Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical characterization of pentamidine isethionate during freeze-drying-relevance to development of stable lyophilized product.

The purpose of this study was to perform physical characterization of pentamidine isethionate (PI) in frozen and freeze-dried systems and to monitor the phase behavior during all the stages of freeze-drying. Frozen aqueous PI solutions as well as the final lyophiles were characterized by differential scanning calorimetry and X-ray diffractometry. The effect of cosolutes, cosolvents, and processing conditions on the PI crystallization behavior during freeze-drying was evaluated. In frozen aqueous solutions, irrespective of the cooling rate and the initial solute concentration, PI readily crystallized as a trihydrate (C(19) H(24) N(4) O(2) ·3H(2) O). It dehydrated to a poorly crystalline anhydrate upon drying at 100 mTorr. The presence of a readily crystallizing cosolute or an organic cosolvent did not influence the physical form of PI in the final lyophile. On the contrary, even in the absence of cosolutes and cosolvents, the crystalline trihydrate was retained when the chamber pressure was increased to 500 mTorr. By altering the drying conditions, it was possible to obtain either a crystalline trihydrate or a poorly crystalline anhydrate. The stability of PI is dependent on its physical form and only the amorphous PI undergoes discoloration. The PI stability can be enhanced by retaining it in a crystalline state in the lyophile.
Human exposure to high natural background radiation: what can it teach us about radiation risks?

Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.
Phytic acid in green leaves.

Phytic acid or phytate, the free-acid form of myo-inositolhexakiphosphate, is abundant in many seeds and fruits, where it represents the major storage form of phosphorus. Although also known from other plant tissues, available reports on the occurrence of phytic acid, e.g. in leaves, have never been compiled, nor have they been critically reviewed. We found 45 published studies with information on phytic acid content in leaves. Phytic acid was almost always detected when studies specifically tried to detect it, and accounted for up to 98% of total P. However, we argue that such extreme values, which rival findings from storage organs, are dubious and probably result from measurement errors. Excluding these high values from further quantitative analysis, foliar phytic acid-P averaged 2.3 mg·g(-1) , and represented, on average, 7.6% of total P. Remarkably, the ratio of phytic acid-P to total P did not increase with total P, we even detected a negative correlation of the two variables within one species, Manihot esculenta. This enigmatic finding warrants further attention.
High Cholesterol, Triglycerides, and Body-Mass Index in Suicide Attempters

ABSTRACT Low cholesterol concentrations and cholesterol-lowering therapies have been suggested to be associated with increased suicidality. This article examined the association of cholesterol, triglycerides, and body-mass index (BMI) with suicidal ideation and suicide attempts. Findings are based on a nationally representative community sample of n = 4,181 subjects (18–65 years) examined with a standardized diagnostic interview (CIDI) for (DSM-IV) mental disorders. Controlling for age and gender the study revealed a moderate positive association between cholesterol, triglycerides, BMI, and suicide attempts in subjects with depressive symptoms during the past 12 months (n = 1,205). The results of this study are compatible with two recent epidemiological cohort studies showing a positive association between cholesterol and completed suicide.
Who are more at risk for acute mountain sickness: a prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula.

