Miracle-dz/UniFAR-FTUs huggingface dataset:
Reissner's Membrane in the Human Cochlea

The vestibular membrane of Reissner, no longer regarded as a passive partition between endolymph and perilymph, is now thought to have a significant role in maintaining the separate ionic compositions of the two cochlear fluids. Present theories-P-" suggest a "radial flow" of the endolymph involving the active participation of Reissner's membrane, rather than a "longitudinal flow" toward the endolymphatic duct and sac as envisioned by Cuild. Since Hallpike and Cairns-? first reported labyrinthine hydrops in two cases with Meniere's syndrome, there has been great concern about pathologic distension of Reissner's membrane. Several other authors have confirmed the bulging of the membrane into scala vestibuli. but virtually nothing is known about possible alterations in the membrane itself in this or in any other pathologic states.
AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.

BACKGROUND The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. METHODS We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy. RESULTS A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients. CONCLUSIONS AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01802632.).
Meningococcal Outer Membrane Protein NhhA Is Essential for Colonization and Disease by Preventing Phagocytosis and Complement Attack

ABSTRACT Neisseria meningitidis is a leading cause of meningitis and septicemia worldwide, with a rapid onset of disease and a high morbidity and mortality. NhhA is a meningococcal outer membrane protein included in the family of trimeric autotransporter adhesins. The protein binds to the extracellular matrix proteins heparan sulfate and laminin and facilitates attachment to host epithelial cells. In this study, we show that NhhA is essential for bacterial colonization of the nasopharyngeal mucosa in a murine model of meningococcal disease. Successful colonization depends on bacterial attachment but also to the capacity to overcome innate host immune responses. We found that NhhA protected bacteria from phagocytosis, which is important for the mucosal survival of bacteria. In addition, NhhA mediated extensive serum resistance that increased bacterial survival in blood and promoted lethal sepsis. The presence of NhhA protected bacteria from complement-mediated killing by preventing the deposition of the membrane attack complex. Taken together, the results of this work reveal that NhhA inhibits phagocytosis and protects bacteria against complement-mediated killing, which enhances both nasal colonization and the development of sepsis in vivo.
Crescent Excision for Minimizing Operative Scars in Circular Skin Lesions

To remove a circular scar or nevus, direct excision is most popularly used, but when the postexcision defect is large, adjacent tissues may become distorted, or direct closure may be difficult because of excessive skin tension. Skin grafting and staged excision have been used alternatively, but the grafted skin usually differs in color and texture from the adjacent tissue. Staged excision may be preferred in spite of multiple operations, but it may result in scars longer than the lesion’s original diameter. When the length of excision is too much shorter than the width, a dog-ear can occur. Correcting a dog-ear can result in a longer scar. To minimize the length and size of the scar for treating circular skin lesions of varying sizes, a crescent-shaped excision was designed within the lesion. We hereby report the method and results of this technique.
Monoclonal IgA antibody-mediated expulsion of Trichinella from the intestine of mice

To assess the potential role of IgA antibody in expulsion of the nematode of the genus Trichinella from the intestine, a panel of IgA monoclonal antibodies (mAbs) were produced from the mesenteric lymph node cells from BALB/c mice orally vaccinated with irradiated muscle larvae of Trichinella britovi. One IgA mAb, HUSM-Tb1, formed immunoprecipitates on the surface of live muscle larvae, and by immunohistochemistry reacted with their stichocytes and cuticular surface, but not with those tissues of the adult stage or newborn larvae. Intraperitoneal injection of BALB/c mice with this mAb 5 h before challenge conferred a high level of protection (more than 95%) against T. britovi infection, when 2·0 mg of specific IgA/20 g body weight was given to a mouse. The same treatment produced a similar effect in SCID mice lacking functional T- and B-cells, indicating no requirement of synergistc T-cell factors for the effect. Passive transfer of the mAb at the time of challenge or later showed less or no effect upon worm expulsion. It is concluded that the mucosal IgA response, when adequately induced, can impede the establishment of infective Trichinella parasites in the mouse intestine.
Longitudinal changes in disabled husbands' and wives' receipt of care.

