bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Performance Analysis of Mixed Flow Turbine Rotors With Extended Blade Chord
Authors: Leonard Thomas , Spence Stephen , Filsinger Dietmar , Starke Andre
Published: July 2020

Mixed flow turbines offer additional design freedom compared with conventional radial turbines. This is useful in the automotive turbocharger application to reduce rotor inertia, which can be very beneficial for the transient response of a highly boosted downsized passenger car powertrain. A previously published study from the authors analyzed a series of nine mixed flow turbine rotors with varying blade cone angle and inlet blade angle. This paper reports an extension of that study with two further mixed flow turbine rotors where the chord length of the rotor blade was extended. The aim of this work was to understand both the aerodynamic and mechanical impacts of varying the chord length, particularly for the turbocharger application where off-design performance and transient response are very important. The baseline mixed flow rotor for this study had a blade cone angle of 30 deg and an inlet blade angle of 30 deg. Two further variations were produced; one with the trailing edge (TE) extended in the downstream direction across the entire blade span. In the second variation, the chord was extended at the hub corner only, while the shroud corner of the TE remained unchanged, with the aim of achieving some aerodynamic improvement while meeting mechanical requirements. When the blade was extended at both the hub and shroud, the inertia and stress levels increased significantly and the blade eigenfrequencies reduced. There was a significant improvement in peak efficiency, but the mechanical performance was unfavourable. The improvement in peak efficiency was mainly due to better exhaust diffuser performance and, therefore, would not be realized in most turbocharger installations. The blade that was extended at only the hub corner incurred very little additional inertia, and the centrifugal stresses and blade eigenfrequencies were improved. Consequently, it was possible to reduce the blade thickness at the TE in order to achieve a more aerodynamically optimized design. In this case, the mechanical performance was acceptable and there were efficiency improvements of up to 1.1% points at off-design conditions, with no reduction in peak efficiency or maximum mass flowrate. Therefore, the blade that was extended only at the hub produced some improvement within acceptable mechanical limits. The flow field features were considered for the three rotor geometries to explain the changes in loss and efficiency across the operating range.
Carbohydrate Hydrogel Products Do Not Improve Performance or Gastrointestinal Distress During Moderate-Intensity Endurance Exercise
Authors: King Andy J. , Rowe Joshua T. , Burke Louise M.
Published: July 2020

The benefits of ingesting exogenous carbohydrate (CHO) during prolonged exercise performance are well established. A recent food technology innovation has seen sodium alginate and pectin included in solutions of multiple transportable CHO, to encapsulate them at pH levels found in the stomach. Marketing claims include enhanced gastric emptying and delivery of CHO to the muscle with less gastrointestinal distress, leading to better sports performance. Emerging literature around such claims was identified by searching electronic databases; inclusion criteria were randomized controlled trials investigating metabolic and/or exercise performance parameters during endurance exercise >1 hr, with CHO hydrogels versus traditional CHO fluids and/or noncaloric hydrogels. Limitations associated with the heterogeneity of exercise protocols and control comparisons are noted. To date, improvements in exercise performance/capacity have not been clearly demonstrated with ingestion of CHO hydrogels above traditional CHO fluids. Studies utilizing isotopic tracers demonstrate similar rates of exogenous CHO oxidation, and subjective ratings of gastrointestinal distress do not appear to be different. Overall, data do not support any metabolic or performance advantages to exogenous CHO delivery in hydrogel form over traditional CHO preparations; although, one study demonstrates a possible glycogen sparing effect. The authors note that the current literature has largely failed to investigate the conditions under which maximal CHO availability is needed; high-performance athletes undertaking prolonged events at high relative and absolute exercise intensities. Although investigations are needed to better target the testimonials provided about CHO hydrogels, current evidence suggests that they are similar in outcome and a benefit to traditional CHO sources.
Different Time Course of Recovery in Achilles Tendon Thickness After Low-Load Resistance Training With and Without Blood Flow Restriction
Authors: Chulvi-Medrano Iván , Picón-Martínez Moisés , Cortell-Tormo Juan Manuel , Tortosa-Martínez Juan , Alonso-Aubin Diego Alexandre , Alakhdar Yasser
Published: July 2020

Context: Blood flow restriction research has focused on muscular strength and hypertrophy. Limited data have been reported about the blood flow restriction effect on the tendon. Objective: To analyze and compare the time course of recovery in Achilles tendon thickness after a single bout of low-intensity resistance training (LI-RT) and low-intensity blood flow restriction training (LI-BFRT). Methods: A total of 56 healthy participants (24.60 [4.0] y; 23.65 [3.4] body mass index) were included. The dominant leg was assigned for LI-BFRT using low load (30% 1-repetition maximum) and 30% of the total occlusion pressure (52.21 [17.89] mm Hg) in plantar-flexion exercise (1 × 30 + 3 × 15 repetitions). The nondominant leg was assumed as a control condition. Main Outcome Measure: Sonography images were taken before the intervention, immediately posttraining, and 24 hours after exercise (post-24) for the Achilles tendon thickness. Results: Changes in Achilles tendon thickness for LI-BFRT group were significant post- (−14.5%; P < .05) and post-24 (−9.2%; P < .05). In contrast, LI-RT group showed a transient decrease after exercise (−9.67%; P < .05) followed by a recovery of thickness post-24 (−1.06%; P < .05). Thickness post-24 was different between LI-BFRT versus LI-RT (P < .01). Hedge effect size analysis showed a large effect (g = 0.90) in LI-BFRT pre–post condition and a medium effect (g = 0.57) in post- to post-24. The LI-RT obtained a medium effect (g = 0.53) in pre–post condition and a small effect (g = 0.49) in post- to post-24. Conclusions: This study showed a different time course of the acute response in Achilles tendon thickness between LI-BFRT and LI-RT. This may be associated with intratendinous fluid movement in response to LI-BFRT.
Direct observation of anisotropic growth of water films on minerals driven by defects and surface tension
Authors: Yalcin Sibel Ebru , Legg Benjamin A. , Yeşilbaş Merve , Malvankar Nikhil S. , Boily Jean-François
Published: July 2020

Nanometer-thick water films grow anisotropically over single mineral nanoparticles.
Diverse noncoding mutations contribute to deregulation of cis-regulatory landscape in pediatric cancers
Authors: He Bing , Gao Peng , Ding Yang-Yang , Chen Chia-Hui , Chen Gregory , Chen Changya , Kim Hannah , Tasian Sarah K. , Hunger Stephen P. , Tan Kai
Published: July 2020

Joint analysis of genomic and transcriptomic data reveals diverse noncoding mutation landscapes in five types of pediatric cancers.
Expression of inhibitory receptors by B cells in chronic human infectious diseases restricts responses to membrane-associated antigens
Authors: Ambegaonkar Abhijit A. , Kwak Kihyuck , Sohn Haewon , Manzella-Lapeira Javier , Brzostowski Joseph , Pierce Susan K.
Published: July 2020

Atypical memory B cell antigens must be membrane associated to force exclusion of inhibitory receptors from the immune synapse.
Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA
Authors: Wang Kai , Lin Ruei-Zeng , Hong Xuechong , Ng Alex H. , Lee Chin Nien , Neumeyer Joseph , Wang Gang , Wang Xi , Ma Minglin , Pu William T. , Church George M. , Melero-Martin Juan M.
Published: July 2020

Temporal activation of ETV2 enables robust differentiation of human pluripotent stem cells into competent endothelial cells.
Extraordinary curtailment of massive typhus epidemic in the Warsaw Ghetto
Authors: Stone Lewi , He Daihai , Lehnstaedt Stephan , Artzy-Randrup Yael
Published: July 2020

A massive typhus epidemic was brought to a grinding halt in Warsaw Ghetto 1941 by the ghetto inmates.
In Vitro
Susceptibility of Treponema pallidum subsp.
pallidum
to Doxycycline
Authors: Edmondson Diane G. , Wormser Gary P. , Norris Steven J.
Published: July 2020

Doxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for
Treponema pallidum
subsp.
pallidum
has not been reported previously. In this study, an
in vitro
culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of
T. pallidum
subsp.
The Basis of Peracetic Acid Inactivation Mechanisms for Rotavirus and Tulane Virus under Conditions Relevant for Vegetable Sanitation
Authors: Fuzawa Miyu , Bai Hezi , Shisler Joanna L. , Nguyen Thanh H.
Published: July 2020

In this study, we examined the inactivation mechanisms of peracetic acid (PAA), a sanitizer commonly used for postharvest vegetable washing, for two enteric viruses: Tulane virus (TV) as a human norovirus surrogate and rotavirus (RV). PAA disinfection mechanisms for RV were mainly due to genome damage. In contrast, PAA disinfection in TV was due to damage of the proteins important for binding to its host receptor. We also observed that PAA triggered aggregation of TV to a much greater extent than RV. These studies demonstrate that different viruses are inactivated via different PAA mechanisms. This information is important for designing an optimal sanitation practice for postharvest vegetable washing to minimize foodborne viral diseases.
Light Response of
Pseudomonas putida
KT2440 Mediated by Class II LitR, a Photosensor Homolog
Authors: Sumi Satoru , Mutaguchi Naotaka , Ebuchi Teppei , Tsuchida Hiroaki , Yamamoto Takahiro , Suzuki Maki , Natsuka Chihiro , Shiratori-Takano Hatsumi , Shintani Masaki , Nojiri Hideaki , Ueda Kenji , Takano Hideaki
Published: July 2020

