Miracle-dz/UniFAR-FTUs huggingface dataset:
The diagnosis of occupational asthma from serial measurements of lung function at and away from work

The diagnosis of occupational asthma has serious consequences for a worker, who is often left with much less money and no job (at least in the UK). ' It is important that the diagnostic process is available and accurate. In most instances the diagnosis of occupational asthma can be strongly suspected from the history alone, by finding a temporal relationship between symptoms and occupational exposure. Some asthmatics substantially under or over report symptoms in relation to changes in lung function and not all workers can be relied on to tell the truth. It is therefore wise to obtain further proof of the diagnosis of occupational asthma before counselling workers to avoid exposures which might cost them their jobs. Managers usually require proof of a problem before money is allotted to remove or control occupational sensitising agents. For those still at work the most appropriate next step in the diagnostic process is the serial measurement of lung function in relation to work. Peak expiratory flow (PEF) has usually been selected as the most appropriate parameter to measure because of the availability of portable meters for its measurement. It is likely that similar changes will be shown in forced expiratory volume in one second (FEVI). Although some believe that the FEVy is more sensitive in detecting the airflow obstruction, particularly in the late asthmatic reaction,2 3not all agree.3 4 If occupational asthma exists there should be measurable changes in PEF in relation to occupational exposure. The problem lies in differentiating the effects of work exposure from the spontaneous diurnal variation in airway calibre and its other determinants such as treatment, exercise, respiratory infection, exposure to non-specific irritants
A systematic review of targeted agents for non-small cell lung cancer

Abstract Background: advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes. Method: this systematic literature review was conducted by reviewing all relevant literature in PubMed. Six separate searches were performed: Three searches where controlled entry terms were used and three free text searches. Furthermore, other relevant publications were included manually. A total of seventy-two studies met the search criteria and were thus further analyzed and evaluated. Results: In the included studies, various TAs and their effect on different molecular targets have been evaluated. Clinical responses vary considerably among the different genetic aberrations. The majority of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1) rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2), Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal-epithelial transition factor (MET) were included as well. In general, studies comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK) rearranged patients after use of either TA or standard chemotherapy, present significant better results after TA. Conclusions: This systematic review provides an overview of available literature in PubMed regarding NSCLC and TA. Included studies point toward that TA appears to be a promising therapeutic tool in treating NSCLC patients and use of TA is expected to result in improved treatment outcomes.
Virus-mediated release of endosomal content in vitro: different behavior of adenovirus and rhinovirus serotype 2

Endosomal penetration by nonenveloped viruses might be accomplished by either local breakdown of the endosomal membrane (e.g., adenovirus) or formation of a membrane-spanning pore by capsid proteins. Uncoating of the nonenveloped virus human rhinovirus serotype 2 (HRV2) has been shown to occur from late endosomes and to be entirely dependent on the acidic pH in this compartment (Prchla, E., E. Kuechler, D. Blaas, and R. Fuchs. 1994. J. Virol. 68: 3713-3723). To investigate further the mechanism of uncoating of HRV2, an in vitro assay was established to test viruses or virus-derived peptides for their capacity to release cointernalized biotin-dextran of different molecular mass (10 and 70 kD) from isolated endosomes. The suitability of the assay was demonstrated by use of a fusogenic peptide derived from influenza virus hemagglutinin (GALA-INF3). Whereas adenovirus induced a low pH- dependent release of up to 46% of the internalized biotin-dextran and did not show any significant size selectivity (as expected for endosome disruption), HRV2 mediated release of 27% of the 10 kD dextran and only traces of the 70-kD dextran. Similarly, GALA-INF3-induced release of biotin-dextran was also size dependent. The potential role of the capsid protein VP1 in HRV2 uncoating in vivo was also substantiated in our in vitro system using an amphipathic, NH2-terminal peptide of VP1. Taken together, these data favor the model of a specific pore-forming mechanism for HRV2 uncoating which is in contrast to the membrane- disrupting mechanism of adenovirus.
STOP‐Bang questionnaire is superior to Epworth sleepiness scales, Berlin questionnaire, and STOP questionnaire in screening obstructive sleep apnea hypopnea syndrome patients