BACKGROUND It is important to determine the incidence of acute mountain sickness (AMS) among workers at altitudes between 3500 m and 5000 m on Mt. Tanggula during the construction of the Qinghai-Tibet railroad. This study explored the risk factors predisposing workers to developing AMS and attempted to develop more effective ways of preventing and treating AMS. METHODS A total of 11,182 workers were surveyed by completing twice daily a Lake Louise questionnaire, and a score ≥ 3 indicated AMS. The contributing risk factors were assessed for at least 2 months for the duration of the study in the years from 2001 to 2003. A risk model was developed by multiple Logistic regression. Standard statistical methods were used to analyze data. RESULTS AMS occurred in 56% of workers working at high altitudes on Mt. Tanggula. The incidence of AMS increased with increasing altitude. Rapid ascent to an altitude above 3500 m, sea-level or lowland newcomers, young people under 25 years of age, heavy physical exertion, obese person, and arterial oxygen saturation (SaO2) below 80% were independent AMS risk factors. No significant association was found between AMS and sex or taking Rhodiola. Medical education contributed to an early diagnosis of AMS. CONCLUSIONS This study used the Lake Louise scoring system suggesting that it is a well-validated standard for field evaluation of AMS and for making an early diagnosis. These studies have described many variables regarding risk factors for the development of AMS. Risk factors which can be modified should be attended to, and the physicians should carry out check-ups and tests to identify subjects who are more at risk. Prevention consists in continuous gradual ascent, medical education, and prompt descent to avoid progression in patients with serious AMS. It is most important to effectively control the risk factors of AMS.
Smooth pursuit of small-amplitude sinusoidal motion.

Subjects used smooth eye movements to track small-amplitude sinusoidal target motions. Target frequencies (0.05 to 5 Hz) and amplitudes (1.9 to 30 min of arc) were in the range of those found in the retinal image during fixation of a stationary target while the head is not artificially supported. Smooth pursuit was poor at high target frequencies in several ways: Large uncompensated drifts were observed for target frequencies between 1 and 4 Hz. The drifts were superimposed upon oscillations of the eye in response to the target motion. Mean retinal-image speeds were higher than retinal-image speeds during slow control (smooth eye movements with stationary targets) for target frequencies above 0.5 Hz. Mean retinal-image speeds were as high as target speed for target frequencies above 3 Hz. The ratio of eye speed to target speed decreased as target frequency and amplitude increased. The dependence on amplitude could be reduced and often eliminated by computing an adjusted ratio in which a constant (approximately equal to the mean speed of slow control) was subtracted from eye speed before dividing by target speed. Adjusted ratios declined for frequencies above 0.5 to 1 Hz and did not depend on amplitude. These results show that the response of the smooth-pursuit subsystem to target motion above 0.5 Hz is poor, even though the velocity and the acceleration of th motions are low. Models of smooth pursuit in which the response of the eye depends exclusively on the velocity, acceleration, or position of the target do not account for our results. (ABSTRACT TRUNCATED AT 250 WORDS)
Performance comparison of Single Carrier Modulation with frequency domain equalization an OFDM for wireless communications

Orthogonal Frequency Division Multiplexing (OFDM) has the inherent problem of high peak to average power ratio (PAPR). Moreover, it suffers from high sensitivity to frequency offsets and narrowband interference (NBI). Contrary to this, Single Carrier Modulation (SCM) offers smaller PAPR and reduced sensitivity to NBI. However, it requires an efficient channel equalization technique. In literature, frequency domain channel equalization has been proposed for SCM systems in wireless communications. It also possesses the advantage of lower complexity in signal processing, as in the case of OFDM. This paper presents performance comparison between OFDM and SCM with frequency domain equalization for multipath wireless channel. SCM utilizes minimum mean square error (MMSE) algorithm for the training of the frequency domain equalizer. It is shown that SCM employing a frequency domain MMSE equalizer has a better bit error rate (BER) performance than OFDM. Also, the performance comparison of SCM and OFDM systems in the presence of NBI over additive white gaussian noise (AWGN) link shows that SCM is less sensitive to NBI.
Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031.

BACKGROUND The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. PATIENTS AND METHODS Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m(2)/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m(2)/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. RESULTS Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months (95% CI 23.4-34.1 months), respectively. CONCLUSIONS Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects.
Training Auditory‐Visual Speech Reception in Adults with Moderate Sensorineural Hearing Loss

A new method of training auditory-visual speech reception is described and evaluated on an experimental group of 12 hearing-impaired adult patients. The method involves simultaneous, live presentation of the visible and acoustic components of the therapist's speech, where the acoustic signal is degraded under the therapist's control with a voice-activated switch. Pre-and post-training performance was assessed with an auditory-visual sentence recognition task. The performance of the experimental group, who received 10 hours of individual training, is described and compared to a control group who received a traditional aural rehabilitation program and to a group of normals who received no training. The experimental training resulted in significantly greater improvement than the control group. A description of the training, including rationale and suggestions for implementation in a clinical setting, is provided.
Emergence of drug-resistant pneumococcal infections in the United States.

