bluuebunny/crossref_metadata_2025 huggingface dataset:
A graph convolutional network model for evaluating potential congestion spots based on local urban built environments
Authors: Qin Kun , Xu Yuanquan , Kang Chaogui , Kwan Mei‐Po
Published: June 2020

Automatically identifying potential congestion spots in cities has significant practical implications for efficient urban development and management. It requires the ability to examine the relationships between urban built environment features and traffic congestion situations. This article presents a novel and effective approach for achieving the task based on a machine‐learning technique and publicly available street‐view imagery and point‐of‐interest (POI) data. The proposed multiple‐graph‐based convolutional network architecture can: (a) extract essential urban built environment features from street‐view imagery and neighboring POIs; (b) model the spatial dependencies between traffic congestion on road networks via graph convolution; and (c) evaluate the risk level of road intersections to emerging congestion situations based on local built environment features. We apply the model to Wuhan in China, and predict the potential congestion spots across the city. The results confirm that the model prediction is highly consistent (about 85.5%) when compared to the ground‐truth data based on traffic indices derived from a big taxi GPS trajectory dataset. This research enhances the understanding of traffic congestion situations under various geographic, societal, and economic contexts based on easily accessible road, street‐view, and POI datasets at large spatiotemporal scales.
Achieving a high cure rate with direct‐acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi‐clinic demonstration project
Authors: Coyer Liza , Njoya Oudou , Njouom Richard , Mossus Tatiana , Kowo Mathurin Pierre , Essomba Frida , Boers Alexander , Coutinho Roel , Ondoa Pascale ,   the HEP C‐IMPACT Team
Published: June 2020

Objectives

Highly effective direct‐acting antivirals (DAAs) for Hepatitis C treatment are largely inaccessible in sub‐Saharan Africa. Data on treatment feasibility and outcomes in clinical settings are limited. We assessed the feasibility of achieving a high (≥90%) cure rate with DAAs in six gastroenterology clinics in Cameroon.

Methods

Patients with chronic Hepatitis C virus (HCV) infection were treated for 12 or 24 weeks with ledipasvir/sofosbuvir, ledipasvir/sofosbuvir/ribavirin or sofosbuvir/ribavirin, depending on the stage of liver disease and HCV genotype. The cure rate was defined as the proportion of patients with a sustained virological response 12 weeks after treatment completion (SVR12) among all treatment completers.

Results

We identified 190 HCV RNA positive patients between September‐2017 and August‐2018, 161 (84.7%) of whom started treatment. 105 (65.2%) were female, median age was 61.3 years [IQR = 55.9–66.9] and 11 (6.8%) were HIV‐positive. Median plasma HCV RNA was 6.0 log10 IU/mL [IQR = 5.6–6.4]. HCV genotypes identified were 1 (34.8%), 2 (13.7%), 4 (50.9%), 1 and 4 (0.6%); 46 (28.6%) strains of 160 single‐genotype infections were non‐subtypeable. Of 158 treatment completers, 152 (96.2%, 95%CI = 91.9–98.6%) achieved SVR12. Six patients did not achieve SVR12: five carried HCV with NS5A resistance mutations and one with NS5B resistance mutations. Three patients died before and two after treatment completion. The most common adverse events were asthenia (12.0%), headache (11.4%) and dizziness (18.9%).

Conclusion

High cure rates of Hepatitis C with DAAs are achievable in clinical settings of Cameroon. However, the accessibility and provision of HCV screening, diagnosis, treatment, monitoring and care should be addressed for large‐scale implementation.
Clinical morbidity associated with Schistosoma haematobium infection in pre‐school age children from an endemic district in Zimbabwe
Authors: Mduluza‐Jokonya Tariro L. , Naicker Thajasvarie , Kasambala Maritha , Jokonya Luxwell , Vengesai Arthur , Midzi Herald , Choto Emilia , Musonza Kimpton , Rusankaniko Simbarashe , Sibanda Elopy , Mutapi Francisca , Mduluza Takafira
Published: June 2020

Objective

To investigate Schistosoma haematobium morbidity in infected pre‐school age children and establish their disease burden.

Methodology

Pre‐school age children (1–5 years) who were lifelong residents of the study area and had no other infections were included in the study. Participants underwent a physical examination with clinicians blinded to their infection status. Diagnosis of S. haematobium was by urine filtration.