Background Obstructive sleep apnea hypopnea syndrome (OSAHS) is underdiagnosed. Screening patients at high risk of OSAHS is extremely important. Using the standard questionnaire to screen OSAHS is a practical method. This study aimed to evaluate the value of the STOP‐Bang questionnaire (SBQ) in screening OSAHS in sleep‐disordered breathing clinic by comparing it with the Epworth sleepiness scales (ESS), Berlin questionnaire, and STOP questionnaire. Methods In this study, 212 patients at the sleep‐disordered breathing clinic of the Peking Union Medical College Hospital between May 2011 and January 2012 were prospectively included. They were asked to fill in the SBQ, ESS, Berlin questionnaire, and STOP questionnaire before overnight polysomnography (PSG). Using PSG as gold standard, the sensitivities and specificities of SBQ were compared with those of ESS, Berlin questionnaire, and STOP questionnaire. Results There was no significance in applying ESS score ≥11 to screen OSAHS and detect moderate and severe OSAHS (P >0.05). SBQ was superior to Berlin questionnaire and STOP questionnaire in screening OSAHS and detecting the severity of OSAHS patients. The sensitivities of SBQ score ≥3 with apnea hypopnea index (AHI) ≥5/h, AHI ≥15/h, and AHI ≥30/h as gold standards were 94.9%, 96.5%, and 97.7%, respectively. The specificities were 50.0%, 28.6%, and 17.9%, respectively. The area upper curves were 0.815 (0.706–0.925, P <0.01), 0.746 (0.665–0.828, P <0.01), and 0.751 (0.686–0.817, P <0.01), respectively. According to SBQ, the population was classified into high‐risk group and low‐risk group. The gender, BMI, neck circumference, AHI, LSpO2, and number of subjects of AHI ≥5/h, AHI ≥15/h, and AHI ≥30/h of these two groups were significantly different. Conclusions The SBQ has superior predictive value compared with ESS, Berlin questionnaire, and STOP questionnaire. It should be used further in screening for OSAHS in the general population.
CA-Tree: A Hierarchical Structure for Efficient and Scalable Coassociation-Based Cluster Ensembles

Cluster ensembles have attracted a lot of research interests in recent years, and their applications continue to expand. Among the various algorithms for cluster ensembles, those based on coassociation matrices are probably the ones studied and used the most because coassociation matrices are easy to understand and implement. However, the main limitation of coassociation matrices as the data structure for combining multiple clusterings is the complexity that is at least quadratic to the number of patterns N. In this paper, we propose CA-tree, which is a dendogram-like hierarchical data structure, to facilitate efficient and scalable cluster ensembles for coassociation-matrix-based algorithms. All the properties of the CA-tree are derived from base cluster labels and do not require the access to the original data features. We then apply a threshold to the CA-tree to obtain a set of nodes, which are then used in place of the original patterns for ensemble-clustering algorithms. The experiments demonstrate that the complexity for coassociation-based cluster ensembles can be reduced to close to linear to N with minimal loss on clustering accuracy.
A novel female-specific member of the CYP3A gene subfamily in the mouse liver.

Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we determined the primary structure of its cDNA and examined its expression profile. This cytochrome P450 consisted of 504 amino acids and showed 92, 68, 88, and 69% amino acid sequence identity with mouse CYP3A11, 3A13, 3A16, and 3A25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to those of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of animals of both sexes, but increased with age in females, whereas it was gradually reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicated that estradiol and testosterone were able to induce and suppress the expression of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not affect the level of CYP3A41 mRNA in the liver of either sex. On the other hand, pregnenolone 16alpha-carbonitrile and phenobarbital suppressed CYP3A41 level to half that of untreated female mice. These observations indicated that CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in the female mouse liver.
Molecular Determinants of the Prothrombogenic and Inflammatory Phenotype Assumed by the Postischemic Cerebral Microcirculation

Background and Purpose— Circulating blood cells have been implicated in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury and stroke. The objective of this study was to define the magnitude and molecular determinants of the platelet- and leukocyte–endothelial cell adhesive interactions induced by I/R in the mouse brain. Methods— Bilateral common carotid artery occlusion was induced for 1 hour in C57BL/6 mice, followed by either 40 minutes or 4 hours of reperfusion. Fluorescent platelets were administered intravenously, and the frontal brain surface was observed with intravital fluorescence microscopy. Leukocyte–endothelial cell adhesion was monitored with the use of rhodamine-6G. Results— Ischemia followed by 40 minutes of reperfusion resulted in the rolling (125.1±23.6/mm2) and firm adhesion (109.5±25.8/mm2) of leukocytes but not platelets in venules. However, with 4 hours of reperfusion, rolling (138.8±24.6/mm2) and firm adhesion (153.7±22.3/mm2) of platelets were detected, and this was accompanied by a more intense recruitment of rolling (374.5±54.6/mm2) and adherent (445.2±57.1/mm2) leukocytes. In mice deficient in either P-selectin (P-selectin−/−) or intercellular adhesion molecule-1 (ICAM-1) (ICAM-1−/−), the I/R-induced platelet–endothelial cell (by 80% and 60%, respectively) and leukocyte–endothelial cell (by 84% and 78%, respectively) interactions were significantly blunted compared with those of wild-type mice. Conclusions— These findings indicate that I/R promotes the adhesion of both platelets and leukocytes in cerebral venules, with the accumulation of adherent leukocytes preceding the recruitment of platelets. Both P-selectin and ICAM-1 contribute to the inflammatory and prothrombogenic state induced by cerebral I/R.
Discrepancy in the near‐solute electric dipole moment calculated from the electric field

