Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathology of Hereditary Nonpolyposis Colorectal Cancer

Abstract: The magnitude of the pathologist's role in the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) is underestimated. The diagnostic features are not specific to HNPCC cancers, but relate to all cancers showing high levels of DNA microsatellite instability (MSI‐H). Three major groups of MSI‐H cancers can be recognized by histopathological criteria: (1) right‐sided poorly differentiated cancers, (2) right‐sided mucinous cancers, and (3) adenocarcinomas in any location showing tumor‐infiltrating (intraepithelial) lymphocytes (TIL). The poorly differentiated cancers are relatively well circumscribed and the cells are arranged in sheets or trabeculae. TIL may be very numerous in poorly differentiated cancers. The presence of TIL as estimated in H&E sections equates with a percentage of intraepithelial T cells (CD3+) in the range of 4 to 30%. Most of the T cells are CD8+ (cytotoxic T cells). Peritumoral lymphocytes and the so‐called Crohn's‐like reaction are associated with TIL, but are harder to quantify. Of the 15% of colorectal cancers that are MSI‐H, 13% will be sporadic and 2% will occur in the context of HNPCC. HNPCC should be suspected if the patient is young (less than 55 years) because sporadic MSI‐H cancers (associated with hypermethylation of the promoter region of hMLH1) occur almost exclusively in elderly subjects. Workup of a suspected case should include DNA microsatellite testing with a panel of mononucleotide (e.g., BAT26, BAT25) and dinucleotide (e.g., D5S346, D2S123, and D177S250) markers before referral to a cancer family or clinical genetics clinic. Immunohistochemical staining for hMLH1 and hMSH2 identifies the underlying mutation in a proportion of cases. The colorectal adenoma is the usual precursor lesion in HNPCC, though serrated polyps are implicated in a small subset.
Homology Cloning of cDNA or Genomic DNA

The principle of cloning utilizes hybridization of single‐stranded DNA probes to denatured DNA fixed on membranes to detect the identical DNA molecules present in a large population of diverse DNAs. In homology or low‐stringency cloning, hybridization of oligonucleotide, cDNA, or genomic DNA probes to denatured DNA from plasmid or bacteriophage libraries is carried out under low‐stringency conditions that promote hybridization in the presence of sequence mismatch (i.e., mispaired nucleotides). The procedures used are identical to those for screening libraries at high stringency, with the exception that hybridization and washing conditions are altered to permit hybridization with mismatched sequence; salt concentration is increased and the hybridization and wash temperatures are decreased. This unit describes conditions that have been used to clone and identify novel genes and cDNA clones using low‐stringency hybridization of known probes to membranes that contain libraries of bacterial or bacteriophage DNA.
The GRIM2005 Study of Migraine Consultation in France I. Determinants of Consultation for Migraine Headache in France

The aim of this study was to evaluate determinants of consultation for migraine in a representative sample of the French general adult population. We interviewed 10 032 subjects, of whom 1534 fulfilled the International Headache Society diagnostic criteria for migraine. These were categorized into migraine, probable migraine and chronic migraine. Information was collected on consultation experience; 436 subjects (28.4%) had never consulted for headache, 473 (30.8%) were in active consultation and 625 (40.7%) had previously consulted but lapsed. Subjects with chronic migraine showed the highest active consultation rates (51.8%). All subjects completed rating instruments for headache [Headache Impact Test (HIT)-6], psychiatric (Hospital Anxiety and Depression Scale scale) and psychological [Brief Illness Perception Questionnaire (BIPQ), Brief COPE Inventory and Coping Strategy Questionnaire] variables. The strongest determinants of active consultation were BIPQ scores, HIT-6 scores and migraine type. Consultation was associated with maladaptive coping strategies (social support, emotional expression and acceptance). Determinants of remaining in consultation were catastrophizing coping scores and previous consultation experience.
Cost-effectiveness of pegfilgrastim versus 6-day filgrastim primary prophylaxis in patients with non-Hodgkin's lymphoma receiving CHOP-21 in United States

