, the activity of 2‐DG uptake of starved cells remained constant for 12 h and then slowly decreased, whereas that of fed cells decreased rapidly. These findings suggest that glucose starvation regulates glucose transport by changing the rate of net synthesis of the transporter in neuronal cells in culture.
The Heart of the Matter: The Effects of Humor on Well-Being During Recovery From Cardiovascular Disease

This study examines the uses of humor among cardiovascular patients to test the associations between humor use, satisfaction with companion relationships, and health during recovery. Self-report data were collected from members of two national support groups for patients recovering from cardiovascular disease. As expected, general humorousness associated with social and psychological well-being. Several specific functions of humor in cardiovascular recovery were identified and linked with health perceptions. Antidote humor increased social and psychological health perceptions, whereas conversation regulation humor and distancing humor were negatively related to perceived social and psychological health. Relationship satisfaction mediated most effects. The findings offer new insight into the variability of humor effects, particularly following cardiovascular treatment.
Untargeted analysis to monitor metabolic changes of garlic along heat treatment by LC–QTOF MS/MS

Black garlic is increasing its popularity in cuisine around the world; however, scant information exists on the composition of this processed product. In this study, polar compounds in fresh garlic and in samples taken at different times during the heat treatment process to obtain black garlic have been characterized by liquid chromatography coupled to tandem mass spectrometry in high resolution mode. Ninety‐five compounds (mainly amino acids and metabolites, organosulfur compounds, and saccharides and derivatives) were tentatively identified in all the analysed samples and classified as a function of the family they belong to. Statistical analysis of the results allowed establishing that the major changes in garlic occur during the first days of treatment, and they mainly affect to the three representative families. The main pathways involved in the synthesis of the compounds affected by heat treatment, and their evolution during the process were studied.
Antibodies directed against receptor tyrosine kinases

Approximately 30 therapeutic monoclonal antibodies have already been approved for cancers and inflammatory diseases, and monoclonal antibodies continue to be one of the fastest growing classes of therapeutic molecules. Because aberrant signaling by receptor tyrosine kinases (RTKs) is a commonly observed factor in cancer, most of the subclasses of RTKs are being extensively studied as potential targets for treating malignancies. The first two RTKs that have been targeted by antibody therapy, with five currently marketed antibodies, are the growth factor receptors EGFR and HER2. However, due to systemic side effects, refractory patients and the development of drug resistance, these treatments are being challenged by emerging therapeutics. This review examines current monoclonal antibody therapies against RTKs. After an analysis of agents that have already been approved, we present an analysis of antibodies in clinical development that target RTKs. Finally, we highlight promising RTKs that are emerging as new oncological targets for antibody-based therapy.
Q Fever 1985‐1998: Clinical and Epidemiologic Features of 1,383 Infections

In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.
Drug, Healthcare and Patient Safety Dovepress Predictors of Poor Glycemic Control in Type 2 Diabetic Patients Attending Public Hospitals in Dar Es Salaam

Background: Tanzania has recently experienced a significant rise in the burden of diabetes, and it is estimated that more than 400,000 people are living with diabetes. A major concern in the management of diabetes is the occurrence of diabetic complications that occur as a result of poor glycemic control. Identification of the factors associated with poor glycemic control is important in order to institute appropriate interventions for the purpose of improving glycemic control and prevention of chronic complications. Aim: The aim of this study was to determine the level of glycemic control and explore the factors associated with poor glycemic control among patients with type 2 diabetes mellitus (T2DM). Methodology: A cross-sectional study was carried out at the diabetic clinics for T2DM patients at the national and municipal hospitals in Dar es Salaam. A total of 469 patients were enrolled over a period of 8 weeks from March 2013 to May 2013. Patients' information such as socio-demographic characteristics, self-care management behaviors, and medication adherence were obtained through interviews. Blood pressure, weight, and height were measured during the day of the interview. All available last readings for fasting blood glucose (FBG) measurements, lipid profile, and other clinical characteristics were obtained from patients' records. Results: The mean age of patients was 54.93 years. The majority (63.5%) of patients were females and only eight patients had records of lipid profile measurements. Out of 469 patients, 69.7% had FBG of $7.2 mmol/L, indicating poor glycemic control. Females aged between 40 years and 59 years had significantly higher poor glycemic control (76.1%) as compared with their male counterparts. Thirty-eight percent of patients had poor medication adherence, which was associated with poor glycemic control. The proportion of poor glycemic control increased with age. A significantly high proportion of poor glycemic control was observed in patients who had had the disease for more than 20 years since diagnosis. Factors associated with poor glycemic control included lack of health insurance, using more than one oral hypoglycemic agent, normal body mass index, obesity, and nonadherence to diabetic medications. Conclusion: Patients in this study had generally poor glycemic control. From these findings it is recommended that diabetic patients should be routinely screened for lipid profile to determine levels of cholesterol, triglycerides, and low-density lipoproteins, which are risk factors for cardiovascular events. An education program should be developed to educate patients on the importance of medication adherence and weight management for …
Finite element modelling to assess the effect of position and size of the piezoelectric layer of a hybrid beam

