bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI3Kα inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8+T cells and promoting fatty acid metabolism
Authors: Sun Pu , Zhang Xi , Wang Rong-Jing , Ma Qing-Yang , Xu Lan , Wang Yi , Liao Hui-Ping , Wang Hai-Long , Hu Lan-Dian , Kong Xiangyin , Ding Jian , Meng Ling-Hua 
Published: August 2021

BackgroundThe phosphatidylinositol 3-kinase (PI3K) is frequently hyperactivated in cancer and plays important roles in both malignant and immune cells. The effect of PI3Kα inhibitors on the tumor microenvironment (TME) remains largely unknown. Here, we investigated the modulation of the TME by a clinical PI3Kα-specific inhibitor CYH33.MethodsThe activity of CYH33 against a panel of murine tumors in the immune-competent context or athymic mice was detected. Single-cell RNA sequencing and multi-parameter flow cytometry were performed to determine the immune profiling of TME. The effect of CYH33 on immune cells was conducted with primary murine cells.ResultsCYH33 exhibited more potent antitumor activity in immune-competent context. CYH33 enhanced the infiltration and activation of CD8+T and CD4+T cells, while attenuating M2-like macrophages and regulatory CD4+T cells. Increase in memory T cells was confirmed by the induction of long-term immune memory on CYH33 treatment. Mechanistically, CYH33 relieved the suppressed expansion of CD8+T cells via preferential polarization of the macrophages to the M1 phenotype. CYH33 promoted fatty acid (FA) metabolism in the TME, while FA enhanced the activity of CD8+T cells in vitro. The combination of CYH33 with the FA synthase (FASN) inhibitor C75 synergistically inhibited tumor growth with enhanced host immunity.ConclusionsCYH33 induces immune activation and synergizes with FASN inhibitor to further promote the antitumor immunity, which gains novel insights into how PI3K inhibitors exert their activity by modulating TME and provides a rationale for the concurrent targeting of PI3K and FASN in breast cancer treatment.
Leadership gender disparity in the fifty highest ranking North American universities: Thematic analysis under a theoretical lens
Authors: Azizi Hawmid , Abdellatif Waleed , Nasrullah Muazzam , Ali Shozab , Ding Jeffrey , Khosa Faisal 
Published: August 2021

AbstractBackgroundDespite changes in the discourse around gender distributions within academic leadership, women continue to be under-represented in academia. Our study aims to identify the extent of gender disparity in the academic leadership in the top 50 North American universities and to critically analyse the contributing factors through a comprehensive theoretical framework.MethodsWe adopted the theoretical framework of leadership continuum model. A retrospective analysis of the gender of the leadership ranks was conducted between December 2018 and March 2019 for the top 50 universities in North America (2019 Quacquarelli Symonds World University Ranking system). The leadership hierarchy was classified into six tiers.ResultsA total of 5806 faculty members from 45 US and five Canadian universities were included. Women were overall less likely to be in a senior leadership role than men (48.7% vs 51.3%; p value=0.05). Women accounted for fewer positions than men for resident/chancellor (23.8% vs 76.2%; p value&lt;0.001), vice-president/vice-chancellor (36.3% vs 63.7%; p value&lt;0.001), vice provost (42.7% vs 57.3%; p value=0.06), dean (38.5% vs 61.5%; p value&lt;0.001) and associate dean (48.2% vs 51.8%; p-value=0.05). Women however were in a greater proportion in the assistant dean positions (63.8% vs 36.2%; p value&lt;0.001).ConclusionLeadership gender imbalance is trans-organisational and transnational within the top 50 universities of North America and progressively widens towards the top leadership pyramid. This correlates with the lack of women leadership progress and sustainability in later cycles of the leadership continuum model (beyond assistant dean).
Constraints on the spatial variation of Planck constant
Authors: Fiordilino Emilio 
Published: August 2021

AbstractInspired by recently published researches, we present two protocols for setting an upper limit to the claimed variation of$$\hbar $$ħupon the position. The protocols, both within today state of art, involve the use of two delayed laser pulses driving an atom. The distinct positions of the laboratory, due to the Earth motion, affects$$\hbar $$ħand hence the atomic dynamics. The first protocol measures the difference in population of the atomic ground state while the second one the red-shift of the harmonics emitted by the atom in the two moments of the experiment. The protocols improve the reported upper limit of$$\varDelta \hbar /\hbar $$Δħ/ħ. The theory shows that$$\hbar (\varvec{r})$$ħ(r)induces a chaotic evolution to the atom. This form of Chaos is generated by a variation of a physical parameter and is one example of Parametric Chaos.
The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets
Authors: van Tilburg Cornelis M. , Pfaff Elke , Pajtler Kristian W. , Langenberg Karin P.S. , Fiesel Petra , Jones Barbara C. , Balasubramanian Gnana Prakash , Stark Sebastian , Johann Pascal D. , Blattner-Johnson Mirjam , Schramm Kathrin , Dikow Nicola , Hirsch Steffen , Sutter Christian , Grund Kerstin , von Stackelberg Arend , Kulozik Andreas E. , Lissat Andrej , Borkhardt Arndt , Meisel Roland , Reinhardt Dirk , Klusmann Jan-Henning , Fleischhack Gudrun , Tippelt Stephan , von Schweinitz Dietrich , Schmid Irene , Kramm Christof M. , von Bueren André O. , Calaminus Gabriele , Vorwerk Peter , Graf Norbert , Westermann Frank , Fischer Matthias , Eggert Angelika , Burkhardt Birgit , Wößmann Wilhelm , Nathrath Michaela , Hecker-Nolting Stefanie , Frühwald Michael C. , Schneider Dominik T. , Brecht Ines B. , Ketteler Petra , Fulda Simone , Koscielniak Ewa , Meister Michael T. , Scheer Monika , Hettmer Simone , Schwab Matthias , Tremmel Roman , Øra Ingrid , Hutter Caroline , Gerber Nicolas U. , Lohi Olli , Kazanowska Bernarda , Kattamis Antonis , Filippidou Maria , Goemans Bianca , Zwaan C. Michel , Milde Till , Jäger Natalie , Wolf Stephan , Reuss David , Sahm Felix , von Deimling Andreas , Dirksen Uta , Freitag Angelika , Witt Ruth , Lichter Peter , Kopp-Schneider Annette , Jones David T.W. , Molenaar Jan J. , Capper David , Pfister Stefan M. , Witt Olaf 
Published: August 2021

Abstract

INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99–not applicable], compared with 117 days (95% CI, 106–143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases.

Significance:
The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes.
See related commentary by Eggermont et al., p. 2677 .
This article is highlighted in the In This Issue feature, p. 2659
Why does rapid contraction of the radius of maximum wind precede rapid intensification in tropical cyclones?
Authors: Li Yuanlong , Wang Yuqing , Lin Yanluan , Wang Xin 
Published: August 2021

AbstractThe radius of maximum wind (RMW) has been found to contract rapidly well preceding rapid intensification in tropical cyclones (TCs) in recent literature but the understanding of the involved dynamics is incomplete. In this study, this phenomenon is revisited based on ensemble axisymmetric numerical simulations. Consistent with previous studies, because the absolute angular momentum (AAM) is not conserved following the RMW, the phenomenon can not be understood based on the AAM-based dynamics. Both budgets of tangential wind and the rate of change in the RMW are shown to provide dynamical insights into the simulated relationship between the rapid intensification and rapid RMW contraction. During the rapid RMW contraction stage, due to the weak TC intensity and large RMW, the moderate negative radial gradient of radial vorticity flux and small curvature of the radial distribution of tangential wind near the RMW favor rapid RMW contraction but weak diabatic heating far inside the RMW leads to weak low-level inflow and small radial absolute vorticity flux near the RMW and thus a relatively small intensification rate. As RMW contraction continues and TC intensity increases, diabatic heating inside the RMW and radial inflow near the RMW increase, leading to a substantial increase in radial absolute vorticity flux near the RMW and thus the rapid TC intensification. However, the RMW contraction rate decreases rapidly due to the rapid increase in the curvature of the radial distribution of tangential wind near the RMW as the TC intensifies rapidly and RMW decreases.
Global Mesoscale Convective System Latent Heating Characteristics from GPM Retrievals and an MCS Tracking Dataset
Authors: Liu Nana , Leung L. Ruby , Feng Zhe 
Published: August 2021

AbstractThe distribution of latent heating released by mesoscale convective systems (MCSs) plays a crucial role in global energy and water cycles. To investigate the characteristics of MCS latent heating, five years (2014–19) of Global Precipitation Measurement (GPM) Ku-band Precipitation Radar observations and latent heating retrievals are combined with a newly developed global high-resolution (~10 km, hourly) MCS tracking dataset. The results suggest that midlatitude MCSs are shallower and have a lower maximum precipitation rate than tropical MCSs. However, MCSs occurring in the midlatitudes have larger precipitation areas and higher stratiform rain volume fraction, in agreement with previous studies. With substantial spatial and seasonal variability, MCS latent heating profiles are top-heavier in the middle and high latitudes than those in the tropics. Larger magnitudes of latent heating in the stratiform regions are found over the ocean than over land, which is the case for both the tropics and midlatitudes. The larger magnitude is related to a larger precipitating area/volume rather than a higher storm height or more intense convective core typically associated with land systems. A majority of midlatitude MCSs have a relatively high (>70%) stratiform fraction while this is not the case for tropical MCSs, suggesting that midlatitude MCSs tend to produce more stratiform rain while tropical MCSs are more convective. Importantly, the results of this study indicate that storm intensity, latent heating, and rainfall are different metrics of MCSs that can provide multiple constraints to inform development of convection parameterizations in global models.
Statistical Relationships between Two Types of Heavy Rainfall and Low-Level Jets in South China
Authors: Li Xiaoqing , Du Yu 
Published: August 2021

AbstractTwo types of heavy rainfall, namely warm-sector and frontal heavy rainfall, coexist in South China during the presummer rainy season and manifest as varying mechanisms and features. They both exhibit close relationships with two types of low-level jets (LLJs): the boundary layer jet (BLJ) and synoptic-system-related low-level jet (SLLJ), but in different ways. The motivation of the present study is to elucidate the statistical relations between the two types of heavy rainfall and LLJs over South China using TRMM rainfall data and ERA5 reanalysis. Generally, warm-sector heavy rainfall mainly occurs over coastal areas and during the early morning, which is primarily caused by the interaction between the nocturnal BLJ and land breeze. In contrast, frontal heavy rainfall is mostly concentrated in inland regions and modulated by distinct diurnal forcings at different locations. Statistical analysis indicates that 76% (62%) of the warm-sector (frontal) heavy rainfall events are associated with LLJs. In the presence of heavy rainfall, low-level winds are often strengthened over Beibu Gulf, northern South China Sea, and the south side of fronts, corresponding to two branches of southerly BLJs at ~950 hPa over the ocean and the southwesterly SLLJs at ~850–700 hPa on land, respectively. Furthermore, BLJs are shown to be linked to both types of heavy rainfall and with the most frequent occurrences of rainfall in their exit region, whereas SLLJs are more closely associated with frontal heavy rainfall. The left side (entrance) of the SLLJ axis is favorable for frontal (warm-sector) heavy rainfall production. The regional rainfall distributions are affected by the structures and locations of LLJs.
Temporal variations in COVID-19: an epidemiological discussion with a practical application
Authors: Derakhshan Mahnaz , Ansarian Hamid Reza , Ghomshei Mory 
Published: August 2021

Objective We aimed to characterize the temporal variation in coronavirus disease 2019 (COVID-19) infection and mortality as a possible tool to monitor and control the spread of this disease. Methods We analyzed cyclicity and synchronicity in cases of COVID-19 infection and time series of deaths using Fourier transform, its inverse method, and statistical treatments. Epidemiological indices (e.g., case fatality rate) were used to quantify the observations in the time series. The possible causes of short-term variations are reviewed. Results We observed that were both short-term and long-term variations in the COVID-19 time series. The short cycles were 7 days and synchronized among all countries. This periodicity is believed to be caused by weekly cycles in community social factors, combined with diagnostic and reporting cycles. This could also be related to virus–host–community dynamics. Conclusion The observed synchronized weekly cycles could serve as herd defense by providing a form of social distancing in time. The effect of such temporal distancing could be enhanced if combined with spatial distancing. Integrated spatiotemporal distancing is therefore recommended to optimize infection control strategies, taking into account the quiescent and active intervals of COVID-19.
Leonurine negatively modulates T cells activity by suppressing recombination activation gene protein 2 in pulmonary fibrosis
Authors: Zhu Yongping , Lin Bixia , Ding Fadian , Ma Fenfen , Zhou Xiaohui , Zong Haiyang , Feng Gao , Chen Qingquan , Chen Gongping , Lv Xiaoting 
Published: August 2021

Introduction The key transformed T cell transcription factor recombination activation gene protein 2 (RAG2) is regulated during inflammation to allow for the acquisition of effector T cells functions. The present study was designed to investigate whether stress signals elicited by leonurine (LEO) could lead to the degradation of RAG2 through v-akt murine thymoma viral oncogene homolog (AKT) signaling in lung fibrosis. Methods A total of 120 female mice were randomly divided into five groups (Group I–V): Normal group, bleomycin (BLM), BLM+LEO 50 mg/kg/d, BLM+LEO 100 mg/kg/d, and BLM+LEO 50 mg/kg/d+LY294002. Hematoxylin-eosin, Masson’s, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were performed to observe the pathomorphological changes. The expression of CD3+, TGF-β, RAG2, and Bcl proteins was examined by immunodetection, while that of E-cadherin (ECAD), AKT, TGF-β1, alpha-actin-2, Bax, and RAG2 was detected by Western blot analysis. Results The level of T lymphocytes was reduced sharply in LEO-treated mice as compared to the other groups. The AKT signal was greatly inhibited in the BLM group and activated with LEO treatment on day 14. In addition, RAG2 was attenuated by LEO on day 14 and day 28. LY294002 could reverse the expression of AKT and RAG2 on day 28. Remarkably, the low dose of LEO has a greater protective efficacy as compared to the high-dose LEO group in terms of pulmonary fibrosis, T cell inactivation, and apoptosis in alveolar cells. Conclusion The results of the present study suggested that LEO has a protective effect on lung fibrosis with possible mechanisms of attenuating apoptosis and inflammation via the upregulation of the AKT signal in transformed T cells by suppressing the expression and activity of RAG2.
Dopamine signaling regulates hematopoietic stem and progenitor cell function
Authors: Liu Yang , Chen Qi , Jeong Hyun-Woo , Han Dong , Fabian Jörg , Drexler Hannes C.A. , Stehling Martin , Schöler Hans R. , Adams Ralf H. 
Published: August 2021

Abstract
Hematopoietic stem and progenitor cell (HSPC) function in bone marrow (BM) is controlled by stroma-derived signals, but the identity and interplay of these signals remain incompletely understood. Here, we show that sympathetic nerve–derived dopamine directly controls HSPC behavior through D2 subfamily dopamine receptors. Blockade of dopamine synthesis, as well as pharmacological or genetic inactivation of D2 subfamily dopamine receptors, leads to reduced HSPC frequency, inhibition of proliferation, and low BM transplantation efficiency. Conversely, treatment with a D2-type receptor agonist increases BM regeneration and transplantation efficiency. Mechanistically, dopamine controls expression of the lymphocyte-specific protein tyrosine kinase (Lck), which, in turn, regulates MAPK-mediated signaling triggered by stem cell factor in HSPCs. Our work reveals critical functional roles of dopamine in HSPCs, which may open up new therapeutic options for improved BM transplantation and other conditions requiring the rapid expansion of HSPCs.
Prognosis of hypoglycemia episode in cirrhotic patients during hospitalization
Authors: Hung Tsung-Hsing , Tseng Chih-Wei , Tsai Chih-Chun , Lee Hsing-Feng 
Published: August 2021

Abstract
Background
Studies have shown that hyperglycemia in cirrhotic patients increases mortality. However, no population-based study has evaluated the influence of hypoglycemia upon hospital admission on death in these patients. The aim of this study was to assess the effect of hypoglycemia at admission on the mortality of patients with liver cirrhosis.

Methods
The Taiwan National Health Insurance Database was searched, and 636 cirrhotic patients without baseline diabetes mellitus who presented with hypoglycemia upon hospitalized from 2010 to 2013 were included in the study. A one-to-four propensity score matching was performed to select a comparison group based on age, sex and comorbidities.

Results
The overall 30-day mortality rate was 30.2% in the hypoglycemia group and 7.4% in the non-hypoglycemia group (P < 0.001). After Cox regression modeling adjusting for age, sex and comorbid disorders, cirrhotic patients with hypoglycemia had a hazard ratio (HR) of 30-day mortality of 4.96 (95% confidence interval [CI] 4.05–6.08, P < 0.001) as compared to the non-hypoglycemia group. In subgroup analysis, the cirrhotic patients with hypoglycemia and hepatocellular carcinoma (HCC) had a 30-day mortality HR of 6.11 (95% confidence interval [CI] 4.40–8.49, P < 0.001) compared to those with neither hypoglycemia nor HCC.

Conclusions
Hypoglycemia is a very important prognostic factor in the 30-day mortality of cirrhotic patients, especially in those with underlying HCC.
Age and sex distribution of Mycobacterium tuberculosis infection and rifampicin resistance in Myanmar as detected by Xpert MTB/RIF
Authors: Seifert Marva , Aung Hlaing Thazin , Besler Nicole , Harris Victoria , Mar Tin Tin , Colman Rebecca E. , Rodwell Timothy C. , Aung Si Thu 
Published: August 2021

Abstract
Background
Detection of tuberculosis disease (TB) and timely identification of Mycobacterium tuberculosis (Mtb) strains that are resistant to treatment are key to halting tuberculosis transmission, improving treatment outcomes, and reducing mortality.

Methods
We used 332,657 Xpert MTB/RIF assay results, captured as part of the Myanmar Data Utilization Project, to characterize Mtb test positivity and rifampicin resistance by both age and sex, and to evaluate risk factors associated with rifampicin resistance.

Results
Overall, 70% of individuals diagnosed with TB were males. Test positivity was higher among males (47%) compared to females (39%). The highest positivity by age occurred among individuals aged 16–20, with test positivity for females (65%) higher than for males (57%). Although a greater absolute number of males were rifampicin resistant, a greater proportion of females (11.4%) were rifampicin resistant as compared to males (9.3%). In the multivariate model, history of previous treatment, age less than 30, testing in the Yangon region, and female sex were significantly positively associated with rifampicin resistance after adjusting for HIV status and year test was performed.

Conclusions
Our results indicate that young adults were more likely to test positive for TB and be identified as rifampicin resistant compared to older adults.
Prevalence and factors associated with trichomonas vaginalis infection among female sex workers in Togo, 2017
Authors: TCHANKONI Martin Kouame , Bitty-Anderson Alexandra Marie , SADIO Arnold Junior , GBEASOR-KOMLANVI Fifonsi Adjidossi , FERRÉ Valentine Marie , ZIDA-COMPAORE Wendpouiré Ida Carine , DORKENOO Ameyo Monique , SAKA Bayaki , DAGNRA Anoumou Claver , CHARPENTIER Charlotte , EKOUEVI Didier Koumavi 
Published: August 2021

Abstract
Background
The aim of this study was to estimate the prevalence and factors associated with Trichomonas vaginalis (T. vaginalis) among female sex workers (FSW) in Togo in 2017. A cross-sectional bio-behavioral study was conducted from August to October 2017 using a respondent-driven sampling method in four cities in Togo.

Method
A standardized questionnaire was used to record socio-demographic data and sexual behavior patterns. T. vaginalis detection by molecular biology tests was performed using Allplex STI Essential Assay which detect also 6 others micro-organisms. A blood sample was drawn and serological test using SD Bioline Duo VIH/Syphilis rapid test was performed for Human immunodeficiency virus (HIV) and syphilis testing.

Results
A total of 310 FSW with median age 25 years, interquartile range (IQR) [21–32 years] were included. The prevalence of T. vaginalis was 6.5% (95%CI = [4.1–9.9]) and, overall, prevalence of other STI ranged from 4.2% (95%CI = [2.3–7.2]) for N. gonorrhoeae to 10.6% (95% CI = [7.5–14.7]) for HIV. Binary logistic regression was conducted to assess factors associated with T. vaginalis infection. Living in Lomé (aOR = 3.19; 95%CI = [1.11–11.49]), having had sexual intercourse before the age of 18 (aOR = 5.72; 95%CI = [1.13–10.89]), and being infected with C. trachomatis (aOR = 3.74; 95%CI = [2.95–12.25]) were factors associated with T. vaginalis among FSW.

Conclusion
The prevalence of T. vaginalis infection using molecular test was low among FSW in Togo. Extensive studies are needed to confirm and to better understand the epidemiology of T. vaginalis among this population and in other populations in Togo.