Miracle-dz/UniFAR-FTUs huggingface dataset:
Spectrum of fungal keratitis: clinicopathologic study of 44 cases.

AIM To determine the causative agents of fungal keratitis and study the predisposing factors over a period of ten years in a single tertiary care hospital. METHODS A retrospective analysis of fungal corneal ulcers was done from 2003-2012. Patients' clinical data were noted from the file records. Correlation of histopathological diagnosis was done with the report on fungal culture. RESULTS Mycotic keratitis was established in 44 cases by a positive fungal culture. Direct microscopic examination of potassium hydroxide (KOH) mounts revealed fungal elements in 39 cases while 40 cases showed fungus on Gram stained smears. Males (54.55%) were more commonly affected than the females (45.45%). The age ranged from 18 to 82 years. Most common age group to be involved was 41-60 years. Predisposing risk factors were seen in 34 (77.27%) cases. Most common findings on clinical examination were anterior chamber reaction and conjunctival injection seen in all the cases. Other common findings were stromal infiltration and hypopyon seen in 20 (45.45%) and 18 (40.91%) cases respectively. On histopathological examination the fungus was typed, as aspergillus in 34 cases while no definite typing was possible in 10 cases. The predominant isolate was aspergillus flavus (59.09%) followed by fusarium (15.91%). Mixed fungal and bacterial infection was seen in 3 (6.82%) cases. CONCLUSION Although culture is the gold standard for definitive diagnosis of fungal keratitis, direct microscopic examination of corneal scrapings or histomorphological evaluation of biopsies allow a rapid preliminary diagnosis. Early administration of antifungal treatment helps in preventing dreadful complications.
The productions of atrial natriuretic peptide and arginine vasopressin in small cell lung cancer with brain metastases and their associations with hyponatremia.

OBJECTIVE Hyponatremia is one of the most frequently encountered electrolyte disorder in small cell lung cancer (SCLC) patients. It was shown that some SCLC cell lines could produce atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). The aim of the study was to assess the secretion of ANP, AVP and their relative contributions to hyponatremia in SCLC patients, especially in patients with brain metastases. PATIENTS AND METHODS In total, 194 SCLC patients including 51 patients with brain metastases were collected. The levels of ANP and AVP were measured with radioimmunoassay kits. And then their associations with serum sodium were investigated. The progression-free survival (PFS) was compared between the hyponatremia group and the normal serum sodium group. RESULTS Serum sodium was negatively correlated with the plasma levels of ANP (r=-0.171, p=0.017) and AVP (r = -0.244, p=0.001) in all SCLC patients. In the brain metastatic subgroup, there was also a negative correlation between serum sodium and ANP (r=-0.399, p=0.004), while there was no correlation between serum sodium and AVP (r=-0.232, p=0.101). The occurrence rate of hyponatremia (serum sodium values below 135 mmol/l) in patients with brain metastases (21/51, 41.18%) was higher than that in patients without brain metastases (37/143, 25.87%) (p=0.040). The progression-free survival (PFS) in the hyponatremia group was significantly shorter than that in patients of the group without hyponatremia (p=0.010). Moreover, compared with patients which regained normal serum sodium after the treatment, the PFS of patients still with hyponatremia after the treatment was significantly shorter (p=0.049). CONCLUSIONS ANP might play a leading role in the formation of hyponatremia of SCLC patients with brain metastases. Correcting hyponatremia timely and appropriately could improve SCLC patients' prognosis.
Teaching for understanding in medical classrooms using multimedia design principles

Objectives In line with a recent report entitled Effective Use of Educational Technology in Medical Education from the Association of American Medical Colleges Institute for Improving Medical Education (AAMC‐IME), this study examined whether revising a medical lecture based on evidence‐based principles of multimedia design would lead to improved long‐term transfer and retention in Year 3 medical students. A previous study yielded positive effects on an immediate retention test, but did not investigate long‐term effects.
Sex Differences in Fluid Reasoning: Manifest and Latent Estimates from the Cognitive Abilities Test

The size and nature of sex differences in cognitive ability continues to be a source of controversy. Conflicting findings result from the selection of measures, samples, and methods used to estimate sex differences. Existing sex differences work on the Cognitive Abilities Test (CogAT) has analyzed manifest variables, leaving open questions about sex differences in latent narrow cognitive abilities and the underlying broad ability of fluid reasoning (Gf). This study attempted to address these questions. A confirmatory bifactor model was used to estimate Gf and three residual narrow ability factors (verbal, quantitative, and figural). We found that latent mean differences were larger than manifest estimates for all three narrow abilities. However, mean differences in Gf were trivial, consistent with previous research. In estimating group variances, the Gf factor showed substantially greater male variability (around 20% greater). The narrow abilities varied: verbal reasoning showed small variability differences while quantitative and figural showed substantial differences in variance (up to 60% greater). These results add precision and nuance to the study of the variability and masking hypothesis.
Aurivillius ceramics: Bi4Ti3O12-based piezoelectrics

