bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1‐driven acute lymphoblastic leukemia
Authors: Nguyen Tra Ly , Nokin Marie‐Julie , Terés Silvia , Tomé Mercedes , Bodineau Clément , Galmar Oriane , Pasquet Jean‐Max , Rousseau Benoit , van Liempd Sebastian , Falcon‐Perez Juan Manuel , Richard Elodie , Muzotte Elodie , Rezvani Hamid‐Reza , Priault Muriel , Bouchecareilh Marion , Redonnet‐Vernhet Isabelle , Calvo Julien , Uzan Benjamin , Pflumio Françoise , Fuentes Patricia , Toribio Maria L. , Khatib Abdel‐Majid , Soubeyran Pierre , Murdoch Piedad del Socorro , Durán Raúl V.
Published: December 2020

The cellular receptor Notch1 is a central regulator of T‐cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T‐cell acute lymphoblastic leukemia (T‐ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T‐ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti‐Notch therapies in T‐ALL models. In this work, we report that Notch1 upregulation in T‐ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1‐driven T‐ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1‐induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1‐driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1‐driven leukemia.
Investigation of effect of filter on the stand‐up technique for total skin irradiation by Monte Carlo simulation
Authors: Tseng Wenchih , Li Ruiqi , Wu Qiuwen
Published: December 2020

Purpose

The aim of this study was to investigate dosimetric effects of scattering filter on the stand‐up technique for total skin irradiation (TSI) with a single electron field by Monte Carlo (MC) simulation.

Methods

MC simulations were performed with BEAMnrc and DOSXYZnrc packages under EGSnrc environment. Scattering filter of a metal disc was mounted in the accessory slot. The filter materials (Cu, Fe, Au, Zn, Ag) were investigated, with thickness ranging from 0.05 to 0.55 mm, depending on material. The extended source to skin distance (SSD) ranging from 250 to 350 cm was studied. The following dosimetric quantities were evaluated: percent depth dose (PDD), profiles and output factor at depth of maximum, and composite dose distribution on a 30‐cm diameter cylindrical phantom. They were compared with the standard dual beam technique used at our clinic. The effects on different patient sizes were also studied.

Results

No filter produced acceptable profile flatness (±10% within the central 160 cm) at 250 cm SSD. At 300 cm SSD, Au (0.1 mm), Ag (0.25 mm), Cu (0.5 mm) produced acceptable flatness while Zn (0.45 mm) required 325 cm SSD. For these four configurations, the dmax was 0.90–0.99 cm, similar to dual beam (0.97 cm); R50 was 1.85–1.91 cm, compared with dual beam of 2.06 cm; the output factor ranged from 0.025 to 0.029, lower than the dual beam (0.080). With the composite fields for four configurations, the dmax was 0.10 cm, compared with dual beam (0.16 cm). The surface dose was 97%, similar to dual beam (96%). B‐factor was 3.3–3.4, compared with dual beam of 3.1. The maximum X‐ray contamination was 3%, higher than dual beam (1%).

Conclusions

The investigation suggests the TSI stand‐up technique can be implemented using a single electron beam if a customized filter is used. More dosimetric measurements are needed to validate the MC results and clinical implementation.
Systematic review of CMTX1 patients with episodic neurological dysfunction
Authors: Tian Dandan , Zhao Yating , Zhu Ruixia , Li Qu , Liu Xu
Published: December 2020

Objective

X‐linked Charcot‐Marie‐Tooth type 1 (CMTX1) is an inherited peripheral neuropathy caused by mutations in the gap junction beta 1 (GJB1) gene, which encodes the connexin32 protein. A small number of patients withGJB1mutations present with episodic neurological dysfunction and reversible white matter lesions, which has not been adequately reported. Here, we aim to enable clinicians to further understand this particular situation through systematically reviewing all published relevant cases.

Methods

We conducted a comprehensive search of the PubMed electronic database for medical literature relevant to CMTX1 patients with episodic neurological dysfunction and then fully analyzed the general information, clinical manifestations, and characteristics of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and nerve conduction study (NCS).

Results

We identified 47 cases of CMTX1 associated with episodic central nervous system (CNS) dysfunction from 38 publications. CMTX1 patients experienced episodic CNS deficits at a young age, ranging from infancy to 26 years, and 45 (95.7%) of them were male. The CNS symptoms manifested as facial, lingual, or limb weakness in 44 (93.6%), dysarthria or dysphagia in 39 (83.0%), facial or limb numbness in 15 (31.9%), and ataxia in 10 (21.3%) patients. The duration of episodic symptoms ranged from 3 minutes to 6 months. Thirty (63.8%) CMTX1 cases have reported obvious predisposing factors, among which the most common factors were infection or fever (27.7%), travel to high altitude (12.8%), and intensive exercise (8.5%). As for brain MRI, most abnormal signals were found in bilateral deep white matter (88.9%) and corpus callosum (80.0%). In addition, most of the NCS results were abnormal, including prolonged latency, reduced amplitude, and slowed conduction velocity. The motor nerve conduction velocity (MNCV) of median nerve was the most detectable and valuable, ranging from 25 to 45 m/s.

Interpretation

We have reported the most comprehensive summary of the demographic and clinical profile from 47 CMTX1 patients with episodic CNS deficits and provided new insight into the phenotype spectrum of CMTX1. We hope that our study can help clinicians make early diagnosis and implement the best prevention and treatment strategies for CMTX1 patients with episodic CNS deficits.
Distributed stubborn‐set‐membership filtering with a dynamic event‐based scheme: The Takagi‐Sugeno fuzzy framework
Authors: Mao Jingyang , Ding Derui , Wei Guoliang
Published: December 2020

The article develops a novel stubborn set‐membership filtering with the dynamic event‐triggered scheme for discrete‐time nonlinear systems with the state‐delays, unknown‐but‐bounded noises as well as abnormal measurements. First, in comparison with traditional event schemes, a dynamic event‐triggered scheme with a time‐varying auxiliary offset variable in the threshold is employed to schedule the access token with the purpose of mitigating the communication burden. A novel fuzzy stubborn filter in a distributed way is then constructed to obtain the ellipsoid set including the real state while constraining the direct influence of abnormal measurements, which could come from outliers or a malicious modification by attackers. An algorithm with the form of recursive linear matrix inequalities is presented to determine the desired ellipsoids as well as the distributed filter gains, where the operation of the algorithm do not depend on the global information of network topology. Finally, the validity of the proposed scheme is illustrated via an inverted pendulum system.
3D‐Bioprinted Inflammation Modulating Polymer Scaffolds for Soft Tissue Repair
Authors: Shin Crystal S. , Cabrera Fernando J. , Lee Richard , Kim John , Ammassam Veettil Remya , Zaheer Mahira , Adumbumkulath Aparna , Mhatre Kirti , Ajayan Pulickel M. , Curley Steven A. , Scott Bradford G. , Acharya Ghanashyam
Published: December 2020

Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented. The bioscaffold design is based on the idea that, if the excess proinflammatory cytokines are sequestered from the site of injury by the surgical implantation of a bioscaffold, the inflammatory response can be modulated, and the visceral adhesion formations and postsurgical complications can be minimized. The bioscaffold is fabricated by 3D‐bioprinting of an in situ phosphate crosslinked poly(vinyl alcohol) polymer. In vivo efficacy of the bioscaffold is evaluated in a rat ventral hernia model. In vivo proinflammatory cytokine expression analysis and histopathological analysis of the tissues have confirmed that the bioscaffold acts as an inflammation trap and captures the proinflammatory cytokines secreted at the implant site and effectively modulates the local inflammation without the need for exogenous anti‐inflammatory agents. The bioscaffold is very effective in inhibiting visceral adhesions formation and minimizing postsurgical complications.
Engineering the Electrochemical Interface of Oxygen Reduction Electrocatalysts with Ionic Liquids: A Review
Authors: Favero Silvia , Stephens Ifan E. L. , Titirici Maria Magdalena
Published: December 2020

Hydrogen fuel cells are a promising technology for the environmentally sustainable production of electricity. However, their commercialization is hindered by the sluggish kinetics of the oxygen reduction reaction and by the high cost of the state‐of‐the‐art platinum catalysts. To address these challenges, research has focused on the enhancement of the activity of platinum and platinum group metal (PGM)‐free electrocatalysts, by modifying their composition and topology. Recently, a new approach has emerged to boost the activity of ORR catalysts, based on engineering the electrochemical interface. Herein, the recent developments in the use of ionic liquids (ILs) to modify the triple‐point interface of ORR catalysts are summarized. In this review, the current understanding in the literature of the effect of IL layers is presented, along with the open questions and remaining challenges. A short perspective on the applicability of this simple and effective modification to other electrochemical reactions is discussed.
Postpartum amenorrhea duration by sex of the newborn in two natural fertility populations
Authors: Hoi Amber Gigi , Daiy Katherine , Altman Rachel MacKay , Venners Scott , Valeggia Claudia , Nepomnaschy Pablo
Published: December 2020

Objectives

Postpartum amenorrhea (PA) affects the length of interbirth intervals and thus is intimately related to human life history strategies. PA duration appears to be influenced by maternal energetic status. In humans, as in other mammals, sons are costlier than daughters. Thus, we hypothesize that, in energetically constrained environments, a newborn's sex should be associated with PA duration.

Methods

We analyzed data from two natural fertility populations in which mothers have differing energy budgets: Qom women (n = 121) from a periurban village in Argentina, who have a comparatively calorically dense diet and are sedentary (prepregnancy mean BMI = 24.8 ± 4.5 kg/m2 in 1997), and agropastoral Kaqchikel Maya women (n = 88), who have a comparatively calorically restricted diet and high physical activity levels (mean BMI = 21.8 ± 3.7 kg/m2). We predict that (a) mothers of sons exhibit longer PA duration than mothers of daughters and (b) this association between offspring sex and PA duration is stronger in the Maya, who have smaller energy budgets.

Results

Maya mothers with sons exhibited estimated mean and median PA durations that were 1.34 times the estimated mean and median PA duration of mothers with daughters (p = 0.02). Among the Qom, mean, and median PA duration did not differ significantly in relation to offspring sex (p = 0.94).

Conclusions

Maya mothers with sons exhibited longer PA duration than those with daughters. This phenomenon was not observed in the well‐nourished Qom, possibly due to “buffering” effects from larger energy budgets. Offspring sex may influence birth spacing and maternal life history strategies in energetically constrained environments.
Fat Bloom Caused by Partial De‐Oiling on Chocolate Surfaces after High‐Temperature Exposure
Authors: Sato Sohei , Hondoh Hironori , Ueno Satoru
Published: December 2020

Fat bloom in chocolate is a substantial problem that affects its sensory properties, such as texture and appearance. This phenomenon is because of diffuse light reflection on a roughened surface of chocolate, caused by structural changes of fat crystals subjected to various temperature conditions. The purpose of this study is to characterize the fat bloom formed through gradual two‐step cooling after exposure to temperatures (35–37 °C) slightly above the cocoa butter Form βV melting point (33.8 °C). To clarify the fat bloom formation process, the structural changes in cocoa butter and on the chocolate surface, at the dynamic thermal condition for bloom formation, was investigated using X‐ray diffraction (XRD), fluorescence light microscopy, and scanning electron microscopy (SEM). The results revealed that an entirely light brown fat bloom occurred, even in the absence of the Form βVI or other polymorphic transformation. Microscopic observation showed that the light brown appearance was because of the porous structure on the chocolate surface. This porous structure was formed by liquid oil moving inside of chocolate from the surface. The formation of a coarse network and the subsequent de‐oiling, because of movement of unsolidified liquid fat into the chocolate, appeared to be the main causes of bloom formation. Therefore, a coarsened fat network and oil movement besides the conventional principles of polymorphic transformation of cocoa butter should be considered.
Sodium alginate/bismuth (III) oxide composites for γ‐ray shielding applications
Authors: Prabhu Srilakshmi , S. G. Bubbly , Gudennavar Shivappa B.
Published: December 2020

In the present work, we have explored the efficacy of bismuth (III) oxide (Bi2O3) loaded, calcium ion cross‐linked solution cast sodium alginate composite films for radioprotective applications. Calcium ion cross‐linking increased the water and chemical resistance, which further improved on introduction of Bi2O3into the composites. The 40 wt% Bi2O3loaded films showed good heat resistance with the peak degradation temperature reaching as high as 251°C. The Bi2O3loaded composites showed enhanced tensile strength (TS) and Youngs modulus (YM). Compared to high‐modulus polymers like epoxy, high‐density polyethylene (HDPE) and poly (vinyl chloride) (PVC), these exhibit relatively greater extent of stretching before breaking. The γ‐ray attenuation experiments showed that mass attenuation coefficients of the composites at various γ‐ray energies increased with filler loading. These composites are effective in shielding γ‐rays from radioactive sources like137Cs,22Na,133Ba, and60Co that are widely employed in several medical and industrial applications. The overall enhancement in thermal, mechanical, and radiation shielding characteristics of the composites may be attributed to the uniform distribution of the fillers in alginate matrix. These nontoxic sodium alginate/Bi2O3composites can be used as soft and biodegradable radiation shields, which may be processed to wearable forms.
Thermal and mechanical properties of UHMWPE/HDPE/PCL and bioglass filler: Effect of polycaprolactone
Authors: Alemán Espinosa Elzy , Escobar‐Barrios Vladimir , Palestino Escobedo Gabriela , Waldo Mendoza Miguel A.
Published: December 2020

Polymeric composites based on polyethylene, high‐density polyethylene (HDPE) and ultra‐high‐molecular‐weight polyethylene (UHMWPE) with polycaprolactone (PCL) and a ceramic filler (bioglass type) were studied in terms of their thermal and mechanical behavior. Two polyethylene ratios (10/90 and 30/70% wt/wt of UHMWPE/HDPE) and two PCL content ratios (5% and 10% wt/wt) were used. The obtained composites were characterized by differential scanning calorimetry, melt flow index, Fourier transform infrared spectroscopy, scanning electron microscopy, and X‐ray diffraction. The results indicate a nonchemical interaction between polyethylene, especially the UHMWPE, and PCL and that the composites' thermal transitions vary from the parent polymers and depend on the PCL concentration. The PCL's melting temperature in the composite was reduced, showing a new one. Also, the melting enthalpy of polyethylene was reduced when the concentration of PCL increased. The mechanical behavior depends on both the polyethylene ratio and the PCL content. The composite with 30% wt/wt of UHMWPE and 10% wt/wt of PCL showed the highest toughness value due to the good interaction between polymers. These new composites may be attractive for biomedical applications and could be evaluated, for example, as materials for prostheses.
Integrated use of unmanned aerial vehicle photogrammetry and terrestrial laser scanning to support archaeological analysis: The Acropolis of Selinunte case (Sicily, Italy)
Authors: Costanzo Antonio , Pisciotta Antonino , Pannaccione Apa Maria Ilaria , Bongiovanni Simona , Capizzi Patrizia , D'Alessandro Antonino , Falcone Sergio , La Piana Carmelo , Martorana Raffaele
Published: December 2020

Southwestern Sicily is an area of infrequent seismic activity; however, some studies carried out in the archaeological Selinunte site suggest that, between the fourth century BC and the early Middle Ages, probably at least two earthquakes strucked this area with enough energy to damage and cause the collapse and kinematics of much of the architecture of Selinunte. Take into account that, in 2008, a noninvasive archaeological prospection and traditional data gathering methods along the Acropolis north fortifications were carried out. Following these first studies, after about 10 years, a new geophysical campaign was carried out. This second campaign benefited from the application of modern technologies for the acquisition and processing of the point cloud data on the northern part of the Acropolis, like terrestrial laser scanning and unmanned aerial vehicle photogrammetry. In this paper, we present the application of these techniques and a strategy for their integration for the 3D modelling of buildings and cultural heritages. We show how the integration of data acquired independently by these two techniques is an added value able to overcome the intrinsic limits of the individual techniques. The application to Selinunte's Acropolis allowed it to highlight and measure with high accuracy fractures, dislocation, inclinations of walls, depressions of some areas and other interesting observations, which may be important starting points for future investigations.
Comparison of Adaptive Functioning in Children with Williams Beuren Syndrome and Autism Spectrum Disorder: A Cross‐Syndrome Study
Authors: Alfieri Paolo , Scibelli Francesco , Digilio Maria C. , Novello Roberta L. , Caciolo Cristina , Valeri Giovanni , Vicari Stefano
Published: December 2020

Williams Beuren syndrome (WBS) and autism spectrum disorder (ASD) have been long considered as “polar opposite” disorders. Although children with WBS appears to be hypersociable, recent researches have revealed difficulties in socio‐communicative skills such as shared attention, showing or giving objects, social relationships comprehension, pragmatic use of language, and emotion's recognition. The aim of this cross‐syndrome study is to compare clinician‐report adaptive profiles of two wide developmental range children by means of Vineland Adaptive Behavior Scales—Interview Edition, Survey Form. Eighty individuals, 40 with WBS and 40 with ASD (31 preschoolers and 49 scholars) with ASD and WBS matched for chronological age and developmental/cognitive level were recruited. Analysis of domains and subdomains have been reported. Results showed no significant difference in global adaptive level between WBS and ASD in both preschooler and scholar children. Communication domain significantly differ in preschoolers (higher in WBS children), but not in scholars. Expressive subdomain significantly differ in both preschoolers and scholars (higher in WBS children). Play and Leisure subdomain significantly differ in scholars (higher in WBS children), but not in preschoolers. Our results support hypothesis on a shared global adaptive impairment in children with WBS and ASD, by extending this findings to scholar‐age children. Analysis of domains and subdomains differences highlight the need for interventions targeting social‐pragmatic skills since first years of life. Differences in preschoolers and scholars adaptive profiles could be explained through a developmental perspective.

Lay Summary

Little is known about differences in adaptive profiles between Williams Beuren syndrome and autism spectrum disorder. Our results show similarities in global adaptive level and difference in communication level. Furthermore, expressive skills seem to be higher in Williams Beuren Syndrome. Autism Res 2021, 14: 748–758. © 2020 International Society for Autism Research and Wiley Periodicals LLC
Determination of amlodipine, indapamide and perindopril in human plasma by a novel LC–MS/MS method: Application to a bioequivalence study
Authors: Rezk Mamdouh R. , Badr Kamal A.
Published: December 2020

A robust and rapid UPLC–MS/MS method has been developed, optimized and validated for determination of amlodipine (AML), indapamide (IND) and perindopril (PRN) in human plasma. A positive electrospray ionization mode was used in a Xevo TQD LC–MS/MS instrument. A single sample preparation step using extraction technique was applied to extract the three analytes from plasma samples. There was no need to extract indapamide from blood samples in a further step. Extraction of the three drugs and internal standards was done using a solvent mixture composed of methyl tertiary butyl ether, dichloromethane and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC HSS C18 (100 × 2.1 mm, 1.7 μm) column. Ammonium acetate and methanol, pumped at a flow rate of 0.3 ml/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.2–15 ng/ml for AML, 0.5–50 ng/ml for IND and 0.5–120 ng/ml for PRN. Accuracy and precision were estimated and found to be within the acceptable ranges. The rapid chromatography permits analysis of many samples per batch, making the method suitable for clinical and pharmacokinetic investigations. The developed and validated method was applied to estimate AML, IND, and PRN in a fasting bioequivalence study in healthy human volunteers.
A simple HPLC assay for determining eltrombopag concentration in human serum
Authors: Yanagimachi Naoya , Obara Naoshi , Sakata‐Yanagimoto Mamiko , Chiba Shigeru , Doki Kosuke , Homma Masato
Published: December 2020

Eltrombopag, a thrombopoietin receptor agonist, is used for the treatment of idiopathic thrombocytopenic purpura (ITP) and aplastic anemia. We developed a HPLC assay for the determination of serum eltrombopag concentration in ITP patients. An aliquot of a serum sample spiked with diclofenac as the internal standard (IS) was treated with acetonitrile to precipitate the proteins. Eltrombopag and the IS were separated on an octadecylsilyl silica‐gel column using a mobile phase consisting of 10 mM 1‐pentanesulfonic acid sodium salt, acetonitrile, and acetic acid. The detection wavelength was set at 265 nm. The calibration curve was linear at the concentration range of 0.15–12.5 μg/mL for eltrombopag (r = 0.9987). The recoveries of eltrombopag from the serum samples were greater than 95.9% with coefficients of variation (CVs) being less than 2.8%. The CVs for the intra‐day and inter‐day assays were 1.9–11.8% and 1.0–11.8%, respectively. This assay method could be used for therapeutic drug monitoring of eltrombopag in ITP patients.
Changes in the anterior cingulate cortex in Crohn’s disease: A neuroimaging perspective
Authors: Kong Ning , Gao Chen , Xu Maosheng , Gao Xuning
Published: December 2020

Introduction

Evidence suggests that Crohn's disease (CD) pathophysiology goes beyond the gastrointestinal tract and is also strongly associated with the brain. In particular, the anterior cingulate cortex (ACC), which plays an integral role in the first brain as part of the default mode network (DMN) and pain matrix, shows abnormalities using multiple neuroimaging modalities. This review summarizes nine related studies that investigated changes in the ACC using structural magnetic resonance imaging, resting‐state functional magnetic resonance imaging, and magnetic resonance spectroscopy.

Methods

An extensive PubMed literature search was conducted from 1980 to August 2020. In a review of the articles identified, particular attention was paid to analysis methods, technical protocol characteristics, and specific changes in the ACC.

Results

In terms of morphology, a decrease in gray matter volume and cortical thickness was observed along with an increase in local gyrification index. In terms of function, functional connectivity (FC) within the DMN was increased. FC between the ACC and the amygdala was decreased. Higher amplitudes of low‐frequency fluctuation and graph theory results, including connectivity strength, clustering coefficient, and local efficiency, were detected. In terms of neurotransmitter changes, the concentrations of glutamate increased along with a decrease in gamma‐aminobutyric acid, providing a rational explanation for abdominal pain. These changes may be attributed to stress, pain, and negative emotions, as well as changes in gut microbiota.

Conclusions

For patients with CD, the ACC demonstrates structural, functional, and metabolic changes. In terms of clinical findings, the ACC plays an important role in the onset of depression/anxiety and abdominal pain. Therefore, successful modulation of this pathway may guide treatment.
Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first‐line treatment of advanced esophageal squamous cell carcinoma
Authors: Zhang Bo , Qi Ling , Wang Xi , Xu Jianping , Liu Yun , Mu Lan , Wang Xingyuan , Bai Lidan , Huang Jing
Published: December 2020

Background

Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti‐angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first‐line treatment of advanced ESCC.

Methods

In this single‐arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m2, and nedaplatin 50 mg/m2 on day 1, and apatinib 250 mg on days 1‐14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety.

Results

We enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow‐up was 24.98 months (95% confidence interval [CI]: 23.05‐26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%‐92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%‐99.9%). The median PFS was 6.85 months (95% CI: 4.46‐14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months – not reached). The most common grade 3‐4 treatment‐related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment‐related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment‐related deaths occurred.

Conclusions

Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first‐line treatment demonstrated feasible anti‐tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted.

Trial registration

This trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).
Characteristics and mechanisms to control a COVID‐19 outbreak on a leukemia and stem cell transplantation unit
Authors: Greiner Jochen , Götz Marlies , Malner‐Wagner Waltraud , Wendt Constanze , Enders Martin , Durst Christine , Michel Detlef , von Harsdorf S , Jung Susanne
Published: December 2020

Immunosuppressed patients like patients with leukemia or lymphoma, but also patients after autologous or allogeneic stem cell transplantation are at particular risk for an infection with COVID‐19. We describe a COVID‐19 outbreak on our leukemia and stem cell transplantation unit (LSCT‐Unit) originating from a patient with newly diagnosed acute myeloid leukemia. The patient was treated with intensive induction chemotherapy and we characterize the subsequent outbreak of COVID‐19 on a LSCT‐Unit. We describe the characteristics of the 36 contacts among the medical team, the results of their PCR and antibody tests and clinical aspects and features of infected employees. Of these 36 close contacts, 9 employees of the LSCT‐Unit were infected and were tested positive by PCR and/or antibody‐testing. 8/9 of them were symptomatic, 3/9 with severe, 5/9 with mild symptoms, and one person without symptoms. Due to stringent hygiene measures, the outbreak did not lead to infections of other patients despite ongoing clinical work. Moreover, we demonstrate that incubation period and clinical course of a COVID‐19 infection in an immunosuppressed patient could be unusual compared to that of immunocompetent patients. Consistent PCR and antibody testing are helpful to understand, control, and prevent outbreaks. For the safety of health‐care workers and patients alike, all employees wore FFP2 masks and were trained to adhere to several further safety guidelines. The implementation of rigorous hygiene measures is the key to controlling an outbreak and preventing infections of other patients.
Conditional survival in patients with esophageal or gastroesophageal junction cancer after receiving various treatment modalities
Authors: Deng Wei , Yang Zhao , Dong Xin , Yu Rong , Wang Weihu
Published: December 2020

Background

To estimate the adjusted conditional overall survival (COS) in patients with esophageal cancer after receiving various treatment modalities via a national population‐based database, and to investigate the possible time‐dependent effects.

Materials and Methods

Eligible patients diagnosed with esophageal cancer between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. The Kaplan‐Meier method was used to calculate conventional survival time. The inverse probability of treatment weighting method was used to estimate the adjusted COS in patients receiving different treatment modalities. Landmark analysis was employed to investigate the possible time‐dependent effects of different treatment modalities in patients who had survived a certain period of time.

Results

A total of 25,232 patients were included in the final analysis. The conventional 5‐year overall survival was 19.3%. The 5‐year adjusted COS increased most for the first 3 years, and increased slightly afterwards. In patients with regional esophageal or gastroesophageal junction cancer, stage‐specific analysis showed that surgery only and preoperative radiation therapy benefited most for patients with localized disease, preoperative radiation therapy plus surgery benefited regional, and preoperative radiation therapy plus surgery benefited distant disease, with the 5‐year adjusted COS given patients had survived 3 years being 67.0% (95% CI 65.2%–68.7%), 59.9% (95% CI 58.3%–61.5%), 58.4% (95% CI 56.3%–60.5%), and 61.8% (95% CI 59.5%–64.1%), respectively. In time‐dependent analysis, the benefits of surgery only in localized cases were prominent within 48 months after diagnosis. Preoperative radiation therapy showed long‐lasting benefits in patients with regional disease. In patients with distant disease, all treatment modalities showed similar and short‐term effects.

Conclusions

The adjusted COS in patients with esophageal cancer increased as time accrued after receiving various treatment modalities. The time‐dependent effects in specific tumor stage provided a dynamic view on optimization of treatment strategies.
Immune landscape and a promising immune prognostic model associated with TP53 in early‐stage lung adenocarcinoma
Authors: Wu Chengde , Rao Xiang , Lin Wei
Published: December 2020

Purpose

TP53 mutation, one of the most frequent mutations in early‐stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early‐stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early‐stage LUAD and formulate a TP53‐associated immune prognostic model (IPM) that can estimate prognosis in early‐stage LUAD patients.

Materials and methods

Immune‐associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT) and TP53 wild‐type (TP53WT) early‐stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune‐associated DEGs. We constructed and validated an IPM based on the TCGA and a meta‐GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application.

Results

TP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early‐stage LUAD. Sixty‐seven immune‐associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune‐associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta‐GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43–3.06, p < 0.001). Increased expressions of PD‐L1, CTLA‐4, and TIGIT were revealed in the high‐risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility.

Conclusion

The IPM based on TP53 status is a reliable and robust immune signature to identify early‐stage LUAD patients with high risk of unfavorable survival.
Assessment of Thiosemicarbazone‐Containing Compounds as Potential Antileukemia Agents against P‐gp Overexpressing Drug Resistant K562/A02 Cells
Authors: Gu Xiaoke , Guan Mingyu , Jiang Chunyu , Song Qinghua , Li Xin , Sun Nan , Chen Jing , Qiu Jingying
Published: December 2020

