Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206

Background Despite remarkable results with salvage standard-dose or high-dose chemotherapy ∼15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods Single arm phase II trial investigating pembrolizumab 200 mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age ≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT. Clinical trial information NCT02499952.
Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.
Mental Health Pathways Linking Childhood Maltreatment to Interpersonal Revictimization During Adolescence for Girls in the Child Welfare System

This study compares the association of histories of childhood emotional, physical, and sexual abuse, and physical neglect with revictimization among adolescent girls, and investigates the role of posttraumatic stress and symptoms of depression as mediators. Participants were 234 girls aged 12 to 19 years, who have been involved with the child welfare system in a Midwestern urban area. Data were collected from baseline surveys of a trauma-focused group program to which the participants were referred. The majority of participants were youths of color (75%) who were primarily African American (70%), and the remaining participants were White, non-Hispanic (25%). Data were collected through surveys that assessed histories of child abuse and neglect, symptoms of posttraumatic stress and depression, and experiences of physical, verbal, and relational revictimization in the last 3 months. All types of abuse and neglect were significantly associated with higher frequencies of revictimization and higher levels of posttraumatic stress and depressive symptoms. Parallel mediation analyses demonstrated that both posttraumatic stress and depression fully mediated the relationships between emotional abuse and revictimization, and sexual abuse and revictimization. Physical abuse was fully mediated by posttraumatic stress, but not by depression. Results also indicated that neither posttraumatic stress nor depression were mediators for the relationship between neglect and revictimization. There were similar pathways to revictimization in adolescents from emotional and sexual abuse through posttraumatic stress and depression. Evidence is mounting for the deleterious effects of emotional abuse. There is evidence that treatment of both posttraumatic stress and depression in emotionally and sexually abused adolescents involved in child welfare is warranted to prevent future revictimization.
The Effect of Expertise of Service Provider , Relational Benefit on Loyalty-An Empirical Study of Hairstyle Franchise System

The purpose of the study is to propose and test an integrated model investigating the relationship among relational benefit, the attributes of service provider, relationship quality on the loyalty. Data collected in face-to-face interviews with 257 customers of 15 hairstyle franchise outlets. Structural equations modeling were used to test the proposed model. The findings indicate that the expertise of service provider has a significant impact on customer trust and satisfaction in high involvement services. Preferential treatment is shown to positively influence on satisfaction, increased purchases and word of mouth. Managerial and academic implications are delineated and directions for future research are offered.
Estimation of the Land Surface Temperature over the Tibetan Plateau by Using Chinese FY-2C Geostationary Satellite Data

During the process of land–atmosphere interaction, one of the essential parameters is the land surface temperature (LST). The LST has high temporal variability, especially in its diurnal cycle, which cannot be acquired by polar-orbiting satellites. Therefore, it is of great practical significance to retrieve LST data using geostationary satellites. According to the data of FengYun 2C (FY-2C) satellite and the measurements from the Enhanced Observing Period (CEOP) of the Asia–Australia Monsoon Project (CAMP) on the Tibetan Plateau (CAMP/Tibet), a regression approach was utilized in this research to optimize the split window algorithm (SWA). The thermal infrared data obtained by the Chinese geostationary satellite FY-2C over the Tibetan Plateau (TP) was used to estimate the hourly LST time series. To decrease the effects of cloud, the 10-day composite hourly LST data were obtained through the approach of maximal value composite (MVC). The derived LST was used to compare with the product of MODIS LST and was also validated by the field observation. The results show that the LST retrieved through the optimized SWA and in situ data has a better consistency (with correlation coefficient (R), mean absolute error (MAE), mean bias (MB), and root mean square error (RMSE) values of 0.987, 1.91 K, 0.83 K and 2.26 K, respectively) than that derived from Becker and Li’s SWA and MODIS LST product, which means that the modified SWA can be applied to achieve plateau-scale LST. The diurnal variation of the LST and the hourly time series of the LST over the Tibetan Plateau were also obtained. The diurnal range of LST was found to be clearly affected by the influence of the thawing and freezing process of soil and the summer monsoon evolution. The comparison between the seasonal and diurnal variations of LST at four typical underlying surfaces over the TP indicate that the variation of LST is closely connected with the underlying surface types as well. The diurnal variation of LST is the smallest at the water (5.12 K), second at the snow and ice (5.45 K), third at the grasslands (19.82 K) and largest at the barren or sparsely vegetated (22.83 K).
Technological progress on detoxification and comprehensive utilization of chromium containing slag

Chromium salt is an important industrial material, but vast waste slag containing chrome(Ⅵ) is brought out in the process of its production. The slag is seriously harmful to environments and human health. The technologies on detoxification and comprehensive utilization of chromium containing slag were summarized abroad and at home. And various methods were also described for the detoxification mechanism, technology process, and practical application effects in detail. A new concept for detoxification of chromium containing slag, furthermore, was put forward by using microorganism.
An Improved Quadrilateral Fitting Algorithm for the Water Column Contribution in Airborne Bathymetric Lidar Waveforms