PURPOSE OF THE STUDY This study contrasts 2-year adjustments in disabled husbands' and wives' amount of received care following both worsening and recovery in personal (activities of daily living [ADLs]) and routine care (instrumental activities of daily living [IADLs]) disability. DESIGN AND METHODS Using longitudinal data on 789 husbands and 778 wives from the Health and Retirement Study (2000 and 2002), changes in marital partners' monthly hours of spousal and nonspousal care were jointly modeled using bivariate Tobit models. In addition, asymmetry in the magnitude of responses to worsening and improvement of function was examined. RESULTS Disabled husbands receive more hours of spousal and nonspousal care following worsening in ADL function than wives. Conversely, disabled wives lose more spousal and nonspousal care hours following improvements in ADL disability than husbands. Moreover, wives recovering in ADL function lose more hours of spousal care than they receive following worsening in personal care disability. There is no evidence of corresponding gender differences in the dynamics of assistance received following changes in IADL function. IMPLICATIONS Compared with husbands, disabled wives are disadvantaged in the adjustment of their personal care hours. Although disabled married community residents receive more hours of care than their unmarried counterparts, there are important gender differences in the advantages offered by marriage.
A Vibrio vulnificus Type IV Pilin Contributes to Biofilm Formation, Adherence to Epithelial Cells, and Virulence

ABSTRACT Vibrio vulnificus expresses a multitude of cell-associated and secreted factors that potentially contribute to pathogenicity, although the specific roles of most of these factors have been difficult to define. Previously we have shown that a mutation in pilD (originally designated vvpD), which encodes a type IV prepilin peptidase/N-methyltransferase, abolishes expression of surface pili, suggesting that they belong to the type IV class. In addition, a pilD mutant exhibits reduced adherence to HEp-2 cells, a block in secretion of several exoenzymes that follow the type II secretion pathway, and decreased virulence. In this study, we have cloned and characterized a V. vulnificus type IV pilin (PilA) that shares extensive homology to group A type IV pilins expressed by many pathogens, including Vibrio cholerae (PilA), Pseudomonas aeruginosa (PilA), and Aeromonas hydrophila (TapA). The V. vulnificus pilA gene is part of an operon and is clustered with three other pilus biogenesis genes, pilBCD. Inactivation of pilA reduces the ability of V. vulnificus to form biofilms and significantly decreases adherence to HEp-2 cells and virulence in iron dextran-treated mice. Southern blot analysis demonstrates the widespread presence of both pilA and pilD in clinical as well as environmental strains of V. vulnificus.
Sub‐clinical cerebral oedema does not occur regularly during treatment for diabetic ketoacidosis

Fulminant cerebral oedema is an uncommon, fatal complication of diabetic ketoacidosis (DKA) in children. This study aimed to find out whether the sub‐clinical compression of the brain ventricles found by an earlier study, is a general phenomenon during intravenous treatment for DKA. Four boys and four girls were examined. Blood glucose values ranged from 40 to 24. 6mmol/l, base excess ‐34. 6 to ‐ 13. 6 and capillary blood pH 6. 89–7. 22. The patients received fluids containing both glucose and electrolytes, and insulin intravenously. After about lOh, blood glucose was 8. 7–21. 8mmol/l and base excess had decreased substantially (‐9. 5 to ‐2. 9) in seven of the eight cases. Computerized tomography of the brain was then performed, and again after full recovery. Only two of the patients had an initial decrease in intercaudate distance, which exceeded the variability found in a reference group. Compression of the cerebral ventricles does not occur regularly during treatment for DKA.
Caffeine Inhibits Checkpoint Responses without Inhibiting the Ataxia-Telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) Protein Kinases*

The ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) kinases regulate cell cycle checkpoints by phosphorylating multiple substrates including the CHK1 and -2 protein kinases and p53. Caffeine has been widely used to study ATM and ATR signaling because it inhibits these kinases in vitro and overcomes cell cycle checkpoint responses in vivo. Thus, caffeine has been thought to overcome the checkpoint through its ability to prevent phosphorylation of ATM and ATR substrates. Surprisingly, I have found that multiple ATM-ATR substrates including CHK1 and -2 are hyperphosphorylated in cells treated with caffeine and genotoxic agents such as hydroxyurea or ionizing radiation. ATM autophosphorylation in cells is also increased when caffeine is used in combination with inhibitors of replication suggesting that ATM activity is not inhibited in vivo by caffeine. Furthermore, CHK1 hyperphosphorylation induced by caffeine in combination with hydroxyurea is ATR-dependent suggesting that ATR activity is stimulated by caffeine. Finally, the G2/M checkpoint in response to ionizing radiation or hydroxyurea is abrogated by caffeine treatment without a corresponding decrease in ATM-ATR-dependent signaling. This data suggests that although caffeine is an inhibitor of ATM-ATR kinase activity in vitro, it can block checkpoints without inhibiting ATM-ATR activation in vivo.
Successive Approximation Methods for Solving Nested Functional Equations in Markov Decision Problems

