Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms

OBJECTIVES:Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod.METHODS:After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill ≥2 Rome diarrhea criteria ≥25% of the time. Adverse events were recorded.RESULTS:Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported.CONCLUSIONS:In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.
Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease

Muscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post‐translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle.
A kinetic model describing Shewanella oneidensis MR‐1 growth, substrate consumption, and product secretion

Aerobic growth of Shewanella oneidensis MR‐1 in minimal lactate medium was studied in batch cultivation. Acetate production was observed in the middle of the exponential growth phase and was enhanced when the dissolved oxygen (DO) concentration was low. Once the lactate was nearly exhausted, S. oneidensis MR‐1 used the acetate produced during growth on lactate with a similar biomass yield as lactate. A two‐substrate Monod model, with competitive and uncompetitive substrate inhibition, was devised to describe the dependence of biomass growth on lactate, acetate, and oxygen and the acetate growth inhibition across a broad range of concentrations. The parameters estimated for this model indicate interesting growth kinetics: lactate is converted to acetate stoichiometrically regardless of the DO concentration; cells grow well even at low DO levels, presumably due to a very low Km for oxygen; cells metabolize acetate (maximum specific growth rate, µmax,A of 0.28 h−1) as a single carbon source slower than they metabolize lactate (µmax,L of 0.47 h−1); and growth on acetate is self‐inhibiting at a concentration greater than 10 mM. After estimating model parameters to describe growth and metabolism under six different nutrient conditions, the model was able to successfully estimate growth, oxygen and lactate consumption, and acetate production and consumption under entirely different growth conditions. Biotechnol. Bioeng. 2007;96: 125–133. © 2006 Wiley Periodicals, Inc.
Liquid–liquid phase separation of tau protein: The crucial role of electrostatic interactions

Recent studies have indicated that tau, a protein involved in Alzheimer's disease and other neurodegenerative disorders, has a propensity to undergo liquid–liquid phase separation (LLPS). However, the mechanism of this process remains unknown. Here, we demonstrate that tau LLPS is largely driven by intermolecular electrostatic interactions between the negatively charged N-terminal and positively charged middle/C-terminal regions, whereas hydrophobic interactions play a surprisingly small role. Furthermore, our results reveal that, in contrast to previous suggestions, phosphorylation is not required for tau LLPS. These findings provide a foundation for understanding the mechanism by which phosphorylation and other posttranslational modifications could modulate tau LLPS in the context of specific physiological functions as well as pathological interactions.
Associations between socioeconomic status and blood cadmium levels in Korea

OBJECTIVES Although smoking is associated with both low socioeconomic status and blood cadmium (Cd) levels, the association between socioeconomic status and Cd levels remains unclear. Therefore, our study aimed to examine this association and to clarify whether smoking is a confounding or mediating variable in this relationship. METHODS Data (n=7,734) were drawn from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008- 2011), including years that contained data on blood Cd and urinary cotinine levels. We investigated the associations of income, education, and occupation with blood Cd levels. Smoking was investigated by categorizing participants by smoking status (never, former, and current) and pack-years into quartiles. The weekly frequency of rice and barley intake was analyzed to gain insights into participants’ dietary patterns. Additionally, urinary cotinine levels were used to ensure the validity of the smoking variables. RESULTS Participants earning a low income and with less formal education had higher blood Cd levels. After controlling for smoking, the association between income and Cd levels substantially weakened. Further controlling for education, the association between income and Cd levels disappeared. However, there was a strong negative association between education and Cd levels, even after controlling for smoking history, pack-years, and urinary cotinine levels. CONCLUSIONS In cross-sectional data from the KNHANES, blood Cd levels were significantly higher among those with a low income and less formal education. Smoking history contributed to, but did not fully explain, these associations.
Burden of Caregiving in Mild to Moderate Dementia: An Asian Experience

This survey sought to determine (a) the prevalence of carer stress in patients with mild to moderate dementia, (b) whether caregiver burden was already associated with plans to institutionalize patients, and (c) which patient-related and caregiver-related variables best predicted caregiver burden. The principal caregivers of 93 Asian patients with mild to moderate dementia attending an outpatient cognitive assessment clinic were interviewed via a structured questionnaire that focused upon (a) patient-related variables such as their behavioral and functional abnormalities; and (b) caregiver-related variables such as whether they were having problems looking after the patients, the duration of their caregiving, their associated feelings of anger and/or depression, and their financial status as well as intentions to institutionalize patients. Forty-nine percent of caregivers reported problems in looking after the patients, and their perception of difficulties was significantly associated with institutionalization plans for the patients. Logistic regression analysis using a forward variable selection procedure showed two of the patients' behavioral abnormalities (repetition, agitation) and one of their functional impairments (urinary incontinence) as well as the carers' depressed feelings to be predictive of the carers' problematic status, explaining 40% of the variance. It is important that even in the early stages of dementia, the medical assessment also evaluate behavioral, functional, and social dimensions of the illness, so that appropriate interventions can be implemented to reduce caregiving burden and delay institutionalization.
Active Case Finding for Malaria: A 3-Year National Evaluation of Optimal Approaches to Detect Infections and Hotspots Through Reactive Case Detection in the Low-transmission Setting of Eswatini

Abstract Background Reactive case detection (RACD) is a widely practiced malaria elimination intervention whereby close contacts of index cases receive malaria testing to inform treatment and other interventions. However, the optimal diagnostic and operational approaches for this resource-intensive strategy are not clear. Methods We conducted a 3-year prospective national evaluation of RACD in Eswatini, a malaria elimination setting. Loop-mediated isothermal amplification (LAMP) was compared to traditional rapid diagnostic testing (RDT) for the improved detection of infections and for hotspots (RACD events yielding ≥1 additional infection). The potential for index case–, RACD-, and individual-level factors to improve efficiencies was also evaluated. Results Among 377 RACD events, 10 890 participants residing within 500 m of index cases were tested. Compared to RDT, LAMP provided a 3-fold and 2.3-fold higher yield to detect infections (1.7% vs 0.6%) and hotspots (29.7% vs 12.7%), respectively. Hotspot detection improved with ≥80% target population coverage and response times within 7 days. Proximity to the index case was associated with a dose-dependent increased infection risk (up to 4-fold). Individual-, index case–, and other RACD-level factors were considered but the simple approach of restricting RACD to a 200-m radius maximized yield and efficiency. Conclusions We present the first large-scale national evaluation of optimal RACD approaches from a malaria elimination setting. To inform delivery of antimalarial drugs or other interventions, RACD, when conducted, should utilize more sensitive diagnostics and clear context-specific operational parameters. Future studies of RACD’s impact on transmission may still be needed.
A Wireless Sensor Networks' Analytics System for Predicting Performance in On-Demand Deployments

The need for advanced tools that provide efficient design of on-demand deployment of wireless sensor networks (WSN) is critical for meeting our nation's demand for increased intelligence, reconnaissance, and surveillance. For practical applications, WSN deployments can be time consuming and error prone since they have the utmost challenge of guaranteeing connectivity and proper area coverage upon deployment. This creates an unmet demand for decision-support systems that help manage this complex process. This paper presents research to develop a system for predicting optimal deployments of WSN. Specifically, it presents results of image processing algorithms for terrain classification, results of modeling WSN signal propagation under different terrain conditions, results of optimization and visualization techniques for high-dimensional deployments, and system architecture for efficient integration and future deployment. Results show a feasible approach that can be used to automatically determine areas of high signal obstruction-which is essential to estimate obstruction parameters in simulations-and mapping of accurate WSN path-loss models to enhance the overall decision-making process during predeployment of large-scale WSN.
Utility of fibrinogen in the coagulation screen

tion system identifies autonomously proliferating B cell precursors in human bone marrow. Journal of Immunology (Baltimore, Md.: 1950), 192, 1044–1054. Mahadeo, K.M. , Masinsin, B. , Kapoor, N. , Shah, A.J., Abdel-Azim, H. & Parkman, R. (2014) Immunologic resolution of human chronic graft-versus-host disease. Biology of Blood and Marrow Transplantation, 20, 1508–1515. Nakatani, K. , Imai, K. , Shigeno, M. , Sato, H. , Tezuka, M. , Okawa, T. , Mitsuiki, N. , Isoda, T. , Tomizawa, D. , Takagi, M. , Nagasawa, M. , Kajiwara, M. , Yamamoto, M. , Arai, A. , Miura, O. , Kamae, C. , Nakagawa, N. , Honma, K. , Nonoyama, S. , Mizutani, S. & Morio, T. (2014) Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation. Bone Marrow Transplantation, 49, 1155–1161. Shimabukuro-Vornhagen, A. , Hallek, M.J., Storb, R.F. & von Bergwelt-Baildon, M.S. (2009) The role of B cells in the pathogenesis of graft-versus-host disease. Blood, 114, 4919–4927. Watkins, B.K. , Horan, J., Storer, B. , Martin, P.J., Carpenter, P.A. & Flowers, M.E. (2017) Recipient and donor age impact the risk of developing chronic GvHD in children after allogeneic hematopoietic transplant. Bone Marrow Transplantation, 52, 625–626.
Serotonin content and melatonin production in the pineal gland of the male Djungarian hamster (Phodopus sungorus)

Abstract: Diurnal variations in serum melatonin levels and pineal concentrations of serotonin (5‐HT), N‐acetylserotonin (NAS), 5‐hydroxyindole acetic acid (5‐HIAA), and melatonin were estimated in adult male Djungarian hamsters kept under long‐day (LD 16:8) or short‐day (LD 8:16) photoperiods. The nocturnal increase in melatonin production was accompanied by a marked drop in pineal serotonin concentrations. Serotonin levels, however, decreased approximately 4 hr before pineal melatonin increased. Correlations of the mean values for pineal serotonin and pineal melatonin indicated significant correlations at both LD 16:8 (r = ‐0.92, P < 0.001) and LD 8:16 (r = ‐0.85, P < 0.001). The mean levels of pineal serotonin and serum melatonin were correlated as well (LD 16:8, r = ‐0.91, P < 0.001; LD 8:16, r = ‐0.81, P < 0.01). The levels of pineal serotonin declined at approximately the same time as serum melatonin levels increased. These data suggest that the drop in pineal serotonin is primarily a consequence of melatonin production (as reflected by increasing serum concentrations). Consequently, pineal concentrations of melatonin may not be the best estimate of actual melatonin production, but a measure of how much melatonin is accumulated within the pineal due to high synthesis rates while the release of the hormone from the gland is limited.
KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

Vascular endothelial growth factor-C (VEGF-C) acts primarily on endothelial cells, but also on non-vascular targets, for example in the CNS and immune system. Here we describe a novel, unique VEGF-C form in the human reproductive system produced via cleavage by kallikrein-related peptidase 3 (KLK3), aka prostate-specific antigen (PSA). KLK3 activated VEGF-C specifically and efficiently through cleavage at a novel N-terminal site. We detected VEGF-C in seminal plasma, and sperm liquefaction occurred concurrently with VEGF-C activation, which was enhanced by collagen and calcium binding EGF domains 1 (CCBE1). After plasmin and ADAMTS3, KLK3 is the third protease shown to activate VEGF-C. Since differently activated VEGF-Cs are characterized by successively shorter N-terminal helices, we created an even shorter hypothetical form, which showed preferential binding to VEGFR-3. Using mass spectrometric analysis of the isolated VEGF-C-cleaving activity from human saliva, we identified cathepsin D as a protease that can activate VEGF-C as well as VEGF-D.
Implementing an intervention to improve decision making around referral and admission to intensive care: Results of feasibility testing in three NHS hospitals

Abstract Rationale, aims, and objectives Decisions about whether to refer or admit a patient to an intensive care unit (ICU) are clinically, organizationally, and ethically challenging. Many explicit and implicit factors influence these decisions, and there is substantial variability in how they are made, leading to concerns about access to appropriate treatment for critically ill patients. There is currently no guidance to support doctors making these decisions. We developed an intervention with the aim of supporting doctors to make more transparent, consistent, patient‐centred, and ethically justified decisions. This paper reports on the implementation of the intervention at three NHS hospitals in England and evaluates its feasibility in terms of usage, acceptability, and perceived impact on decision making. Methods A mixed method study including quantitative assessment of usage and qualitative interviews. Results There was moderate uptake of the framework (28.2% of referrals to ICU across all sites during the 3‐month study period). Organizational structure and culture affected implementation. Concerns about increased workload in the context of limited resources were obstacles to its use. Doctors who used it reported a positive impact on decision making, with better articulation and communication of reasons for decisions, and greater attention to patient wishes. The intervention made explicit the uncertainty inherent in these decisions, and this was sometimes challenging. The patient and family information leaflets were not used. Conclusions While it is feasible to implement an intervention to improve decision making around referral and admission to ICU, embedding the intervention into existing organizational culture and practice would likely increase adoption. The doctor‐facing elements of the intervention were generally acceptable and were perceived as making ICU decision making more transparent and patient‐centred. While there remained difficulties in articulating the clinical reasoning behind some decisions, the intervention offers an important step towards establishing a more clinically and ethically sound approach to ICU admission.
Analysis, Design, and Experimentation of a Dimmable Resonant-Switched-Capacitor LED Driver With Variable Inductor Control

This paper proposes a new 48-V dc-fed dimmable LED driver based on a resonant-switched-capacitor topology (RSCT), where the analog-based dimming feature is accomplished by means of a variable inductor (VI). The proposed topology is based on the classic RSCT step-up double mode converter and it provides a simple and cost-effective solution while guaranteeing a wide dimming range. In order to implement an analog-based dimming, the control of the dc current in the LED lamp is required. This technique proposes to replace the resonant inductor by a VI, which will control the rms value of the resonant current, and, therefore, the mean value of the LED lamp current. In order to evaluate the feasibility and performance of this method, a 22-W LED lamp and driver prototypes were built. The most relevant experimental results are presented and briefly described.
Body condition impacts blood and muscle oxygen storage capacity of free-living beluga whales (Delphinapterus leucas)

