bluuebunny/crossref_metadata_2025 huggingface dataset:
Domain‐Dependent National Pride and Support for the Radical Right: Pride in the Nation's History
Authors: Lubbers Marcel , Smeekes Anouk
Published: September 2022

Populist radical right‐wing's rhetoric often includes a reference to the nation's past when everything was supposed to be better. This runs from considered heroic times of the country in terms of war victory and economic grandeur to an idealized past which fits the ideology of nativism, meaning that a homogeneous society is preferred over a multicultural one. In this contribution, we study to what extent voters for the radical right indeed differ from voters of other party families in their pride in the nation's history. We compare this to other forms of domain‐dependent national pride. Earlier studies suggested that not only nostalgia differentiates the radical right electorate from others, but that other positive attitudes in relation to the nation may do so as well. Making use of the International Social Survey Program data on national identity, we study domain‐dependent national pride across European nations to answer whether it is pride in the nation's history that characterizes radical right voters when accounting for other dimensions of national attitudes.
Taming Airbnb Locally: Analysing Regulations in Amsterdam, Berlin and London
Authors: Hübscher Marcus , Kallert Till
Published: September 2022

European cities have responded differently to the growing number of short‐term rentals (such as Airbnb) and proposed a variety of regulations, although little is known about their efficiency. This paper contributes to filling the gap by analyzing both policy documents and spatial distributions of Airbnb listings between 2015 and 2020 using Amsterdam, Berlin, and London as case studies. We also compare the results with those of nine other European capitals. Our results show that cities follow highly individualized approaches. According to the strictness of each regulation, we see different intensities in the growth (and drop) of Airbnb listings, the share of multi‐hosts, and the share of apartments withdrawn from the regular housing market. There is also a spatial dispersion of listings from the center to the periphery. Our numbers insinuate that dynamically changing regulations force hosts to adapt continuously–which tames an uncontrolled proliferation, but more research is necessary.
Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV): A threat for xenotransplantation?
Authors: Mueller Nicolas J. , Denner Joachim
Published: September 2022

The potential for a donor‐derived transmission of porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) to the recipient has been recognized since pigs were considered candidate donors for xenotransplantation. This review gives a short description of the viral properties and summarizes the current evidence of the effects of PCMV/PRV transmission in preclinical xenotransplantation. Despite evidence that PCMV/PRV does not infect human and non‐human primate cells, activation in the transplanted organ and detrimental systemic complications have been described. As PCMV/PRV is a herpesvirus able to establish latency, the importance of adequate screening of donor pigs is emphasized, as no efficient treatment is available. Furthermore, easy and successful ways of elimination of PCMV/PRV from pig herds are indicated.
Bayesian spatiotemporal modelling analysis of hemorrhagic fever with renal syndrome outbreaks in China using R‐INLA
Authors: Teng Jiaqi , Ding Shuzhen , Zhang Huiguo , Wang Kai , Hu Xijian
Published: September 2022

Hemorrhagic fever with renal syndrome (HFRS) is a category B infectious disease caused by Hantavirus infection, which can cause acute kidney injury and has a high mortality rate. At present, China is the country most severely afflicted by HFRS in the world, and it is critical to carry out efficient HFRS prevention and management in a scientific and accurate manner. The study used data on the incidence of HFRS in mainland China from 2015 to 2018, built a Bayesian hierarchical spatiotemporal distribution model, and applied the Integrated Nested Laplace Approximation algorithm to analyse the factors influencing the development of HFRS, the spatial and temporal distribution characteristics, and the threshold exceedance locations. The results revealed that the woodland and grassland area (RR = 1.357, 95% CI: 1.005–1.791), economic level (RR = 1.299, 95% CI: 1.007–1.649), and traffic level (RR = 2.442, 95% CI: 1.825–3.199) were all significantly and positively associated with the development of HFRS, with traffic level having the strongest promoting effect. The seasonal cycle was obvious in time, with peaks in May–June and October–December each year, most notably in November. Spatially, there was a south‐heavy north‐light trend, with a high risk of incidence largely in places rich in mountain and forest vegetation, of which Guizhou, Guangxi, Guangdong, and Jiangxi provinces continuing to have a high incidence in recent years, and the evolution of the epidemic in Hubei and Hunan was becoming more serious. When the early warning threshold was set at 0.2, the detection impact was best, and Guizhou, Guangxi, Guangdong, Jiangxi, Hainan, and Tianjin were positioned near the critical point of the exceedance threshold with the highest risk of incidence. It is recommended that the relevant managers call for active vaccination of outdoor workers, such as those working in agriculture and construction sites, implement rat prevention and extermination before winter arrives, and warn high‐risk and medium‐high‐risk areas to conduct early outbreak surveillance. Move the prevention and control gates forward based on the exceedance threshold for doing preventive and control detection and epidemic research and judgement work.
Estimation of Simulated Left Ventricle Elastance Using Lumped Parameter Modelling and Gradient-Based Optimization With Forward-Mode Automatic Differentiation Based on Synthetically Generated Noninvasive Data
Authors: Laubscher Ryno , Van Der Merwe Johan , Herbst Philip , Liebenberg Jacques
Published: September 2022