This paper presents a successive approximation method for solving systems of nested functional equations which arise, e.g., when considering Markov renewal programs in which policies that are maximal gain or optimal under more selective discount—and average overtaking optimality criteria are to be found. In particular, a successive approximation method is given to find the optimal bias vector and bias-optimal policies. Applications with respect to a number of additional stochastic control models are pointed out. Our method is based on systems of simultaneously generated (single-equation) value-iteration schemes.
Quality of specimens and sputum culture results: a retrospective study.

A retrospective study of laboratory reports of sputums examined in the first 3 months of 1977 and of 1978 showed some interesting findings, which were similar in these 2 years. Analysis of the findings demonstrated that information from a proportion of sputum cultures were not helpful to the clinicians. Probable causes of such unhelpful results and some ways to overcome these problems were discussed, along with reviews of relevant literature. A conclusion drawn at the end of the discussion was that, under present circumstances, it was not expected that sputum cultures would produce totally reliable aetiological agents, unless attempts were made to obtain a better quality of specimen, e.g. those obtained by transtracheal or bronchoscopic aspirations.
WIP is essential for lytic granule polarization and NK cell cytotoxicity

Natural killer (NK) cells play important roles in host immunity by killing virus-infected and tumor cells. Killing of the target cell is achieved by formation of an immune synapse and localized secretion of lytic granules containing perforin and granzymes. Here, we demonstrate that Wiskott–Aldrich syndrome protein (WASp)-interacting protein (WIP), important in generation of a large complex of proteins involved in actin cytoskeleton rearrangements, is indispensable for NK cell cytotoxicity. WIP knockdown completely inhibited cytotoxicity, whereas overexpression of WIP enhanced NK cell cytolytic ability. WIP was found to colocalize with lytic granules. WIP segregated to the lysosomal fraction, where granzyme B activity was also found, and the interaction between WIP and granules was independent of WASp. Importantly, WIP knockdown inhibited polarization of lytic granules to the immune synapse, but not conjugate formation. These results indicate that WIP is involved in lytic granule transport and is essential for regulation of NK cell cytotoxic function.
Online TV Buzz An analysis of the interaction between Social Networks and TV audience

This thesis aims at analyzing the possible interactions between the popularity of a TV program episode and its features.We propose an innovative approach in order to grasp these possible connections. The idea is that of building a network, which changes over time, where the nodes represents the guests of the episode. The edges of the network are due to the co-participation of the guests to the same episode. We aim at showing that the popularity of an episode is connected to the popularity of its guests. The popularity of the guests is defined on the basis of centrality measures we extract from the network, while the popularity of a TV program episode is defined on the number of the tweets posted while the episode is on air, that contain the title of the program. We show that there are some connections between the popularity of the guests and that of an episodes as we defined them, however these are more marked in TV programs types for which guests are really fundamental and that have titles which are more recognizable in the Twitter cloud. Furthermore, we propose a new ontology to represent Electronic Program Guide (EPG) in a novel way.
Mobility improvement in nanowire junctionless transistors by uniaxial strain

Improvement of current drive in n- and p-type silicon junctionless MOSFETs using strain is demonstrated. The extracted piezoresistance coefficients are in good agreement with the piezoresistive theory and the published coefficients for bulk silicon even for 10 nm-thick silicon nanowires as narrow as 20 nm.
input-output examples [ 8 ] , among others .