ABSTRACT Arctic marine ecosystems are currently undergoing rapid environmental changes. Over the past 20 years, individual growth rates of beluga whales (Delphinapterus leucas) have declined, which may be a response to climate change; however, the scarcity of physiological data makes it difficult to gauge the adaptive capacity and resilience of the species. We explored relationships between body condition and physiological parameters pertaining to oxygen (O2) storage capacity in 77 beluga whales in the eastern Beaufort Sea. Muscle myoglobin concentrations averaged 77.9 mg g−1, one of the highest values reported among mammals. Importantly, blood haematocrit, haemoglobin and muscle myoglobin concentrations correlated positively to indices of body condition, including maximum half-girth to length ratios. Thus, a whale with the lowest body condition index would have ∼27% lower blood (26.0 versus 35.7 ml kg−1) and 12% lower muscle (15.6 versus 17.7 ml kg−1) O2 stores than a whale of equivalent mass with the highest body condition index; with the conservative assumption that underwater O2 consumption rates are unaffected by body condition, this equates to a >3 min difference in maximal aerobic dive time between the two extremes (14.3 versus 17.4 min). Consequently, environmental changes that negatively impact body condition may hinder the ability of whales to reach preferred prey sources, evade predators and escape ice entrapments. The relationship between body condition and O2 storage capacity may represent a vicious cycle, in which environmental changes resulting in decreased body condition impair foraging, leading to further reductions in condition through diminished prey acquisition and/or increased foraging efforts. Summary: The relationship between body condition and blood and muscle O2 stores in beluga whales may represent a vicious cycle, in which decreases in condition impair foraging ability, leading to further reductions in condition.
Responses and roles of roots, microbes, and degrading genes in rhizosphere during phytoremediation of petroleum hydrocarbons contaminated soil

Abstract Rhizodegradation performed by plant roots and the associated bacteria is one of the major mechanisms that contribute to removal of petroleum hydrocarbons (PHCs) during phytoremediation. In this study, the pot-culture experiment using wild ornamental Hylotelephium spectabile (Boreau) H. Ohba was designed to explore responses and roles of roots, microbes, and degrading genes in the rhizodegradation process. Results showed that PHCs degradation rate by phytoremediation was up to 37.6–53.3% while phytoaccumulation accounted for a low proportion, just at 0.3–13.3%. A total of 37 phyla were classified through the high throughput sequencing, among which Proteobacteria, Actinobacteria, and Acidobacteria were the three most dominant phyla, accounting for >60% of the phylum frequency. The selective enrichment of PHC degraders with high salt-tolerance, including Alcanivorax and Bacteroidetes, was induced. Generally, relative abundance of the PHC degrading genes increased significantly with an increase in PHCs concentrations, and the gene copy number in the phytoremediation group was 1.46–14.44 times as much as that in the unplanted controls. Overall, the presence of PHCs and plant roots showed a stimulating effect on the development of specific degraders containing PHC degrading genes, and correspondingly, a biodegradation-beneficial community structure had been constructed to contribute to PHCs degradation in the rhizosphere.
REVERSAL OF STEROID- AND ANTI-LYMPHOCYTE ANTIBODY- RESISTANT REJECTION USING INTRAVENOUS IMMUNOGLOBULIN (IVIG) IN RENAL TRANSPLANT RECIPIENTS

Background. Despite the recent advances in immunosuppression, steroid-resistant rejection remains a difficult problem in renal transplant recipients. Methods. We reviewed our experience with i.v. immunoglobulin (IVIG) in the treatment of steroid- and antilymphocyte antibody-resistant rejection in renal transplant patients. Between September 1996 and March 1999, 17 patients were treated with IVIG to reverse steroid- or antilymphocyte antibody-resistant rejection. A total of 2 g/kg of IVIG was administered to patients during each treatment course. Results. With a mean follow-up of 21.5±9.5 months from the time of IVIG administration, patient and graft survival rates were 94% (16/17) and 71% (12/17), respectively. The baseline mean serum creatinine level prior to rejection was 2.2±0.7 mg/dl and peaked at 3.3±1.1 mg/dl at the time of the diagnosis of refractory rejection. IVIG therapy was associated with a fall in the mean creatinine to 2.8±1.1 mg/dl. The most recent serum creatinine in patients with functioning grafts was 2.8±1.6 mg/dl. In 82% of allograft biopsies after IVIG, reversal or reduction in the severity of rejection was demonstrated. In addition, IVIG therapy rescued three of four patients with antilymphocyte antibody-resistant rejection. Conclusions. IVIG rescue therapy for steroid- or antilymphocyte antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival.