Miracle-dz/UniFAR-FTUs huggingface dataset:
GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.

STUDY QUESTION Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.
Natural Frequencies of Human Corticothalamic Circuits

The frequency tuning of a system can be directly determined by perturbing it and by observing the rate of the ensuing oscillations, the so called natural frequency. This approach is used, for example, in physics, in geology, and also when one tunes a musical instrument. In the present study, we employ transcranial magnetic stimulation (TMS) to directly perturb a set of selected corticothalamic modules (Brodmann areas 19, 7, and 6) and high-density electroencephalogram to measure their natural frequency. TMS consistently evoked dominant α-band oscillations (8–12 Hz) in the occipital cortex, β-band oscillations (13–20 Hz) in the parietal cortex, and fast β/γ-band oscillations (21–50 Hz) in the frontal cortex. Each cortical area tended to preserve its own natural frequency also when indirectly engaged by TMS through brain connections and when stimulated at different intensities, indicating that the observed oscillations reflect local physiological mechanisms. These findings were reproducible across individuals and represent the first direct characterization of the coarse electrophysiological properties of three associative areas of the human cerebral cortex. Most importantly, they indicate that, in healthy subjects, each corticothalamic module is normally tuned to oscillate at a characteristic rate. The natural frequency can be directly measured in virtually any area of the cerebral cortex and may represent a straightforward and flexible way to probe the state of human thalamocortical circuits at the patient's bedside.
Effector γδ T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors

γδ T lymphocytes are programmed into distinct IFN-γ–producing CD27+ (γδ27+) and IL-17–producing CD27− (γδ27−) subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their αβ Th1 (for γδ27+) and Th17 (for γδ27−) cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector γδ27+, γδ27−CCR6−, and γδ27−CCR6+ γδ T cell subsets and αβ T cells. We found they share dependence on the master transcription factors T-bet and RORγt for IFN-γ and IL-17 production, respectively. However, Eomes is fully dispensable for IFN-γ production by γδ T cells. Furthermore, the Th17 cell auxiliary transcription factors RORα and BATF are not required for IL-17 production by γδ27− cell subsets. We also show that γδ27− (but not γδ27+) cells become polyfunctional upon IL-1β plus IL-23 stimulation, cosecreting IL-17A, IL-17F, IL-22, GM-CSF, and IFN-γ. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between γδ27+ and γδ27− T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector γδ versus αβ T cell subsets.
Parasympathetic contribution to bradycardia induced by endurance training in man.

Seven normal subjects of sedentary habits were submitted to a 10 week period of endurance physical training on a cycloergometer. The training programme produced a mean 15.6 +/- 1.4% (+/- SE) increase in VO2max (from 39.7 +/- 2.0 ml . kg-1 . min-1 to 45.9 +/- 2.4 ml . kg-1 . min-1) and a reduction in resting heart rate (HR) from 69 +/- 1.9 to 58 +/- 1.7 beats . min-1 in the supine position. After pharmacological blockade of the parasympathetic system with atropine sulphate, HR rose on average by 53 +/- 3.9 beats . min-1 before training and 47 +/- 3.6 beats . min-1 after training, the difference being statistically nonsignificant. The magnitude of respiratory sinus arrhythmia (RSA) was similar before and after the period of physical conditioning. The respiratory variation in HR ( Delta HR) at the 1 litre tidal volume was 20 +/- 2.4 beats . min-1 and 20 +/- 2.6 beats . min-1 before and after training, respectively. At the 2 litre tidal volume, these values were 25 +/- 3.2 and 27 +/- 4.5 beats . min-1. Similar results were obtained with the RSA test when a group of 13 sedentary individuals (VO2max = 39.4 +/- 1.3 ml . kg-1 . min-1) was compared with a group of 7 athletes who are medium distance runners (VO2max = 53.8 +/- 1.3 ml . kg-1 . min-1). (ABSTRACT TRUNCATED AT 250 WORDS)
Rethinking Overspecification in Terms of Incremental Processing

Speakers often overspecify their referring descriptions by including more information than what is required to uniquely distinguish a referent. Although overspecification has received a substantial amount of attention, the factors that play a role in determining this behaviour are not yet well understood. Given evidence of cross-linguistic difference between English and Spanish regarding overspecification with colour adjectives, we argue that a factor that contributes to the inclusion of arguably redundant properties in a description is their incremental informativity in comprehension. We sketch a generation model that can account for this phenomenon by allowing for incremental interaction between content selection and linguistic realisation and for interdependencies between generation and processing.
Effect of anti-rat ovary antiserum on the fertilization of rat, mouse and hamster eggs in vivo and in vitro.

The effect of anti-rat-ovary antiserum prepared in the rabbit on the fertilization of rat mouse and hamster eggs was studied in vivo and in vitro. 2-4 bands were formed against rat serum testis ovary and other rat tissues while only 1 weak band was formed against mouse ovary and no band was formed against rat spermatozoa and hamster ovary. The in vitro fertilization of rat eggs was significantly by anti-ovary-rat antiserum when compared with the results with normal serum (p less than .001). Uterine insemination with rat spermatozoa exposed antiovery antiserum also caused a significant reduction in the fertilization rate (p less than .001). Fertilization was inhibited to a greater extent in rat and mouse eggs than in hamster eggs after a single injection of the antiserum. Anti-rat-ovary antiserum completely inhibited fertilization of mouse eggs and significantly inhibited fertilization of hamster eggs (p less than .001). Although fertilization failed in vitro whenever there was a precipitate on the zona pellucida of mouse and hamster eggs this was not the case with rat eggs with follicular cells. The results indicate that anti-rat-ovary antiserum is not species-specific in regard to the inhibition of fertilization.
Novel 4 GHz Interleaved SRAM Cells With Asymmetrical Precharge in 45 nm PDSOI Technology

Novel 9T/8T SRAM cell designs are demonstrated using a fully functional 75-kb L1-cache compatible interleaved hardware based design in 45 nm SOI. An integrated read stack, together with an asymmetrical precharge topology, leads to significant improvement in performance and stability. The proposed cells' yield outperforms that of register file like cells as well as other literature cells. The usage of a larger number of cells on bitlines through statistical simulations indicates that the new cells improve the array efficiency for domino based designs. The extension of the work to 32 nm technology shows the scalability of these cells with lower operating voltage, compared with conventional 6T/8T cells. Hardware based key features include improved read performance/stability, half select stability, and the ability to operate with single read and write wordline over register file like 8T cell. The measured access time improvement is shown to be more than 15% and a Vcsmin reduction of 170 mV is demonstrated at Vdd = 1 V.
Development of social-moral reasoning among Kibbutz adolescents: A longitudinal cross-cultural study.

The development of social-moral judgment among Israeli kibbutz adolescents was studied from the perspective of Kohlberg's theory of moral judgment development. The sample included 92 adolescents, 64 of whom were interviewed longitudinally over a two-to-nine year period. The study's purpose was to evaluate the validity of Kohlberg's model and measure in a cross-cultural context and to assess the cultural uniqueness of social-moral reasoning among kibbutzniks. The developmental findings strongly supported the validity of Kohlberg's structuraldevelopmental understanding of moral judgment. Stage change was found to be upward, gradual, and without significant regressions. Analyses also supported the internal consistency of the stages as operationally defined in the standardized scoring manual. There were no significant sex differences in moral development and fewer cultural differences than expected. Overall, the distribution of stage scores among the kibbutz subjects was unusually high when compared to the results of parallel studies in the United States and Turkey, the two previous longitudinal studies of moral judgment development that have used the standardized scoring system. The most important cultural variation involved the use of Stages 4/5 and 5. Whereas all of Kohlberg's stages were present among kibbutz members, not all elements of kibbutz postconventional reasoning were present in Kohlberg's model or scoring manual. In particular, the communal emphasis and collective moral principles of the kibbutz subjects were partially missed or misunderstood. This article presents the results of a longitudinal study of social-moral reasoning among Israeli adolescents. The research oh
DEMOGRAPHIC GENETICS OF A PIONEER TROPICAL TREE SPECIES: PATCH DYNAMICS, SEED DISPERSAL, AND SEED BANKS

