Miracle-dz/UniFAR-FTUs huggingface dataset:
Retrospective analysis of bendamustine and rituximab use in indolent and mantle cell non-Hodgkin lymphoma based on initial starting dose

Abstract The initial dose of bendamustine, an alkylating agent used in treating indolent lymphoma (iNHL) and mantle cell lymphoma, is variable in clinical practice. 134 patients treated with bendamustine and rituximab were evaluated for starting dosage, patient characteristics, toxicities, and clinical outcome. The starting dosage ranged from 50 to 90 mg/m2. Lower starting dosage (<90 mg/m2) was associated with relapsed disease, increased age and worse performance status (PS), histologic subtype other than follicular lymphoma, baseline renal impairment, and cytopenias. No significant difference was observed in toxicities between patients treated with 90 mg/m2 compared with lower doses. The starting dose of 90 mg/m2 was associated with a higher complete response rate (56% vs. 29%) and longer progression free survival (PFS) (39.5 months vs. 19.7 months). However, in a multivariable model, the higher starting dose was not associated with longer PFS in those with similar age, histology, PS, and number of prior therapies.
Are simple IMRT beams more robust against MLC error? Exploring the impact of MLC errors on planar quality assurance and plan quality for different complexity beams

This study investigated the impact of beam complexities on planar quality assurance and plan quality robustness by introducing MLC errors in intensity‐modulate radiation therapy. Forty patients' planar quality assurance (QA) plans were enrolled in this study, including 20 dynamic MLC (DMLC) IMRT plans and 20 static MLC (SMLC) IMRT plans. The total beam numbers were 150 and 160 for DMLC and SMLC, respectively. Six different magnitudes of MLC errors were introduced to these beams. Gamma pass rates were calculated by comparing error‐free fluence and error‐induced fluence. The plan quality variation was acquired by comparing PTV coverage. Eight complexity scores were calculated based on the beam fluence and the MLC sequence. The complexity scores include fractal dimension, monitor unit, modulation index, fluence map complexity, weighted average of field area, weighted average of field perimeter, and small aperture ratio (<5cm2 and<50 cm2). The Spearman's rank correlation coefficient was calculated to analyze the correlation between these scores and gamma pass rate and plan quality variation. For planar QA, the most significant complexity index was fractal dimension for DMLC (p=−0.40) and weighted segment area for SMLC (p=0.27) at low magnitude MLC error. For plan quality, the most significant complexity index was weighted segment perimeter for DMLC (p=0.56) and weighted segment area for SMLC (p=0.497) at low magnitude MLC error. The sensitivity of planar QA was weakly associated with the field complexity with low magnitude MLC error, but the plan quality robustness was associated with beam complexity. Plans with simple beams were more robust to MLC error. PACS number(s): 87.55
Stereochemical considerations in pharmacokinetic processes of representative antineoplastic agents

Abstract The vast majority of chemical drugs or drug candidates contain stereocenter(s) in their molecular structures. In these molecules, stereochemical properties are vital properties that influence or even determine their drug actions. Therefore, studying the stereochemical issues of drugs (or drug candidates) is necessary for rational drug use. These stereochemical issues are usually involved with the stereoselectivity in pharmacokinetic processes, especially in the metabolism process. Thus, the investigation of the stereochemical issues in drug metabolism process deserves great attention, especially in those chiral/prochiral antineoplastic agents exhibiting pharmacodynamics and toxicologic differences between stereoisomers. Published reviews concerning this certain issue are inspiring, however they were covering all drug types and only limited antineoplastic drugs were discussed. Here in this review, the research on stereochemical issues in pharmacokinetic processes of some representative antineoplastic agents were described, especially focusing on some newly developed compounds. We highlight the chemical transformations in pharmacokinetic processes of these chiral/prochiral compounds and discuss their different behaviors with metabolic enzymes or transporter proteins, to explicate the observed stereoselectivity intrinsically.
Correlations of 18F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease

Clinical PET studies using 18F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent 18F-THK5351 and 11C-Pittsburgh compound B PET before death. Results: Regional in vivo 18F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. Conclusion: 18F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.
Obese adolescents with polycystic ovarian syndrome have elevated cardiovascular disease risk markers

Women with polycystic ovarian syndrome (PCOS) have evidence of subclinical cardiovascular disease (CVD). However, insulin resistance, an important factor in the development of CVD in adults, is common in adolescents with PCOS, yet data in adolescents are limited. Therefore, we sought to measure insulin resistance and CVD markers in obese youth with and without PCOS. Thirty-six PCOS and 17 non-PCOS adolescent girls who were obese, sedentary, and non-hypertensive were recruited from clinics located within the Children’s Hospital Colorado. Following 3 days of controlled diet and restricted exercise, fasting plasma samples were obtained prior to a hyperinsulinemic euglycemic clamp. PCOS girls were more insulin resistant than controls (glucose infusion rate 5.24±1.86 mg/kg/min vs 9.10±2.69; p<0.001). Girls with PCOS had blood pressure in the normal range, but had greater carotid intima–media thickness (cIMT) (0.49±0.07 mm vs 0.44±0.06; p=0.038), beta stiffness index (5.1±1.3 U vs 4.4±0.9; p=0.037), and reduced arterial compliance (1.95±0.47 mm2/mmHg × 10−1 vs 2.13±0.43; p=0.047). PCOS girls had a normal mean lipid profile, yet had a more atherogenic lipoprotein cholesterol distribution and had persistent elevations of free fatty acids despite hyperinsulinemia (68±28 μmol/mL vs 41±10; p=0.001), both potential contributors to CVD. Free fatty acid concentrations correlated best with all CVD markers. In summary, adolescent girls with PCOS have greater cIMT and stiffer arteries than girls without PCOS, perhaps related to altered lipid metabolism, even when clinical measures of blood pressure and cholesterol profiles are ‘normal’. Therefore, management of adolescent PCOS should include assessment of CVD risk factor development.
Neonatal diagnosis and treatment of Menkes disease.

BACKGROUND Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in a copper-transport gene, ATP7A. Early treatment with copper injections may prevent death and illness, but presymptomatic detection is hindered by the inadequate sensitivity and specificity of diagnostic tests. Exploiting the deficiency of a copper enzyme, dopamine-beta-hydroxylase, we prospectively evaluated the diagnostic usefulness of plasma neurochemical levels, assessed the clinical effect of early detection, and investigated the molecular bases for treatment outcomes. METHODS Between May 1997 and July 2005, we measured plasma dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in 81 infants at risk. In 12 newborns who met the eligibility criteria and began copper-replacement therapy within 22 days after birth, we tracked survival and neurodevelopment longitudinally for 1.5 to 8 years. We characterized ATP7A mutations using yeast complementation, reverse-transcriptase-polymerase-chain-reaction analysis, and immunohistochemical analysis. RESULTS Of 81 infants at risk, 46 had abnormal neurochemical findings indicating low dopamine-beta-hydroxylase activity. On the basis of longitudinal follow-up, patients were classified as affected or unaffected by Menkes disease, and the neurochemical profiles were shown to have high sensitivity and specificity for detecting disease. Among 12 newborns with positive screening tests who were treated early with copper, survival at a median follow-up of 4.6 years was 92%, as compared with 13% at a median follow-up of 1.8 years for a historical control group of 15 late-diagnosis and late-treatment patients. Two of the 12 patients had normal neurodevelopment and brain myelination; 1 of these patients had a mutation that complemented a Saccharomyces cerevisiae copper-transport mutation, indicating partial ATPase activity, and the other had a mutation that allowed some correct ATP7A splicing. CONCLUSIONS Neonatal diagnosis of Menkes disease by plasma neurochemical measurements and early treatment with copper may improve clinical outcomes. Affected newborns who have mutations that do not completely abrogate ATP7A function may be especially responsive to early copper treatment. (ClinicalTrials.gov number, NCT00001262.)
Organic and Mineral Nitrogen Fertilization for Processing Tomato in Southern Italy