Results

The prevalence of S. haematobium was 35.1% (146/416). The clinical features observed in patients with Schistosoma haematobium were as follows: wheezes (morbidity attributable factor (AF = 93.9%), haematuria (AF = 92.6%), ascites (AF = 91.5%), atopy (AF = 76.9%), inguinal lymphadenopathy (AF = 68.4%), stunting (AF = 38.2), malnutrition (MUAC)(AF = 20%) and weight for height scales (AF = 5%). Schistosoma. haematobium infected children were at greater odds ratio of presenting with inguinal lymphadenopathy (AOR)=99.2(95% CI 24.2 to 854.5), wheezes in the chest (AOR = 35.4 95% CI 15.3 to 94.2), Distended abdomen with ascites (AOR = 23.9 95% CI 11.4 to 54), haematuria (AOR = 12.6 95% CI 11.6 to 14.1), atopy history (AOR = 5.6 95% CI 1.85 to 20.2), malnutrition (AOR = 2.3 95% CI 1.4 to 3.2) and stunting (AOR = 1.9 95% CI 1.1 to2.7).

Conclusion

The study is novel as it demonstrates for the first time clinical morbidity markers associated with S. haematobium infection in pre‐school age children. Furthermore the study adds scientific evidence to the call for inclusion of pre‐school age children in schistosomiasis control programmes. These morbidity markers highlight the need for early diagnosis and screening for S. haematobium in pre‐school age children.
A 24‐base pair deletion in the ABO gene causes a hereditary splice site defect: a novel mechanism underlying ABO blood group O
Authors: Matzhold Eva Maria , Drexler Camilla , Wagner Andrea , Bernecker Claudia , Pessentheiner Ariane , Bogner‐Strauß Juliane Gertrude , Helmberg Wolfgang , Wagner Thomas
Published: June 2020

BACKGROUND

Blood group A and B antigens are synthesized by glycosyltransferases regulated by a complex molecular genetic background. A multibase deletion in the ABO gene was identified in two related blood donors. To define its hereditary character and to evaluate genotype–phenotype associations, a detailed study including 30 family members was conducted.

METHODS AND MATERIALS

ABO phenotyping was performed with agglutination techniques and adsorption‐elution tests. The secretor status was determined. Allele‐specific sequencing of ABO and genotyping of family members by a mutation‐specific polymerase chain reaction were carried out. Functional analysis included cloning of complementary DNA and transfection experiments in HeLa cells. The antigen expression was investigated by flow cytometry and adsorption‐elution method.

RESULTS

Sequencing analysis revealed a 24‐bp deletion in Exon 5 and the adjacent intronic region of ABO. The alteration was inherited by 16 family members. Nine of them being heterozygous for the mutated allele failed to express A antigen on their erythrocytes as found by routine typing. In particular samples, however, adsorption‐elution studies indicated inconclusive results. HeLa cells transfected with aberrant gene transcripts did not express blood group antigen A.

CONCLUSION

The variation causes defects in messenger RNA splicing, most likely inactivating the transferase as observed by serological typing and in vitro expression analysis. These data suggest a novel mechanism associated with blood group O and extend the knowledge of exceptionally rare ABO splice site mutations and deletions. With increased understanding of the molecular bases of ABO, the diagnostics may be further enhanced to ensure the safest possible use of the blood supply.
Phonetic categorization and discrimination of voice onset time under divided attention
Authors: Chiu Faith , Rakusen Lyndon L. , Mattys Sven L.
Published: June 2020

Event durations are perceived to be shorter under divided attention. “Time shrinkage” is thought to be due to rapid attentional switches between tasks, leading to a loss of input samples, and hence, an under-estimation of duration. However, few studies have considered whether this phenomenon applies to durations relevant to time-based phonetic categorization. In this study, participants categorized auditory stimuli varying in voice onset time (VOT) as /ɡ/ or /k/. They did so under focused attention (auditory task alone) or while performing a low-level visual task at the same time (divided attention). Under divided attention, there was increased response imprecision but no bias toward hearing /ɡ/, the shorter-VOT sound. It is concluded that sample loss under divided attention does not apply to the perception of phonetic contrasts within the VOT range.
Acute:Chronic Workload Ratio: Conceptual Issues and Fundamental Pitfalls
Authors: Impellizzeri Franco M. , Tenan Matthew S. , Kempton Tom , Novak Andrew , Coutts Aaron J.
Published: June 2020

The number of studies examining associations between training load and injury has increased exponentially. As a result, many new measures of exposure and training-load-based prognostic factors have been created. The acute:chronic workload ratio (ACWR) is the most popular. However, when recommending the manipulation of a prognostic factor in order to alter the likelihood of an event, one assumes a causal effect. This introduces a series of additional conceptual and methodological considerations that are problematic and should be considered. Because no studies have even tried to estimate causal effects properly, manipulating ACWR in practical settings in order to change injury rates remains a conjecture and an overinterpretation of the available data. Furthermore, there are known issues with the use of ratio data and unrecognized assumptions that negatively affect the ACWR metric for use as a causal prognostic factor. ACWR use in practical settings can lead to inappropriate recommendations, because its causal relation to injury has not been established, it is an inaccurate metric (failing to normalize the numerator by the denominator even when uncoupled), it has a lack of background rationale to support its causal role, it is an ambiguous metric, and it is not consistently and unidirectionally related to injury risk. Conclusion: There is no evidence supporting the use of ACWR in training-load-management systems or for training recommendations aimed at reducing injury risk. The statistical properties of the ratio make the ACWR an inaccurate metric and complicate its interpretation for practical applications. In addition, it adds noise and creates statistical artifacts.
Ultrathin water-stable metal-organic framework membranes for ion separation
Authors: Jian Meipeng , Qiu Ruosang , Xia Yun , Lu Jun , Chen Yu , Gu Qinfen , Liu Ruiping , Hu Chengzhi , Qu Jiuhui , Wang Huanting , Zhang Xiwang
Published: June 2020