The LitR/CarH family is a new group of photosensor homologous to MerR-type transcriptional regulators. Proteins of this family are distributed to various nonphototrophic bacteria and grouped into at least five classes (I to V).
Pseudomonas putida
retaining three class II LitR proteins exhibited a genome-wide response to light. All three paralogs were functional and mediated photodependent activation of promoters directing the transcription of light-induced genes or operons. Two LOV (light, oxygen, or voltage) domain proteins, adjacently encoded by two
litR
genes, were also essential for the photodependent transcriptional control. Despite the difference in light-sensing mechanisms, the DNA binding consensus of class II LitR [T(G/A)TA(C/T)A] was the same as that of class I. This is the first study showing the actual involvement of class II LitR in light-induced transcription.
A Cytoplasmic Heme Sensor Illuminates the Impacts of Mitochondrial and Vacuolar Functions and Oxidative Stress on Heme-Iron Homeostasis in Cryptococcus neoformans
Authors: Bairwa Gaurav , Sánchez-León Eddy , Do Eunsoo , Jung Won Hee , Kronstad James W.
Published: July 2020

Invasive fungal diseases are increasing in frequency, and new drug targets and antifungal drugs are needed to bolster therapy. The mechanisms by which pathogens obtain critical nutrients such as iron from heme during host colonization represent a promising target for therapy. In this study, we employed a fluorescent heme sensor to investigate heme homeostasis in
Cryptococcus neoformans
. We demonstrated that endocytosis is a key aspect of heme acquisition and that vacuolar and mitochondrial functions are important in regulating the pool of available heme in cells. Stress generated by oxidative conditions impacts the heme pool, as do the drugs artemisinin and metformin; these drugs have heme-related activities and are in clinical use for malaria and diabetes, respectively. Overall, our study provides insights into mechanisms of fungal heme acquisition and demonstrates the utility of the heme sensor for drug characterization in support of new therapies for fungal diseases.
Impact of Glyphosate on the Honey Bee Gut Microbiota: Effects of Intensity, Duration, and Timing of Exposure
Authors: Motta Erick V. S. , Moran Nancy A.
Published: July 2020

As is true of many animal species, honey bees depend on their gut microbiota for health. The bee gut microbiota has been shown to regulate the host immune system and to protect against pathogenic diseases, and disruption of the normal microbiota leads to increased mortality. Understanding these effects can give broad insights into vulnerabilities of gut communities, and, in the case of honey bees, could provide information useful for promoting the health of these economically critical insects, which provide us with crop pollination services as well as honey and other products. The bee gut microbiota is acquired early in adult life and can be compromised by antibiotics and other chemicals. The globally used weed killer glyphosate was previously found to impact the gut microbiota of honey bees following sustained exposure. In the present study, we address how this impact depends on concentration, duration of exposure, and stage of community establishment. We found that sublethal doses of glyphosate reduce the abundance of beneficial bacteria and affect microbial diversity in the guts of honey bees, regardless of whether exposure occurs during or after microbiota acquisition. We also compared the effects of glyphosate to those of tylosin, an antibiotic used in beekeeping, and observed that tylosin effects diverge from those caused by glyphosate and are greater during microbiota acquisition. Such perturbations are not immediately lethal to bees but, depending on exposure level, can decrease survivorship under laboratory conditions.
Proteomic Study of the Survival and Resuscitation Mechanisms of Filamentous Persisters in an Evolved Escherichia coli Population from Cyclic Ampicillin Treatment
Authors: Sulaiman Jordy Evan , Lam Henry
Published: July 2020

Persisters are a subpopulation of cells with enhanced survival toward antibiotic treatment and have the ability to resume normal growth when the antibiotic stress is lifted. Although proteomics is the most suitable tool to study them from a system-level perspective, the number of persisters that present naturally is too few for proteomics analysis, and thus the complex mechanisms through which they are able to survive antibiotic stresses and resuscitate in fresh medium remain poorly understood. To overcome that challenge, we studied an evolved
Escherichia coli
population with elevated persister fraction under ampicillin treatment and obtained its proteome profiles during antibiotic treatment and resuscitation. We discovered that during treatment with ampicillin, this tolerant population employs an active oxidative stress response and exhibits lower ROS levels than the wild type. Moreover, an inner membrane protein which has implications in various stress responses, ElaB, was found to be highly upregulated in the persisters during resuscitation, and its knockout caused increased formation of small colony variants after ampicillin treatment, suggesting that ElaB is important for persisters to resume normal growth.
Oval window perilymph fistula in child with recurrent meningitis and unilateral hearing loss
Authors: Ng Miane Min Yan , D'Arco Felice , Chorbachi Raouf , Nash Robert
Published: July 2020

A 2-year-old boy presented to Ears, Nose and Throat (ENT) surgeons with unilateral hearing loss. Following a prodrome of upper respiratory tract infection (URTI), he developed two episodes of pneumococcal meningitis in quick succession. This case demonstrates an unusual cause of perilymph fistula diagnosed on imaging and confirmed surgically. He had failed the Newborn Hearing Screening Programme and was therefore referred to audiology, who confirmed profound sensorineural hearing loss in the right ear. MRI showed incomplete partitioning (type 1) of the right cochlea, suggesting cerebrospinal fluid (CSF) leak from the region of the stapes. Exploratory tympanotomy confirmed this, and proceeded to CSF leak repair, obliteration of the Eustachian tube, subtotal petrosectomy, abdominal fat grafting and blind sac closure. Although middle ear effusions are common; particularly in children with recent URTI, the possibility of otogenic CSF leak needs to be considered, especially in cases of recurrent meningitis.
Clinical burden of diabetes in Italy in 2018: a look at a systemic disease from the ARNO Diabetes Observatory
Authors: Bonora Enzo , Cataudella Salvatore , Marchesini Giulio , Miccoli Roberto , Vaccaro Olga , Fadini Gian Paolo , Martini Nello , Rossi Elisa
Published: July 2020

Introduction

Diabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.

Research design and methods

We investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.

Results

We identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p<0.001). Age was 69±15 (mean±SD). As compared with non-diabetic subjects, patients with diabetes received more prescriptions of any drugs (+30%, p<0.001), laboratory tests, radiologic exams and outpatient specialist consultations (+20%, p<0.001) and were hospitalized more frequently (+86%, p<0.001), with a longer stay (+1.4 days, p<0.001). Although cardiovascular diseases accounted for many hospital discharge diagnoses, virtually all diseases contributed to the higher rate of hospital admissions in diabetic subjects (235 vs 99 per 1000 person-years, p<0.001). Healthcare costs were >2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.

Conclusions

The burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.
Interventions to reduce inequalities in avoidable hospital admissions: explanatory framework and systematic review protocol
Authors: Sowden Sarah , Nezafat-Maldonado Behrouz , Wildman Josephine , Cookson Richard , Thomson Richard , Lambert Mark , Beyer Fiona , Bambra Clare
Published: July 2020

Introduction

Internationally there is pressure to contain costs due to rising numbers of hospital admissions. Alongside age, socioeconomic disadvantage is the strongest risk factor for avoidable hospital admission. This equity-focussed systematic review is required for policymakers to understand what has been shown to work to reduce inequalities in hospital admissions, what does not work and where the current gaps in the evidence-base are.

Methods and analysis

An initial framework shows how interventions are hypothesised to reduce socioeconomic inequalities in avoidable hospital admissions. Studies will be included if the intervention focusses exclusively on socioeconomically disadvantaged populations or if the study reports differential effects by socioeconomic status (education, income, occupation, social class, deprivation, poverty or an area-based proxy for deprivation derived from place of residence) with respect to hospital admission or readmission (overall or condition-specific for those classified as ambulatory care sensitive). Studies involving individuals of any age, undertaken in OECD (Organisation for Economic Co-operation and Development) countries, published from 2000 to 29th February 2020 in any language will be included. Electronic searches will include MEDLINE, Embase, CINAHL, Cochrane CENTRAL and the Web of Knowledge platform. Electronic searches will be supplemented with full citation searches of included studies, website searches and retrieval of relevant unpublished information. Study inclusion, data extraction and quality appraisal will be conducted by two reviewers. Narrative synthesis will be conducted and also meta-analysis where possible. The main analysis will examine the effectiveness of interventions at reducing socioeconomic inequalities in hospital admissions. Interventions will be characterised by their domain of action and approach to addressing inequalities. For included studies, contextual information on where, for whom and how these interventions are organised, implemented and delivered will be examined where possible.

Ethics and dissemination

Ethical approval was not required for this protocol. The research will be disseminated via peer-reviewed publication, conferences and an open-access policy-orientated paper.

PROSPERO registration number

CRD42019153666.
Comparison of visceral fat area measured by CT and bioelectrical impedance analysis in Chinese patients with gastric cancer: a cross-sectional study
Authors: Gao Bo , Liu Yu , Ding Chao , Liu Shunli , Chen Xiaotian , Bian Xiaojie
Published: July 2020

Objectives

Bioelectrical impedance analysis (BIA) is a simple and inexpensive method to estimate body composition. However, the accuracy of BIA is unknown. We aimed to assess the accuracy of BIA in estimating visceral fat area (VFA) in patients with gastric cancer.

Study design

This was a cross-sectional study comparing the accuracy of BIA in estimating VFA with the gold standard method measured by CT. VFA was measured in enrolled patients both by CT and BIA. VFA by CT at umbilical level ≥100 cm2 was considered as visceral obesity. Reliability between the two methods was assessed by intraclass correlation coefficient (ICC) and consistency was assessed by Bland-Altman method (95% limits of agreement). The area under the receiver operating characteristic curve (AUROC) was used to assess the performance of BIA in diagnosing visceral obesity.

Setting

The study was conducted in China.

Participants

From 1 January 2017 to 1 December 2018, a total of 157 patients diagnosed with gastric cancer were enrolled.

Results

Overall, VFA by CT and BIA in patients was 84.39±46.43 cm2 and 71.94±22.44 cm2, respectively. VFA estimated by BIA was positively correlated with VFA measured by CT using Pearson’s test (r=0.650, p<0.001). Overall, ICC for the two methods was 0.675. The mean bias between the two measurements was 12.45±36.13 cm2. The 95% limits of agreement ranged from −58.36 cm2 to 83.26 cm2. The cut-off value for diagnosing visceral obesity by BIA was 81 cm2 (AUROC: 0.822, p<0.001, 95% CI 0.758 to 0.887).

Conclusions

VFA measured by BIA showed satisfactory reliability with that measured by CT. However, the absolute values of the two methods were not interchangeable. The cut-off value for VFA by BIA in diagnosing visceral obesity was 81 cm2 for patients with gastric cancer in the Chinese population.
Experiences of digital communication with automated patient interviews and asynchronous chat in Swedish primary care: a qualitative study
Authors: Entezarjou Artin , Bolmsjö Beata Borgström , Calling Susanna , Midlöv Patrik , Milos Nymberg Veronica
Published: July 2020

Objectives

To explore staff experiences of working with a digital communication platform implemented throughout several primary healthcare centres in Sweden.

Design

A descriptive qualitative approach using focus group interviews. Qualitative content analysis was used to code, categorise and thematise data.

Setting

Primary healthcare centres across Sweden, in both rural and urban settings.

Participants

A total of three mixed focus groups, comprising 19 general practitioners and nurses with experience using a specific digital communication platform.

Results

Five categories emerged: ‘Fears and Benefits of Digital Communication’, ‘Altered Practice Workflow’, ‘Accepting the Digital Society’, ‘Safe and Secure for Patients’ and ‘Doesn't Suit Everyone and Everything’. These were abstracted into two comprehensive themes: ‘Adjusting to a novel medium of communication’ and ‘Digitally filtered primary care’, describing how staff experienced integrating the software as a useful tool for certain clinical contexts while managing the communication challenges associated with written communication.

Conclusions

Family medicine staff were ambivalent concerning the use of digital communication but, after a period of adjustment, it was seen as a useful communication tool especially when combined with continuity of care. Staff acknowledged limitations regarding use by inappropriate patient populations, information overload and misinterpretation of text by both staff and patients.
Keeping afloat: a case study tracing the emergence of drowning prevention as a health issue in Bangladesh 1999–2017
Authors: Dodd Madeleine , Zwi Anthony , Rahman Aminur , Chowdhury Fazlul Kader , Ivers Rebecca Q , Jagnoor Jagnoor
Published: July 2020

Background

Drowning is a leading cause of child death in Bangladesh. The present study investigated the emergence of drowning reduction as a priority within Bangladesh and the position it currently holds on the national policy agenda.

Methods

This case study documents the evolution of policy responses to drowning, reporting on data from semistructured interviews and a document analysis. To identify key factors that have facilitated the prioritisation of drowning prevention, data were synthesised using Shiffman and Smith’s 2007 Policy Prioritisation Framework. Furthermore, an inductive approach was used to identify key themes unique to drowning prevention that were not embedded in the framework.

Results

Four key phases of policy development for drowning prevention were distinguishable: (1) identification of issue and the emergence of actor support; (2) enhanced leadership and the accumulation of issue characteristics; (3) the formation of an internal frame and its impact on global support; and (4) enhanced national recognition and supportive global normative factors. Four additional themes unique to the case of drowning were also identified: competing health priorities, limited issue awareness, shift of disease burden to non-communicable diseases and the multisectoral nature of drowning.

Conclusion

This study demonstrates that the level of political prioritisation given to drowning prevention has evolved over the last decade and a half. A comprehensive understanding of factors that have elevated the issue onto the policy agenda will ensure future stakeholder engagement activities can be designed to foster deeper and more sustained commitment by key actors and organisations.
Clinical outcomes of prexasertib monotherapy in recurrentBRCAwild-type high-grade serous ovarian cancer involve innate and adaptive immune responses
Authors: Lampert Erika J , Cimino-Mathews Ashley , Lee Joo Sang , Nair Jayakumar , Lee Min-Jung , Yuno Akira , An Daniel , Trepel Jane B , Ruppin Eytan , Lee Jung-Min
Published: July 2020

Background

Preclinical data suggest cell cycle checkpoint blockade may induce an immunostimulatory tumor microenvironment. However, it remains elusive whether immunomodulation occurs in the clinical setting. To test this, we used blood and fresh tissue samples collected at baseline and post therapy from a phase II trial of the cell cycle checkpoint 1 inhibitor (CHK1i) prexasertib in recurrent ovarian cancer.

Methods

Paired blood samples and fresh core biopsies, taken before treatment was started at baseline (cycle 1 day 1 (C1D1)) and post second dose on day 15 of cycle 1 (C1D15), were collected. To evaluate changes in the immune responses after treatment, multiparametric flow cytometry for DNA damage markers and immune cell subsets was performed on paired blood samples. RNA sequencing (RNAseq) of paired core biopsies was also analyzed. Archival tissue immune microenvironment was evaluated with immunohistochemistry. All correlative study statistical analyses used two-sided significance with a cut-off of p=0.05.

Results

Flow cytometric analysis showed significantly increased γ-H2AX staining after CHK1i treatment, accompanied by increased monocyte populations, suggestive of an activated innate immune response (median 31.6% vs 45.6%, p=0.005). Increased expressions of immunocompetence marker HLA-DR (Human Leukocyte Antigen DR antigen) on monocytes and ofTBK1,a marker of STING (stimulator of interferon genes) pathway activation, in biopsies were associated with improved progression-free survival (PFS) (9.25 vs 3.5 months, p=0.019; 9 vs 3 months, p=0.003, respectively). Computational analysis of RNAseq data indicated increased infiltration of tumor niches by naïve B-cells and resting memory T-cells, suggestive of a possibly activated adaptive immune response, and greater T-reg infiltration after treatment correlated with worse PFS (9.25 vs 3.5 months, p=0.007). An immunosuppressive adaptive immune response, perhaps compensatory, was also observed on flow cytometry, including lymphodepletion of total peripheral CD4+ and CD8+T cells after CHK1i and an increase in the proportion of T-regs among these T-cells. Additionally, there was a trend of improved PFS with greater tumor-infiltrating lymphocytes (TILs) in archival tissues (13.7 months >30% TILs vs 5.5 months ≤30% TILs, p=0.05).

Conclusion

Our study demonstrates that a favorable clinical response in high-grade serous ovarian carcinoma patients treated with CHK1i is possibly associated with enhanced innate and adaptive immunity, requiring further mechanistic studies. It is supportive of current efforts for a clinical development strategy for therapeutic combinations with immunotherapy in ovarian cancer.
Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study
Authors: Chardin David , Paquet Marie , Schiappa Renaud , Darcourt Jacques , Bailleux Caroline , Poudenx Michel , Sciazza Aurélie , Ilie Marius , Benzaquen Jonathan , Martin Nicolas , Otto Josiane , Humbert Olivier
Published: July 2020

Background

Reliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors.

Methods

Maximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD).

Results

A high MTV and a high TLG were significantly associated with a lower OS (p<0.001). The median OS in patients with MTV above the median (36.5 cm3) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively).

Conclusion

MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.
‘Should we stop or continue conventional synthetic (including glucocorticoids) and targeted DMARDs before surgery in patients with inflammatory rheumatic diseases?’
Authors: Goodman Susan M , George Michael D
Published: July 2020

Total hip and total knee arthroplasty) remain important interventions to treat symptomatic knee and hip damage in patients with rheumatoid arthritis, with little change in utilisation rates despite the increasingly widespread use of potent conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and targeted DMARDs including Janus kinase inhibitors and biologics. The majority of patients are receiving these immunosuppressing medications and glucocorticoids at the time they present for arthroplasty. There is minimal randomised controlled trial data addressing the use of DMARDs in the perioperative period, yet patients and their physicians face these decisions daily. This paper reviews what is known regarding perioperative management of targeted and csDMARDs and glucocorticoids.
Biological activities of commercial bovine lactoferrin sources
Authors: Lönnerdal Bo , Du Xiaogu , Jiang Rulan
Published: July 2020

Lactoferrin (Lf) samples from several manufacturers were evaluated in vitro. The purity and protein form of each Lf were examined by SDS–PAGE, Western blot, and proteomics analysis. Assays were conducted to evaluate uptake of Lfs and iron from Lfs by enterocytes as well as Lf bioactivities, including effects on intestinal cell proliferation and differentiation, IL-18 secretion, TGF-β1 transcription, and growth of enteropathogenic Escherichia coli (EPEC). Composition of the Lfs varies; some only contain a major Lf band (∼80 kDa), and some also contain minor forms. All Lfs and iron from the Lfs were absorbed by Caco-2 cells, with various efficiencies. The bioactivities of the Lfs varied considerably, but there was no consistent trend. All Lfs promoted intestinal cell proliferation, secretion of IL-18, and transcription of TGF-β1. Some Lfs exhibited pro-differentiation effects on Caco-2 cells. Effects of pasteurization (62.5 °C for 30 min, 72 °C for 15 s, or 121 °C for 5 min) on integrity, uptake, and bioactivities were examined using Dicofarm, Tatua, and native bovine Lfs. Results show that pasteurization did not affect protein integrity, but variously affected uptake of Lf and its effects on intestinal proliferation, differentiation, and EPEC growth. To choose a Lf source for a clinical trial, assessment of bioactivities is recommended.
The Canadian Fungal Research Network: current challenges and future opportunities
Authors: Horianopoulos Linda C. , Gluck-Thaler Emile , Benoit Gelber Isabelle , Cowen Leah E. , Geddes-McAlister Jennifer , Landry Christian R. , Schwartz Ilan S. , Scott James A. , Sellam Adnane , Sheppard Donald C. , Spribille Toby , Subramaniam Rajagopal , Walker Allison K. , Harris Steven D. , Shapiro Rebecca S. , Gerstein Aleeza C.
Published: July 2020

Fungi critically impact the health and function of global ecosystems and economies. In Canada, fungal researchers often work within silos defined by subdiscipline and institutional type, complicating the collaborations necessary to understand the impacts fungi have on the environment, economy, and plant and animal health. Here, we announce the establishment of the Canadian Fungal Research Network (CanFunNet, https://fungalresearch.ca ), whose mission is to strengthen and promote fungal research in Canada by facilitating dialogue among scientists. We summarize the challenges and opportunities for Canadian fungal research that were discussed at CanFunNet’s inaugural meeting in 2019, and identify 4 priorities for our community: (i) increasing collaboration among scientists, (ii) studying diversity in the context of ecological disturbance, (iii) preserving culture collections in the absence of sustained funding, and (iv) leveraging diverse expertise to attract trainees. We have gathered additional information to support our recommendations, including a survey identifying underrepresentation of fungal-related courses at Canadian universities, a list of Canadian fungaria and culture collections, and a case study of a human fungal pathogen outbreak. We anticipate that these discussions will help prioritize fungal research in Canada, and we welcome all researchers to join this nationwide effort to enhance knowledge dissemination and funding advocacy.
Chern–Simons quantum mechanics and fractional angular momentum in atom system
Authors: Ma Yao-Yao , Zhang Qiu-Yue , Wang Qing , Jing Jian
Published: July 2020

The model of a planar atom which possesses a nonvanishing electric dipole moment interacting with magnetic fields in a specific setting is studied. Energy spectra of this model and its reduced model, which is the limit of cooling down the atom to the negligible kinetic energy, are solved exactly. We show that energy spectra of the reduced model cannot be obtained directly from the full ones by taking the same limit. In order to get the energy spectra of the reduced model from the full model, we must regularize energy spectra of the full model properly when the limit of the negligible kinetic energy is taken. It is one of the characteristics of the Chern–Simons quantum mechanics. Besides this, the canonical angular momentum of the reduced model will take fractional values although the full model can only take integers. It means that it is possible to realize the Chern–Simons quantum mechanics and fractional angular momentum simultaneously by this model.
Structural and thermal properties of Cu1.75−xMxTe crystals
Authors: Aliyev Y. I. , Asadov Y. G. , Rustamova L. B. , Dashdemirov A. O. , Ismayilova N. A. , Ayubov A. A. , Jabarov S. H.
Published: July 2020

Single crystals of Cu[Formula: see text]Te, Cu[Formula: see text]Zn[Formula: see text]Te and Cu[Formula: see text]Cd[Formula: see text]Te compounds were synthesized by Brijmen method and their crystal structure was studied by X-ray diffraction. The hexagonal, orthorhombic aand cubic structure phases of these compounds have been determined at room-temperature. Phase transitions at high-temperatures were observed. Lattice parameters for hexagonal, orthorhombic and cubic phases have been determined in the temperature range of [Formula: see text]–1073 K. From the temperature dependences of the lattice parameters, the coefficients of thermal expansion of the existing modifications in the main crystallographic directions were calculated.
Structural, magnetic and electrical characterization of Cr-doped lead-free multiferroic AlFeO3 prepared by co-precipitation and solid state method
Authors: Amami Mongi , Farhat Lamia Ben , Ahmed Samia Ben , Ezzine Safa
Published: July 2020

Polycrystalline samples AlFe[Formula: see text]Cr[Formula: see text]O3 synthetized by a solid state and a co-precipitation (cop) method show an orthorhombic system in space group Pc21n. It was found that the cation distribution and magnetic ordering depend toughly on the preparation conductions. The dielectric and conductivity properties of samples were studied as function of frequency and temperature. We deployed impedance spectroscopy in studying the dielectric behavior of AlFe[Formula: see text]Cr[Formula: see text]O3. The significant results of this work are as follows: For both samples, permittivity and dielectric loss are very sensitive to temperature and frequency variation. The presence of additional effects and conducting species in AFCr5 ceramics leads to high dielectric permittivity. The activation energy values point towards the small range motion of oxygen at low-temperature and long range motion at high-temperature. The dielectric response, in case of AFCr5-s, was assigned to both grain and grain boundaries. However, additional entity pores also contribute to dielectric belongings of AFCr5-cop.
Lévy noise-induced inverse stochastic resonance on Newman–Watts networks of Hodgkin–Huxley neurons
Authors: Li Dongxi , Song Shuling , Zhang Ni
Published: July 2020

