Miracle-dz/UniFAR-FTUs huggingface dataset:
Descemet Membrane Endothelial Keratoplasty Donor Preparation: Navigating Challenges and Improving Efficiency

Purpose: The aim of this study was to describe the challenges in Descemet membrane endothelial keratoplasty (DMEK) donor preparations and provide new strategies to achieve success. Methods: A series of 263 consecutive DMEK preparation attempts by a novice surgeon during a corneal fellowship are described. In all cases, the Descemet membrane (DM) and the endothelium were peeled off from the donor cornea while it was submerged in corneal storage medium. Results: The success rate of preparing DMEK tissue was 99%. Three donor preparations of 263 (1.1%) could not be completed successfully because spots of strong adherence between the DM and the stroma caused multiple horseshoe-shaped tears (HST) to form in the DM. Lamellar splitting of the DM (“partial thickness HST”) preceded the formation of most HSTs. At least 1 HST occurred in 13% of donor preparations. In donor pairs (right and left corneas of 1 individual donor), if 1 cornea had any HSTs, there was a 60% chance that the contralateral cornea would have at least 1 HST. If 1 cornea had multiple HSTs, there was an 80% chance that the contralateral cornea would have at least 1 HST. Noting this trend, 3 donor corneas were returned to the eye bank unopened for other uses after their mates had multiple HSTs. Conclusions: With appropriate techniques, DMEK donor preparation can be highly successful, even for a novice surgeon. When a donor develops multiple HSTs, we recommend not using the mate for DMEK because of a higher risk of encountering a preparation difficulty.
Pre-hypertension as a significant predictor of chronic kidney disease in a general population: the Ohasama Study.

BACKGROUND Hypertension is associated with an increased risk of development of chronic kidney disease (CKD). However, it is unclear whether pre-hypertension is related to the incidence of CKD. METHODS The incidence of CKD defined as positive proteinuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) was examined in 2150 inhabitants without pre-existing CKD from the general Japanese population. The association of blood pressure and CKD incidence was examined using a Cox regression model adjusted for age, sex, habitual smoking and drinking, obesity, history of cardiovascular disease, diabetes mellitus or hypercholesterolemia, eGFR at baseline, number of follow-up examinations and year of baseline examination. Participants were categorized according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. RESULTS Participants were categorized into normotension (n = 586, 27.3 % ), pre-hypertension (n = 815, 37.9 % ), Stage 1 hypertension (n = 386, 18.0 % ) and Stage 2 hypertension (n = 363, 16.9 % ). During a mean follow-up of 6.5 years (14 023 person-years), 461 incidences of CKD were recorded. Compared to normotension, adjusted hazard ratios of CKD were significantly higher for pre-hypertension (1.49, P < 0.003), Stage 1 (1.83, P < 0.001) and Stage 2 (2.55, P < 0.001) hypertension. The population-attributable fraction of pre-hypertension (12.1 % ) was considered to be compatible to that of Stage 1 (8.6 % ) and Stage 2 (14.9 % ) hypertension. CONCLUSION This was the first study to demonstrate that pre-hypertension was significantly associated with an increased risk of CKD and was one of the considerable causes of CKD in the general population.
AURKA F31I Polymorphism and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Consortium of Investigators of Modifiers of BRCA1/2 Study

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1416–21)
Computation of liquid-liquid equilibria and phase stabilities: implications for RH-dependent gas/particle partitioning of organic-inorganic aerosols

Abstract. Semivolatile organic and inorganic aerosol species partition between the gas and aerosol particle phases to maintain thermodynamic equilibrium. Liquid-liquid phase separation into an organic-rich and an aqueous electrolyte phase can occur in the aerosol as a result of the salting-out effect. Such liquid-liquid equilibria (LLE) affect the gas/particle partitioning of the different semivolatile compounds and might significantly alter both particle mass and composition as compared to a one-phase particle. We present a new liquid-liquid equilibrium and gas/particle partitioning model, using as a basis the group-contribution model AIOMFAC (Zuend et al., 2008). This model allows the reliable computation of the liquid-liquid coexistence curve (binodal), corresponding tie-lines, the limit of stability/metastability (spinodal), and further thermodynamic properties of multicomponent systems. Calculations for ternary and multicomponent alcohol/polyol-water-salt mixtures suggest that LLE are a prevalent feature of organic-inorganic aerosol systems. A six-component polyol-water-ammonium sulphate system is used to simulate effects of relative humidity (RH) and the presence of liquid-liquid phase separation on the gas/particle partitioning. RH, salt concentration, and hydrophilicity (water-solubility) are identified as key features in defining the region of a miscibility gap and govern the extent to which compound partitioning is affected by changes in RH. The model predicts that liquid-liquid phase separation can lead to either an increase or decrease in total particulate mass, depending on the overall composition of a system and the particle water content, which is related to the hydrophilicity of the different organic and inorganic compounds. Neglecting non-ideality and liquid-liquid phase separations by assuming an ideal mixture leads to an overestimation of the total particulate mass by up to 30% for the composition and RH range considered in the six-component system simulation. For simplified partitioning parametrizations, we suggest a modified definition of the effective saturation concentration, Cj*, by including water and other inorganics in the absorbing phase. Such a Cj* definition reduces the RH-dependency of the gas/particle partitioning of semivolatile organics in organic-inorganic aerosols by an order of magnitude as compared to the currently accepted definition, which considers the organic species only.
Methylenetetrahydrofolate Reductase 677CT Polymorphism and Cobalamin, Folate, and Homocysteine Status in Spanish Adolescents