Given a semantic constraint specified by a logical formula, and syntactic constraints specified by a context-free grammar, the SyntaxGuided Synthesis (SyGuS) problem is to find an expression that satisfies both the syntactic and semantic constraints. An enumerative approach to solve this problem is to systematically generate all expressions from the syntactic space with some pruning, and has proved to be surprisingly competitive in the newly started competition of SyGuS solvers. It performs well on small to medium sized benchmarks, produces succinct expressions, and has the ability to generalize from input-output examples. However, its performance degrades drastically with the size of the smallest solution. To overcome this limitation, in this paper we propose an alternative approach to solve SyGuS instances. The key idea is to employ a divide-and-conquer approach by separately enumerating (a) smaller expressions that are correct on subsets of inputs, and (b) predicates on inputs that distinguish these subsets. These smaller expressions and predicates are then combined using decision trees to obtain an expression that is correct on all inputs. We view the problem of combining expressions and predicates as a multi-label decision tree learning problem. We propose a novel technique of associating a probability distribution over the set of labels that a sample can be labeled with. This enables us to use standard information-gain based heuristics to learn a compact decision tree. We report a prototype implementation and evaluate it on the benchmarks from the SyGuS 2015 competition. Our tool is able to match the running times and the succinctness of solutions of both standard enumerative solver as well as the latest white-box solvers in most cases. Further, our solver is able to solve a large number of instances from the ICFP class of benchmarks, which were previously unsolved by all existing solvers. The experimental results in this report are outdated. The implementation has undergone several major improvements—the latest version of the tool can be found at https://bitbucket.org/abhishekudupa/eusolver/.
Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.
Altered GNAS imprinting due to folic acid deficiency contributes to poor embryo development and may lead to neural tube defects

Disturbed epigenetic modifications have been linked to the pathogenesis of Neural Tube Defects (NTDs) in those with folate deficiency during pregnancy. However, evidence is lacking to delineate the critical region in epigenome regulated by parental folic acid and mechanisms by which folate deficiency affects normal embryogenesis. Our data from clinical samples revealed the presence of aberrant DNA methylation in GNAS imprinting cluster in NTD samples with low folate concentrations. Results from mouse models indicated that the establishment of GNAS imprinting was influenced by both maternal and paternal folate-deficient diets. Such aberrant GNAS imprinting was present prior to the gametogenesis period. Imprinting in Exon1A/GNAS gDMR was abolished in both spermatozoa and oocytes upon treating with a parental folate-deficient diet (3.6% in spermatozoa, 9.8% in oocytes). Interestingly, loss of imprinting in the GNAS gene cluster altered chromatin structure to an overwhelmingly open structure (58.48% in the folate-free medium group vs. 39.51% in the folate-normal medium group; P < 0.05), and led to a disturbed expression of genes in this region. Furthermore, an elevated cyclic AMP levels was observed in folate acid deficiency group. Our results imply that GNAS imprinting plays major roles in folic acid metabolism regulation during embryogenesis. Aberrant GNAS imprinting is an attribute to NTDs, providing a new perspective for explaining the molecular mechanisms by which folate supplementation in human pregnancy provides protection from NTDs.
Echocardiographic Parameters to Predict Atrial Fibrillation in Clinical Routine—The EAHsy-AF Risk Score

Background Echocardiographic parameters representing impaired left atrial (LA) function and remodeling are of high value to predict atrial fibrillation (AF). This study aimed to develop a prediction model for AF easily to apply in clinical routine containing echocardiographic parameters associated with LA remodeling and—function. Methods and Results This monocentric, semi-blinded, controlled analysis included 235 patients to derive a prediction model. This prediction model was tested in a validation cohort encompassing 290 cardiovascular inpatients. The derivation and validation cohort included 54 (23%) and 66 (23%) patients with AF, respectively. Transthoracic echocardiography, comprising parameters indicating left atrial remodeling [septal/lateral total atrial conduction time (s/l PA-TDI)] and left atrial volume indexed to a' (LAVI/a') was performed in each patient. Based on multivariable regressions analysis, four variables were enclosed into the EAHsy (Echocardiography, Age, Hypertension)-AF risk score for AF prediction: Hypertension, Age, LAVI/a‘ and septal PA-TDI. In the validation cohort discrimination was strong (C-statistic 0.987, 95%CI 0.974–0.991) with an adequately performed calibration. The EAHsy-AF risk score was associated with a more precise prediction of AF in comparison to commonly used AF-scores (CHADS2-, ATLAS-, ARIC-, CHARGE-AF score). Conclusion The EAHsy-AF-Score containing age, hypertension and echocardiographic parameters of atrial dysfunction and remodeling precisely predicts the incidence of AF in a general population of patients with cardiovascular disease. The EAHsy-AF risk score may enable more selective rhythm monitoring in specific patients at high risk for AF.