bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting phosphatidylinositol 3‐kinase gamma (PI3Kγ): Discovery and development of its selective inhibitors
Authors: Zhu Jingyu , Li Kan , Yu Li , Chen Yun , Cai Yanfei , Jin Jian , Hou Tingjun 
Published: December 2020

AbstractPhosphatidylinositol 3‐kinase gamma (PI3Kγ) has been regarded as a promising drug target for the treatment of advanced solid tumors, leukemia, lymphoma, and inflammatory and autoimmune diseases. However, the high level of structural conservation among the members of the PI3K family and the diverse physiological roles of Class I PI3K isoforms (α, β, δ, and γ) highlight the importance of isoform selectivity in the development of PI3Kγ inhibitors. In this review, we provide an overview of the structural features of PI3Kγ that influence γ‐isoform selectivity and discuss the structure‐selectivity‐activity relationship of existing clinical PI3Kγ inhibitors. Additionally, we summarize the experimental and computational techniques utilized to identify PI3Kγ inhibitors. The insights gained so far could be used to overcome the main challenges in development and accelerate the discovery of PI3Kγ‐selective inhibitors.
The role of hypoxia‐inducible factor 1 in tumor immune evasion
Authors: You Li , Wu Wenda , Wang Xu , Fang Liurong , Adam Vojtech , Nepovimova Eugenie , Wu Qinghua , Kuca Kamil 
Published: December 2020

AbstractHypoxia‐inducible factor 1 (HIF‐1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF‐1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF‐1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF‐1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E2, and programmed death‐ligand 1/programmed death‐1. Moreover, HIF‐1 blocks tumor‐associated antigen presentation via major histocompatibility complex class I chain‐related/natural killer group 2, member D signaling. Tumor‐associated autophagy and the release of tumor‐derived exosomes contribute to HIF‐1‐mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF‐1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF‐1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF‐1 in the regulation of tumor‐derived exosomes, as well as the roles of HIF‐1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF‐1‐mediated tumor immune evasion, leading to the development of effective HIF‐1‐targeting drugs and immunotherapies.
Association of pelvic floor function with postoperative urinary incontinence in cervical cancer patients after the radical hysterectomy
Authors: Wang Shiyan , Wang Runzhi , Wen Hongwu , Gao Yunong , Lv Qiubo , Li Hongyu , Wang Sumei , Wang Yanlong , Liu Qing , Han Jinsong , Wang Haibo , Li Yi , Wang Qing , Cao Tingting , Wang Sha , Sun Huaxin , Wang Zhiqi , Sun Xiuli , Wang Jianliu 
Published: December 2020

AbstractAimsTo assess the pelvic floor function in cervical cancer patients after radical hysterectomy and its relationship with urinary incontinence (UI).MethodsCervical cancer patients who underwent radical hysterectomy were recruited from 18 hospitals in China from January 2012 to March 2015. Pelvic floor examinations were conducted by measuring the pelvic floor muscle strength, fatigue of pelvic floor muscle fatigue, dynamic pressure of vaginal, nerve injury, A3 feedback, muscle potential, static tension, and dynamic tension. Postoperative urinary incontinence (UI) was identified using the International Consultation on Incontinence Questionnaire. Multivariable logistic regression analysis was used to assess the association of pelvic floor function examination results with postoperative UI.ResultsTotally 169 patients were included in this study. The prevalence of UI was 39.6% (67/169). The proportion of abnormal fatigue of Type I muscle (64% vs. 36%, p = .04) and abnormal A3 feedback (53.9% vs. 46.1%, p = .03) were higher among patients with postoperative UI compared to those without UI. In the multivariable analysis, abnormal fatigue of Type I muscle (odds ratio [OR] = 3.73, 95% confidence interval [CI]: 1.42–9.84), abnormal A3 feedback (OR = 2.40, 95% CI: 1.04–5.51), and length of resected vagina > 3 cm (OR = 3.44, 95% CI: 1.27–9.31) were associated with postoperative UI. Compared to laparoscopy, laparotomy was less likely to cause postoperative UI (OR = 0.12, 95% CI:0.04–0.33).ConclusionsThe abnormal function of the pelvic floor muscle is related to postoperative UI. Early assessment among these patients is needed to prevent the development of pelvic floor disorder postoperatively.
OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children
Authors: Austin Paul F. , Franco Israel , Dobremez Eric , Kroll Pawel , Titanji Wilson , Geib Till , Jenkins Brenda , Hoebeke Piet B. 
Published: December 2020

AbstractAimsThis study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children.MethodsThis was a 48‐week prospective, multicenter, randomized, double‐blind study in children (aged 5–17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed.ResultsThere was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (−1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%−80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6−63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, −12.9; 100 U, −20.1; 200 U, −27.3 cmH2O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent.ConclusionsOnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.
Predictive value of classification systems and single fistula‐related factors in surgical management of vesicovaginal fistula
Authors: Streit–Ciećkiewicz Dominika , Nowakowski Łukasz , Grzybowska Magdalena E. , Futyma Konrad 
Published: December 2020

AbstractAimsThe aim of this study was to find the most clinically useful vesicovaginal fistula (VVF) classification system or single fistula‐related factor, which would be helpful in determining the most proper management leading to successful treatment.MethodsBetween 2018 and 2020, 30 patients were diagnosed with VVF and underwent the Latzko procedure. Nineteen patients, after previously failed surgery, were injected with platelet‐rich‐plasma (PRP) before a final attempt to close VVF. Patients with primary VVF were included into the surgery only group and patients with secondary VVF were included into PRP and surgery group. Each patient was classified according to 13 different classification systems.ResultsStatistical evaluation revealed some significant differences between the patients who required PRP injection and repeated surgery, compared with patients who were successfully treated at first surgery but only with Lawson, Waaldijk, Arrowsmith, and Tafesse classifications. Patients who succeded with the fistula closure after the first surgical procedure had significantly higher body mass index (BMI) when compared with patients who required PRP injection prior surgical procedure (30.9 vs. 25.7, respectively; p < .05).ConclusionsNone of the classification systems allows to precisely predict VVF surgery outcome. There are several factors such as previous surgery, lack of urethral involvement, lack of circumferential defect which might suggest that PRP injection would help to preserve watertightness of the closure. The most important finding is that overweight is the most positive predicting demographic feature of surgical success. Thus we may conclude that Martius flap technique should be taken into consideration in patients with low BMI.
Computational examination of Casson nanofluid due to a non‐linear stretching sheet subjected to particle shape factor: Tiwari and Das model
Authors: Jamshed Wasim , Kumar Vivek , Kumar Vikash 
Published: December 2020

AbstractIn this research, heat transfer along with entropy of an unsteady non‐Newtonian Casson nanofluid flow is studied. The fluid is positioned over a stretched flat surface moving non‐uniformly. The nanofluid is analyzed for its flow and heat transport properties by subjecting it to a slippery surface, which is convectively heated. The governing mathematical equations describing the physical characteristics of Casson nanofluid flow as well as heat transfer models are abridged under boundary layer flow assumptions and Roseland approximations. Governing equations of flow problem are formulated in partial differential equations. A computative technique, Keller box accustomed to find the self‐similar solution of equations that converted into ordinary differential equations (ODEs) by using proper transformations. Two different classes of nanofluids, copper‐methanol (Cu–MeOH) and titanium‐methanol (TiO2–MeOH) are considered for our analysis. Significant results of various parameters in flow, heat, skin friction, Nusselt number and entropy analysis are elaborate graphically. The remarkable finding of this work is that the Cu–MeOH nanofluid is better transfer source as compared to TiO2–MeOH nanofluid.
Numerical investigations onCOVID‐19 model through singular and non‐singular fractional operators
Authors: Kumar Sunil , Chauhan R. P. , Momani Shaher , Hadid Samir 
Published: December 2020

AbstractNowadays, the complete world is suffering from untreated infectious epidemic disease COVID‐19 due to coronavirus, which is a very dangerous and deadly viral infection. So, the major desire of this task is to propose some new mathematical models for the coronavirus pandemic (COVID‐19) outbreak through fractional derivatives. The adoption of modified mathematical techniques and some basic explanation in this research field will have a strong effect on progressive society fitness by controlling some diseases. The main objective of this work is to investigate the dynamics and numerical approximations for the recommended arbitrary‐order coronavirus disease system. This system illustrating the probability of spread within a given general population. In this work, we considered a system of a novel COVID‐19 with the three various arbitrary‐order derivative operators: Caputo derivative having the power law, Caputo–Fabrizio derivative having exponential decay law and Atangana–Baleanu‐derivative with generalized Mittag–Leffler function. The existence and uniqueness of the arbitrary‐order system is investigated through fixed‐point theory. We investigate the numerical solutions of the non‐linear arbitrary‐order COVID‐19 system with three various numerical techniques. For study, the impact of arbitrary‐order on the behavior of dynamics the numerical simulation is presented for distinct values of the arbitrary powerβ.
Directed Electron Transfer in Flavin Peptides with Oligoproline‐Type Helical Conformation as Models for Flavin‐Functional Proteins
Authors: Wörner Samantha , Leier Julia , Michenfelder Nadine C. , Unterreiner Andreas‐Neil , Wagenknecht Hans‐Achim 
Published: December 2020

AbstractTo mimic the charge separation in functional proteins we studied flavin‐modified peptides as models. They were synthesized as oligoprolines that typically form a polyproline type‐II helix, because this secondary structure supports the electron transfer properties. We placed the flavin as photoexcitable chromophore and electron acceptor at the N‐terminus. Tryptophans were placed as electron donors to direct the electron transfer over 0–3 intervening prolines. Spectroscopic studies revealed competitive photophysical pathways. The reference peptide without tryptophan shows dominant non‐specific ET dynamics, leading to an ion pair formation, whereas peptides with tryptophans have weak non‐specific ET and intensified directed electron transfer. By different excitation wavelengths, we can conclude that the corresponding ion pair state of flavin within the peptide environment has to be energetically located between the S1 and S4 states, whereas the directed electron transfer to tryptophan occurs directly from the S1 state. These photochemical results have fundamental significance for proteins with flavin as redoxactive cofactor.
Evaluation of healing models to predict the weld line strength of the amorphous thermoplastic polystyrene by injection molding simulation
Authors: Onken Jakob , Verwaayen Steffen , Hopmann Christian 
Published: December 2020

AbstractIn many injection molded parts weld lines are often unavoidable. These cause optical defects and a reduction of the mechanical properties of the part. Therefore, the predictability of the weld line strength at an early stage of development would provide a significant advantage by avoiding costly iterations of the mold and increases the understanding of the correlation between process history of the melt and weld line strength. For this purpose, a calculation routine has been developed to predict the weld line strength based on injection molding simulation. Different models to calculate the healing of a weld line are compared and analyzed. By adding a factor to consider the shear rate in addition to the temperature and the pressure and after calibration to one design of experiment setting of the experimental data, the prediction of the weld line strength shows good agreement for all examined process setpoints of the experimental data for polystyrene.
Implications for body weight extremes in solid organ transplantation
Authors: Campara Maya , Lourenco Laura M. , Melaragno Jennifer I. , Kaiser Tiffany E. 
Published: December 2020

AbstractThe pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life‐sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non‐pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug‐drug interactions with popular weight management products.
How Physician Compensation and Education Debt Affects Financial Stress and Burnout: A Survey Study of Women in Physical Medicine and Rehabilitation
Authors: Verduzco‐Gutierrez Monica , Larson Allison R. , Capizzi Allison N. , Bean Allison C. , Zafonte Ross D. , Odonkor Charles A. , Bosques Glendaliz , Silver Julie K. 
Published: December 2020

AbstractObjectiveTo investigate the contribution of financial stress to physician burnout and satisfaction among women physiatrists. Relationships among education debt and compensation with demographic, sociologic, and workplace factors were also assessed.DesignThis was a cross‐sectional survey study of women physicians in the field of physical medicine and rehabilitation (PM&R) in the United States. The survey consisted of 51 questions covering demographic information (current and maximum education debt, race/ethnicity, years out of training, practice type and setting, hours worked, family structure, and domestic duties), work/life satisfaction, and burnout. The association between current/maximum debt and demographic characteristics, work/life satisfaction, and physician burnout were examined.ResultsOf the 245 U.S. women attending physiatrists who met inclusion criteria, 222 (90.6%) reported ever having education debt (median category $101 000‐150 000) and 162 (66.1%) reported current debt (median category ≤ $50 000). Of these participants, 218 (90.5%) agreed that they would have fewer burnout symptoms if they were able to do more work that is core to their professional mission and 226 (92.2%) agreed that feeling undervalued at work is linked to physiatrists’ burnout symptoms. Greater debt was seen in those who identified as Black/African American, were fewer years out of training, practiced general physiatry, and had both inpatient and outpatient responsibilities. Greater current debt had a significant relationship with measurements of work/life dissatisfaction. Burnout was associated with higher debt, lower compensation, more hours worked per week, and fewer hours of exercise performed per week.ConclusionsThis study examined women physiatrists’ perceptions of financial stress and found that greater education debt was associated with personal life dissatisfaction, career regret, and burnout. Further research is needed to address related causes and solutions.
Online options for future conferences will have an important positive impact for Early Career Researchers in pediatric pain
Authors: Hartley Caroline 
Published: December 2020

AbstractThe extent to which the COVID‐19 pandemic will have a negative impact on Early Career Researchers (ECRs) within the field of pediatric pain and in general is still unclear, but it is likely to be far reaching and may disproportionality affect women. Yet, there is also great opportunity to take advantage of the rapid adaptions to working life that we have all undertaken during the pandemic. In particular, continuing to have online options for conference attendance I think will have a positive impact on ECRs, and in particular female ECRs, now and in the future. Moreover, the pediatric pain research community is relatively small and highly international; by enabling wider participation in our conferences we will diversify our research output and expedite our aim of providing better treatment of pediatric pain.
Cis‐1,3,4,6‐Tetranitrooctahydroimidazo‐[4,5‐d]Imidazole (BCHMX) as a Part of Low Sensitive Compositions based on DATB or HNAB
Authors: Hussein Ahmed K. , Zeman Svatopluk , Elbeih Ahmed 
Published: December 2020

AbstractA new focus in the fields of energetic materials is on preserving high performance while enhancing manipulation safety. In this work, a special type of plastic‐bonded explosive (PBX) mixture has begun to be developed by combining a new nitramine, cis‐1,3,4,6‐tetranitrooctahydroimidazo‐[4,5‐d]imidazole (BCHMX), with the thermally stable explosives 1,3‐diamino‐2,4,6‐trinitrobenzene (DATB) and 2,2’,4,4’,6,6’‐hexanitroazobenzene (HNAB) bonded by a styrene‐butadiene rubber (SBR) binder. The studied PBXs prepared are insensitive explosives. They have been compared with Czech plastic explosives (SEMTEX 10 and SEMTEX 1H), a new Egyptian plastic explosive (EPX‐1), a Swedish plastic explosive (Sprängdeg m/46) and with analogous PBXs, filled by 1,3,5‐trinitro‐1,3,5‐triazinane (RDX), β‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (β‐HMX), and cis‐1,3,4,6‐tetranitrooctahydroimidazo‐[4,5‐d]imidazole (BCHMX). The individual explosives, PETN, BCHMX, β‐HMX and RDX, have been studied as well. Thermal behavior of the pure active components has been investigated. The impact and friction sensitivities have been obtained along with the measured detonation velocities. The detonation characteristics have also been calculated using the EXPLO5 code. The relationship between performance and sensitivity to mechanical impulses has been investigated. The results have shown that DATB has a significant influence on the reduction of the sensitivity of BCHMX to a level close to TNT and much lower than all the other studied plastic explosives. In addition, the new PBX based on BCHMX and DATB has higher detonation characteristics than the commercial PBXs and TNT. The influence of DATB on BCHMX is a promising topic requiring more research for its application.
Role of moist and dry air advection in the development of Mediterranean tropical‐like cyclones (medicanes)
Authors: Miglietta Mario Marcello , Carnevale Daniele , Levizzani Vincenzo , Rotunno Richard 
Published: December 2020

AbstractTwo tropical‐like cyclones in the Mediterranean Sea, aka medicanes, are analysed herein by means of numerical simulations. The cyclones, which were recently investigated in Miglietta and Rotunno, Quarterly Journal of the Royal Meteorological Society, 2019, 145, are reconsidered in the present study, in which we focus on their respective preconditioning phases. In particular, here we analyse how local evaporation and/or long‐range transport of air masses may precondition the environment where the Mediterranean cyclones form. Numerical simulations indicate a rather different behaviour for the two cyclones. The first medicane (December 13–15, 2005) developed over the southern Mediterranean Sea, in a region of high low‐level humidity content, which existed before the cyclone formation; the air, originally dry over the eastern Balkans and the African mainland, gained humidity during its transit over the sea surface. In contrast, the second medicane (October 6–10, 1996) strongly intensified while benefitting from the intense sea‐surface fluxes due to the outbreak of Tramontane and Cierzo winds near the Balearic Islands, where the cyclone developed. Although limited to just two case studies, these results identify two different mechanisms conducive to an environment favourable for the intensification of medicanes in the western or southern Mediterranean. In addition, the role of dry air near the cyclone core, associated with upper‐tropospheric dry intrusions, is analysed. Sensitivity experiments were performed, constraining the relative humidity in the initial and boundary conditions to values above 50%. The advantage of this strategy is the ability to change the humidity content in the dry regions without modifying the associated strong potential vorticity anomalies. For both cases, we find that the humidity increase had the effect of inducing an earlier onset of cyclone development and of producing stronger, longer‐lasting vortices.