Background: Folate and cobalamin are responsible for healthy growth. However, the B-vitamin and homocysteine status of adolescents is not well known. The aim was to assess the status of folate, cobalamin, and homocysteine in healthy Spanish adolescents. Methods: Serum cobalamin, serum folate, homocysteine, methylenetetrahydrofolate reductase 677C>T variant, BMI, smoking habits, and Tanner stage were determined according to gender in 165 adolescents (84 females, 81 males; 13–18.5 years) using the Student’s t test, Mann-Whitney U test and χ2 test, respectively. Interactions between socioeconomic status, age group, methylenetetrahydrofolate reductase polymorphism, BMI, smoking habits, Tanner stage, and vitamin status, respectively, were examined by ANOVA or Kruskal-Wallis H test (p < 0.05). Results: Boys had markedly higher homocysteine (males 8.92 (5.51–22.94) µmol/l; females 7.91 (5.09–13.86) µmol/l), whereas girls showed higher serum cobalamin concentrations (males 540.00 (268.00–946.47) pmol/l; females 594.82 (280.63–1,559.64) pmol/l). Data are shown as medians and the 2.5th to 97.5th percentiles in parentheses. Adolescents with the homozygous variant of methylenetetrahydrofolate reductase displayed significantly higher homocysteine and lower serum folate: normal 5.73 (3.09–10.73) ng/ml serum folate, 7.57 (4.94–12.94) µmol/l homocysteine; homozygous 4.10 (2.75–7.88) ng/ml serum folate, 10.83 (7.00–22.82) µmol/l homocysteine. Conclusion: The present study provides data on the folate, cobalamin, and homocysteine status of Spanish adolescents. To assure a better assessment, revision of references for adolescents is still needed.
Determination of mangiferin in rat eyes and pharmacokinetic study in plasma after oral administration of mangiferin-hydroxypropyl-beta-cyclodextrin inclusion.

PURPOSE To determine whether mangiferin can enter the eye, because the eye possesses the unique blood-ocular barrier. METHODS Due to the low solubility of mangiferin, hydroxypropyl-beta-cyclodextrin was applied to improve the absorbance. A reversed-phase high-performance liquid chromatography assay for mangiferin in rat plasma and eye fluid was developed. The mobile phase consisted of methanol-0.6% glacial acetic acid (27:73, v/v) at a flow rate of 1.0 mL/min. RESULTS Peak areas of mangiferin were linear over a concentration range of 0.40-20.00 microg/mL in blood samples and a range of 0.10-5.00 microg/mL in eye samples, respectively. Intra- and interassay precision and accuracy of mangiferin fell well within the predefined limits of acceptability (<15%). The recovery was 81.12%-87.18% in the plasma and 79.96%-85.52% in the eye, respectively. The analytical method had excellent sensitivity using a small sample volume (20 microL) with the lower limit of quantification, 0.4 and 0.10 microg/mL for plasma and eye, respectively. Pharmacokinetic parameters of mangiferin in plasma were obtained as follows: T(max) = 7 h, C(max) = (4.43 +/- 0.62)microg/mL. The time point of 7 h was chosen for eye sample detection, as it had maximum plasma concentration. The concentration of mangiferin in the eye tissue 7 h after oral administration was (0.34 +/- 0.13)microg/mL (n = 6), coefficient of variation % = 38.24%. CONCLUSIONS Mangiferin can pass the blood-ocular barrier and is suitable to be used as an antioxidant in eye diseases.
Clinical study concerning the relationship between community-acquired pneumonia and viral infection in northern Thailand.

OBJECTIVE The etiological agents associated with community-acquired pneumonia (CAP) in Thailand have been studied extensively in bacterial pathogens, but not in viral pathogens. To clarify the association of viral pathogens with CAP, we conducted a comprehensive study of viral and bacterial pathogens in patients with CAP. METHODS We enrolled 119 hospitalized patients with CAP in Nakornping Hospital, Chiang Mai, Thailand between 2006 and 2008. The severity of pneumonia was classified and the risk factors for death were estimated. Bacterial and fungal pathogens were determined from specimens taken from blood and sputum, and viral pathogens were identified from nasopharyngeal specimens by RT-PCR using primers specific for 7 respiratory viruses. RESULTS Overall, 29 patients were HIV-infected and 90 patients were non-HIV-infected. The microbial pathogens most commonly isolated among HIV-infected patients were: 4 Klebsiella pneumoniae, 4 Mycobacterium tuberculosis and 3 Haemophilus influenzae. Among non-HIV infected patients, predominant microbial pathogens were: 6 Pseudomonas aeruginosa, 5 Haemophilus influenzae and 4 Klebsiella pneumoniae. As for viral pathogens for CAP, influenza virus was identified from 2 HIV-infected patients and 5 non-HIV infected patients. In addition, human rhinovirus (HRV) and respiratory syncytial virus (RSV) were identified from 2 patients each among non-HIV-infected patients. CONCLUSION Our study demonstrates that the most common viral agent was influenza virus (5%), followed by HRV (2%) and RSV (2%) among CAP patients in northern Thailand. The underlying chronic obstructive pulmonary disease (COPD) seems to be correlated with the severity of illness.
S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism.