P‐Glycoprotein (P‐gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone‐containing compounds were prepared and evaluated as potential antileukemia agents against drug resistant K562/A02 cell overexpressing P‐gp. Among them, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could significantly inhibit K562/A02 cells proliferation with an IC50 value of 0.96 μM. Interestingly, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could dose‐dependently increase ROS levels of drug resistant K562/A02 cells, thus displaying a potential collateral sensitivity (CS)‐inducing effect and selectively killing K562/A02 cells. Furthermore, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide possessed potent inhibitory effect on HDAC1 and HDAC6, and could promote K562/A02 cells apoptosis via dose‐dependently increasing Bax expression, reducing Bcl‐2 protein level, and inducing the cleavage of PARP and caspase3. These present findings suggest that N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide might be a promising lead to discover novel antileukemia agents against P‐gp overexpressing leukemic cells.
Comparison of ultrasound‐guided versus angiography‐guided endovascular treatment for femoropopliteal artery occlusive disease
Authors: Tokuda Takahiro , Mori Shinsuke , Oba Yasuhiro , Koshida Ryoji , Kagase Ai , Matsuda Hiroaki , Suzuki Yoriyasu , Murata Akira , Ito Tatsuya , Hirano Keisuke
Published: December 2020

Purpose

This study aimed to compare the efficacy of ultrasound‐guided and angiography‐guided intraluminal approach for femoropopliteal (FP) artery occlusive disease.

Methods

A retrospective analysis was performed using the data collected regarding patients that underwent endovascular treatment (EVT) for FP artery occlusive disease between January 2010 and April 2018 at two centers. A total of 221 consecutive de novo lesions were analyzed according to the method of recanalization. Propensity score‐matched analysis was performed to compare the clinical outcomes of recanalization methods for FP occlusive lesions. The prognostic value was analyzed based on the number of guidewires, wire cross time, distal puncture rate, radiation exposure, the amount of contrast media, primary patency, and clinically driven‐target lesion revascularization (CD‐TLR) at 1 year.

Results

A total of 44 matched pairs of patients were analyzed after propensity score‐matched analysis. The number of guidewires, distal puncture rate, wire passage time, radiation exposure, and the amount of contrast media were significantly lower in the ultrasound‐guide group, with 3.4 vs. 4.7, 9.1% vs. 54.5%, 47 min vs. 83 min, 207 mGy vs. 821 mGy, 66 ml vs. 109 ml, respectively (p < .01), but there were no significant differences between the two groups in terms of primary patency and CD‐TLR.

Conclusions

The ultrasound‐guided EVT for FP occlusive disease significantly reduced the number of guidewires, wire cross time, the rate of distal puncture, radiation exposure, and the amount of contrast media used.
Encountering the accessory polar renal artery during retroperitoneal lymphadenectomy
Authors: Karadağ Ceyda , Birge Ozer , Bakir Mehmet Sait , Doğan Selen , Tuncer Hasan Aykut , Şimşek Tayup
Published: December 2020

Because of the accessory polar renal artery (APRA) is functional, it is extremely important to be careful with vascular injuries, to prevent ischemic damage and not to cause kidney failure complications.
Listeria monocytogenes infectious abdominal aortic aneurysm: Case report and review of the literature
Authors: Järve Heli , Kals Jaak
Published: December 2020

Listeria monocytogenes‐caused primary infected abdominal aortic aneurysm is a very rare disease. Aortic wall tissue sampling is essential for confirmation of diagnosis. Surgical repair and long‐term antibacterial treatment are crucial for management.
Type of atrial fibrillation and outcomes in patients without oral anticoagulants
Authors: Ren Jiameng , Yang Yanmin , Zhu Jun , Wu Shuang , Wang Juan , Zhang Han , Shao Xinghui , Lyu Siqi
Published: December 2020

Background

The effect of type of atrial fibrillation (AF) on adverse outcomes in Chinese patients without oral anticoagulants (OAC) was controversial.

Hypothesis

The type of AF associated with adverse outcomes in Chinese patients without OAC.

Methods

A total of 1358 AF patients without OAC from a multicenter, prospective, observational study was included for analysis. Univariable and multivariable Cox regression models were utilized. Net reclassification improvement analysis was performed for the assessment of risk prediction models.

Results

There were 896(66%) patients enrolled with non‐paroxysmal AF (NPAF) and 462(34%) with paroxysmal AF (PAF). The median age was 70.9 ± 12.6 years, and 682 patients (50.2%) were female. During 1 year of follow‐up, 215(16.4%) patients died, and 107 (8.1%) patients experienced thromboembolic events. Compared with the PAF group, NPAF group had a notably higher incidence of all‐cause mortality (20.2% vs. 9.4%, p < .001), thromboembolism (10.5% vs. 3.8%, p < .001). After multivariable adjustment, NPAF was a strong predictor of thromboembolism (HR 2.594, 95%CI 1.534–4.386; p < .001), all‐cause death (HR 1.648, 95%CI 1.153–2.355; p = .006). Net reclassification improvement analysis indicated that the addition of NPAF to the CHA2DS2‐VASc score allowed an improvement of 0.37 in risk prediction for thromboembolic events (95% CI 0.21–0.53; p < .001).

Conclusions

In Chinese AF patients who were not on OAC, NPAF was an independent predictor of thromboembolism and mortality. The addition of NPAF to the CHA2DS2‐VASc score allowed an improvement in the accuracy of the prediction of thromboembolic events.
TowardsoperandoIR‐ and UV‐vis‐Spectro‐Electrochemistry: A Comprehensive Matrix Factorisation Study on Sensitive and Transient Molybdenum and Tungsten Mono‐Dithiolene Complexes**
Authors: Elvers Benedict J. , Sawall Mathias , Oberem Elisabeth , Heckenberger Kilian , Ludwig Ralf , Neymeyr Klaus , Schulzke Carola , Krewald Vera , Fischer Christian
Published: December 2020

The redox sequences of sensitive aliphatic mono‐dithiolene complexes [MII(CO)2(cydt)(dppe)] (M=Mo, W) were studied with extensive cyclic voltammetrical and spectro‐electrochemical (SEC) investigations using UV‐vis and IR spectroscopy. With a newly developed matrix factorisation technique, the pure component spectra and temporal evolution of the developed species were ascertained, including sensitive and transient ones. The concentration of all involved compounds at the working electrode as dependent on the respective applied potential was derived with very high accuracy. The assignment of the species’ geometries and electronic structures was further verified by quantum chemical calculations. Overall, the combined electrochemical, spectroscopic, quantum chemical and mathematical approach facilitates a comprehensive understanding of the underlying electrochemical transformations and equilibria. Since only a single CV run is needed to obtain all data required to identify the individual species, the method presented here is expected to be applicable to a wide range of complicated electrochemically responsive systems and thus opens a path towards developing a deeper mechanistic understanding of the underlying chemistry.
The Quasi Curvature‐Dimension Condition with Applications to Sub‐Riemannian Manifolds
Authors: Milman Emanuel
Published: December 2020

We obtain the best known quantitative estimates for the Lp‐Poincaré and log‐Sobolev inequalities on domains in various sub‐Riemannian manifolds, including ideal Carnot groups and in particular ideal generalized H‐type Carnot groups and the Heisenberg groups, corank 1 Carnot groups, the Grushin plane, and various H‐type foliations, Sasakian and 3‐Sasakian manifolds. Moreover, this constitutes the first time that a quantitative estimate independent of the dimension is established on these spaces. For instance, the Li‐Yau / Zhong‐Yang spectral‐gap estimate holds on all Heisenberg groups of arbitrary dimension up to a factor of 4.

We achieve this by introducing a quasi‐convex relaxation of the Lott‐Sturm‐Villani CD(K, N) condition we call the “quasi curvature‐dimension condition” QCD(Q, K, N). Our motivation stems from a recent interpolation inequality along Wasserstein geodesics in the ideal sub‐Riemannian setting due to Barilari and Rizzi. We show that on an ideal sub‐Riemannian manifold of dimension n, the measure contraction property MCP(K, N) implies QCD(Q, K, N) with Q = 2N − n ≥ 1, thereby verifying the latter property on the aforementioned ideal spaces; a result of Balogh‐Kristály‐Sipos is used instead to handle nonideal corank 1 Carnot groups. By extending the localization paradigm to completely general interpolation inequalities, we reduce the study of various analytic and geometric inequalities on QCD spaces to the one‐dimensional case. Consequently, we deduce that while (strictly) sub‐Riemannian manifolds do not satisfy any type of CD condition, many of them satisfy numerous functional inequalities with exactly the same quantitative dependence (up to a factor of Q) as their CD counterparts. © 2020 Wiley Periodicals LLC
Screening of suitable genotype for Bangladesh conditions based on genetic variability and path analysis in F2 white maize populations
Authors: Hasan Md. Mahmudul , Rahman Jamilur , Sultana Fahmida , Fatima Kaniz , Shahriar Saleh Ahmed , Imtiaz Abdullah All , Subramaniam Sreeramanan , Uddain Jasim
Published: December 2020

White maize is the new maize (Zea mays L.) cultivar in Bangladesh. The country needs high‐yielding white maize varieties for farmers’ cultivation, but developing such variety requires appropriate inbred lines. Here, nine F2 populations of white maize were evaluated through assessment of their genetic variability, heritability, and character association for selection of promising lines based on yield and growth parameters. Analysis of genetic variability showed that there were significant variations among the various genotypes of F2 populations. High heritability coupled with large genetic advances in percentage means were obtained in plant height, cob height, number of branches per tassel, number of cobs bearing node, leaf blade area, and grain yield per plant. The analysis of path coefficient indicated positive direct contribution towards yield per plant through days to 50% tasseling, days to 50% silking, cob height, days to maturity, number of branches of the tassel, cob breadth, and number of grains per row. The results thus indicated that indirect selection based on plant height, days to maturity, cob height, leaves per plants, cob length, number of rows per cob, and number of grains per row are reliable to select the appropriate lines for yield improvement in white maize. In view of the yield and its contributing characteristics, the population of KS 510 has a high yield potential for improvement of the varietal performance of white maize.