A one dimensional finite element model is presented to assess the effect of position and size of the piezoelectric layer of a hybrid beam. The efficient layerwise zigzag theory is used for making the finite element model. The 1D beam element has eight mechanical and a variable number of electrical degrees of freedom. The codes are developed in Matlab based on the FE formulation. The beams are also modelled in 2D planar modelling space as a deformable shell using FE package ABAQUS for comparison of results. An 8‐noded piezoelectric quadrilateral element is used for piezo layers and an 8‐noded quadrilateral element with reduced integration is used for the elastic layers of hybrid beams for making the finite element mesh in ABAQUS. The accuracy of the used elements are assessed for static re‐ sponse. Cantilever hybrid beams with a piezoelectric layer bonded on top of the elastic substrate are considered for the analysis. The beams are sub‐ jected to electromechanical loading. A detailed study is conducted to high‐ light the influence of positon and size of piezoelectric layer on the deflec‐ tion profiles, tip deflections and through the thickness distribution of dis‐ placements and stresses of hybrid composite/sandwich beams. The shape control using various numbers of piezoelectric patches is also studied. The 1D‐FE results are compared with the 2D‐FE results.
Fisher Information and Semiclassical Treatments

We review here the difference between quantum statistical treatments and semiclassical ones, using as the main concomitant tool a semiclassical, shift-invariant Fisher information measure built up with Husimi distributions. Its semiclassical character notwithstanding, this measure also contains abundant information of a purely quantal nature. Such a tool allows us to refine the celebrated Lieb bound for Wehrl entropies and to discover thermodynamic-like relations that involve the degree of delocalization. Fisher-related thermal uncertainty relations are developed and the degree of purity of canonical distributions, regarded as mixed states, is connected to this Fisher measure as well.
Parallel algorithms for approximation of distance maps on parametric surfaces

We present an efficient O(n) numerical algorithm for first-order approximation of geodesic distances on geometry images, where n is the number of points on the surface. The structure of our algorithm allows efficient implementation on parallel architectures. Two implementations on a SIMD processor and on a GPU are discussed. Numerical results demonstrate up to four orders of magnitude improvement in execution time compared to the state-of-the-art algorithms.
FUNCTIONAL ANATOMY OF THE LYMPHOCYTE IN IMMUNOLOGICAL REACTIONS IN VITRO

The motile lymphocyte in vitro has a prominent "tail" that becomes a means of "attachment" to other cells and debris during interaction. The term "uropod" is proposed to designate this specialized cytoplasmic projection which appears totally different, anatomically and functionally, from the pseudopods. Observations of lymphoblasts during mitosis indicate that the uropod is formed immediately following mitosis at the point of final cytoplasmic connection between daughter cells, a fact that may prove significant as lymphocyte function is better understood. In the mixed leukocyte reaction the lymphocyte interacts with macrophages, cell debris, and lymphoblasts via the uropod, suggesting that stimulatory material may be acquired through this specialized appendage. Lymphoblast-lymphocyte interaction is noteworthy and implies that immunologically committed cells may be mustered through horizontal as well as vertical processes: horizontally by lymphoblast-lymphocyte interaction and vertically by mitosis of transformed lymphoblasts. The possible relevance of these in vitro observations to lymphocyte functions in vivo is discussed.
Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses

We performed a comparison between Neuropathy Impairment Scale‐sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS‐motor vs. the Medical Research Council sum score in patients with Guillain‐Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance‐related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch‐transformed (RT)‐intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2–4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM‐MGUSP: 23) were serially examined with 12 months follow‐up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT‐mISS compared to RT‐NISs. Responsiveness was equal for the RT‐motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow‐up in the latter group of patients.
What is hippotherapy? The indications and effectiveness of hippotherapy

Hippotherapy is a form of physical, occupational and speech therapy in which a therapist uses the characteristic movements of a horse to provide carefully graded motor and sensory input. A foundation is established to improve neurological function and sensory processing, which can be generalized to a wide range of daily activities. Unlike therapeutic horseback riding (where specific riding skills are taught), the movement of the horse is a means to a treatment goal when utilizing hippotherapy as a treatment strategy. Hippotherapy has been used to treat patients with neurological or other disabilities, such as autism, cerebral palsy, arthritis, multiple sclerosis, head injury, stroke, spinal cord injury, behavioral disorders and psychiatric disorders. The effectiveness of hippotherapy for many of these indications is unclear, and more research has been needed. Here, we purpose to give information about hippotherapy which is not known adequately by many clinicians and health workers.
Spruce Beetle Biology, Ecology and Management in the Rocky Mountains: An Addendum to Spruce Beetle in the Rockies