An ultrathin porous membrane can completely separate ions from water.
Microfibers in oceanic surface waters: A global characterization
Authors: Suaria Giuseppe , Achtypi Aikaterini , Perold Vonica , Lee Jasmine R. , Pierucci Andrea , Bornman Thomas G. , Aliani Stefano , Ryan Peter G.
Published: June 2020

Contrary to global production, most fibers floating in the ocean are not synthetic but natural fibers of animal or plant origin.
Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer
Authors: Zhang Yusheng , Chan Ho Lam , Garcia-Martinez Liliana , Karl Daniel L. , Weich Natalia , Slingerland Joyce M. , Verdun Ramiro E. , Morey Lluis
Published: June 2020

RING1B co-operates with ERα to regulate estrogen-mediated gene and enhancer activities and chromatin reorganization.
Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study
Authors: Grunwald Juan E , Pistilli Maxwell , Ying Gui-Shuang , Maguire Maureen G , Daniel Ebenezer , Whittock-Martin Revell , Parker-Ostroff Candace , Jacoby Douglas , Go Alan S , Townsend Raymond R , Gadegbeku Crystal Ann , Lash James P , Fink Jeffrey Craig , Rahman Mahboob , Feldman Harold , Kusek John W , Xie Dawei
Published: June 2020

Purpose

Chronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.

Design

We assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.

Methods

Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.

Results

Worsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.

Conclusion

Progression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.
Study protocol for an international, multicentre stepped-wedge cluster randomised trial to evaluate the impact of a digital antimicrobial stewardship smartphone application
Authors: Helou R I , Catho Gaud , Peyravi Latif Annabel , Mouton Johan , Hulscher M , Teerenstra Steven , Conly John , Huttner Benedikt D , Tängdén Thomas , Verbon Annelies
Published: June 2020

Introduction

With the widespread use of electronic health records and handheld electronic devices in hospitals, informatics-based antimicrobial stewardship interventions hold great promise as tools to promote appropriate antimicrobial drug prescribing. However, more research is needed to evaluate their optimal design and impact on quantity and quality of antimicrobial prescribing.

Methods and analysis

Use of smartphone-based digital stewardship applications (apps) with local guideline directed empirical antimicrobial use by physicians will be compared with antimicrobial prescription as per usual as primary outcome in three hospitals in the Netherlands, Sweden and Switzerland. Secondary outcomes will include antimicrobial use metrics, clinical and process outcomes. A multicentre stepped-wedge cluster randomised trial will randomise entities defined as wards or specialty regarding time of introduction of the intervention. We will include 36 hospital entities with seven measurement periods in which the primary outcome will be measured in 15 participating patients per time period per cluster. At participating wards, patients of at least 18 years of age using antimicrobials will be included. After a baseline period of 2-week measurements, six periods of 4 weeks will follow in which the intervention is introduced in 6 wards (in three hospitals) until all 36 wards have implemented the intervention. Thereafter, we allow use of the app by everyone, and evaluate the sustainability of the app use 6 months later.

Ethics and dissemination

This protocol has been approved by the institutional review board of each participating centre. Results will be disseminated via media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications.

Trial registration number

ClinicalTrials.gov registry (NCT03793946). Stage; pre-results.
Personal-recovery-oriented community mental healthcare: qualitative evaluation of a developmental project
Authors: Beckers Thijs , Jaeqx - van Tienen Lia , Willems Rudy , Koopmans Martijn , Corstens Dirk
Published: June 2020

Objectives

Mental healthcare is commonly aimed at reducing symptoms in individual service users. When only symptomatic recovery is addressed, not all service users experience sufficient recovery, and when care is aimed only at individuals (instead of the neighbourhood), not all people in need of mental healthcare are reached. This study evaluated a project that aimed to improve mental healthcare in a neighbourhood, by improving healthcare providers’ outreach to the residents living in the neighbourhood, by improving collaboration among healthcare providers and focussing on the residents’ personal recovery. This project was carried out by several public health services. It aimed to change the goal of mental healthcare provided in the neighbourhood from symptom reduction to personal recovery.

Design

The study included qualitative focus groups and inductive content analysis.

Setting

Primary and secondary mental healthcare that healthcare workers from different healthcare services provided.

Participants

The evaluation was conducted through three focus group interviews with services users, their friends and relatives, neighbourhood residents, neighbourhood representatives and the healthcare services that were involved (n = 24).

Results

Evaluation indicated that the most valued part of the project was the utilisation of peer workers at the initiation of mental healthcare. Improved communication among healthcare providers that the project fostered was also highly regarded. The aim of the project to align it with existing initiatives in the neighbourhood was also considered important, although it was difficult to achieve.

Conclusions

The project did not find a panacea for recovery-oriented community mental healthcare. A variety of its components did, however, contribute to the mental health of the community residents.
Study protocol of validating a numerical model to assess the blood flow in the circle of Willis
Authors: Shen Yuanyuan , Wei Yanji , Bokkers Reinoud P H , Uyttenboogaart Maarten , van Dijk J Marc C
Published: June 2020

Introduction

We developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions.

Methods and analysis

This study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients.

Ethics and dissemination

This study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen: METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication.

Trial registration number

NL8114.
Parents’ perceptions of core outcomes in neonatal research in two Nigerian neonatal units
Authors: Read Sarah Kathryn , Jibril Aisha , Tongo Olukemi , Akindolire Abimbole , Abdulkadir Isa , Nabwera Helen , Sinha Ian , Allen Stephen
Published: June 2020

Background

There is a scarcity of information regarding the most important outcomes for research in neonatal units in low-resource settings. Identification of important outcomes by different stakeholder groups would inform the development of a core outcome set (COS) for use in neonatal research.

Objective

To determine the perceptions and opinions of parents of newborn babies regarding what outcomes were most important to them in order to contribute towards development of a COS for neonatal research in sub-Saharan Africa.

Methods

Semistructured interviews were undertaken with parents, mostly mothers, of babies admitted to one neonatal unit in North central and one in Southwest Nigeria. Participants were purposively sampled to include parents of babies with common neonatal problems such as prematurity.

Results

We conducted 31 interviews. The most frequently raised outcomes were breast feeding, good health outcomes for their baby, education, growth and financial cost. Parents placed more emphasis on quality of life and functional status than health complications.

Conclusions

The opinions of parents need to be considered in developing a COS for neonatal research in low-resource settings. Further research should assess the opinions of families in other low-resource settings and also engage a broader range of stakeholders.
Prescribing for pregnancy: epilepsy
Authors: Johansen-Bibby Anja
Published: June 2020

Topics for DTB review articles are selected by DTB’s editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.
SETDB1 is required for intestinal epithelial differentiation and the prevention of
intestinal inflammation
Authors: Južnić Lea , Peuker Kenneth , Strigli Anne , Brosch Mario , Herrmann Alexander , Häsler Robert , Koch Michael , Matthiesen Liz , Zeissig Yvonne , Löscher Britt-Sabina , Nuber Alexander , Schotta Gunnar , Neumeister Volker , Chavakis Triantafyllos , Kurth Thomas , Lesche Mathias , Dahl Andreas , von Mässenhausen Anne , Linkermann Andreas , Schreiber Stefan , Aden Konrad , Rosenstiel Philip C , Franke Andre , Hampe Jochen , Zeissig Sebastian
Published: June 2020

Objective

The intestinal epithelium is a rapidly renewing tissue which plays central roles
in nutrient uptake, barrier function and the prevention of intestinal inflammation.
Control of epithelial differentiation is essential to these processes and is dependent
on cell type-specific activity of transcription factors which bind to accessible
chromatin. Here, we studied the role of SET Domain Bifurcated Histone Lysine
Methyltransferase 1, also known as ESET (SETDB1), a histone H3K9 methyltransferase, in
intestinal epithelial homeostasis and IBD.

Design

We investigated mice with constitutive and inducible intestinal epithelial
deletion of Setdb1, studied the expression of SETDB1 in
patients with IBD and mouse models of IBD, and investigated the abundance of
SETDB1 variants in healthy individuals and patients with
IBD.

Results

Deletion of intestinal epithelial Setdb1 in mice was
associated with defects in intestinal epithelial differentiation, barrier disruption,
inflammation and mortality. Mechanistic studies showed that loss of SETDB1 leads to
de-silencing of endogenous retroviruses, DNA damage and intestinal epithelial cell
death. Predicted loss-of-function variants in human SETDB1
were considerably less frequently observed than expected, consistent with a critical
role of SETDB1 in human biology. While the vast majority of patients with IBD showed
unimpaired mucosal SETDB1 expression, comparison of IBD and non-IBD exomes revealed
over-representation of individual rare missense variants in
SETDB1 in IBD, some of which are predicted to be
associated with loss of function and may contribute to the pathogenesis of intestinal
inflammation.

Conclusion

SETDB1 plays an essential role in intestinal epithelial homeostasis. Future work
is required to investigate whether rare variants in SETDB1
contribute to the pathogenesis of IBD.
New considerations about Chiari‐like malformation, syringomyelia and their management
Authors: Rusbridge Clare
Published: June 2020

Background: Chiari‐like malformation (CM) is a developmental condition, characterised by a conformational change and overcrowding of the brain and cranial cervical spinal cord. CM‐associated pain (CM‐P) and syringomyelia are increasingly being diagnosed, due to the rising popularity of predisposed brachycephalic breeds and the availability of MRI in veterinary practices.

Aim of the article: This article aims to update the veterinary profession on these conditions, and provides a guide to diagnosis and treatment of clinically relevant disease.
Incidence and Risk Factors for Hpv-Associated Cancers in Women with End-Stage Renal Disease
Authors: Han Joan , Waller Jennifer L , Colombo Rhonda E , Spearman Vanessa , Young Lufei , Kheda Mufaddal F , Mohammed Azeem , Bollag Wendy B , Nahman Norris Stanley , Baer Stephanie L
Published: June 2020

Human papillomavirus (HPV) causes the majority of cervical, anal/rectal, and oropharyngeal cancers in women. End-stage renal disease (ESRD) is also associated with an increased risk of malignancy, but the incidence of and risk factors for HPV-associated cancers in US dialysis patients are not defined. We queried the US Renal Data System for women with HPV-associated cancers and assessed for incidence of cancer diagnosis and association of risk factors. From 2005 to 2011, a total of 1032 female patients with ESRD had 1040 HPV-associated cancer diagnoses. Patients had a mean age of 65 years, were mostly white (63%), and on hemodialysis (92%). Cervical cancer (54%) was the most common, followed by anal/rectal (34%), and oropharyngeal (12%). The incidence of HPV-associated cancers in patients with ESRD increased yearly, with up to a 16-fold increased incidence compared with the general population. Major risk factors associated with the development of any HPV-associated cancer included smoking (adjusted relative risk=1.89), alcohol use (1.87), HIV (2.21), and herpes infection (2.02). Smoking, HIV, and herpes infection were prominent risk factors for cervical cancer. The incidence of HPV-associated cancers in women with ESRD is rising annually and is overall higher than in women of the general population. Tobacco use is a universal risk factor. For cervical cancer, the presence of HIV and herpes are important comorbidities. Recognizing risk factors associated with these cancers may improve diagnosis and facilitate survival. The role of HPV vaccination in at-risk dialysis patients remains to be defined but warrants further study.
Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab
Authors: Hopkins Ashley M , Kichenadasse Ganessan , Karapetis Chris S , Rowland Andrew , Sorich Michael J
Published: June 2020

Background

Preliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs.

Methods

The study pooled data from patients with NSCLC in the randomized trials OAK and POPLAR (atezolizumab vs docetaxel; n=1464), and single-arm atezolizumab trials BIRCH and FIR (n=797). The association between ETS (≥10% decrease in pretreatment sum-of-longest diameters of target-lesions at 6 weeks) and overall survival (OS), progression-free survival (PFS), time to deterioration (TDD) in health-related quality-of-life (HRQoL) and physical function (PF) was assessed using Cox proportional hazard analysis.

Results

ETS occurred in 20% of atezolizumab-treated patients with NSCLC within OAK and POPLAR and was associated with highly favorable OS (HR 0.33, p<0.001), PFS (HR 0.31, p<0.001), TDD in HRQoL (HR 0.73, p=0.01) and PF (HR 0.52, p<0.001). The results were replicated in the BIRCH and FIR data. Atezolizumab-treated patients achieving ETS had markedly improved OS compared with docetaxel-treated patients achieving ETS (24-month OS 55% vs 32%); PFS was also markedly improved (24-month PFS 31% vs 4%). In contrast, for patients not achieving ETS, atezolizumab-treatment was associated with more modest OS (24-month OS 23% vs 20%) and PFS (24-month PFS 3% vs 1%) improvement compared with docetaxel. Overall, the effect size for ETS within the atezolizumab-treated patients was significantly greater than that in the docetaxel-treated patients (P(interaction)=0.002 for OS and P(interaction)<0.001 for PFS).

Conclusions

ETS is an easily measurable biomarker, predictive of highly favorable survival and patient-reported outcomes with atezolizumab treatment for advanced NSCLC. Further, ETS identifies patients with significantly greater treatment benefit for ICI therapy.
Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
Authors: Trager Megan H , Coley Shana M , Dube Geoffrey , Khan Shaheer , Ingham Matthew , Samie Faramarz H , Geskin Larisa J , McDonnell Diana , Brouder Daniel , Saenger Yvonne , Carvajal Richard
Published: June 2020

Background

Immune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.

Case presentations

Here we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.

Conclusions

These cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.

Trial Registration number

NCT03816332.
Strengthening the impairment argument against abortion
Authors: Blackshaw Bruce Philip , Hendricks Perry
Published: June 2020

Perry Hendricks’ impairment argument for the immorality of abortion is based on two premises: first, impairing a fetus with fetal alcohol syndrome (FAS) is immoral, and second, if impairing an organism to some degree is immoral, then ceteris paribus, impairing it to a higher degree is also immoral. He calls this the impairment principle (TIP). Since abortion impairs a fetus to a higher degree than FAS, it follows from these two premises that abortion is immoral. Critics have focussed on the ceteris paribus clause of TIP, which requires that the relevant details surrounding each impairment be sufficiently similar. In this article, we show that the ceteris paribus clause is superfluous, and by replacing it with a more restrictive condition, the impairment argument is considerably strengthened.
Is informed consent required for the diagnosis of brain death regardless of consent for organ donation?
Authors: Muramoto Osamu
Published: June 2020

In the half-century history of clinical practice of diagnosing brain death, informed consent has seldom been considered until very recently. Like many other medical diagnoses and ordinary death pronouncements, it has been taken for granted for decades that brain death is diagnosed and death is declared without consideration of the patient’s advance directives or family’s wishes. This essay examines the pros and cons of using informed consent before the diagnosis of brain death from an ethical point of view. As shared decision-making in clinical practice became increasingly indispensable, respect for the patients’ autonomous wishes regarding how to end their lives has a significant role in deciding how death is diagnosed. Brain death, as a fully technologically controlled death, may require a different ethical framework from the old one for traditional cardiac death. With emerging and proliferating options in end-of-life care for those who suffer from catastrophic brain injury, the traditional reasoning that ‘death gives no choice, hence no consent’ requires another examination. Patients facing imminent brain death now have options other than undergoing the diagnostic workup for brain death, such as donation after circulatory death and withdrawal of life-sustaining treatment with maximum comfort measures for death with dignity. Nevertheless, just as in the debate over opt-in versus opt-out organ donation policies, informed consent before the diagnosis of brain death faces fierce opposition from consequentialists urging the expansion of the donor pool. This essay examines these objections and provides constructive replies along with a proposal to accommodate this morally required consent.
On the excitation of the $$2^+_1$$ state in $$^{12}$$C in the $$(e,e'\gamma )$$ reaction
Authors: Jakubassa-Amundsen D. H. , Ponomarev V. Yu.
Published: June 2020

The excitation of the carbon$$2^+$$2+state at 4.439 MeV by$$70{-}150$$70-150MeV electron impact and its subsequent decay to the ground state by photon emission is described within the distorted-wave Born approximation. The transition densities are obtained from the nuclear quasiparticle phonon model. The photon angular distributions are compared with earlier results and with experiment, including the influence of bremsstrahlung. Predictions for spin asymmetries in the case of polarized electron impact are also made.
An early estimation of the number of affected people in South Asia due to Covid-19 pandemic using susceptible, infected and recover model
Authors: Hoque Md. Enamul
Published: June 2020

The Susceptible, Infected and Recover (SIR) model is a very simple model to estimate the dynamics of an epidemic. In the current pandemic due to Covid-19, the SIR model has been used to estimate the dynamics of infection for Bangladesh, India, Pakistan and compared with that of China. Numerical solutions are used to obtain the value of parameters for the SIR model. It is predicted that the active case in Pakistan due to the SARS-CoV-2 will be comparable with that in China whereas it will be low for Bangladesh and India. The basic reproduction number, with fluctuations, for South Asian countries are predicted to be less than that of China. The susceptible population is also estimated to be under a million for Bangladesh and India but it becomes very large for Pakistan.
Nanoparticle and shape factor for improving solidification rate
Authors: Zhang Wenjie , Hosseini Taleghani Ali , Ayani M. , Hajizadeh Mohammed Reza , Babazadeh Houman
Published: June 2020

The main aim of this paper is to examine the discharging process with insertion of wavy surface and changing shape of nanoparticles. Contours were presented in the form of contours and profiles of energy and temperatures. To get the acceptable accuracy, adaptive grid is employed and time steps for each iteration are variable. The outputs indicate that augmenting A and selection of platelet shape lead to a faster solidification. With augment of [Formula: see text], 14% reduction has been reported for ([Formula: see text]). Such percentage augments with the rise of [Formula: see text] and 14.03% reduction were reported for ([Formula: see text]). At [Formula: see text], augmenting [Formula: see text] from 0.1 to 0.3 makes the time to reduce from 44.16[Formula: see text]s to 37.96[Formula: see text]s. Lower level of energy was reported for platelet shapes, which means higher liquid fraction of domain. Temperature declines with augment of [Formula: see text] and [Formula: see text] prolongs process of about 14.03% in the existence of platelet shape.
Product and After-Sales Maintenance Service Pricing Decisions in a Risk-Averse Supply Chain
Authors: Ullah Azmat , Huang Wenpo , Jiang Wei
Published: June 2020