ABSTRACT Objectives: Prophylaxis with granulocyte-colony stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. Randomized clinical trials have shown that pegfilgrastim, a 2nd-generation G-CSF, is at least as effective as the 1st-generation G-CSF filgrastim. In the meta-analysis of trials pegfilgrastim performed better than filgrastim with respect to FN risk. The incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) with pegfilgrastim versus filgrastim used for 6 days (as is often used in clinical practice) was estimated in patients with aggressive non-Hodgkin's lymphoma (NHL) receiving myelosuppressive chemotherapy in the United States. Methods: A decision-analytic model was constructed from a health insurer's perspective with a life-time study horizon. The model considered direct medical costs and outcomes related to reduced FN and potential survival benefits due to reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values. Results: The incremental cost-effectiveness (ICER) of pegfilgrastim versus 6-day filgrastim primary prophylaxis was $2167/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of $5532/LY gained or $6190/QALY gained. When the potential benefit of optimized chemotherapy was included, the ICER was $1494/LY gained or $1677/QALY gained. The most influential factors included cost of pegfilgrastim, relative risk of FN between pegfilgrastim and filgrastim, FN case-fatality rate, cost of filgrastim and baseline FN risk. Conclusions: Pegfilgrastim is cost-effective in primary prophylaxis of FN compared to 6 days per cycle of filgrastim, in patients with NHL receiving myelosuppressive chemotherapy (e.g., cyclophosphamide + doxorubicin + vincristine + prednisolone [CHOP-21]) chemotherapy. Study limitations included lack of direct evidence linking G-CSF use with a reduction in FN-related mortality and limited data that show a relationship between relative dose intensity (RDI) and cancer-specific patient survival.
Medication Safety: Effect of Content and Format of Prescription Drug Labels on Readability, Understanding, and Medication Use: A Systematic Review

Objective: To evaluate the evidence regarding the optimal content and format of prescription labels that might improve readability, understanding, and medication use. Data Sources: We performed a systematic review of randomized controlled trials, observational studies, and systematic reviews from MEDLINE and the Cochrane Database (1990–June 2005), supplemented by reference mining and reference lists from a technical expert panel. Study Selection: We selected studies that focused on the content of physician–patient communication about medications and the content and format of prescription drug iabels. Data Extraction: Two reviewers extracted and synthesized information about study design, populations, and outcomes, Data Synthesis: Of 2009 articles screened, 36 that addressed the content of physician–patient communication about medications and 69 that were related to the content or format of medication labels met review criteria. Findings showed that patients request information about a drug's indication, expected benefits, duration of therapy, and a thorough list of potential adverse effects. The evidence about label format supports the use of larger fonts, lists, headers, and white space, using simple language and logical organization to improve readability and comprehension. Evidence was not sufficient to support the use of pictographic icons. Little evidence linked label design or content to measurable health outcomes, adherence, or safety. Conclusions: Evidence suggests that specific content and format of prescription drug labels facilitate communication with and comprehension by patients. Efforts to improve the labels should be guided by such evidence, although additional study assessing the influence of label design on medication-taking behavior and health outcomes is needed. Several policy options exist to require minimal standards to optimize medical therapy, particularly in light of the new Medicare prescription drug benefit.
Evaluation of Multidrug Therapy With Azithromycin, Rifampin, and Ethambutol for the Treatment of Mycobacterium avium subsp avium in Ring-neck Doves (Streptopelia risoria): An Uncontrolled Clinical Study

Abstract An uncontrolled clinical study was conducted to evaluate the efficacy of a multidrug protocol in 16 ring-neck doves (Streptopelia risoria) from a flock naturally infected with Mycobacterium avium subsp avium. The doves were considered infected on the basis of a high prevalence of infection in a group of 29 birds that were euthanatized from the same flock and clinical signs and pathologic results consistent with infection in the remaining birds. All birds were treated with azithromycin (43 mg/kg), rifampin (45 mg/kg), and ethambutol (30 mg/kg) administered orally once daily for 180 days. Five birds died during treatment and were confirmed positive for mycobacteriosis on postmortem examination. Of the remaining 11 birds, infection and disease were present in 9 (81.8%) at the end of the treatment. Postmortem investigation showed that 2 mycobacterial isolates were resistant to ethambutol, intermediately sensitive to rifampin, and sensitive to azithromycin. Microscopic examination of liver sections equivalent of those that would be taken for biopsy showed that biopsy as a method of monitoring birds for treatment success had poor sensitivity. Toxicity associated with drug therapy was not observed in these doves nor in 6 outwardly healthy ring-neck doves exposed to the same treatment. The results of this study showed that this protocol of azithromycin, rifampin, and ethambutol has poor efficacy when administered for 180 days for treatment of doves infected with M avium subsp avium.
Experimental verification and implementation of a isolated ZVT boost converter for high step-up electric traction