AIM To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosyl-methionine (AdoMet). METHODS Primary hepatocyte cultures were pretreated with 100 micromol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by Ellman's method and reactive oxygen species (ROS) generation by cell cytometry. RESULTS The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decrease in ethanol-induced apoptosis (P< 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity, and prevented cytochrome c release and pro-caspase 3 cleavage. CONCLUSION The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.
A selective review of the first 20 years of instrumental variables models in health-services research and medicine

Abstract Background: The method of instrumental variables (IV) is useful for estimating causal effects. Intuitively, it exploits exogenous variation in the treatment, sometimes called natural experiments or instruments. This study reviews the literature in health-services research and medical research that applies the method of instrumental variables, documents trends in its use, and offers examples of various types of instruments. Methods: A literature search of the PubMed and EconLit research databases for English-language journal articles published after 1990 yielded a total of 522 original research articles. Citations counts for each article were derived from the Web of Science. A selective review was conducted, with articles prioritized based on number of citations, validity and power of the instrument, and type of instrument. Results: The average annual number of papers in health services research and medical research that apply the method of instrumental variables rose from 1.2 in 1991–1995 to 41.8 in 2006–2010. Commonly-used instruments (natural experiments) in health and medicine are relative distance to a medical care provider offering the treatment and the medical care provider’s historic tendency to administer the treatment. Less common but still noteworthy instruments include randomization of treatment for reasons other than research, randomized encouragement to undertake the treatment, day of week of admission as an instrument for waiting time for surgery, and genes as an instrument for whether the respondent has a heritable condition. Conclusion: The use of the method of IV has increased dramatically in the past 20 years, and a wide range of instruments have been used. Applications of the method of IV have in several cases upended conventional wisdom that was based on correlations and led to important insights about health and healthcare. Future research should pursue new applications of existing instruments and search for new instruments that are powerful and valid.
The Yeast Hsp110 Family Member, Sse1, Is an Hsp90 Cochaperone*

In eukaryotes, production of the diverse repertoire of molecular chaperones during normal growth and in response to stress is governed by the heat shock transcription factor HSF. TheHSC82 and HSP82 genes, encoding isoforms of the yeast Hsp90 molecular chaperone, were recently identified as targets of the HSF carboxyl-terminal activation domain (CTA), whose expression is required for cell cycle progression during prolonged heat stress conditions. In the present study, we have identified additional target genes of the HSF CTA, which include nearly all of the heat shock-inducible members of the Hsp90 chaperone complex, demonstrating coordinate regulation of these components by HSF. Heat shock induction of SSE1, encoding a member of the Hsp110 family of heat shock proteins, was also dependent on the HSF CTA. Disruption ofSSE1 along with STI1, encoding an established subunit of the Hsp90 chaperone complex, resulted in a severe synthetic growth phenotype. Sse1 associated with partially purified Hsp90 complexes and deletion of the SSE1 gene rendered cells susceptible to the Hsp90 inhibitors macbecin and geldanamycin, suggesting functional interaction between Sse1 and Hsp90. Sse1 is required for function of the glucocorticoid receptor, a model substrate of the Hsp90 chaperone machinery, and Hsp90-based repression of HSF under nonstress conditions. Taken together, these data establish Sse1 as an integral new component of the Hsp90 chaperone complex in yeast.
A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group.

BACKGROUND Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.
Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation–induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation–induced systolic blood pressure increase was blunted in the main renal arteries (&Dgr; systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (&Dgr; systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability.
A CMOS 45 GHz power amplifier with output power > 600 mW using spatial power combining

A single-chip 45 GHz power amplifier implemented in 45nm CMOS SOI is described, which feeds its RF output power to a 2×2 antenna array on an accompanying printed circuit board. The chip results in a maximum RF output power of 28 dBm (630 mW), and the system achieves a peak equivalent isotropic radiated power (EIRP) of 10 Watts (for a 2×2 antenna gain of 12 dB). The power amplifier is composed of 4 unit amplifier cells, each of which has pseudo-differential outputs. Stacking of 4 transistors was used in order to increase allowable voltage swings. The overall chip dimensions are 4.5 × 2.5 mm2. The DC power consumption was 4.9 W from 5.5 V and 4.0 V supplies, corresponding to a power-added efficiency of 13.5%.