A four-year field experiment to evaluate the effects of different types of organic fertilizers on yield and quality of processing tomato and on soil chemical evolution, was carried out in Southern Italy during the 2002–2005 period on a siltyclay soil. The fertilization treatments aimed to supply 100 kg ha -1 of N and were: 1) an organic biological fertilizer (BIO); 2) an experimental compost composed by olive residues, sludge and straw (COMP); 3) a mix (MIX) of an organic fertilizer (50%) and ammonium nitrate (50%); 4) a traditional chemical fertilizer (ammonium nitrate, MIN). At harvest the main productive and qualitative parameters were assessed (fresh and dried yield; biomass and marketable yield). Chemical analyses of the soil were made at the start and at the end of experiment. Fruit yield did not differ among the fertilization treatments, but unripe fruit yield was higher in the MIN and BIO treatment; MIN showed also smaller fruit than BIO and COMP. The N availability during crop cycle influenced the mean fruit weight, date, and simultaneity of maturity during the ripening process. Soil characteristics changed during the four years of application for mineral N and among treatments (P2O5 for BIO and COMP and mineral N for MIN and MIX fertilization treatments). Heavy metals: cupper and zinc did not increase their concentration in the soil; instead, lead increased below the Italian law’s limit in COMP. The possibility to use organic fertilizer for processing tomatoes has been evaluated and the conclusions are that organic fertilization is, in same cases, more suitable than mineral one from a productive and soil fertility standpoint of view.
SC-FDE Based Full-Duplex Relay Communication Robust to Residual Loop Interference

In this letter, we consider a full-duplex (FD) relay communication network on flat fading Rayleigh channels, where the relay is allowed to receive and transmit at the same time and over the same frequency band. Based on single carrier frequency domain equalization, we propose an amplify-and-forward protocol FD relaying scheme, which is robust to the residual loop interference. In this scheme, the relay only needs to amplify and forward the received signal by controlling the amplifying factor and as a result the processing at the relay is simple. The amplifying factor is optimized in terms of system parameters such as the length of cyclic prefix, noise power, and estimated channel state information. Simulation results are presented to evaluate the performance of the proposed scheme and verify the theoretical analysis.
Video-assisted thoracic surgery for thymoma: long-term follow-up results and prognostic factors-single-center experience of 150 cases.

Background The use of video-assisted thoracic surgery (VATS) in the treatment of thymoma is becoming more and more common. The aim of this study was to evaluate safety and effectiveness of thoracoscopic treatment of thymoma and, more importantly, to report long-term follow-up results of a large single-center cohort. Methods A retrospective review of a prospective database was performed. In total, 150 patients who underwent VATS resection for thymoma at Peking University People's Hospital from April 2001 to November 2014 were retrospectively reviewed. Results Average operation time was 140.1±54.2 min, median blood loss was 50 mL (range, 10-700 mL), median post-operative drainage time was 3 days (range, 1-11 days), and median length of post-op stay was 5 days (range, 2-20 days); 134 patients (89.3%) were followed up successfully. Median follow-up was 59.5 months (range, 2-187 months). Five- and 10-year recurrence free survival (RFS) rates of entire group were 96.5% and 94.4%, respectively; 5- and 10-year RFS rates for Masaoka stages I + II were 98.1% and 98.1%, respectively; 5- and 6-year RFS rates for Masaoka stage III were 90% and 60%, respectively. One case of recurrence in five Masaoka stage IV patients was observed, and 4-year RFS was 80%. Multivariable analysis indicated that recurrence tended to occur in Masaoka stages III + IV patients (P=0.037, HR =12.69, 95% CI: 1.17-138.22) and older patients had a lower risk of recurrence (P=0.029, HR =0.87, 95% CI: 0.77-0.99). Myasthenia gravis (MG) presented in 44 patients (29.3%), of which 36 patients (81.8%) were followed up. Nine patients achieved complete remission, and 19 patients had symptom improvement after surgery. Overall response rate of MG was 77.8% (28/36). Conclusions VATS was a safe and effective procedure for treatment of thymomas with satisfactory prognosis. MG with thymoma treated by VATS had comparable neurological outcome to that associated with the trans-sternal approach.
Severe Hypertriglyceridemia Possibly Masked Acute Pancreatitis and Led to a Difficult Diagnosis in an Obese Patient with Ketoacidosis-onset Type 2 Diabetes

A young obese man with ketoacidosis-onset type 2 diabetes mellitus, associated with severe hypertriglyceridemia, was admitted to a local hospital complaining of abdominal pain. Although the abdominal pain worsened, his serum amylase level remained normal with persistent severe hypertriglyceridemia until the second day of hospitalization. The next day, computed tomography showed severe acute pancreatitis (AP) with serum amylase elevation, while the patient's triglyceride level decreased to 558 mg/dL. He was transferred to our hospital and recovered after intensive care. AP accompanied by diabetic ketoacidosis is not rare but an early diagnosis can be difficult to make due to normal amylase levels in the presence of severe hypertriglyceridemia.
Plasma corticosterone, epinephrine, and norepinephrine levels increase during administration of nitrous oxide in rats

Abstract Nitrous oxide (N2O) is a gaseous drug with abuse potential. Despite its common clinical use, little is known about whether N2O administration activates the HPA axis and/or the sympathetic adrenomedullary system. The goal of this study was to determine whether 60% N2O alters plasma concentrations of corticosterone (CORT), epinephrine (EPI), and norepinephrine (NE) in male Long-Evans rats. A gas-tight swivel assembly in the lid of a gas administration chamber allowed the remote collection of blood samples from an indwelling jugular vein catheter at four time-points: baseline and at 30, 60, and 120 min during a two-hour administration of 60% N2O. Relative to baseline, plasma CORT (n = 9) was significantly elevated at all three time-points during N2O inhalation (mixed model analysis, p = .001) and plasma EPI and NE levels were each significantly elevated (n = 8, p ≤ .001) at the 30 min assessment. EPI then declined and did not differ from baseline at the 60 and 120 min assessments (p > .05) whereas NE remained elevated (120 min, p = .001). Administration of 60% N2O increases circulating CORT, EPI, and NE, supporting N2O as a physiological stressor. An N2O-induced increase in CORT is consistent with the observation that addictive drugs typically activate the HPA axis causing increased plasma levels of glucocorticoids. Allostatic models of drug addiction typically involve stress systems and the possible role of stress hormones in N2O-induced allostatic dysregulation is discussed.
Real-Time EEG Signal Enhancement Using Canonical Correlation Analysis and Gaussian Mixture Clustering

Electroencephalogram (EEG) signals are usually contaminated with various artifacts, such as signal associated with muscle activity, eye movement, and body motion, which have a noncerebral origin. The amplitude of such artifacts is larger than that of the electrical activity of the brain, so they mask the cortical signals of interest, resulting in biased analysis and interpretation. Several blind source separation methods have been developed to remove artifacts from the EEG recordings. However, the iterative process for measuring separation within multichannel recordings is computationally intractable. Moreover, manually excluding the artifact components requires a time-consuming offline process. This work proposes a real-time artifact removal algorithm that is based on canonical correlation analysis (CCA), feature extraction, and the Gaussian mixture model (GMM) to improve the quality of EEG signals. The CCA was used to decompose EEG signals into components followed by feature extraction to extract representative features and GMM to cluster these features into groups to recognize and remove artifacts. The feasibility of the proposed algorithm was demonstrated by effectively removing artifacts caused by blinks, head/body movement, and chewing from EEG recordings while preserving the temporal and spectral characteristics of the signals that are important to cognitive research.
Nine unanswered questions about cytokinesis

Experiments on model systems have revealed that cytokinesis in cells with contractile rings (amoebas, fungi, and animals) depends on shared molecular mechanisms in spite of some differences that emerged during a billion years of divergent evolution. Understanding these fundamental mechanisms depends on identifying the participating proteins and characterizing the mechanisms that position the furrow, assemble the contractile ring, anchor the ring to the plasma membrane, trigger ring constriction, produce force to form a furrow, disassemble the ring, expand the plasma membrane in the furrow, and separate the daughter cell membranes. This review reveals that fascinating questions remain about each step.
Domain-Specific Preferences for Causal Reasoning and Planning

We address the issue of incorporating domain-specific preferences in planning systems, where a preference may be seen as a "soft" constraint that it is desirable, but not necessary, to satisfy. To this end, we identify two types of preferences, choice preferences that give a preference over which formulas (typically subgoals) to establish, and temporal preferences, which specify a desirable ordering on the establishment of formulas. Preferences may be constructed from actions or fluents but, as we show, this distinction is immaterial. In fact, we allow preferences on arbitrary formulas build from action and fluent names. These preference orderings induce preference ordering on resulting plans, the maximal elements of which yield the preferred plans. We argue that the approach is general and flexible; as well, it handles conditional preferences. Our framework is developed in the context of transition systems; hence, it is applicable to a large number of different action languages, including the well-known language C. Furthermore, our results are applicable to general planning formalisms.
Cost analysis of different cervical cancer screening strategies in Mexico.

OBJECTIVE To compare the costs and number of undetected cases of four cervical cancer screening strategies (CCSS) in Mexico. MATERIALS AND METHODS We estimated the costs and outcomes of the following CCSS: a) conventional Papanicolaou smear (Pap) alone; b) high-risk human papilloma virus testing (HR-HPV) as primary screening with Pap as reflex triage; c) HR-HPV as primary screening with HPV-16/18 typing, liquid-based cytology (LBC) and immunostaining for p16/Ki67 testing as reflex triage, and d) co-testing with HR-HPV and LBC with HPV-16/18 typing and immunostaining for p16/Ki67 as reflex triage. The outcome of interest was high-grade cervical lesions or cervical cancer. RESULTS HR-HPV testing, HPV typing, LBC testing and immunostaining is the best alternative because it is the least expensive option with an acceptable number of missed cases. CONCLUSIONS The opportunity costs of a poor quality CCSS is many false negatives. Combining multiple tests may be a more cost-effective way to screen for cervical cancer in Mexico.
A multicentre survey of the antibiotic susceptibility of clinical Bacteroides species from Hungary

Abstract Background: The species of the Bacteroides fragilis group are important components of human microbiota, but as opportunistic pathogens they can be the causative agents of severe infections. Methods: The major aims of our investigation were the evaluation of the susceptibility of 400 different Hungarian B. fragilis group isolates to 10 antibiotics by the agar dilution method, the comparison of our resistance data with previous national and international antibiotic resistance data and the comparison of present data in regional aspect. The MIC-values on 10 antibiotics of all the strains were determined with the agar dilution method by CLSI. The presence of the cfiA gene in Division II B. fragilis strains was confirmed by RT-PCR. Results: We detected a relatively high resistance rate of ampicillin, moxifloxacin, clindamycin and tetracycline, but amoxicillin/clavulanic acid, metronidazole, tigecycline and chloramphenicol showed excellent activity. In this study, we found that 6.75% of the isolates were resistant to cefoxitin and 7% to meropenem, while 8.58% of our B. fragilis strains harboured the cfiA gene. Most of the meropenem resistant strains were isolated in one of the participating centres. In the case of meropenem, cefoxitin, clindamycin and high-level-ampicillin-resistant strains, we found significant regional differences. Discussion: Most of the results of our study were concordant with previous national and international data, with the exception of amoxicillin/clavulanic acid, cefoxitin and meropenem. Conclusions: Our study highlighted the importance of the periodic monitoring of the antimicrobial susceptibility of Bacteroides species providing important information for the appropriate therapy.