julilili42/papers huggingface dataset:
The progress and prospect of assessment measures of uterine cavity function for infertility patients
2021-05-13

Objective: To explore the progress and prospect of evaluation methods for infertility patients. Methods: From September 2017 to December 2020, 199 cases of infertility patients who have accepted mini-hysteroscopy examination in the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. The patients who had primary ovary insufficiency, tubal infertility were excluded; patients with hysteroscopy contradiction, such as acute or sub-acute vaginal tract inflammation, endometrium lesion or endometrium carcinoma, severe cardiovascular, liver or kidney insufficiency were excluded. 40 patients were excluded and 15 patients lost follow up, 144 patients were eventually included in the analysis. The patient's age, body mass index, infertility etiology, preoperative and postoperative stimulate ovulation cycle, pregnancy state and pregnancy time were recorded. The effect of mini-hysteroscopy on ovulation induction cycle was analyzed in pregnant patients. Results: The average age of 144 patients was 32.10±4.67 years old. 96 (66.67%) patients were found to have intrauterine abnormalities, while 48 (33.33%) patients were found to have normal intrauterine cavity. 48 cases of pregnancy, accounting for 33.33%; the median and interquartile ranges [M (Q1, Q3)] of ovulation induction cycles before and after surgery were respectively [3 (0, 5)], [2 (1,3)], the difference was statistically significant (P < 0.05). Among the 48 pregnant patients, 32 of them had no structural lesions in hysteroscopy, the ovulation induction cycle of these patients before and after hysteroscopy were respectively [5 (0, 9)], [1 (0, 3)], the difference was statistically significant (P < 0.05). Conclusion: Uterine cavity evaluation is important for the assessments of fertility. As an advanced diagnosis instrument, mini-hysteroscopy can not only timely detect the intrauterine abnormalities of patients, but also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.
Effects of the treatment of the mass quadrupole moment on ray-tracing applications for rapidly rotating neutron stars
2021-05-13

ABSTRACT The Neutron Star Interior Composition Explorer (NICER) mission has provided a unique opportunity to constrain the equation of state of neutron stars by using the technique of pulse-profile modelling. This technique requires accurate and efficient ray-tracing, that in turn requires a robust representation of the space–time around a neutron star. Several exact and approximate metrics have been proposed, and used, to perform ray-tracing around neutron stars, with both moderate and fast rotation. In this paper, we perform a comparison between several of these metrics, when used for ray-tracing. We calculate the shape of the neutron star as seen by a distant observer using two different surface formulae, the thermal spectrum and pulse profiles from circular and crescent-shaped hotspots, for four configurations of pulsars with rotation rates ranging from 622 to 1000 Hz, and using both a moderate and a stiff equation of state to include realistic and extreme cases. We find small differences between the metrics for rotation frequencies starting at that could theoretically be used for constraining the quadrupole moment or the space–time models. We also determine the practicality of use of each metric in larger-scale applications such as pulse-profile modelling.
Exploring the Unfolding of Dynamic Effects with Continuous-Time Models: Recommendations Concerning Statistical Power to Detect Peak Cross-Lagged Effects
2021-05-14

Cross-lagged panel models have been commonly applied to investigate the dynamic interplay of variables. In such discrete-time models, the size of the cross-lagged effects depends on the length of the time interval between the measurement occasions. Continuous-time modeling allows to explore this interval dependence of cross-lagged effects and thus to identify the maximal “peak” cross-lagged effects. To detect these peak effects, sufficient statistical power is needed. Based on results from a simulation study, we employed machine learning algorithms to identify a highly accurate prediction model. Results are incorporated into a Shiny App (available at https://psychtools.shinyapps.io/ContinuousTimePowerCalculation) for easy power calculations. Although limitations apply, our results might be helpful for study planning.
Relative Age-Related Biases in Objective and Subjective Assessments of Performance in Talented Youth Soccer Players
2021-05-14