This paper primarily investigates the inverse stochastic resonance (ISR) of neuron network driven by Lévy noise with electrical autapse and chemical autapse, respectively. Firstly, the discharge of Hodgkin–Huxley (HH) neuron network under different noise parameters, autapse parameters and network coupling strength is shown. Then, the variation of average firing rate with Lévy noise in the case of electrical autapse and chemical autapse is presented. We find that there exists a minimum value of the average firing rate curve caused by stability index and noise intensity of Lévy noise across the whole network, which is the phenomenon of ISR. With the increase of autaptic intensity and coupling strength, the ISR inhibitory effect of neuron discharge is weakened. In addition, with the increase of coupling strength, the neuron discharge of neural network is more intense and regular. As a consequence, our work suggests that autaptic intensity and coupling efficient of neuronal network can regulate the neuronal firing activities and suppress the effect of ISR, and Lévy noise can induce ISR phenomenon in Newman–Watts neuronal network.
A New Diagnosis Method of ECG Diseases Based on Deep Learning
Authors: Song Weibo , Wang Wei , Jiang Fengjiao
Published: July 2020

The research of ECG diagnosis based on deep learning is a hot topic at present. ECG signals are collected from human body surface electrodes and electrocardiograms are obtained. The research process is to integrate engineering technology into the medical field, reflecting the new direction of interdisciplinary combination. This paper introduces the basic principle of ECG signal and the basic analysis method of ECG. The experimental results show that the application of one-dimensional convolutional neural network is more effective and accurate than the traditional methods. The design of the theoretical method has provided the technical support and theoretical basis for the further study of electrophysiological signals and the clinical diagnosis.
Interacting holographic dark energy in Bianchi type-V and IX universes with variable deceleration parameter
Authors: Eser H. , Kilinc C. B.
Published: July 2020

In this paper, we study spatially homogeneous and anisotropic Bianchi type-V and IX universes filled with interacting dark matter and holographic dark energy. We obtained the solution of the field equations by using the variable deceleration parameter in the form [Formula: see text]. The cosmological parameters of the models like deceleration and equation of state are obtained. We observe that the deceleration parameter tends to [Formula: see text] which shows an accelerated universe, and the equation of state tends to [Formula: see text] which belongs to [Formula: see text]CDM model. Moreover, we establish the correspondence between holographic dark energy model and quintessence scalar field.
General Intelligence: An Ecumenical Heuristic for Artificial Consciousness Research?
Authors: Shevlin Henry
Published: July 2020

The science of consciousness has made great strides in recent decades. However, the proliferation of competing theories makes it difficult to reach consensus about artificial consciousness. While for purely scientific purposes we might wish to adopt a ‘wait and see’ attitude, we may soon face practical and ethical questions about whether, for example, agents artificial systems are capable of suffering. Moreover, many of the methods used for assessing consciousness in humans and even non-human animals are not straightforwardly applicable to artificial systems. With these challenges in mind, I propose that we look for ecumenical heuristics for artificial consciousness to enable us to make tentative assessments of the likelihood of consciousness arising in different artificial systems. I argue that such heuristics should have three main features: they should be (i) intuitively plausible, (ii) theoretically-neutral, and (iii) scientifically tractable. I claim that the concept of general intelligence — understood as a capacity for robust, flexible, and integrated cognition and behavior — satisfies these criteria and may thus provide the basis for such a heuristic, allowing us to make initial cautious estimations of which artificial systems are most likely to be conscious.
Ranking and selecting fault models using flow-indicator fault properties and simple streamline simulations
Authors: Wilson Paul , Smith Stewart , Povey Danny , Harris Simon
Published: July 2020

Fault zones in porous sandstones are commonly divided into two parts: a fault core and a damage zone. Both fault-zone elements could influence subsurface fluid flow and should be incorporated in a geologically realistic model. The fault core can be implemented in the model as a transmissibility multiplier (TM), while the damage zone can be implemented by modifying the grid permeability in the cells adjacent to the model faults. Each of the input parameters used in calculating the TM and damage-zone permeability modification is subject to geological uncertainty. Here an iterative workflow is employed to define probability distribution functions for each of the input parameters, with the result being many fault-model realizations. Here two methods are examined for ranking and selecting the fault-model realizations for further analysis: (i) calculating the flow-indicator fault properties (effective cross-fault transmissibility and effective cross-fault permeability) from the static model; and (ii) employing a simplified flow-based connectivity calculation, returning dynamic measures of model connectivity. The aims are to outline the methodology and workflow used, evaluate the impact of the different input parameters on the results, and examine the results of the static and dynamic approaches to understand how the ranking and selection of models compares between the two.

Our results are dependent on the structural model. In a strongly compartmentalized model based on the Gullfaks Field, North Sea, fluid-flow-indicator fault properties are weakly correlated with measures of dynamic behaviour. In particular, models with low fault transmissibility show a much greater range of dynamic behaviour, and are less predictable, than models with high fault transmissibility. In a weakly compartmentalized model with strongly channelized fluvial facies based on the Whitley Bay area in NE England, there was a strong correlation between flow-indicator fault properties and measures of dynamic behaviour. We ascribe these results to the greater complexity of flow paths expected when a highly compartmentalized model contains faults that are likely to be baffles to cross-fault flow.

Thematic collection:
This article is part of the Fault and top seals collection available at:
https://www.lyellcollection.org/cc/fault-and-top-seals-2019