bluuebunny/crossref_metadata_2025_split huggingface dataset:
High potency STING agonists engage unique myeloid pathways to reverse pancreatic cancer immune privilege
Authors: Ager Casey R , Boda Akash , Rajapakshe Kimal , Lea Spencer Thomas , Di Francesco Maria Emilia , Jayaprakash Priyamvada , Slay Ravaen B , Morrow Brittany , Prasad Rishika , Dean Meghan A , Duffy Colm R , Coarfa Cristian , Jones Philip , Curran Michael A 
Published: August 2021

BackgroundIntratumoral injection of cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway engages innate immune activation and priming of adaptive immune effectors to foster local and distal tumor clearance. Despite proven therapeutic efficacy in preclinical models, a thorough understanding of how CDNs reprogram suppressive myeloid stroma in mouse and man is lacking.MethodsHere, we perform deep transcript-level and protein-level profiling of myeloid-derived suppressor cells and M2 macrophages following stimulation with CDNs of ascending potency. Additionally, we leverage orthotopicKras+/G12DTP53+/R172HPdx1-Cre(KPC) derived models of pancreatic adenocarcinoma (PDAC) to determine the capacity for locally administered CDNs to sensitize PDAC to immune checkpoint blockade. We use bioluminescent in vivo imaging and 30-parameter flow cytometry to profile growth kinetics and remodeling of the tumor stroma post-therapy.ResultsHighly potent synthetic STING agonists repolarize suppressive myeloid populations of human and murine origin in part through inhibition of Myc signaling, metabolic modulation, and antagonism of cell cycle. Surprisingly, high-potency synthetic agonists engage qualitatively unique pathways as compared with natural CDNs. Consistent with our mechanistic observations, we find that intratumoral injection of the highest activity STING agonist, IACS-8803, into orthotopic pancreatic adenocarcinoma lesions unmasks sensitivity to checkpoint blockade immunotherapy. Dimensionality reduction analyses of high parameter flow cytometry data reveals substantial contributions of both myeloid repolarization and T cell activation underlying the in vivo therapeutic benefit of this approach.ConclusionsThis study defines the molecular basis of STING-mediated myeloid reprogramming, revealing previously unappreciated and qualitatively unique pathways engaged by CDNs of ascending potency during functional repolarization. Furthermore, we demonstrate the potential for high potency CDNs to overcome immunotherapy resistance in an orthotopic, multifocal model of PDAC.
Ab initio investigation of strain effects on the physical properties of PdVTe alloy
Authors: Djamila Khodja , Tayeb Djaafri , Abdelkader Djaafri , Aicha Bendjedid , Khelifa Hamada , Norredine Marbouh 
Published: August 2021

The investigations of the strain effects on magnetism, elasticity, electronic, optical, and thermodynamic properties of PdVTe half-Heusler alloy are carried out using the most accurate methods to obtain electronic band structure (i.e., the full-potential linearized augmented plane wave plus a local orbital (FP-LAPW + lo) approach). The analysis of the band structures and the density of states reveals half-metallic behavior with a small indirect band gap Eg of 0.51 eV around the Fermi level for the minority spin channels. The study of magnetic properties led to the predicted value of total magnetic moment µtot = 3µB, which nicely follows the Slater–Pauling rule µtot = Zt – 18. Several optical properties are calculated for the first time and the predicted values are in line with the Penn model. It is shown from the imaginary part of the complex dielectric function that the investigated alloy is optically metallic. The variations of thermodynamic parameters calculated using the quasi-harmonic Debye model agree well with the results predicted by the Debye theory. Moreover, the dynamical stability of the investigated alloy is computed by means of the phonon dispersion curves, the density of states, and the formation energies. Finally, the analysis of the strain effects reveals that PdVTe alloy preserves its ferromagnetic half-metallic behavior, it remains mechanically stable, the ionic nature dominates the atomic bonding, and the thermodynamic and the optical properties keep the same features in a large interval of pressure.
A comparison between higher-order nonclassicalities of superposition engineered coherent and thermal states
Authors: Deepak  , Chatterjee Arpita 
Published: August 2021