Talent research has recommended that multidimensional assessments of performance are needed to improve the identification and development of talented young athletes. However, factors such as the relative age effect may cloud our ability to assess factors related to performance. The aim of this study was to determine the extent of any relationship between soccer players' chronological and relative age, and objective and subjective performance assessments. Data for highly talented male soccer players selected into the German Soccer Associations' talent promotion program ( N = 16,138) for U12 to U15 age groups ( M age = 12.62 ± 1.04 years) were examined. Besides anthropometric assessments, players completed a battery of five motor tests that objectively assessed speed abilities and technical skills (specifically sprint, agility, dribbling, ball control, and juggling). In addition, coaches subjectively rated players on their kicking, tactical, and psychosocial skills, as well as providing holistic evaluations of each player's current and future performance levels. Correlation analyses were used to investigate the extent of any relationships between the chronological and relative age of players and their results for each of the assessments. A strong linear decrease in the frequency of later-born players confirmed the overrepresentation of early-born players in all age groups (0.92 ≤ | r| ≤ 0.95, each p &amp;lt; 0.001). From U12 to U15, significant (each p &amp;lt; 0.001) correlations were found between the chronological age of players and their height (| r | = 0.70), weight (| r | = 0.69), speed abilities (| r| = 0.38), and technical skills (| r| = 0.43). When evaluating each age group separately, small effects were found when correlating relative age with the anthropometric assessments (0.18 ≤ | r| ≤ 0.26), and only trivial effects with speed abilities and technical skills (0.01 ≤ | r| ≤ 0.06). Similarly, low correlations were found for the subjective evaluations of kicking, tactical, and psychosocial skills with chronological age across age groups (0.03 ≤ | r | ≤ 0.07), and with relative age in each age group (0.01 ≤ | r | ≤ 0.11). The results show a skewed distribution toward early-born players and—in reference to their relative age—advanced performance in late-born athletes. However, trends toward a better holistic rating of early-born players for current and future performance levels were found. Coaches should be aware of these effects during talent selection, but also when interpreting results from subjective and objective assessments of performance.
Randomised controlled trials in medical AI: ethical considerations
2021-05-14

In recent years, there has been a surge of high-profile publications on applications of artificial intelligence (AI) systems for medical diagnosis and prognosis. While AI provides various opportunities for medical practice, there is an emerging consensus that the existing studies show considerable deficits and are unable to establish the clinical benefit of AI systems. Hence, the view that the clinical benefit of AI systems needs to be studied in clinical trials—particularly randomised controlled trials (RCTs)—is gaining ground. However, an issue that has been overlooked so far in the debate is that, compared with drug RCTs, AI RCTs require methodological adjustments, which entail ethical challenges. This paper sets out to develop a systematic account of the ethics of AI RCTs by focusing on the moral principles of clinical equipoise, informed consent and fairness. This way, the objective is to animate further debate on the (research) ethics of medical AI.
Impact of 18F-FDG-PET/CT on Clinical Management in Patients with Cholangiocellular Carcinoma
2021-05-14

Objective: To determine the impact of 18F-FDG-PET/CT on clinical management of patients with cholangiocellular carcinoma (CCA). Methods: Patients with CCA undergoing clinically indicated 18F-FDG-PET/CT between 04/2013 and 08/2018 were prospectively included in a local PET/CT registry study. Intended clinical management (“non-treatment” such as watchful-waiting or additional diagnostic tests, and “palliative” or “curative treatment”) was recorded before and after PET/CT. Changes in intended management after PET/CT were analyzed. Results: 27 patients (mean age: 60 years, IQR: 51.5–67.5 years, 56% males) with 43 PET/CT examinations were included. Intended management changed in 35/43 cases (81.4%) following PET/CT. Major changes (i.e., between “non-treatment” and “treatment” strategies or between a “curative” and “palliative” treatment goal) occurred in 27/43 (62.8%) cases. Before PET/CT, additional imaging and/or biopsy were intended in 21/43 (48.8%) and 9/43 (20.9%) cases, respectively. After PET/CT, further imaging was carried out in one case and imaging-targeted biopsy in eight cases. Although the absolute number of biopsies after PET/CT did not decrease, in only one of these eight cases biopsy had already been planned before PET/CT, whereas in the other eight cases, the originally planned biopsies were dispensable after PET/CT. Conclusions: 18F-FDG-PET/CT significantly impacts clinical management of patients with CCA. It guides decisions on treatment strategy (especially curative vs palliative treatment goal) and on additional tests, particularly by helping referring clinicians to avoid unnecessary imaging and by guiding targeted biopsy. Advances in knowledge: Systematic implementation of 18F-FDG-PET/CT may enable a more appropriate and tailored treatment of patients with CCA, especially in cases of suspected recurrence.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
2021-05-14

In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
Gluon parton densities in soft-wall AdS/QCD
2021-05-14

We study the gluon parton densities [parton distribution functions (PDFs),\\ntransverse momentum distributions (TMDs), generalized parton distributions\\n(GPDs)] and form factors in soft-wall AdS/QCD. We show that the power behavior\\nof gluon parton distributions and form factors at large values of the\\nlight-cone variable and large values of square momentum is consistent with\\nquark counting rules. We also show that the transverse momentum distributions\\nderived in our approach obey the model-independent Mulders-Rodrigues\\ninequalities without referring to specific model parameters. All gluon parton\\ndistributions are defined in terms of the unpolarized and polarized gluon PDFs\\nand profile functions. The latter are related to gluon PDFs via differential\\nequations.\\n
Mass spectrometry for quality control of bispecific antibodies after SDS‐PAGE in‐gel digestion
2021-05-14

Abstract Recombinant bispecific antibodies (bsAbs) are increasingly included in regimens for cancer therapy. Strict good manufacturing practice (GMP) compliant quality control measures are required to ensure quality and safety of these innovative biologicals. Gel electrophoresis (sodium dodecyl sulfate‐polyacrylamide gel electrophoresis [SDS‐PAGE]) and size exclusion chromatography (SEC) are the cornerstones of quality control methods. BsAbs are often prone to aggregation or incomplete synthesis due to their artificial nature. In addition, host cell proteins and host cell DNA as well as impurities from the purification process itself constitute potential contaminants. Such impurities may then appear as additional, unexpected bands or peaks on SDS‐PAGE gels and SEC, respectively. Here we describe a standardized protocol for rapid analysis of recombinant antibodies by mass spectrometry (MS) after tryptic digestion of bands excised from SDS‐PAGE gels. We have used this protocol to characterize unexpected “contaminating bands” that were observed during the clinical development of a novel bsAb with PSMAxCD3 specificity, either during the production of the protein itself or during the development of a surrogate molecule for evaluation in syngeneic mouse models. MS analysis allowed us to precisely determine the origin of these bands, which resulted from artifacts or from incomplete protein synthesis. The combined utilization of SDS‐PAGE und MS can therefore substantially support GMP‐compliant production of recombinant proteins.
Teachers’ Psychological Characteristics: Do They Matter for Teacher Effectiveness, Teachers’ Well-being, Retention, and Interpersonal Relations? An Integrative Review
2021-05-15

Abstract This integrative review aims to render a systematic account of the role that teachers’ psychological characteristics, such as their motivation and personality, play for critical outcomes in terms of teacher effectiveness, teachers’ well-being, retention, and positive interpersonal relations with multiple stakeholders (e.g., students, parents, principals, colleagues). We first summarize and evaluate the available evidence on relations between psychological characteristics and these outcomes derived in existing research syntheses (meta-analyses, systematic reviews). We then discuss implications of the findings regarding the eight identified psychological characteristics—self-efficacy, causal attributions, expectations, personality, enthusiasm, emotional intelligence, emotional labor, and mindfulness—for research and educational practice. In terms of practical recommendations, we focus on teacher selection and the design of future professional development activities as areas that particularly profit from a profound understanding of the relative importance of different psychological teacher characteristics in facilitating adaptive outcomes.
Targeting CSF1R Alone or in Combination with PD1 in Experimental Glioma
2021-05-15

Glioblastoma is an aggressive primary tumor of the central nervous system. Targeting the immunosuppressive glioblastoma-associated microenvironment is an interesting therapeutic approach. Tumor-associated macrophages represent an abundant population of tumor-infiltrating host cells with tumor-promoting features. The colony stimulating factor-1/ colony stimulating factor-1 receptor (CSF-1/CSF1R) axis plays an important role for macrophage differentiation and survival. We thus aimed at investigating the antiglioma activity of CSF1R inhibition alone or in combination with blockade of programmed death (PD) 1. We investigated combination treatments of anti-CSF1R alone or in combination with anti-PD1 antibodies in an orthotopic syngeneic glioma mouse model, evaluated post-treatment effects and assessed treatment-induced cytotoxicity in a coculture model of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) ex vivo. Anti-CSF1R monotherapy increased the latency until the onset of neurological symptoms. Combinations of anti-CSF1R and anti-PD1 antibodies led to longterm survivors in vivo. Furthermore, we observed treatment-induced cytotoxicity of combined anti-CSF1R and anti-PD1 treatment in the PDM/TILs cocultures ex vivo. Our results identify CSF1R as a promising therapeutic target for glioblastoma, potentially in combination with PD1 inhibition.
Therapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel Therapeutic Approach in Breast Cancer
2021-05-15

Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in multiple malignancies, including about 85% of patients with estrogen receptor positive (ER+) breast cancer. Besides being studied as a prognostic marker, BCL-2 is investigated as a therapeutic target in ER+ breast cancer. Here, we introduce a new exosome-based strategy to target BCL-2 using genetically modified natural killer (NK) cells. The NK cell line NK92MI was lentivirally transduced to express and load BCL-2 siRNAs (siBCL-2) into exosomes (NKExos) and then evaluated for its potential to treat ER+ breast cancer. Transfected NK92MI cells produced substantial levels of BCL-2 siRNAs, without substantially affecting NK cell viability or effector function and led to loading of siBCL-2 in NKExos. Remarkably, targeting BCL-2 via siBCL-2 NKExos led to enhanced intrinsic apoptosis in breast cancer cells, without affecting non-malignant cells. Together, our prototypical results for BCL-2 in breast cancer provide proof of concept for a novel strategy to utilize NKExos as a natural delivery vector for siRNA targeting of oncogenes.
Hypoxia‐Inducible Factor 1 Alpha–Mediated RelB/APOBEC3B Down‐regulation Allows Hepatitis B Virus Persistence
2021-05-15

Background and Aims Therapeutic strategies against HBV focus, among others, on the activation of the immune system to enable the infected host to eliminate HBV. Hypoxia‐inducible factor 1 alpha (HIF1α) stabilization has been associated with impaired immune responses. HBV pathogenesis triggers chronic hepatitis‐related scaring, leading inter alia to modulation of liver oxygenation and transient immune activation, both factors playing a role in HIF1α stabilization. Approach and Results We addressed whether HIF1α interferes with immune‐mediated induction of the cytidine deaminase, apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B; A3B), and subsequent covalently closed circular DNA (cccDNA) decay. Liver biopsies of chronic HBV (CHB) patients were analyzed by immunohistochemistry and in situ hybridization. The effect of HIF1α induction/stabilization on differentiated HepaRG or mice ± HBV ± LTβR‐agonist (BS1) was assessed in vitro and in vivo . Induction of A3B and subsequent effects were analyzed by RT‐qPCR, immunoblotting, chromatin immunoprecipitation, immunocytochemistry, and mass spectrometry. Analyzing CHB highlighted that areas with high HIF1α levels and low A3B expression correlated with high HBcAg, potentially representing a reservoir for HBV survival in immune‐active patients. In vitro , HIF1α stabilization strongly impaired A3B expression and anti‐HBV effect. Interestingly, HIF1α knockdown was sufficient to rescue the inhibition of A3B up‐regulation and ‐mediated antiviral effects, whereas HIF2α knockdown had no effect. HIF1α stabilization decreased the level of v‐rel reticuloendotheliosis viral oncogene homolog B protein, but not its mRNA, which was confirmed in vivo . Noteworthy, this function of HIF1α was independent of its partner, aryl hydrocarbon receptor nuclear translocator. Conclusions In conclusion, inhibiting HIF1α expression or stabilization represents an anti‐HBV strategy in the context of immune‐mediated A3B induction. High HIF1α, mediated by hypoxia or inflammation, offers a reservoir for HBV survival in vivo and should be considered as a restricting factor in the development of immune therapies.
Nocathioamides, Uncovered by a Tunable Metabologenomic Approach, Define a Novel Class of Chimeric Lanthipeptides
2021-05-15

Abstract The increasing number of available genomes, in combination with advanced genome mining techniques, unveiled a plethora of biosynthetic gene clusters (BGCs) coding for ribosomally synthesized and post‐translationally modified peptides (RiPPs). The products of these BGCs often represent an enormous resource for new and bioactive compounds, but frequently, they cannot be readily isolated and remain cryptic. Here, we describe a tunable metabologenomic approach that recruits a synergism of bioinformatics in tandem with isotope‐ and NMR‐guided platform to identify the product of an orphan RiPP gene cluster in the genomes of Nocardia terpenica IFM 0406 and 0706 T . The application of this tactic resulted in the discovery of nocathioamides family as a founder of a new class of chimeric lanthipeptides I.
cGMP and mitochondrial K+ channels—Compartmentalized but closely connected in cardioprotection
2021-05-15

The 3′,5′‐cGMP pathway triggers cytoprotective responses and improves cardiomyocyte survival during myocardial ischaemia and reperfusion (I/R) injury. These beneficial effects were attributed to NO‐sensitive GC induced cGMP production leading to activation of cGMP‐dependent protein kinase I (cGKI). cGKI in turn phosphorylates many substrates, which eventually facilitate opening of mitochondrial ATP‐sensitive potassium channels ( mito K ATP ) and Ca 2+ ‐activated potassium channels of the BK type ( mito BK). Accordingly, agents activating mito K ATP or mito BK provide protection against I/R‐induced damages. Here, we provide an up‐to‐date summary of the infarct‐limiting actions exhibited by the GC/cGMP axis and discuss how mito K ATP and mito BK, which are present at the inner mitochondrial membrane, confer mito‐ and cytoprotective effects on cardiomyocytes exposed to I/R injury. In view of this, we believe that the functional connection between the cGMP cascade and mito K + channels should be exploited further as adjunct to reperfusion therapy in myocardial infarction. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc