Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxorubicin in patients with advanced malignancy.

PURPOSE Our intention was to (a) to investigate the safety and tolerability of a potent P-glycoprotein modulator, zosuquidar trihydrochloride (LY335979), when administered i.v. alone or in combination with doxorubicin, (b) to determine the pharmacokinetics of zosuquidar and correlate exposure to inhibition of P-glycoprotein function in a surrogate assay, and (c) to compare the pharmacokinetics of doxorubicin in the presence and absence of zosuquidar. PATIENTS AND METHODS Patients with advanced malignancies who provided written informed consent received zosuquidar and doxorubicin administered separately during the first cycle of therapy and then concurrently in subsequent cycles. Zosuquidar was given i.v. over 48 h in a cohort-dose escalation manner until the occurrence of dose-limiting toxicity or protocol specified maximum exposure. Doxorubicin doses of 45, 60, 75 mg/m(2) were administered during the course of the trial. RESULTS Dose escalation proceeded through 9 cohorts with a total of 40 patients. The maximal doses administered were 640 mg/m(2) of zosuquidar and 75 mg/m(2) of doxorubicin. No dose-limiting toxicity of zosuquidar was observed. Pharmacokinetic analysis revealed that, in the presence of zosuquidar at doses that exceeded 500 mg, there was a modest decrease in clearance (17-22%) and modest increase in area under the curve (15-25%) of doxorubicin. This change was associated with an enhanced leukopenia and thrombocytopenia but was without demonstrable clinical significance. The higher doses of zosuquidar were associated with maximal P-glycoprotein inhibition in natural killer cells. CONCLUSION Zosuquidar can be safely coadministered with doxorubicin using a 48 h i.v. dosing schedule.
Differences in Antipsychotic-Related Adverse Events in Adult, Pediatric, and Geriatric Populations

In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the “off-label” use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age < 18), and geriatric (> 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10-6). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both the numbers and types of adverse events among these age groups and between atypical and typical antipsychotics. It is important for clinicians to be mindful of these differences when prescribing antipsychotics, especially when prescribing medications off-label.
Characteristics of gastric carcinoma invading the muscularis propria

Although gastric carcinomas invading the muscularis propria (mp) are classified among advanced‐stage cancers in Japan, postoperative survival has been reported to approximate that in early gastric carcinoma. Characteristics of gastric carcinomas invading the mp, therefore, were compared to carcinomas invading only the mucosa (m) or submucosa (sm), and to those invading the subserosa (ss) or serosa (se).
Design and measurement of MEMS capacitive ultrasonic transducer

Since the proposing of capacitive micromachined ultrasonic transducer by Khuri Yakub group in 1994 that this kind of transducer occupying the advantages of wide bandwidth, impedance matching well with the propagation medium especially in fluid and air and high sensitivity, has shown a great potential for a wide range of applications such as medical imaging, medical ultrasound diagnosis, therapy and underwater ultrasonic imaging. This paper presents a kind of MEMS capacitive ultrasonic transducer with the novel cavities embedded in the device layer of Silicon On Insulator. Firstly, the geometric dimensions are derived from the theoretical analysis of the vibrating membrane and the electrical analysis of the transducer. Secondly, Finite Element Analysis is adopted to confirm the operation mode and the deflection and equivalent stress under operation/collapse voltage are obtained. Then, the fabrication process is depicted and the fabricated transducer is shown. The test results show that the electromechanical coupling coefficient is 69.65%.
Complications in stroke patients: a study carried out at the Rehabilitation Medicine Service, Changi General Hospital.

AIM The aim of this study was to look at the type and frequencies of complications after an acute stroke in an inpatient rehabilitation setting. We also looked at the type of complications which required the transfer of patient care back to the primary referring physician. MATERIALS AND METHODS A retrospective review of case notes of patients transferred to the rehabilitation team was conducted. The study period was a six-month period from the beginning of January 2001 to the end of June 2001. A list of complications was made. Each pre-determined complication was then defined. The frequency of each complication was then calculated. RESULTS A total of 140 case notes were reviewed. The overall complication rate was 54.3%. The more common complications, in order, from highest to lowest frequencies, were: constipation (complicating 22.9% of strokes); acute retention of urine (ARU, 20.9%); urinary tract infections (UTI, 14.3%); depression (9.3%); and limb pain (8.6%). Females were more likely to have UTI (p=0.038), ARU (p=0.002) and depression (p=0.018). Patients 65 years and above were more likely to suffer multiple complications although the results did not reach statistical significance (p=0.055). The care for eight patients (5.7% of patients with complications) had to be transferred back to the primary referring team or physician. CONCLUSIONS Complications post stroke are common. Some patients required transfer of care back to the primary referring physician. A pro-active approach is ideal in all post stroke patients, in order to identify and treat any complications early, thereby, improving outcome and reducing costs.
Preparing ATLAS reconstruction software for LHC's Run 2

In order to maximize the physics potential of the ATLAS experiment during LHC's Run 2, the reconstruction software has been updated. Flat computing budgets required a factor of three improved execution time, while the new xAOD data format forced changes in the reconstruction algorithms. Physics performance was also made better. This paper presents an overview of the improvements made to the reconstruction software during the long shutdown of the LHC.
Urinary Androsterone, Etiocholanolone, and Dehydroepiandrosterone Responses to 72‐Hr. Avoidance Sessions in the Monkey

&NA; Urinary androsterone, etiocholanolone, and dehydroepiandrosterone levels show substantial responses in association with 72‐hr. avoidance sessions in the monkey. In most instances a biphasic response is observed which is characterized by a decline in levels during avoidance followed by a rebound elevation during the recovery period. The duration of the two response phases, the primary depression and the secondary elevation, may vary from one experiment to the next, but the general configuration of the response curve remains the same. The methodological limitations of the present study as well as the need to include androgen measurements in future psychoendocrine studies are discussed.
Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction

The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impairment (MCI) in T2DM patients in the Indian population and to identify link between cognitive dysfunction in T2DM patients and serum lipid composition through untargeted and targeted lipidomic studies. Using a cross-sectional study, we evaluated 1278 T2DM patients with Montreal cognitive assessment test (MoCA) and digit symbol substitution test (DSST) for cognitive functions. As per MoCA, the prevalences of MCI in T2DM patients in age groups below 40, 41-50, 51-60, 61-70, 71-80 and 81-90 years were 13.7, 20.5, 33.5, 43.7, 57.1 and 75% with DSST scores of 45.8, 41.7, 34.4, 30.5, 24.2 and 18.8% respectively. Binomial logistic regression analysis revealed serum HbA1c ≥ 7.51, duration of T2DM over 20 years, age above 41 years, and females were independent contributors for cognitive dysfunction in T2DM patients. Preliminary studies with untargeted lipidomics of the serum from 20 T2DM patients, including MCI and normal cognition (NC) group, identified a total of 646 lipids. Among the identified lipids, 33 lipids were significantly different between MCI and NC group, which comprised of triglycerides (TGs, 14), sphingolipids (SL, 11), and phosphatidylcholines (PC, 5). Importantly, 10 TGs and 3 PCs containing long-chain polyunsaturated fatty acids (PUFA) were lower, while 8 sphingolipids were increased in the MCI group. Since brain-derived sphingolipids are known to get enriched in the serum, we further quantified sphingolipids from the same 20 serum samples through targeted lipidomic analysis, which identified a total of 173 lipids. Quantitation revealed elevation of 3 species of ceramides, namely Cer (d18:1_24:1), Hex1Cer (d16:0_22:6), and Hex2Cer (d28:1) in the MCI group compared to the NC group of T2DM patients. Overall, this study demonstrated an age-related prevalence of MCI in T2DM patients and highlighted reduced levels of several species of PUFA containing TGs and PCs and increased levels of specific ceramides in T2DM patients exhibiting MCI. Large-scale lipidomic studies in future could help understand the cognitive dysfunction domain in T2DM patients, while studies with preclinical models are required to understand the functional significance of the identified lipids.
Histopathological changes in oral mucosa due to takhzeen al-qat: a study of 70 biopsies.

BACKGROUND Chewing qat leaves (takhzeen al-qat) is a common habit in East Africa and Yemen. It has been reported to cause different systemic effects. At the oral mucosa, it causes clinical changes that appear as white lesions. The aim of this paper was to study the histopathological changes in the oral mucosa related to takhzeen al-qat. METHOD Seventy biopsies were studied. Biopsies were divided into three groups: (G1) Forty biopsies were taken from the oral mucosa of the chewing side. (G2) Twenty biopsies were taken from the oral mucosa of the opposite side and (G3) 10 biopsies were taken from the oral mucosa of non-chewing volunteers. All biopsies were conventionally prepared, paraffin embedded and histopathological protocol was followed for each case to study the histopathological changes. RESULTS Acanthosis appeared in 97.5% (G1) and 50% (G2), parakeratosis in 45% (G1) and 0% (G2), orthokeratosis in 25% (G1) and 10% (G2), abnormal rete ridges in 97.5% (G1) and 25% (G2), intracellular edema in 80% (G1) and 65% (G2), inflammatory infiltration in the subjacent connective tissue of 55% (G1) and 5% (G2), increased amount of collagenous fibers in 47.5% (G1) and 0% (G2), and mild epithelial dysplasia in 25% (G1) and 0% (G2). Biopsies taken from G3 showed no histopathological changes except one case with intracellular edema. Differences were statistically significant. CONCLUSION Takhzeen al-qat caused histopathological changes in the oral mucosa at the side of chewing; however, these changes were innocuous and without any evidence of malignancy.
Probiotics and Its Functionally Valuable Products—A Review

During the past two decades probiotic bacteria have been increasingly proposed as health promoting bacteria in variety of food system, because of its safety, functional, and technological characteristics. Commonly, Lactobacillus spp. , Bifidobacterium spp. , Saccharomyces boulardii, and some other microorganisms have been considered as probiotic strains. Possibly these bacterial strains exerted several beneficial effects into gastrointestinal tract of host while administered with variety of food system. Lactic acid bacteria (LAB) usually produce antimicrobial substances like bacteriocin which have broad spectrum of antagonist effect against closely related Gram positive and Gram negative pathogens. LAB strains often produce polymeric substances such as exopolysaccharides (EPS) which increase the colonization of probiotic bacteria by cell–cell interactions in gastrointestinal tract. LAB also produces biosurfactant which showed that the wide range of antimicrobial activity against bacterial pathogen as well as its antiadhesive properties reduces the adhesion of pathogens into gastric wall membrane. Furthermore, LAB strains have also been reported for production of antioxidants which are ability to scavenge the free radicals such as superoxide anions and hydroxyl radicals. For this sense, this review article is mainly focused on the ecology, biosynthesis, genetics, target sites, and applications of bacteriocins and EPS from LAB strains. Moreover, this review discusses about the production and functions of nutritive essential element folate and iron chelating agent such as siderophores from LAB.
How Grids are Perceived in Healthcare and the Public Service Sector

Computational and data grids have been developed to manage large amounts of data produced in scientific collaborations. While the developed technologies could be employed to help the daily work in the public sector and in healthcare, their wide adaptation has not been seen, yet. In this paper we present a survey, which we conducted to find out how the decision makers and system specialists in the public service sector see the role of Grid technologies in their future work. The respondents of the survey work as decision makers and systems specialists in the healthcare and the public services domain in Switzerland.
Underwater Acoustic Signal Processing

Abstract : The reports cover progress to develop a signal processing structure that exploits available knowledge of the environment and of signal and noise variability induced by the environment. The research is directed toward passive sonar detection and classification, continuous wave (CW) and broadband signals, shallow water operation, both platform-mounted and distributed systems, and frequencies below 1 kHz. The results of this research are expected to lead to new passive sonar detectors and classifiers that take advantage of knowledge of medium variability and uncertainty. The results are mainly applicable to passive processing. However, the active processor can be considered "a detector matched to the estimated ocean. " These results could have significant impact on Navy sonar system applications.
Comparison of technetium-99m-MDP, technetium-99m-WBC and technetium-99m-HIG in musculoskeletal inflammation.