We consider an experimentally obtainable superposition (SUP) operator, defined by using a generalized superposition of products of field annihilation (a) and creation (a†) operators of the type A = saa† + ta†a with s2 + t2 = 1. We apply this SUP operator on coherent and thermal quantum states, and the states thus produced are referred to as SUP-operated coherent state (SOCS) and SUP-operated thermal state (SOTS), respectively. In the present work, we report a comparative study between the higher-order nonclassical properties of SOCS and SOTS. The comparison is performed by using a set of nonclassicality witnesses (e.g., higher-order anti-bunching, higher-order sub-Poissonian photon statistics, higher-order squeezing, Agarwal–Tara parameter, Klyshko’s condition). The existence of higher-order nonclassicalities in SOCS and SOTS have been investigated for the first time. In view of possible experimental verification of the proposed scheme, we present exact calculations to reveal the effect of non-unit quantum efficiency of quantum detector on higher-order nonclassicalities.
Unraveling Ewing Sarcoma Tumorigenesis Originating from Patient-Derived Mesenchymal Stem Cells
Authors: Sole Anna , Grossetête Sandrine , Heintzé Maxime , Babin Loelia , Zaïdi Sakina , Revy Patrick , Renouf Benjamin , De Cian Anne , Giovannangeli Carine , Pierre-Eugène Cécile , Janoueix-Lerosey Isabelle , Couronné Lucile , Kaltenbach Sophie , Tomishima Mark , Jasin Maria , Grünewald Thomas G.P. , Delattre Olivier , Surdez Didier , Brunet Erika 
Published: August 2021

Abstract

Ewing sarcoma is characterized by pathognomonic translocations, most frequently fusing EWSR1 with FLI1. An estimated 30% of Ewing sarcoma tumors also display genetic alterations in STAG2, TP53, or CDKN2A (SPC). Numerous attempts to develop relevant Ewing sarcoma models from primary human cells have been unsuccessful in faithfully recapitulating the phenotypic, transcriptomic, and epigenetic features of Ewing sarcoma. In this study, by engineering the t(11;22)(q24;q12) translocation together with a combination of SPC mutations, we generated a wide collection of immortalized cells (EWIma cells) tolerating EWSR1-FLI1 expression from primary mesenchymal stem cells (MSC) derived from a patient with Ewing sarcoma. Within this model, SPC alterations strongly favored Ewing sarcoma oncogenicity. Xenograft experiments with independent EWIma cells induced tumors and metastases in mice, which displayed bona fide features of Ewing sarcoma. EWIma cells presented balanced but also more complex translocation profiles mimicking chromoplexy, which is frequently observed in Ewing sarcoma and other cancers. Collectively, these results demonstrate that bone marrow–derived MSCs are a source of origin for Ewing sarcoma and also provide original experimental models to investigate Ewing sarcomagenesis.

Significance:
These findings demonstrate that Ewing sarcoma can originate from human bone-marrow–derived mesenchymal stem cells and that recurrent mutations support EWSR1-FLI1 translocation-mediated transformation.
High-resolution observations of the North Pacific transition layer from a Lagrangian float
Authors: Kaminski Alexis K. , D’Asaro Eric A. , Shcherbina Andrey Y. , Harcourt Ramsey R. 
Published: August 2021

AbstractAcrucial region of the ocean surface boundary layer (OSBL) is the strongly-sheared and -stratified transition layer (TL) separating the mixed layer from the upper pycnocline, where a diverse range of waves and instabilities are possible. Previous work suggests that these different waves and instabilities will lead to different OSBL behaviours. Therefore, understanding which physical processes occur is key for modelling the TL. Here we present observations of the TL from a Lagrangian float deployed for 73 days near Ocean Weather Station Papa (50°N, 145°W) during Fall 2018. The float followed the vertical motion of the TL, continuously measuring profiles across it using an ADCP, temperature chain and salinity sensors. The temperature chain made depth/time images of TL structures with a resolution of 6cm and 3 seconds. These showed the frequent occurrence of very sharp interfaces, dominated by temperature jumps of O(1)°C over 6cm or less. Temperature inversions were typically small (≲ 10cm), frequent, and strongly-stratified; very few large overturns were observed. The corresponding velocity profiles varied over larger length scales than the temperature profiles. These structures are consistent with scouring behaviour rather than Kelvin-Helmholtz-type overturning. Their net effect, estimated via a Thorpe-scale analysis, suggests that these frequent small temperature inversions can account for the observed mixed layer deepening and entrainment flux. Corresponding estimates of dissipation, diffusivity, and heat fluxes also agree with previous TL studies, suggesting that the TL dynamics is dominated by these nearly continuous 10cm-scale mixing structures, rather than by less frequent larger overturns.
Examining the Relationship between Tropopause Polar Vortices and Tornado Outbreaks
Authors: Bray Matthew T. , Cavallo Steven M. , Bluestein Howard B. 
Published: August 2021

AbstractMid-latitude jet streaks are known to produce conditions broadly supportive of tornado outbreaks, including forcing for large-scale ascent, increased wind shear, and decreased static stability. Although many processes may initiate a jet streak, we focus here on the development of jet maxima by interactions between the polar jet and tropopause polar vortices (TPVs). Originating from the Arctic, TPVs are long-lived circulations on the tropopause, which can be advected into the mid-latitudes. We hypothesize that when these vortices interact with the jet, they may contribute supplemental forcing for ascent and shear to tornado outbreaks, assuming other environmental conditions supportive of tornado development exist. Using a case set of significant tornado outbreak days from three states—Oklahoma, Illinois, and Alabama—we show that a vortex-jet streak structure is present (within 1250 km) in around two-thirds of tornado outbreaks. These vortices are commonly Arctic in origin (i.e., are TPVs) and are advected through a consistent path of entry into the mid-latitudes in the week before the outbreak, moving across the Northern Pacific and into the Gulf of Alaska before turning equatorward along the North American coast. These vortices are shown to be more intense and longer-lived than average. We further demonstrate that statistically significant patterns of wind shear, quasi-geostrophic forcing for ascent, and low static stability are present over the outbreak regions on the synoptic scale. In addition, we find that TPVs associated with tornadic events occur most often in the spring and are associated with greater low-level moisture when compared to non-tornadic TPV cases.
Attitudes and preferences towards palliative and end of life care in patients with advanced illness and their family caregivers in Latin America: A mixed studies systematic review
Authors: Dittborn Mariana , Turrillas Pamela , Maddocks Matthew , Leniz Javiera 
Published: August 2021

Background: Achieving universal access to palliative care is considered a global and equity priority. Understanding patients and caregivers’ attitudes and preferences towards palliative and end-of-life care in Latin America is essential to develop person-centred services in the region. Aim: To synthesize and appraise the evidence about patients with advanced illness and their caregivers’ attitudes and preferences towards palliative and end-of-life care in Latin America. Design: Mixed studies systematic review with sequential exploratory synthesis (thematic and narrative synthesis). Quality was assessed using the Mixed-Methods Appraisal Tool. Data sources: MEDLINE, Embase, PsychINFO, Lilacs, Web of Science, Scielo and Scopus to March 2021. Empirical studies examining patient or caregiver attitudes and/or preferences towards palliative and end-of-life care were included. Results: Of 3575 records screened, 45 articles were included, comprising 7 countries and a total of 1220 patients and 965 caregivers (26.8% non-cancer-related participants). Data were organized around seven themes: Symptom management and nutrition; End-of-life medical decisions; Communication patterns; Place of end-of-life care and death; God and religious community as source of hope and support; Caregiver’s role; and Mixed understandings of palliative care. Main findings include; conflicted views around palliative care and pain relief; patients’ preference to be informed about their condition contrasting with caregivers’ reluctance to discuss this with patients; common preference for shared decision-making; and overburdened caregivers lacking professional home-care support. Methodological flaws were found in general. Conclusion: Core themes provide context-specific evidence to inform the design of culturally sensitive palliative and end-of-life care services, models and public policies in Latin America.
Role of multimodal anaesthetic in post-operative analgesic requirement for robotic assisted radical prostatectomy
Authors: Masilamani Murugu Kalai Selvan , Sukumar Aiswarya , Cooke Pete William , Rangaswamy Chandrashekar 
Published: August 2021

Purpose: Robotic assisted laparoscopic radical prostatectomy (RARP) is considered as standard of care for surgical management of localised prostate cancer. Procedure specific postoperative pain management (PROSPECT) guidelines are available for open radical prostatectomy. There is a lack of evidence for optimal pain management protocol in patients undergoing robotic radical prostatectomy. This study investigates the impact of multimodal anaesthetic on post-operative analgesic requirements. Methods and materials: In our Institute, RARP is performed with a multimodal anaesthetic technique. Forty-one consecutive cases from October 2018 to March 2019 operated on by the same surgeon and anaesthetised by the same anaesthetic consultant were included in the study. All the patients received standardised multimodal anaesthetic technique. Data from visual analogue pain scores, nausea, vomiting and requirement of analgesics were collected from hospital records and results were analysed. Results: Our results showed that 60% of patients reported either no pain or mild pain. None of the patients required stronger opioids or parenteral analgesic. Only three patients required antiemetic. Length of hospital stay was 1.19 days which is comparable to published outcomes from high volume centres performing RARP. Conclusion: Our study adds to the currently published literature that RARP when combined with the multimodal anaesthetic technique can significantly reduce stronger opioid analgesic requirement in the post-operative period without compromising LOS.
Determinants of pyelonephritis onset in patients with obstructive urolithiasis
Authors: Abi Tayeh Georges , Safa Ali , Sarkis Julien , Alkassis Marwan , Khalil Nour , Nemr Elie , el Helou Elie 
Published: August 2021

Background: Acute obstructive pyelonephritis due to urolithiasis represents a medico-surgical emergency that can lead to life-threatening complications. There are still no established factors that reliably predict progression toward acute pyelonephritis in patients presenting with a simple renal colic. Objective: To investigate clinical and paraclinical factors that are associated with the onset of acute obstructive pyelonephritis. Methods: Patients presenting to the emergency department for renal colic with obstructive urolithiasis on imaging were enrolled in the study. Demographic data, vital signs, medical comorbidities, blood test results, urinalysis, and radiological findings were recorded. Obstructive pyelonephritis was defined by the presence of two or more of the following criteria: fever, flank pain or costovertebral angle tenderness, and a positive urine culture. Results: Seventeen patients out of 120 presenting with renal colic, were diagnosed with acute obstructive pyelonephritis (14%). Parameters that were associated with the onset of obstructive pyelonephritis were: diabetes ( p = 0.03), elevated CRP ( p = 0.01), stone size (>5 mm) ( p = 0.03), dilatation of renal pelvis ( p = 0.01), peri-renal fat stranding ( p = 0.02), and positive nitrites on urinalysis ( p < 0.01). Hyperleukocytosis, acute kidney injury, multiple stones, pyuria (>10/mm3), hypertension, and were not associated with the onset of obstructive pyelonephritis. Conclusion: This study showed that known diabetic status, elevated CRP, positive urine nitrites, stone size (>5 mm), pyelic dilatation, and peri-renal fat stranding were associated with the onset of pyelonephritis in patients presenting to the emergency department with obstructive urolithiasis.
New Onset Poststroke Dementia at one Year in Africans
Authors: Ojagbemi Akin , Bello Toyin , Owolabi Mayowa , Baiyewu Olusegun 
Published: August 2021

Background: There is limited information on new onset poststroke dementia (NPSD) in sub-Saharan Africa (SSA). We estimated incidence, cumulative incidence, risk factors and outcome of NPSD at 1 year in Nigerian survivors of a first-ever stroke. Methods: Hospital-based prospective observational study. Assessments for global cognition, learning, memory, executive and activities of daily life (ADL) functioning were conducted at 3 poststroke timepoints (Baseline, 3- and 12 months). NPSD was ascertained according to the “National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria.” Outcomes were assessed using the modified Rankin Scale (mRS), center for epidemiologic studies depression scale (CES-D 10), health related quality of life in stroke patients (HRQOLISP-26) and caregivers strain index (CSI). Results: Among 144 stroke survivors who were free of dementia at baseline, we found a 1-year cumulative incidence of 4.52% (95% C.I = 3.20, 6.39). In multivariate Cox regression analyses, diabetes was associated with NPSD (Hazard Ratio = 2.10, 95% CI = 1.02, 4.35). NPSD at 3 months was independently associated with motor decline [Mean difference (MD) in mRS = 1.6, 95% C.I = 0.9, 2.3)], depression (MD in CES-D = 2.9, 95% C.I = 0.3, 5.4), caregivers burden (MD in CSI = 1.2, 95% C.I = 0.5, 1.8), and poor quality of life (MD in HRQOLISP-26 = −11.2, 95% C.I = −15.7, −6.8) at 1 year. Conclusion: Approximately 4.5% of stroke survivors in Nigeria had NPSD at 1 year. Diabetes, which can be prevented, represent a primary prevention target for NPSD and its consequences in SSA.
Assessment of the genotoxic potential of tetrachlorvinphos insecticide by cytokinesis-block micronucleus and sister chromatid exchange assays
Authors: Cobanoglu Hayal , Cayir Akin 
Published: August 2021

Tetrachlorvinphos is an organophosphate that is classified as a carcinogen in humans by several authorities. Due to very limited data regarding the genotoxic potential, we aimed to comprehensively investigate in vitro genotoxic potential of tetrachlorvinphos. We performed our study by applying the cytokinesis-block micronucleus cytome and sister chromatid exchange (SCE) assays to human peripheral blood lymphocytes. We evaluated micronucleus (MN) and SCE frequencies and cytokinesis-block proliferation index in both exposed and non-exposed lymphocytes. We also calculated the chromosomal instability level in response to exposure by combining the results of MN and SCE. We found that MN frequency did not increase with exposure to tetrachlorvinphos (0–50 µg/ml). In contrast, we observed that SCE frequencies significantly increased with exposure to ≥5 µg/ml tetrachlorvinphos. Furthermore, exposure to tetrachlorvinphos at concentrations of 50 µg/ml induced a significant increase in chromosomal instability level ( p < 0.05). Cytokinesis-block proliferation index level did not significantly decrease in response to tetrachlorvinphos exposure. Our findings reveal that tetrachlorvinphos resulted in different DNA damages that were measured by two assays. Furthermore, our findings suggested that exposure to tetrachlorvinphos increased chromosomal instability that is a hallmark of many malignancies. We conclude that although tetrachlorvinphos does not significantly increase the MN level, the significant increase of both SCE and CIN frequencies indicates the genotoxic potential of tetrachlorvinphos in human peripheral lymphocytes. Additionally, tetrachlorvinphos is not cytotoxic in the range of tested concentrations.
Synthesis and characterization of polypyrrole/molybdenum oxide composite for ammonia vapour sensing at room temperature
Authors: Shariq Mohd Urooj , Husain Ahmad , Khan Mahfoozurrahman , Ahmad Anees 
Published: August 2021

In this study, polypyrrole (PPy) and polypyrrole/molybdenum oxide composite (PPy/MoO3) were synthesized by the chemical oxidative method in an aqueous medium, using anhydrous ferric chloride (FeCl3) as an oxidant. The successful preparation of materials was confirmed by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmittance electron microscopy (TEM). PPy and PPy/MoO3 were converted into pellets which were used as the sensor. A four-in-line probe device was used for studying DC electrical conductivity–based ammonia vapour–sensing properties at three different ammonia concentrations, that is, 1 M, 0.5 M and 0.1 M. The PPy/MoO3 sensor showed much-improved sensing performance than the PPy sensor in terms of % sensing response and reversibility. PPy/MoO3 sensor showed excellent selectivity for ammonia vapours against various VOCs. The % sensing response of PPy/MoO3 sensor towards ammonia was found to be 2.19, 2.50, 3.16, 3.87, 4.1, 5.15, 6.19, 6.55 and 7.77 times greater than ethanol, methanol, acetone, acetaldehyde, formaldehyde, toluene, benzene, chloroform and n-hexane, respectively. In the end, a sensing mechanism was also proposed, which is based on rapid adsorption–desorption of ammonia molecules on the PPy/MoO3 sensor’s surface.
An Array of Influential Factors for Analyzing Policy Advocacy
Authors: Albert Sasha M. , Gutman Marjorie A. , Barker Dianne C. , Nguyen Samantha , Caughlan Ian , Grob George 
Published: August 2021

This article presents an analytic approach to assessing the relationship between policy advocacy activities and outcomes for discrete episodes of advocacy, using a holistic array of factors that affect the relationship between advocacy and policy change. The factors pertain to not only advocacy organizational structure and strategies, but also the policy environment, the policy issue and available options to address it, and technical assistance that advocates receive. By focusing on the entire context in which advocates operate, this approach can be used to assess both advocacy campaign strategies and the broader contextual factors that contribute to advocacy outcomes. The array of factors also facilitates analytic generalizability across advocacy episodes, as evaluators can compare the role of similar factors across advocacy efforts. This analytic approach is illustrated by its application to a multiple case study evaluation of Voices for Healthy Kids.