Spruce beetle outbreaks have been reported in the Rocky Mountains of western North America since the late 1800s. In their classic paper, Spruce Beetle in the Rockies, Schmid and Frye reviewed the literature that emerged from the extensive outbreaks in Colorado in the 1940s. A new wave of outbreaks has affected Rocky Mountain subalpine spruce-fir forests beginning in the mid-1980s and continuing to the present. These outbreaks have spurred another surge of basic and applied research in the biology, ecology and management of spruce and spruce beetle populations. This paper is a review of literature on spruce beetle focusing on work published since the late 1970s and is intended as an addendum to Spruce Beetle in the Rockies.
ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel disease in humans and mice

Background ClC-3 channel/antiporter plays a critical role in a variety of cellular activities. ClC-3 has been detected in the ileum and colon. Objective To determine the functions of ClC-3 in the gastrointestinal tract. Design After administration of dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), intestines from ClC-3−/− and wild-type mice were examined by histological, cellular, molecular and biochemical approaches. ClC-3 expression was determined by western blot and immunostaining. Results ClC-3 expression was reduced in intestinal tissues from patients with UC or Crohn's disease and from mice treated with DSS. Genetic deletion of ClC-3 increased the susceptibility of mice to DSS- or TNBS-induced experimental colitis and prevented intestinal recovery. ClC-3 deficiency promoted DSS-induced apoptosis of intestinal epithelial cells through the mitochondria pathway. ClC-3 interacts with voltage-dependent anion channel 1, a key player in regulation of mitochondria cytochrome c release, but DSS treatment decreased this interaction. In addition, lack of ClC-3 reduced the numbers of Paneth cells and impaired the expression of antimicrobial peptides. These alterations led to dysfunction of the epithelial barrier and invasion of commensal bacteria into the mucosa. Conclusions A defect in ClC-3 may contribute to the pathogenesis of IBD by promoting intestinal epithelial cell apoptosis and Paneth cell loss, suggesting that modulation of ClC-3 expression might be a new strategy for the treatment of IBD.
Crimean-Congo Hemorrhagic Fever Virus, Greece

Seroprevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) is high in some regions of Greece, but only 1 case of disease has been reported. We used 4 methods to test 118 serum samples that were positive for CCHFV IgG by commercial ELISA and confirmed the positive results. A nonpathogenic or low-pathogenicity strain may be circulating.
Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity

Significance The anti-HIV drug KP1212 was designed to intentionally increase the mutation rate of HIV, thereby causing viral population collapse. Its mutagenicity and thus antiviral activity was proposed to be the result of tautomerization. We used 2D IR spectroscopy to identify rapidly interconverting tautomers under physiological conditions. The traditionally rare enol–imino tautomer for nucleobases was found to be the major species for KP1212, providing a structural support for the tautomer hypothesis. We further found that KP1212 is significantly protonated at physiological pH with a pKa of 7. The protonated KP1212 was shown to be mutagenic, revealing a bimodal mutagenic property of KP1212. The results could prove instrumental in developing the next-generation antiviral treatments. Antiviral drugs designed to accelerate viral mutation rates can drive a viral population to extinction in a process called lethal mutagenesis. One such molecule is 5,6-dihydro-5-aza-2′-deoxycytidine (KP1212), a selective mutagen that induces A-to-G and G-to-A mutations in the genome of replicating HIV. The mutagenic property of KP1212 was hypothesized to originate from its amino–imino tautomerism, which would explain its ability to base pair with either G or A. To test the multiple tautomer hypothesis, we used 2D IR spectroscopy, which offers subpicosecond time resolution and structural sensitivity to distinguish among rapidly interconverting tautomers. We identified several KP1212 tautomers and found that >60% of neutral KP1212 is present in the enol–imino form. The abundant proportion of this traditionally rare tautomer offers a compelling structure-based mechanism for pairing with adenine. Additionally, the pKa of KP1212 was measured to be 7.0, meaning a substantial population of KP1212 is protonated at physiological pH. Furthermore, the mutagenicity of KP1212 was found to increase dramatically at pH <7, suggesting a significant biological role for the protonated KP1212 molecules. Overall, our data reveal that the bimodal mutagenic properties of KP1212 result from its unique shape shifting ability that utilizes both tautomerization and protonation.