After-sales service on a product could be a lucrative source of profits however it is notoriously difficult to manage due to uncertain demand from consumers, and its complex organization such as either to provide warranty or maintenance contract or repair service. This paper focuses on a problem where the manufacturer sells a repairable product while an agent provides after-sales service under uncertain demand. Due to demand volatility, either manufacturer or agent or both the players are risk-averse toward their decisions. The goal of this paper is to design various after-sales service strategies where the optimal price of repair or maintenance contract for the agent whereas the optimal product price for the manufacturer are explicitly determined such that the utility of both players can be maximized. Moreover, the impacts of risk-preference and demand uncertainty are investigated on both players’ price decisions, demand level, and their utility function. Also, the impacts of the agent’s warranty service on product price as well as repair and maintenance contract price are investigated. The interaction between the manufacturer and agent is performed under non-cooperative game where the manufacturer is the leader, and the agent is the follower. The analytical results show that when both players are risk-averse, they should adjust their prices with demand uncertainty and risk-tolerance level in order to maintain the demand stability and get more utility. Further, we consider some special cases where the risk-tolerance level of the manufacturer has an impact on the risk-neutral agent’s decisions whereas the risk-tolerance level of an agent does not have any impact on the risk-neutral manufacturer’s decisions. The analysis also shows that there is a significant impact of the agent’s free-replacement renewing warranty (FRRW) on repair and maintenance price decision if both players are risk-averse. A numerical example is presented to further illustrate the results and related issues.
Game-Theoretic Principles of Decision Management Modeling Under the Coopetition
Authors: Heiets Iryna , Oleshko Tamara , Leshchinsky Oleg
Published: June 2020

The paper considers the two main game-theoretic models, such as coalition and cooperative. The authors are of the opinion that definitions and notions of cooperative games and coalition games are different, but both games are coopetitive games. Transitivity and superadditivity are presented as the main characteristic functions of coopetitive games. The individual and collective rationality were identified as unconditional requirements for the optimal distribution between players. Furthermore, the additional income added to the guaranteed amount occurs in the event of coopetition. Any substantial coopetitive game has an infinite number of transactions. The authors highlighted that the dominant transaction is the transaction that is better for all coalition numbers without exceptions and it can be reached by the coalition. In addition, the authors propose using Shapley system of axioms to identify coopetitive game results.
Weak well-posedness of multidimensional stable driven SDEs in the critical case
Authors: Chaudru de Raynal Paul-Éric , Menozzi Stéphane , Priola Enrico
Published: June 2020

We establish weak well-posedness for critical symmetric stable driven SDEs in [Formula: see text] with additive noise [Formula: see text], [Formula: see text]. Namely, we study the case where the stable index of the driving process [Formula: see text] is [Formula: see text] which exactly corresponds to the order of the drift term having the coefficient [Formula: see text] which is continuous and bounded. In particular, we cover the cylindrical case when [Formula: see text] and [Formula: see text] are independent one-dimensional Cauchy processes. Our approach relies on [Formula: see text]-estimates for stable operators and uses perturbative arguments.
Multi-Scale Shapelets Discovery for Time-Series Classification
Authors: Cai Borui , Huang Guangyan , Xiang Yong , Angelova Maia , Guo Limin , Chi Chi-Hung
Published: June 2020

Shapelets are subsequences of time-series that represent local patterns and can improve the accuracy and the interpretability of time-series classification. The major task of time-series classification using shapelets is to discover high quality shapelets. However, this is challenging since local patterns may have various scales/lengths rather than a unified scale. In this paper, we resolve this problem by discovering shapelets with multiple scales. We propose a novel Multi-Scale Shapelet Discovery (MSSD) algorithm to discover expressive multi-scale shapelets by extending initial single-scale shapelets (i.e., shapelets with a unified scale). MSSD adopts a bi-directional extension process and is robust to extend single-shapelets obtained by different methods. A supervised shapelet quality measurement is further developed to qualify the extension of shapelets. Comprehensive experiments conducted on 25 UCR time-series datasets show that multi-scale shapelets discovered by MSSD improve classification accuracy by around 10% (in average), compared with single-scale shapelets discovered by counterpart methods.
Denoising Protein–Protein interaction network via variational graph auto-encoder for protein complex detection
Authors: Yao Heng , Guan Jihong , Liu Tianying
Published: June 2020

Identifying protein complexes is an important issue in computational biology, as it benefits the understanding of cellular functions and the design of drugs. In the past decades, many computational methods have been proposed by mining dense subgraphs in Protein–Protein Interaction Networks (PINs). However, the high rate of false positive/negative interactions in PINs prevents accurately detecting complexes directly from the raw PINs. In this paper, we propose a denoising approach for protein complex detection by using variational graph auto-encoder. First, we embed a PIN to vector space by a stacked graph convolutional network (GCN), then decide which interactions in the PIN are credible. If the probability of an interaction being credible is less than a threshold, we delete the interaction. In such a way, we reconstruct a reliable PIN. Following that, we detect protein complexes in the reconstructed PIN by using several typical detection methods, including CPM, Coach, DPClus, GraphEntropy, IPCA and MCODE, and compare the results with those obtained directly from the original PIN. We conduct the empirical evaluation on four yeast PPI datasets (Gavin, Krogan, DIP and Wiphi) and two human PPI datasets (Reactome and Reactomekb), against two yeast complex benchmarks (CYC2008 and MIPS) and three human complex benchmarks (REACT, REACT_uniprotkb and CORE_COMPLEX_human), respectively. Experimental results show that with the reconstructed PINs obtained by our denoising approach, complex detection performance can get obviously boosted, in most cases by over 5%, sometimes even by 200%. Furthermore, we compare our approach with two existing denoising methods (RWS and RedNemo) while varying different matching rates on separate complex distributions. Our results show that in most cases (over 2/3), the proposed approach outperforms the existing methods.
Shotgun Wedding: Fiscal and Monetary Policy
Authors: Bassetto Marco , Sargent Thomas J.
Published: June 2020

This review describes interactions between monetary and fiscal policies that affect equilibrium price levels and interest rates by critically surveying theories about ( a) optimal anticipated inflation, ( b) optimal unanticipated inflation, and ( c) conditions that secure a nominal anchor in the sense of a unique price level path. We contrast incomplete theories whose inputs are budget-feasible sequences of government-issued bonds and money with complete theories whose inputs are bond/money strategies described as sequences of functions that map time t histories into time t government actions. We cite historical episodes that confirm the theoretical insight that lines of authority between a Treasury and a central bank can be ambiguous, obscure, and fragile.
Fabrication of CNT/Cu Composite Yarn via Single-Step Electrodeposition
Authors: Arai Susumu , Murakami Ichiro , Shimizu Masahiro , Oshigane Akimasa
Published: June 2020

Carbon nanotube (CNT)/Cu composite yarns were formed via a single-step electrodeposition process. A twisted CNT yarn composed of multiwalled CNTs (MWCNTs) was used. Copper was directly electrodeposited onto the CNT yarn under galvanostatic conditions using copper sulfate baths with and without additives. Four additives (polyethylene glycol (PEG), chloride anion (Cl−), bis(3-sulfopropyl)disulfide (SPS), and Janus green B (JGB)) that are well known as “via-filling additives” were used together. The surface and cross-sectional microstructures of the copper-deposited CNT yarns were analyzed. Copper was electrodeposited only onto the surface of the CNT yarn from the bath without additives, resulting in a copper-coated CNT yarn. By contrast, copper was deposited not only onto the surface but also into the interior of the CNT yarn from the bath with the additives. The amount of copper deposited into the CNT yarn tended to increase with increasing PEG and Cl− concentrations. The current density also affected the size and location of the deposited copper particles. When the electrodeposition conditions were optimized, copper was relatively homogeneously deposited into the interior of the CNT yarn, resulting in a CNT/Cu composite yarn.
Highly Sensitive and Selective H2S Gas Sensor Fabricated with β-Ga2O3/rGO
Authors: Balasubramani V. , Ahamed A. Nowshath , Chandraleka S. , Kumar K. Krishna , Kuppusamy M. R. , Sridhar T. M.
Published: June 2020

Hydrogen Sulfide (H2S) is a common toxic gas released into the environment mainly during the energy production process from coal and crude oil. H2S causes several neurological damages to the human body which could also be fatal and thus needs to be monitored. Here, we report the incorporation of reduced graphene oxide (rGO) on β-Ga2O3 (β-Ga2O3/rGO) sensing layers followed by its deposition on alumina substrate by drop casting method for H2S gas sensing application. The structure and phase purity of the synthesized β-Ga2O3, GO and β-Ga2O3/rGO samples were characterized using X-ray diffraction (XRD). The gas sensing properties of the coated sensing layers of β-Ga2O3 and β-Ga2O3/rGO were analyzed by Electrochemical Impedance Spectroscopy (EIS) at 100 °C. The gas sensing results revealed superior sensitivity and selectivity of β-Ga2O3/rGO towards H2S detection when compared with different interfering gases (NH3, SO2, CO2 and CO). Nyquist plots and equivalent circuit fitting values clearly indicate that the grain boundary resistance was highly affected in H2S gas environment (3 ppm) compared to other interfering gases. Based on the findings the gas sensing mechanism is proposed.