Aurivillius oxides family has attracted great interest in the last years due to their promising electrical properties as high temperature piezoelectric materials. Piezoelectric materials that could operate in extreme conditions of use (elevated temperatures and hostile environments) could be of particular interest for different technological applications. Furthermore, increasing concerns for environmental issues have promoted the study of new lead-free piezoelectric materials. This article examines how the development of these materials has taken place from their discovery at the end of the 40's and the existing knowledge about their processing and properties.
Late admission to the ICU in patients with community-acquired pneumonia is associated with higher mortality.

BACKGROUND Limited data are available on the impact of time to ICU admission and outcomes for patients with severe community acquired pneumonia (CAP). Our objective was to examine the association of time to ICU admission and 30-day mortality in patients with severe CAP. METHODS A retrospective cohort study of 161 ICU subjects with CAP (by International Classification of Diseases, 9th edition, codes) was conducted over a 3-year period at two tertiary teaching hospitals. Timing of the ICU admission was dichotomized into early ICU admission (EICUA, direct admission or within 24 h) and late ICU admission (LICUA, >or= day 2). A multivariable analysis using Cox proportional hazard model was created with the primary outcome of 30-day mortality (dependent measure) and the American Thoracic Society (ATS) severity adjustment criteria and time to ICU admission as the independent measures. RESULTS Eighty-eight percent (n = 142) were EICUA patients compared with 12% (n = 19) LICUA patients. Groups were similar with respect to age, gender, comorbidities, clinical parameters, CAP-related process of care measures, and need for mechanical ventilation. LICUA patients had lower rates of ATS severity criteria at presentation (26.3% vs 53.5%; P = .03). LICUA patients (47.4%) had a higher 30-day mortality compared with EICUA (23.2%) patients (P = .02), which remained after adjusting in the multivariable analysis (hazard ratio 2.6; 95% CI, 1.2-5.5; P = .02). CONCLUSION Patients with severe CAP with a late ICU admission have increased 30-day mortality after adjustment for illness severity. Further research should evaluate the risk factors associated and their impact on clinical outcomes in patients admitted late to the ICU.
Investigation of the thermo hydro mechanical behaviour of large scale experiments - including parametric studies on various critical factors

This thesis presents an investigation into the thermo/hydro/mechanical interactions occurring in two large scale experiments with different geometry setup designed for deep geological disposal of nuclear waste. The analysis of flow and deformation through unsaturated soils was performed using the proposed constitutive model. The following mechanisms are accommodated moisture flow in liquid and vapour forms, dry air flow including the movement of bulk air and the transport of dissolved air in the pore water, heat transfer by conduction, convection and latent heat of vapourisation, and the elasto-plastic deformation of unsaturated soils. The governing differential equations are solved spatially using a finite element technique and temporally using a finite difference technique. The numerical model was subsequently applied to two large scale experiments: AECL's Buffer/Container Experiment and AECL's Horizontal Canister In-room geometry. The analyses involved modelling the coupled thermo/hydro/mechanical interaction between the engineered buffer and the host rock, and the swelling phenomena at the buffer/rock interface. A comprehensive set of material parameters was determined for use in the numerical code. A theoretical formulation was developed to describe a time-dependent adsorption/desorption process associated with the micro/macro swelling phenomena occurring in bentonite-based buffer materials. This was implemented within the numerical model. The transient swelling behaviour of bentonite-based buffer materials was found to be influential in the simulation of an underground repository, in particular the resaturation behaviour in expansive clay. Sensitivity analyses on critical parameters identified for both geometry setups are presented and shown to affect the resaturation processes to varying degrees. This investigation has provided valuable insights into the repositories' behaviour.
Patient‐oncologist alliance and psychosocial well‐being in Chinese society strongly affect cancer management adherence with cancer of unknown primary

Patient‐oncologist alliance and psychosocial well‐being have strong associations with adherence to cancer management. For patients with cancer of unknown primary (CUP), adherence is crucial to treatment or occult primary screening plans. There has been no study investigating the relationship between alliance, psychosocial factors, and adherence in such patients or in Chinese sociocultural settings.
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling

The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its substrates and deactivate inflammatory signaling. We found that LPS activates acetylation of MKP-1. MKP-1 is acetylated by p300 on lysine residue K57 within its substrate-binding domain. Acetylation of MKP-1 enhances its interaction with p38, thereby increasing its phosphatase activity and interrupting MAPK signaling. Inhibition of deacetylases increases MKP-1 acetylation and blocks MAPK signaling in wild-type (WT) cells; however, deacetylase inhibitors have no effect in cells lacking MKP-1. Furthermore, histone deacetylase inhibitors reduce inflammation and mortality in WT mice treated with LPS, but fail to protect MKP-1 knockout mice. Our data suggest that acetylation of MKP-1 inhibits innate immune signaling. This pathway may be an important therapeutic target in the treatment of inflammatory diseases.
Lesion Size Is Exacerbated in Hypoxic Rats Whereas Hypoxia-Inducible Factor-1 Alpha and Vascular Endothelial Growth Factor Increase in Injured Normoxic Rats: A Prospective Cohort Study of Secondary Hypoxia in Focal Traumatic Brain Injury

Background Hypoxia following traumatic brain injury (TBI) is a severe insult shown to exacerbate the pathophysiology, resulting in worse outcome. The aim of this study was to investigate the effects of a hypoxic insult in a focal TBI model by monitoring brain edema, lesion volume, serum biomarker levels, immune cell infiltration, as well as the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Materials and methods Female Sprague-Dawley rats (n = 73, including sham and naive) were used. The rats were intubated and mechanically ventilated. A controlled cortical impact device created a 3-mm deep lesion in the right parietal hemisphere. Post-injury, rats inhaled either normoxic (22% O2) or hypoxic (11% O2) mixtures for 30 min. The rats were sacrificed at 1, 3, 7, 14, and 28 days post-injury. Serum was collected for S100B measurements using ELISA. Ex vivo magnetic resonance imaging (MRI) was performed to determine lesion size and edema volume. Immunofluorescence was employed to analyze neuronal death, changes in cerebral macrophage- and neutrophil infiltration, microglia proliferation, apoptosis, complement activation (C5b9), IgG extravasation, HIF-1α, and VEGF. Results The hypoxic group had significantly increased blood levels of lactate and decreased pO2 (p < 0.0001). On MRI post-traumatic hypoxia resulted in larger lesion areas (p = 0.0173), and NeuN staining revealed greater neuronal loss (p = 0.0253). HIF-1α and VEGF expression was significantly increased in normoxic but not in hypoxic animals (p < 0.05). A trend was seen for serum levels of S100B to be higher in the hypoxic group at 1 day after trauma (p = 0.0868). No differences were observed between the groups in cytotoxic and vascular edema, IgG extravasation, neutrophils and macrophage aggregation, microglia proliferation, or C5b-9 expression. Conclusion Hypoxia following focal TBI exacerbated the lesion size and neuronal loss. Moreover, there was a tendency to higher levels of S100B in the hypoxic group early after injury, indicating a potential validity as a biomarker of injury severity. In the normoxic group, the expression of HIF-1α and VEGF was found elevated, possibly indicative of neuro-protective responses occurring in this less severely injured group. Further studies are warranted to better define the pathophysiology of post-TBI hypoxia.
Genotype–phenotype relationships in trichothiodystrophy patients with novel splicing mutations in the XPD gene

Trichothiodystrophy (TTD) is a rare, autosomal recessive neurodevelopmental disorder most commonly caused by mutations in ERCC2 (XPD), a gene that encodes a subunit of the transcription/repair factor IIH (TFIIH). Here, we describe two TTD cases in which detailed biochemical and molecular investigations offered a clue to explain their moderately affected phenotype. Patient TTD22PV showed new mutated XPD alleles: one contains a nonsense mutation (c.1984C>T) encoding a nonfunctional truncated product (p.Gln662X) whereas the second carries a genomic deletion (c.2191‐18_c.2213del) that affects the splicing of intron 22 and generates multiple out‐of‐frame transcripts from codon 731. XPD mRNA from the second allele corresponds to 20% of the total. The predicted proteins, which are longer than normal, affect the cellular repair activity but only partially interfere with TFIIH stability, suggesting that the observed changes in the C‐ter region of XPD cause minor structural changes that do not drastically compromise the transcriptional activity of TFIIH. Patient TTD24PV was compound heterozygous for a typical TTD allele (c.2164C>T, p.Arg722Trp) and for a new XPD allele with a mutation that partially affects intron 10 splicing, resulting in both mutated and normal XPD transcripts (that together represent 15% of the total XPD mRNA). Compared to the previously described TTD compound heterozygotes for the Arg722Trp change, Patient TTD24PV's cells show similar level of TFIIH but increased repair activity, suggesting that even low amounts of normal XPD subunits are able to partially rescue the functionality of TFIIH complexes. Hum Mutat 0, 1–8, 2008. © 2008 Wiley‐Liss, Inc.
Adverse events associated with mTOR inhibitors