OBJECTIVE To estimate drug susceptibility patterns of Streptococcus pneumoniae in selected hospitals in the United States and to characterize the epidemiology of invasive drug-resistant pneumococcal infections. DESIGN Minimum inhibitory concentrations (MICs) for a variety of commonly used antimicrobial drugs were determined for pneumococcal isolates submitted to the Centers for Disease Control and Prevention (CDC). Risk factors for drug-resistant pneumococcal infection were evaluated. SETTING Hospital laboratories in the United States submitting pneumococcal isolates to the CDC between October 1, 1991, and September 30, 1992. PARTICIPANTS A total of 544 persons with pneumococci isolated from normally sterile sites. RESULTS A total of 13 hospitals in 12 states actively participated in an ongoing pneumococcal surveillance study. Resistance to penicillin was detected in 6.6% of isolates, including 1.3% of isolates with MICs of 2.0 micrograms/mL or more (compared with < 0.02% of isolates with MIC > or = 2.0 micrograms/mL identified by CDC surveillance from 1979 to 1987). A total of 16.4% were resistant to at least one of the following drugs or drug classes: penicillin, cephalosporins, macrolides, combination trimethoprim and sulfamethoxazole, and chloramphenicol. Six serotypes (6B, 23F, 14, 9V, 19A, and 19F) accounted for nearly 85% of strains resistant to at least one drug class. Children were more likely than adults to be infected with strains resistant to trimethoprim-sulfamethoxazole, erythromycin, or chloramphenicol. CONCLUSIONS Emergence of drug-resistant pneumococcal infections will present critical challenges to clinicians for treating patients with pneumococcal disease. Widened and intensified surveillance is needed. These data suggest that current recommendations for use of 23-valent pneumococcal capsular polysaccharide vaccines should be aggressively promoted and that development and evaluation of new conjugate pneumococcal vaccines may be a crucial part of strategies for prevention.
Intention‐to‐Treat Analysis of Liver Transplantation in Selected, Aggressively Treated HCC Patients Exceeding the Milan Criteria

This prospective study analyzed the dropout probability and intention‐to‐treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi‐modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention‐to‐treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16‐month follow‐up (0–69 months). In conclusion, LT may be effective for selected, aggressively‐treated HCC patients exceeding the Milan criteria.
l-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin*

Ascorbic acid has been shown to stimulate endothelial nitric oxide (NO) synthesis in a time- and concentration-dependent fashion without affecting NO synthase (NOS) expression or l-arginine uptake. The present study investigates if the underlying mechanism is related to the NOS cofactor tetrahydrobiopterin. Pretreatment of human umbilical vein endothelial cells with ascorbate (1 μm to 1 mm, 24 h) led to an up to 3-fold increase of intracellular tetrahydrobiopterin levels that was concentration-dependent and saturable at 100 μm. Accordingly, the effect of ascorbic acid on Ca2+-dependent formation of citrulline (co-product of NO) and cGMP (product of the NO-activated soluble guanylate cyclase) was abolished when intracellular tetrahydrobiopterin levels were increased by coincubation of endothelial cells with sepiapterin (0.001–100 μm, 24 h). In contrast, ascorbic acid did not modify the pterin affinity of endothelial NOS, which was measured in assays with purified tetrahydrobiopterin-free enzyme. The ascorbate-induced increase of endothelial tetrahydrobiopterin was not due to an enhanced synthesis of the compound. Neither the mRNA expression of the rate-limiting enzyme in tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I, nor the activities of either GTP cyclohydrolase I or 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the de novo synthesis pathway, were altered by ascorbate. Our data demonstrate that ascorbic acid leads to a chemical stabilization of tetrahydrobiopterin. This was evident as an increase in the half-life of tetrahydrobiopterin in aqueous solution. Furthermore, the increase of tetrahydrobiopterin levels in intact endothelial cells coincubated with cytokines and ascorbate was associated with a decrease of more oxidized biopterin derivatives (7,8-dihydrobiopterin and biopterin) in cells and cell supernatants. The present study suggests that saturated ascorbic acid levels in endothelial cells are necessary to protect tetrahydrobiopterin from oxidation and to provide optimal conditions for cellular NO synthesis.
The R2R3‐MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple

Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate-metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple.
A novel, cleavable peroxisomal targeting signal at the amino‐terminus of the rat 3‐ketoacyl‐CoA thiolase.

Several peroxisomal proteins do not contain the previously identified tripeptide peroxisomal targeting signal (PTS) at their carboxy‐termini. One such protein is the peroxisomal 3‐ketoacyl CoA thiolase, of which two types exist in rat [Hijikata et al. (1990) J. Biol. Chem., 265, 4600–4606]. Both rat peroxisomal thiolases are synthesized as larger precursors with an amino‐terminal prepiece of either 36 (type A) or 26 (type B) amino acids, that is cleaved upon translocation of the enzyme into the peroxisome. The prepieces are necessary for import of the thiolases into peroxisomes because expression of an altered cDNA encoding only the mature thiolase, which lacks any prepiece, results in synthesis of a cytosolic enzyme. When appended to an otherwise cytosolic passenger protein, the bacterial chloramphenicol acetyltransferase (CAT), the prepieces direct the fusion proteins into peroxisomes, demonstrating that they encode sufficient information to act as peroxisomal targeting signals. Deletion analysis of the thiolase B prepiece shows that the first 11 amino acids are sufficient for peroxisomal targeting. We conclude that we have identified a novel PTS that functions at amino‐terminal or internal locations and is distinct from the C‐terminal PTS. These results imply the existence of two different routes for targeting proteins into the peroxisomal matrix.
Nomograms for Pre- and Postoperative Prediction of Long-term Survival for Patients Who Underwent Hepatectomy for Multiple Hepatocellular Carcinomas

Objectives:To develop prognostic nomograms for patients undergoing hepatectomy for multiple hepatocellular carcinomas (mHCCs). Background:The prognostic prediction after hepatectomy for mHCCs has not been well established. Methods:A training cohort (n = 540) was analyzed to construct 2 nomograms based separately on data obtained before and after hepatectomy for mHCCs at the Eastern Hepatobiliary Surgery Hospital between 2000 and 2006. The internal and external validations were performed in 2 independent cohorts (n = 180 each) collected from the Eastern Hepatobiliary Surgery Hospital between 2007 and 2010 and the Sun Yat-Sen University between 2000 and 2007. The predictive accuracy was measured by concordance index (C-index) and calibration curve. Results:Serum &agr;-fetoprotein level, hepatitis B virus deoxyribonucleic acid load, end-stage liver disease score, tumor number, total tumor diameter, and the ratio of largest to smallest tumor diameter were incorporated into the preoperative nomogram for overall survival (OS) prediction. In addition to these variables, microvascular invasion, tumor capsule, type of hepatectomy, and local invasion/metastasis were incorporated into the postoperative nomogram. All calibration curves for probability of OS fitted well. In the training cohort, the preoperative nomogram achieved a C-index of 0.75 (95% confidence interval, 0.72–0.78) in predicting OS and accurately stratified patients into 4 prognostic subgroups (5-year OS rates: 65.9%, 46.3%, 29.6%, and 4.1%, P < 0.001). The postoperative nomogram had a C-index of 0.80, which was higher than those of the 4 conventional staging systems (0.53–0.62). These results were supported by the internal and external validations. Conclusions:The 2 nomograms showed accurate pre- and postoperative prediction of posthepatectomy prognosis in patients with mHCCs.