Lofty power and elevated step-up isolated dc-dc converters have been widely employed in the emerald power systems and especially for electric traction drives. In electronics engineering, a DC to DC converter is a circuit, which converts a source of direct current from one voltage to another. It is a class of power converter. In many DC-DC applications, output isolation may need to be implemented depending on the type of application to meet safety standards to provide impedance matching. This galvanic isolation is required to attain a flexible system reconfiguration. Active lamp boost converter with coupled-inductors is proposed for high step-up electric traction applications. The primary-parallel-secondary-series structure is employed in this project to knob the huge input current, maintain the high output voltage and enlarge the voltage gain. Purpose of the coupled-inductors is to reduce the voltage gain addition and lesser concern in switching. Clamp circuit is used to re circulate the energy. The voltage strain in rectifier is minimized and reverse-recovery problem is eliminated. The hardware unit utilizes embedded technology using PIC microcontroller 16F84A to give gate pulses to the MOSFET converter switches. In this proposed converter only three MOSFET's are used which reduces the number of devices and makes circuit simple in construction. Efficiency, size, and cost are the primary advantages of the proposed isolated ZVT boost converter when compared to other existing converters. Isolated ZVT boost converter employing series-parallel arrangement will have an efficiency of about 88-94%, whereas existing converters are usually 80 to 85% efficient. In the present work, a novel ZVT boost converter for electric traction drive application is developed has been designed in MATLAB/SIMULINK software packages. The simulation result for a 40-V-to-600-V converter is simulated in open circuit and closed loop system. Simulated disturbance is applied at a time period of 0.7 micro second and noted that the output voltage is maintained constant always. The hardware unit and experimental results of a 15V to 85-V ZVT converter is implemented and the results are verified.
The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes

Summary Background Data:Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. Methods:Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. Results:There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. Conclusions:This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.
Villous trophoblast of human placenta: a coherent view of its turnover, repair and contributions to villous development and maturation.

A coherent view of human villous trophoblast as a continuously renewing epithelium is presented. Epithelia undergoing continuous renewal (e.g. intestinal mucosa, epidermis) display clonogenic cells which pass through several transit divisions before migrating out of proliferation zones and into zones of maturation/differentiation. Quantitative relations (e.g. relative numbers of cells) between proliferation and differentiation zones help to define the steady state and this may vary in response to physiological and pathological circumstances. From the differentiation compartment, cells or cell fragments are eventually extruded by mechanisms which may involve apoptosis. All these features are seen in trophoblastic epithelium. Cytotrophoblast cells (CT, proliferation zone) divide continuously throughout gestation and post-mitotic cells are recruited into syncytiotrophoblast (ST, differentiation zone) after membrane fusion. Evidence of fusion events includes localised confluence of CT and ST cytoplasms, and intrasyncytial plasma membrane segments bearing desmosomal remnants. During differentiation, nuclei undergo changes in shape, chromatin condensation and packing density. Densely-clustered nuclei are associated with cytokeratin intermediate filaments and annulate lamellae. Both clustered and non-clustered nuclei show ultrastructural features of pre-apoptosis and apoptosis. Normally, apoptosis is triggered only when nuclei are in the syncytium. Some (pre-)apoptotic nuclear aggregates are sequestered in syncytial knots, extruded as trophoblast fragments into the intervillous space and then deported into the maternal circulation to be phagocytosed at extraplacental sites. During gestation, there is some constancy in the numerical ratios between CT and ST nuclei pointing to a normal steady state. The steady state may be perturbed when the epithelium is damaged locally. Where the epithelium is denuded, fibrin-type fibrinoid from the intervillous space plugs the discontinuity and, with CT proliferation, facilitates reepithelialisation. Features of normal villous development (e.g. sprouting, intervillous bridge formation, bridge abruption, syncytial knot formation) are explicable in the context of trophoblast turnover with early CT proliferation being mainly for growth and later proliferation for renewal and repair. Adaptive re-settings of the epithelial steady state may also occur in abnormal pregnancies.
Distributed Role Selection With ANC and TDBC Protocols in Two-Way Relaying Systems