Introduction: The mTOR (mechanistic target of rapamycin, formerly known as mammalian target of rapamycin) kinase is centrally involved in the regulation of cell growth and metabolism in response to intra- and extracellular energetic stimuli and growth factors. The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 (FK-BP12) to inhibit mTOR complex 1 (MTORC1) activity in an allosteric manner, or the more recent ATP-competitive mTOR inhibitors (mTORi), which target the catalytic site of the enzyme. However, clinical development of these mTORi has revealed that these drugs produced numerous side effects that could be serious and/or debilitating. Despite pharmacological efforts to develop drugs with an improved safety profile, these side effects are often unpredictable and may frequently preclude the efficiency of mTORi. Areas covered: The objective of this review is to perform a comprehensive survey of the safety profiles of various rapalog-based therapies from the available clinical literature. The authors will discuss the potential mechanisms of these therapies, taking into account the knowledge of the biological pathways regulated by mTOR. Expert opinion: A better prevention and management of mTORi-related side effects requires the identification of alterations in related biological pathways that will help to delineate therapeutic targets.
Extensive Cross-Contamination of Specimens withMycobacterium tuberculosis in a Reference Laboratory

ABSTRACT A striking increase in the numbers of cultures positive forMycobacterium tuberculosis was noticed in a mycobacterial reference laboratory in Campinas, Sao Paulo State, Brazil, in May 1995. A contaminated bronchoscope was the suspected cause of the increase. All 91 M. tuberculosis isolates grown from samples from patients between 8 May and 18 July 1995 were characterized by spoligotyping and IS6110 fingerprinting. Sixty-one of the 91 isolates had identical spoligotype patterns, and the pattern was arbitrarily designated S36. The 61 specimens containing these isolates had been processed and cultured in a 21-day period ending on 1 June 1995, but only 1 sample was smear positive for acid-fast bacilli. The patient from whom this sample was obtained was considered to be the index case patient and had a 4+ smear-positive lymph node aspirate that had been sent to the laboratory on 10 May. Virtually all organisms with spoligotype S36 had the same IS6110 fingerprint pattern. Extensive review of the patients’ charts and investigation of laboratory procedures revealed that cross-contamination of specimens had occurred. Because the same strain was grown from all types of specimens, the bronchoscope was ruled out as the outbreak source. The most likely source of contamination was a multiple-use reagent used for specimen processing. The organism was cultured from two of the solutions 3 weeks after mock contamination. This investigation strongly supports the idea that M. tuberculosis grown from smear-negative specimens should be analyzed by rapid and reliable strain differentiation techniques, such as spoligotyping, to help rule out laboratory contamination.
Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies

The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design.
Tunable Fiber Laser Using a MEMS-Based in Plane Fabry-Pérot Filter

We propose a tunable erbium doped fiber laser based on a Fabry-Pérot (F-P) cavity tuned by an electrostatic actuator. The device is made of single crystalline silicon. The F-P cavity consists of two Bragg mirrors, one being displaced by a comb-drives actuator. The F-P cavity, grooves for optical fibers and electro-mechanical structure are fabricated by deep reactive ion etching on a 70 μm silicon on insulator wafer and are integrated in a ring fiber laser. The resulting tunable fiber laser has a tuning range of 35 nm in the C-band and a spectral width of less than 0.06 nm. The maximum applied voltage for full tuning of the laser is 37 V. The mechanical resonance frequency of the actuated mirror is 14.4 kHz allowing fast tuning of the laser. The maximum output power is 1.8 mW.
Individual variation and the endocrine regulation of behaviour and physiology in birds: a cellular/molecular perspective

Investigations of the cellular and molecular mechanisms of physiology and behaviour have generally avoided attempts to explain individual differences. The goal has rather been to discover general processes. However, understanding the causes of individual variation in many phenomena of interest to avian eco-physiologists will require a consideration of such mechanisms. For example, in birds, changes in plasma concentrations of steroid hormones are important in the activation of social behaviours related to reproduction and aggression. Attempts to explain individual variation in these behaviours as a function of variation in plasma hormone concentrations have generally failed. Cellular variables related to the effectiveness of steroid hormone have been useful in some cases. Steroid hormone target sensitivity can be affected by variables such as metabolizing enzyme activity, hormone receptor expression as well as receptor cofactor expression. At present, no general theory has emerged that might provide a clear guidance when trying to explain individual variability in birds or in any other group of vertebrates. One strategy is to learn from studies of large units of intraspecific variation such as population or sex differences to provide ideas about variables that might be important in explaining individual variation. This approach along with the use of newly developed molecular genetic tools represents a promising avenue for avian eco-physiologists to pursue.