We consider whether changes in population‐genetic structure through the life cycle of Cecropia obtusifolia, a tropical pioneer tree, reflect its gap‐dependent demography and the role of evolutionary processes that are important for this species. We asked whether the spatial scale at which population‐genetic subdivision occurs corresponds to the scale of habitat patchiness created by gap dynamics; whether patterns of seed dispersal and storage in the soil affect spatial genetic patterns; and whether spatial genetic patterns change through the species life cycle. We estimated Wright's F‐statistics for six successive life‐history stages for individuals grouped into subpopulations according to occurrence in natural gaps, physical proximity, or occurrence within large quadrats. For each life stage, FST‐statistics were significantly higher when individuals were grouped by gaps, although concordant patterns across life stages for the three grouping methods were obtained. This supports the hypothesis that patchy recruitment in gaps or among‐gap heterogeneity influences the species' genetic structure. F‐statistics of seeds collected from females before dispersal (tree seeds), seed‐rain seeds, soil seeds, seedlings, juveniles, and adults grouped by gaps, were, respectively: FIT = 0.004, 0.160, 0.121, 0.091, –0.0002, –0.081; FIS = –0.032, 0.124, 0.118, 0.029, –0.016, –0.083; and FST = 0.035, 0.041, 0.003, 0.063, 0.015, 0.002. Spatial genetic differentiation in rain seeds was not significantly lower than that of tree seeds. The loss of genetic structure in the soil seed bank, relative to that found in the seed rain may be due to sampling artifacts, but alternative explanations, such as microsite selection or temporal Wahlund effect are also discussed. If structure among soil seeds is unbiased, the peak in seedling FST may be due to microsite selection. FIS of seeds in the rain and soil were significantly greater than zero. A Wahlund effect is the most likely cause of these positive FIS values. Such fine‐scale substructuring could be caused by correlated seed deposition by frugivores. The decrease in FIS from seedlings to adults could result from loss of fine‐scale genetic structure during stand thinning or from selection.
Persistence of parvovirus B19 DNA in synovium of patients with haemophilic arthritis

A progressive arthropathy develops commonly in haemophiliacs and its pathogenesis is not fully understood. Human parvovirus B19 has been associated with several diseases including acute and chronic arthropathy and some studies suggest its implication in chronic inflammatory diseases of the joints such as rheumatoid arthritis. In haemophiliacs parvovirus B19 infection occurs very frequently because of its transmission with plasma derivatives. In order to assess a role of B19 virus in haemophilic arthritis, synovial tissue samples from patients with haemophilia with arthritis and from patients, nonhaemophiliacs, with arthrosis or with joint trauma were examined for B19 DNA by nested PCR. In addition, the prevalence of antibody to parvovirus B19 NS1 protein as a possible serological marker of persistent B19 infection was tested and the association of the outcome of parvovirus infection with genetic diversity of B19 P6 promoter sequences was investigated. B19 DNA was detected in the synovial tissue of 31% of haemophiliacs with progressive arthropathy and of 5% of control patients. Fourteen out of 17 patients (82%) with haemophilic arthritis and with B19 DNA in their synovial membranes had IgG antibodies against the nonstructural protein NS1 of parvovirus B19. On the other hand, 19% of patients with haemophilia with B19 PCR negative synovial tissue and 21% of controls showed anti‐NS1 antibodies. The P6 promoter presented specific sites of point mutations shared frequently by isolates from patients with haemophilia and arthritis. These results indicate that B19 DNA can persist in the synovial membranes of patients with haemophilic arthritis significantly more frequently in comparison to control individuals with arthrosis or joint trauma and show a correlation between anti‐ NS1 antibody presence and B19 DNA persistence in the synovial tissue. J. Med. Virol. 65:402–407, 2001. © 2001 Wiley‐Liss, Inc.
The Effect of Coated- ${\rm Fe}_{3}{\rm O}_{4}$ Nanoparticles on Magnetic Properties of Ferrogels Produced by Diffusion Route

In this paper, we report a novel, nontoxic and environmentally friendly diffusion route to obtain superparamagnetic poly(vinyl alcohol) (PVA)/polyacrylic acid (PAA) coated- Fe3O4 ferrogels (D-PAA). Magnetic properties of these D-PAA ferrogels were compared with regular ones produced with noncoated magnetite nanoparticles (D-NC). Their morphological features were studied by SEM-FEG. Absorption tests were performed in order to assess diffusion of nanoparticles into the PVA-polymeric matrix. D-PAA samples exhibit better dispersion of the nanoparticles within polymeric matrix in comparison with D-NC samples. The effective diffusion coefficients (Deff) obtained, as well as the nature of the functional groups in question, suggests interactions between the PAA and PVA in D-PAA samples. In D-NC samples is presumed that the iron atoms in the surface of the nanoparticles act as Lewis acids and coordinates with molecules that donate lone-pair electrons. The results suggest a reduction in the magnetic interaction for the coated nanoparticles case, due to the improvement of the dispersion of the nanoparticles into the polymeric matrix.
MICROSPHERES AS FLOATING DRUG-DELIVERY SYSTEMS TO INCREASE GASTRIC RETENTION OF DRUGS

Gastric emptying is a complex process, which is highly variable and makes in vivo performance of the drug-delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 h. The floating or hydrodynamically controlled drug-delivery systems are useful in such applications. The present review addresses briefly the physiology of the gastric emptying process with respect to floating drug-delivery systems. In recent years, the multiparticulate drug-delivery systems are used in the oral delivery of drugs. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. Such systems have more advantages over the single-unit dosage forms. The development of floating microspheres involves different solvent evaporation techniques to create the hollow inner core. The present review addresses the preparation and characterization of the floating microspheres for the peroral route of administration of the drug.
Insight Into Electron Traps and Their Energy Distribution Under Positive Bias Temperature Stress and Hot Carrier Aging

The access transistor of SRAM can suffer both positive bias temperature instability (PBTI) and hot carrier aging (HCA) during operation. The understanding of electron traps (ETs) is still incomplete and there is little information on their similarity and differences under these two stress modes. The key objective of this paper is to investigate ETs in terms of energy distribution, charging and discharging properties, and generation. We found that both PBTI and HCA can charge ETs which center at 1.4 eV below conduction band (Ec) of high-k dielectric, agreeing with theoretical calculation. For the first time, clear evidences are presented that HCA generates new ETs, which do not exist when stressed by PBTI. When charged, the generated ETs' peak is 0.2 eV deeper than that of preexisting ETs. In contrast with the power law kinetics for charging the preexisting ETs, filling the generated ETs saturates in seconds, even under an operation bias of 0.9 V. ET generation shortens device lifetime and must be included in modeling HCA. A cyclic and antineutralization ETs model is proposed to explain PBTI and HCA degradation, which consists of preexisting cyclic ETs, generated cyclic ETs, and antineutralization ETs.
Barriers to Peritoneal Dialysis in Aboriginal Patients

Background: Aboriginal people in Canada have an unduly high burden of end-stage kidney disease (ESKD) and many live in rural settings. Peritoneal dialysis (PD) is a home-based dialysis modality that may provide a valuable alternative to in-center hemodialysis which is relatively underutilized by the Aboriginal population. Objective: We aim to assess the barriers to PD utilization in Aboriginal patients with ESKD. Design: This article is a prospective observational cohort study. Setting: The setting involves 3 predialysis clinics in Winnipeg, Kingston, and Moose Factory. Patients: The patients were 99 individuals (67 non-Aboriginal and 32 Aboriginal) who were at least 18 years of age with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2, and were enrolled in one of the 3 study sites from April 2011 to October 2013. Measurements: Patient demographics and comorbidities were documented. Barriers to PD, PD as modality choice, and Aboriginal status were assessed via patient survey upon study enrollment. PD use as the initial dialysis modality was assessed via monthly patient follow-up for 1 year after enrollment in the study. Methods: The patient survey was created based on literature review of known barriers to PD, repaired based on direct patient feedback, and tested for reliability via the test-retest method. Differences in PD choice, barriers to PD, and PD use between Aboriginal and non-Aboriginal patients were determined by chi-square test and logistic regression. Results: All patients enrolled in the study completed the survey. Mean age was 65.5 versus 54.6 years for non-Aboriginals and Aboriginals, respectively. Barriers to PD significantly associated with Aboriginal status were lack of money (odds ratio [OR]: 21.3; 95% confidence interval [CI]: 5.3-86.4; P < .0001) and anxiety (OR: 2.8; 95% CI: 1.1-7.1; P = .03). There was no difference in PD choice between non-Aboriginals and Aboriginals (66.7% vs 68.8%, respectively; P = .83). One of 67 non-Aboriginals (1.5%) and 5 of 32 Aboriginals (15.6%) died prior to initiating dialysis (P = .013). No significant difference was observed between non-Aboriginals (33%) and Aboriginals (28%) in use of PD (P = .81). Limitations: Small sample size was a limitation of this study. Conclusions: Aboriginal people in Canada have a disproportionately large burden of ESKD, and PD could provide an alternative to in-center hemodialysis for those living in rural areas. Our study identified anxiety and lack of money as barriers to PD significantly associated with Aboriginal status. When choosing dialysis modality, shared decision making between physicians and patient is of key importance to weigh all potential benefits and risks and emphasize the Aboriginal patient’s values and preferences. These results can be used to guide future research and to help devise interventions targeting barriers to PD in Aboriginals.