In this paper, an improved method based on a mixture of Gaussian and quadrilateral functions is presented to process airborne bathymetric LiDAR waveforms. In the presented method, the LiDAR waveform is fitted to a combination of three functions: one Gaussian function for the water surface contribution, another Gaussian function for the water bottom contribution, and a new quadrilateral function to fit the water column contribution. The proposed method was tested on a simulated dataset and a real dataset, with the focus being mainly on the performance of retrieving bottom response and water depths. We also investigated the influence of the parameter settings on the accuracy of the bathymetry estimates. The results demonstrate that the improved quadrilateral fitting algorithm shows a superior performance in terms of low RMSE and a high detection rate in the water depth and magnitude retrieval. What’s more, compared with the use of a triangular function or the existing quadrilateral function to fit the water column contribution, the presented method retrieved the least noise and the least number of unidentified waveforms, showed the best performance in fitting the return waveforms, and had consistent fitting goodness for all different water depths.
The Impact of Human Resource Information System (HRIS) on Organizational Effectiveness: A Case Study of the Textile Industry in Thailand

Human resource information system (HRIS) has potential benefits to improve organizational performance. The purpose of this exploratory study is thus to investigate the impact of HRIS on organizational effectiveness. The textile industry in Thailand is taken as a context of the study as it faces many challenges in this globalization era. One of the industry's dilemmas is about worker conditions and the scarcity of workforce. A questionnaire survey was conducted during December 2012-March 2013. About 354 questionnaires were mailed to the random sample drawn from the Textile Directory (2006). A total of 63 usable returned questionnaires were obtained. Descriptive statistics were used to analyze the obtained data. The findings reveal that the sample respondents perceived that HRIS has a positive impact on organizational effectiveness with respect to human resource processes, time savings, cost savings, information effects, decision making and strategic impact of HR role.
Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation

GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein–protein interaction, and they colocalize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5, and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3 dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells.
Banana peel: an effective biosorbent for aflatoxins

ABSTRACT This work reports the application of banana peel as a novel bioadsorbent for in vitro removal of five mycotoxins (aflatoxins (AFB1, AFB2, AFG1, AFG2) and ochratoxin A). The effect of operational parameters including initial pH, adsorbent dose, contact time and temperature were studied in batch adsorption experiments. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and point of zero charge (pHpzc) analysis were used to characterise the adsorbent material. Aflatoxins’ adsorption equilibrium was achieved in 15 min, with highest adsorption at alkaline pH (6–8), while ochratoxin has not shown any significant adsorption due to surface charge repulsion. The experimental equilibrium data were tested by Langmuir, Freundlich and Hill isotherms. The Langmuir isotherm was found to be the best fitted model for aflatoxins, and the maximum monolayer coverage (Q0) was determined to be 8.4, 9.5, 0.4 and 1.1 ng mg−1 for AFB1, AFB2, AFG1 and AFG2 respectively. Thermodynamic parameters including changes in free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) were determined for the four aflatoxins. Free energy change and enthalpy change demonstrated that the adsorption process was exothermic and spontaneous. Adsorption and desorption study at different pH further demonstrated that the sorption of toxins was strong enough to sustain pH changes that would be experienced in the gastrointestinal tract. This study suggests that biosorption of aflatoxins by dried banana peel may be an effective low-cost decontamination method for incorporation in animal feed diets.
Uncovering Differences in Virulence Markers Associated with Achromobacter Species of CF and Non-CF Origin

Achromobacter spp. are recognized as emerging pathogens in hospitalized as well as in cystic fibrosis (CF) patients. From 2012 to 2015, we collected 69 clinical isolates (41 patient) of Achromobacter spp. from 13 patients with CF (CF isolates, n = 32) and 28 patients receiving care for other health conditions (non-CF isolates, n = 37). Molecular epidemiology and virulence potential of isolates were examined. Antimicrobial susceptibility, motility, ability to form biofilms and binding affinity to mucin, collagen, and fibronectin were tested to assess their virulence traits. The nrdA gene sequencing showed that A. xylosoxidans was the most prevalent species in both CF and non-CF patients. CF patients were also colonized with A. dolens/A. ruhlandii, A. insuavis, and A. spiritinus strains while non-CF group was somewhat less heterogenous, although A. insuavis, A. insolitus, and A. piechaudii strains were detected beside A. xylosoxidans. Three strains displayed clonal distribution, one among patients from the CF group and two among non-CF patients. No significant differences in susceptibility to antimicrobials were observed between CF and non-CF patients. About one third of the isolates were classified as strong biofilm producers, and the proportion of CF and non-CF isolates with the ability to form biofilm was almost identical. CF isolates were less motile compared to the non-CF group and no correlation was found between swimming phenotype and biofilm formation. On the other hand, CF isolates exhibited higher affinity to bind mucin, collagen, and fibronectin. In generall, CF isolates from our study exhibited in vitro properties that could be of importance for the colonization of CF patients.
Extracting macroscopic information from Web links