UNLABELLED This study compared three radionuclide techniques in distinguishing musculoskeletal infection from noninfectious inflammation. METHODS Thirty-five orthopedic patients with suspected musculoskeletal infection were examined using three radionuclide techniques in sequence: triphasic bone scintigraphy, 99mTc radioleukocytes (99mTc-WBC) scintigraphy and 99mTc human immunoglobulin (99mTc-Hig) scintigraphy. Two "early" and "late" acquisitions were performed, at 4-6 hr and 20-24 hr postinjection, respectively. Patients who were diagnosed as suffering from noninflammatory lesions became the controls. We calcu"late"d for all studies one index of inflammation (Infl) as the ratio between counts in the uptake area and counts in an equal area of normal tissue. RESULTS The "early" radiolabeled leukocytes and "late" Hig scintigraphy allowed the greatest ability to distinguish between infections and noninfectious inflammations (p < 0.011 and p < 0.016) with a sensitivity of 96.6% and 96.5% and specificity of 71% and 100%, respectively. Hig and radioleukocytes allowed distinguishing infections from noninflammatory diseases at both examinations. CONCLUSION The "early" radioleukocyte scintigraphy allowed us to separate infections from noninfectious inflammations. In contrast, the same result can be obtained only with the "late" scan in the Hig study, but Hig mapped the spread of the inflammation into soft tissues better. Hig might be an alternative to radioleukocytes because of its simple preparation, similar accuracy and safety.
Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect

Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine. We analyzed the TPO gene in 14 unrelated patients with clinical evidence of iodide organification defects. Seven of the affected individuals harbored mutations in the TPO gene; one was compound heterozygous, the others were simply heterozygous for TPO mutations. Five novel mutations have been identified, one of which was found to be a single nucleotide deletion, while the other four were single nucleotide substitutions. A frameshift mutation c.387delC was detected in exon 5 which leads to an early termination signal in exon 7 (p.N129fsX208). Two missense mutations were identified in exon 8. The first, a c.920A>C transversion that results in a p.N307T substitution, was found in two patients. The second, a c.1297G>A transition, results in p.V433M. A c.1496C>T transition was detected in exon 9 that caused the substitution p.P499L. Finally, in exon 14 a c.2422T>C transition was identified, causing a p.C808R change. In addition, the previously reported GGCC duplication in exon 8 (c.1186underscore;1187insGGCC; p.R396fsX472) was also detected in two affected individuals, one of whom was a compound heterozygous (p.R396fsX472/p.V433M). © 2003 Wiley‐Liss, Inc.
Autologous Bone Marrow Concentrate: Review and Application of a Novel Intra-Articular Orthobiologic for Cartilage Disease

Abstract Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged ⩾ 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets (containing growth factors), and cytokines. The anti-inflammatory and immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage repair by increasing aggrecan content and tissue firmness. Following bone marrow aspiration (BMA), BMC is easily prepared using centrifugation, and is available for a same-day procedure with minimal manipulation of cells, thus complying with US Food and Drug Association (FDA) restrictions. To date, there are no published randomized controlled trials on the efficacy of use of autologous BMC intra-articular injections performed as a same-day in-office procedure for treating patients with cartilage disease; however, several publications have reported the ease of use of this method, its strong safety profile, and the fundamental science suggesting great therapeutic potential.
AC boosting compensation scheme for low-power multistage amplifiers

A new power-efficient frequency compensation scheme is proposed, called the AC Boosting Compensation (ACBC) scheme. An ac path is added to the internal stage of the conventional multistage amplifier, which improves significantly the performance such as the gain-bandwidth product and the slew rate without increasing the total power consumption. Analysis shows that the stability can be perfectly ensured. Two three-stage amplifiers have been implemented with and without a feed-forward stage, and fabricated in a 0.35-/spl mu/m CMOS process. The ACBC amplifiers driving a 500-pF capacitance achieved 1.9-MHz gain-bandwidth product (GBW) dissipating only 0.3-mW power with a 2-V supply. An amplifier based on conventional nested Miller compensation (NMC) could only achieve 0.11-MHz GBW with the same load and power conditions, which shows an improvement of a factor of 17 in GBW.
Bienes públicos regionales para la fortificación de alimentos con micronutrientes en Centroamérica

El proyecto de bienes públicos regionales (BPR) en fortificación masiva de alimentos de alto consumo que el BID co-financió en el 2007 para el conjunto de los siete países de la región, se diseñó bajo la premisa que a través de la cooperación transnacional se pueden potenciar los avances en el control de las deficiencias de micronutrientes prevalentes que, hasta entonces, se abordaban mayormente de manera individual.