The electric dipole moment p(r) was computed as the integral of the permanent dipole moment of the solvent molecule μ(r) weighted by the orientational probability distribution Ω(r;O) over all orientations, where O is the orientation of the solvent molecule at r. The relationship between Ω(r;O) and the potential of the mean torque was derived; p(r) is proportional to the electric field E(r) under the following assumptions: (1) the van der Waals (vdW) interaction is independent of the orientation of the solvent molecule at r; (2) the solvent molecule and its electrical effect are modeled as a point dipole moment; (3) the solvent molecule at r is in a region far from the solute; and (4) μE(r) ≪ kBT, where kB is Boltzmann's constant and T is absolute temperature. The errors caused by calculating near‐solute Ω(r) and p(r) from E(r) are unclear. The results show that Ω(r) is inconsistent with the value calculated from E(r) for water molecules in the first and second shells of solute with charge state Q = ±1 e, and a large variation in solvent molecular polarizability γmol(r), which appeared in the first valley of 4πr2E(r) for |Q| < 1 e. Nonetheless, p(r) is consistent with the values calculated from E(r) for |Q| ≤ 1 e. The implication is that the assumptions for calculating p(r) can be ignored in the calculation of the solvation free energy of biomolecules, as they pertain to protein folding and protein–protein/ligand interactions. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Tumour M2-pyruvate kinase: a gastrointestinal cancer marker

Background Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. ‘Tumour M2-pyruvate kinase’ was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate kinase converted to an inactive dimeric form by direct interaction with oncoproteins to channel glucose carbons into DNA synthesis. This review summarizes the current knowledge of this unique tumour marker with regard to its biochemistry, assay and potential use as a diagnostic and screening tool in gastrointestinal cancer. Methods A literature search was conducted for entries from 1980 to 2005 using PubMed and NeLH databases using tumour M2-pyruvate kinase, faecal tumour M2-pyruvate kinase, tumour metabolism, tumour markers and carcinoembryonic antigen as keywords. A total of 56 references relevant to tumour M2-pyruvate kinase were retrieved. Eighteen references were clinical studies involving plasma/faecal tumour M2-pyruvate kinase and gastrointestinal cancer. The remaining 38 references were clinical/nonclinical trials and reviews on tumour metabolism and plasma/faecal tumour M2-pyruvate kinase assay. Seven of the 18 clinical studies involved faecal M2-pyruvate kinase. Three of the 11 plasma tumour M2-pyruvate kinase studies were non-English language and were excluded. The sensitivity, specificity, positive predictive and negative predictive value for plasma/serum tumour M2-pyruvate kinase in the detection of gastrointestinal cancer was determined for each of the remaining eight studies. Data for gastrointestinal cancer M2-pyruvate kinase were compared with other gastrointestinal cancer markers. Data from three of the eight studies using a diagnostic cut-off value of 15 U/ml for ethylenediaminetetraacetic acid (EDTA) plasma tumour M2-pyruvate kinase were analysed together as a small meta-analysis. Results At a diagnostic cut-off value of 15 U/ml for tumour M2-pyruvate kinase in EDTA plasma the sensitivity, specificity, positive predictive and negative predictive value was 57.3, 89, 85.7 and 64.8%, respectively, for colorectal cancers, 62.1, 89, 88 and 64%, respectively, for gastric/oesophageal cancers and 72.5, 89, 58 and 94%, respectively, for pancreatic cancers. As a faecal marker for colorectal cancers, faecal tumour M2-pyruvate kinase has a sensitivity of 73–92% at a cut-off value of 4 U/ml as against 50% sensitivity for Guaiac faecal test. Conclusion Circulating tumour M2-pyruvate kinase is more commonly elevated in oesophageal, gastric and colorectal cancer patients than conventional tumour markers. Faecal M2-pyruvate kinase is a sensitive marker of colorectal cancer. The clinical role of tumour M2-pyruvate kinase in gastrointestinal cancer management should be investigated in large-scale clinical trials.
Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus

Abstract Background: The widespread threat of severe acute respiratory syndrome (SARS) to human life has spawned challenges to develop fast and accurate analytical methods for its early diagnosis and to create a safe antiviral vaccine for preventive use. Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Methods: We synthesized 41 peptides ranging in size from 16 to 25 amino acid residues of relatively high hydrophilicity. The immunoreactivities of the peptides with SARS patient sera were determined by ELISA. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. Notably, N371 and N385, located at the COOH terminus of the N protein, inhibited binding of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of samples from SARS study patients. N385 had the highest affinity for forming peptide-antibody complexes with SARS serum. Conclusions: Five peptides from SARS structural proteins, especially two from the COOH terminus of the N protein, appear to be highly immunogenic and may be useful for serologic assays. The identification of these antigenic peptides contributes to the understanding of the immunogenicity and persistence of SARS coronavirus.
Subcellular Localization of Dhurrin beta-Glucosidase and Hydroxynitrile Lyase in the Mesophyll Cells of Sorghum Leaf Blades.

Studies with purified mesophyll and epidermal protoplasts and bundle sheath strands have shown that the cyanogenic glucoside dhurrin (p-hydroxy-(S)-mandelonitrile-beta-d-glucoside) is localized in the epidermis of sorghum leaves whereas the enzymes involved in its degradation (dhurrin beta-glucosidase and hydroxynitrile lyase) are localized in the mesophyll tissue (Kojima M, JE Poulton, SS Thayer, EE Conn 1979 Plant Physiol 63: 1022-1028). The subcellular localization of these enzymes has now been examined using linear 30 to 55% (w/w) sucrose gradients by fractionation of mesophyll protoplast components. The hydroxynitrile lyase is found in the supernatant fractions suggesting a cytoplasmic (soluble cytoplasm, microsomal or vacuolar location). The dhurrin beta-glucosidase (dhurrinase) is particulate and mostly chloroplast-associated. The dhurrinase activity peak has a shoulder of activity more dense than that of the intact chloroplasts. This shoulder does not coincide with markers of any other cell fraction.In studies of chloroplasts isolated from ruptured mesophyll protoplasts by differential, low-speed centrifugation, the dhurrinase partitions in the same manner as the chloroplast marker triose phosphate dehydrogenase. Chloroplast localization of the beta-glucosidase has also been shown in histochemical studies using 6-bromo-2-naphthyl-beta-d-glucoside substrate coupled with fast Blue B.
Mechanisms and Timing of Deaths from Cerebral Infarction

ClinlcopatboJogic correlations were reriewed in 100 cases of recent cerebral infarctions in the internal carotid artery distribution. The most frequent cause of death was transtentorial bemlation, followed in frequency by pneumonia, cardiac causes, and pulmonary embolism. Thirty-six percent of all patients and 47% of those with transtentorial bemlation died within 48 hours of cerebral infarction. Of the treatable extracerebral causes of death determined at autopsy, only 34% were recorded premortem in the clinician's death summary. Stroke, Vol 12, No 4,1981
GENETIC STUDY: The polymorphism GABABR1 T1974C
 [rs29230] of the GABAB receptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures

As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.
Disease surveillance and waterborne outbreaks

Outbreaks are both a demonstration of a breakdown or failure in the system and, by acting as a ‘natural experiment’, present an opportunity to provide new insights into disease transmission and, perhaps, improvements to the system. This chapter outlines in detail the surveillance systems in Sweden and the US that are designed to detect waterborne disease outbreaks, and examines the actions taken upon suspecting an outbreak. It also examines some of the outbreaks that have occurred, principally from drinking water, details lessons that can be learnt from well-conducted investigations, and briefly looks at the worldwide situation.
Improving the strength performance of high volume periwinkle shell ash blended cement concrete with sodium nitrate as accelerator

The objective of this study is to examine the effect of accelerator (NaNO 3 ) on the strength properties of High volume Periwinkle shell ash blended cement concrete. A mix ratio and water-binder ratio of 1:2:4 (cement: sand: gravel) and 0.60, respectively was used as the reference. The cement was then replaced with 30% Periwinkle Shell Ash (PSA) by weight of cement. Sodium nitrate in the dosages of 1, 2, and 3% by weight of cement was added to the blended mixture of cement and PSA. The strength properties investigated were compressive and splitting tensile strength tested at 7, 14 and 28 days hydration. The results indicated that the compressive strength and the splitting tensile strength generally increases with curing age, and that sodium nitrate of up to 2% dosage greatly improved the strength performance of high volume PSA blended cement concrete over that of the reference. The study concluded that the inclusion of 2% sodium nitrate by weight of cement in the mixture could be considered the optimum dosage for the improvement of both compressive and splitting tensile strength of concrete incorporating up to 30% PSA content.