This paper advocates a distributed role selection strategy to coordinate two-way relaying transmissions among three cooperative nodes. For such, the local channel state information comparison and decision feedback mechanism are merged into classical analog network coding (ANC) and time division broadcast (TDBC) protocols such that the cooperative role of each node can be designated in a distributed fashion. We refer to this distributed role selection rule as d-ROSE. In both ANC-based and TDBC-based two-way relaying scenarios, strict proof for the equivalence of d-ROSE and optimal ROSE is given, which indicates that albeit the different form, their final role decision is essentially the same. Outage analysis for the d-ROSE strategy is carried out and the scaling law of the system outage behavior at high signal-to-noise ratio (SNR) is characterized, which manifests that d-ROSE can enhance the system diversity gain to one-order higher relative to the ANC and TDBC protocols. It is also shown that d-ROSE can reduce the signaling overhead upto 60% to perform the outage-optimal role selection. Finally, the impacts of node placement on the outage performance as well as the average signaling overhead of d-ROSE are numerically evaluated and some useful conclusions are drawn.
DELLAs Regulate Chlorophyll and Carotenoid Biosynthesis to Prevent Photooxidative Damage during Seedling Deetiolation in Arabidopsis[C][W]

This work shows that gibberellin-regulated DELLA proteins regulate chlorophyll and carotenoid biosynthesis to stimulate cotyledon greening during deetiolation. In plants, light represents an important environmental signal that triggers the production of photosynthetically active chloroplasts. This developmental switch is critical for plant survival because chlorophyll precursors that accumulate in darkness can be extremely destructive when illuminated. Thus, plants have evolved mechanisms to adaptively control plastid development during the transition into light. Here, we report that the gibberellin (GA)-regulated DELLA proteins play a crucial role in the formation of functional chloroplasts during deetiolation. We show that Arabidopsis thaliana DELLAs accumulating in etiolated cotyledons derepress chlorophyll and carotenoid biosynthetic pathways in the dark by repressing the transcriptional activity of the phytochrome-interacting factor proteins. Accordingly, dark-grown GA-deficient ga1-3 mutants (that accumulate DELLAs) display a similar gene expression pattern to wild-type seedlings grown in the light. Consistent with this, ga1-3 seedlings accumulate higher amounts of protochlorophyllide (a phototoxic chlorophyll precursor) in darkness but, surprisingly, are substantially more resistant to photooxidative damage following transfer into light. This is due to the DELLA-dependent upregulation of the photoprotective enzyme protochlorophyllide oxidoreductase (POR) in the dark. Our results emphasize the role of DELLAs in regulating the levels of POR, protochlorophyllide, and carotenoids in the dark and in protecting etiolated seedlings against photooxidative damage during initial light exposure.
The management of thrombosis in the antiphospholipid-antibody syndrome.

BACKGROUND The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome. METHODS One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed. RESULTS One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio of > or = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P < 0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of < 3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient-year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively). CONCLUSIONS The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.
Tomato Spotted Wilt Virus Particle Morphogenesis in Plant Cells

ABSTRACT A model for the maturation of tomato spotted wilt virus (TSWV) particles is proposed, mainly based on results with a protoplast infection system, in which the chronology of different maturation events could be determined. By using specific monoclonal and polyclonal antisera in immunofluorescence and electron microscopy, the site of TSWV particle morphogenesis was determined to be the Golgi system. The viral glycoproteins G1 and G2 accumulate in the Golgi prior to a process of wrapping, by which the viral nucleocapsids obtain a double membrane. In a later stage of the maturation, these doubly enveloped particles fuse to each other and to the endoplasmic reticulum to form singly enveloped particles clustered in membranes. Similarities and differences between the maturation of animal-infecting (bunya)viruses and plant-infecting tospoviruses are discussed.