Much has been written about the potential and pitfalls of macroscopic Web-based link analysis, yet there have been no studies that have provided clear statistical evidence that any of the proposed calculations can produce results over large areas of the Web that correlate with phenomena external to the Internet. This article attempts to provide such evidence through an evaluation of Ingwersen's ([1998]) proposed external Web Impact Factor (WIF) for the original use of the Web: the interlinking of academic research. In particular, it studies the case of the relationship between academic hyperlinks and research activity for universities in Britain, a country chosen for its variety of institutions and the existence of an official government rating exercise for research. After reviewing the numerous reasons why link counts may be unreliable, it demonstrates that four different WIFs do, in fact, correlate with the conventional academic research measures. The WIF delivering the greatest correlation with research rankings was the ratio of Web pages with links pointing at research-based pages to faculty numbers. The scarcity of links to electronic academic papers in the data set suggests that, in contrast to citation analysis, this WIF is measuring the reputations of universities and their scholars, rather than the quality of their publications.
The NHS breast screening programme needs independent review

The BMJ has published several articles over the past few years raising concerns about the accuracy and transparency of information provided to women about the benefits and harms of mammography screening for breast cancer (BMJ 2006;332:538, doi:10.1136/bmj.332.7540.538; 2009;338:b86, doi:10.1136/bmj.b86; 2010;340:c3106, doi:10.1136/bmj.c3106). Last month the professor of complex obstetrics Susan Bewley sent us for publication an open letter to England’s cancer tsar. Here we publish the letter and Mike Richards’s response (BMJ 2011;343:d6843, doi:10.1136/bmj.d6843)
A validated bioluminescence-based assay for the rapid determination of the initial rate of kill for discovery antimalarials

Objectives: A future treatment for uncomplicated malaria will contain at least one component that exerts a rapid rate of kill. We describe here the validation and application of a simple, robust and rapid bioluminescence-based assay for the determination of the initial rate of kill in intra-erythrocytic asexual stages of Plasmodium falciparum. Methods: A modification to the concentration–response bioluminescence [here termed bioluminescence relative rate of kill (BRRoK)] assay, utilizing exposure to fold-IC50 concentrations (0.33× to 9×), was used to monitor the immediate cytocidal effect of 372 open-source compounds for antimalarial drug discovery available through the Medicines for Malaria Venture Malaria Box. Results: Antimalarial drugs that exert a rapid cytocidal effect produce a concentration-dependent loss of bioluminescence signal that correlates with available in vitro and in vivo estimates of parasite clearance time and parasite reduction ratio. Following the measurement of IC50 for the Malaria Box compounds in Dd2luc, the BRRoK assay was used to identify and rank 372 compounds for their initial cytocidal activity. Fifty-three compounds in the Malaria Box show an initial relative rate of kill greater than that of chloroquine, with 17 of these having an initial relative rate of kill greater than that of dihydroartemisinin. Conclusions: The BRRoK assay provides a rapid assay format for the estimation of a key pharmacodynamic property of antimalarial drug action. The simplicity and robustness of the assay suggests it would be readily scalable for high-throughput screening and a critical decision-making tool for antimalarial drug development.
Genome-Wide Scan for Signatures of Human Population Differentiation and Their Relationship with Natural Selection, Functional Pathways and Diseases

Genetic differences both between individuals and populations are studied for their evolutionary relevance and for their potential medical applications. Most of the genetic differentiation among populations are caused by random drift that should affect all loci across the genome in a similar manner. When a locus shows extraordinary high or low levels of population differentiation, this may be interpreted as evidence for natural selection. The most used measure of population differentiation was devised by Wright and is known as fixation index, or FST. We performed a genome-wide estimation of FST on about 4 millions of SNPs from HapMap project data. We demonstrated a heterogeneous distribution of FST values between autosomes and heterochromosomes. When we compared the FST values obtained in this study with another evolutionary measure obtained by comparative interspecific approach, we found that genes under positive selection appeared to show low levels of population differentiation. We applied a gene set approach, widely used for microarray data analysis, to detect functional pathways under selection. We found that one pathway related to antigen processing and presentation showed low levels of FST, while several pathways related to cell signalling, growth and morphogenesis showed high FST values. Finally, we detected a signature of selection within genes associated with human complex diseases. These results can help to identify which process occurred during human evolution and adaptation to different environments. They also support the hypothesis that common diseases could have a genetic background shaped by human evolution.