The present study evaluates a parameter discovery approach based on a lumped parameter model of the cardiovascular system in conjunction with optimization to approximate important cardiac parameters, including simulated left ventricle elastances. Important parameters pertaining to ventricular function were estimated using gradient optimization and synthetically generated measurements. Forward-mode automatic differentiation was used to estimate the cost function-parameter matrices and compared to the common finite differences approach. Synthetic data of healthy and diseased hearts were generated as proxies for noninvasive clinical measurements and used to evaluate the algorithm. Twelve parameters including left ventricle elastances were selected for optimization based on 99% explained variation in mean left ventricle pressure and volume. The hybrid optimization strategy yielded the best overall results compared to 1st order optimization with automatic differentiation and finite difference approaches, with mean absolute percentage errors ranging from 6.67% to 14.14%. Errors in left ventricle elastance estimates for simulated aortic stenosis and mitral regurgitation were smallest when including synthetic measurements for arterial pressure and valvular flow rate at approximately 2% and degraded to roughly 5% when including volume trends as well. However, the latter resulted in better tracking of the left ventricle pressure waveforms and may be considered when the necessary equipment is available.
Effect of Rib Width and Cathode Thickness on the Performance of MOLB-Type SOFC
Authors: Yang Lei , Fan Shengliang , Liu Pengwei , Han Xu , Liu Yang , Jin Zunlong
Published: September 2022

In this study, a typical three-dimensional model of single channel mono-block-layer build solid oxide fuel cell (MOLB-type SOFC) was developed. The effects of rib width and cathode thickness on the species concentration distribution, electrochemical performance, and temperature distribution of MOLB-type SOFC were investigated. The results show that adapting a smaller rib width can improve the uniformity of gas distribution, decrease the concentration polarization, and improve the output performance of SOFC. The performance of the cell can be significantly improved by thickening the cathode electrode. When the cathode thickness is 0.45 mm, the maximum output power density is improved by 53.69% compared with that at 0.15 mm. With the increase of the cathode thickness, the enhancement of the cell performance by increasing the cathode thickness gradually decreases. In addition, as the cathode thickness increases, the concentration polarization and temperature gradient of the cell gradually rise, while the activation polarization gradually decreases.
Fused Deposition Modeling Fabrication Evaluation of a Ti-6Al-4V Centrifugal Compressor
Authors: Warner Justin , Celli Dino , Scott-Emuakpor Onome , George Tommy , Tomlin Trevor
Published: September 2022

Centrifugal compressors have a critical impact on the performance of a jet engine and can be made out of aluminum, steel, or titanium alloy. However, if made out of Ti-6Al-4V, it would be more lightweight than if steel were used and stronger than if aluminum were used. Compressors manufactured using traditional techniques can be relatively expensive to manufacture, therefore, fused deposition modeling (FDM) or fused filament fabrication (FFF) can help reduce the cost while maintaining structural integrity. FDM/FFF usually prints polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS) layer-by-layer using an extruder with a spool of material feeding into the extruder. Recently, metal-polymer filaments have become commercially available using this same printing apparatus as common “hobby-class” FDM printers. Using FDM with a metal-polymer matrix allows for a lower cost of production because of the intricate designs it can accomplish with little to no machining involved. Even with the benefits of printing a spool of material using FDM, there has been very little research done of Ti-6Al-4V printed in a FDM format. This document records the feasibility of using Ti-6Al-4V for a centrifugal compressor using FDM by incorporating a three-dimensional structured blue light scanner before heat treatments while also analyzing manufacturing capabilities at the tips of blades as well as the base. This analysis is a first-stage to quantify FDM metal print characteristics and properties.
Improvement of Silicon Nitride Turbine Blade Impact Resistance Under Uniaxial Compression Loading
Authors: Beauchamp Francis , Dubois Patrick K. , Plante Jean-Sébastien , Picard Mathieu
Published: September 2022

The inside-out ceramic turbine (ICT), a novel microturbine rotor architecture, uses monolithic ceramic turbine blades held in compression by a rotating structural shroud instead of traditional superalloy turbine blades in order to increase its maximum turbine inlet temperature (TIT) and cycle efficiency. Previous work has shown that this microturbine architecture has potential to be viable for long-term operation in normal operating conditions. However, foreign object damage (FOD) has been a major concern for ceramic turbine rotor past development efforts, and its effects on the ICT ceramic turbine blades lifespan have not been studied thus far. An experimental approach was used to characterize the effect of the ICT configuration on ceramic turbine blade impact resistance: spherical steel impactors were fired toward silicon nitride specimens simulating blade boundary conditions for both traditional and inside-out turbine layouts. Preload levels ranging from 100 MPa to 400 MPa were applied on the inside-out layout specimens to determine its effect on impact resistance. Results indicate that the inside-out turbine configuration increases the resistance to FOD over a traditional turbine configuration. For the specific conditions of this study, the specimens resisted to over five times the impactor energy when fixed at both ends. Also, results show that applying a higher compression preload on the specimens helps to resist higher energy impacts by about 50% when far from the buckling limit.
The impact of the COVID-19 outbreak on the air traffic noise at the Hannover airport region
Authors: Felix Greco Gil , Mysore Guruprasad Shreyas , Ring Tobias P. , Langer Sabine C.
Published: September 2022

In this work, the impact of the COVID-19 outbreak on the environmental noise generated by the air traffic at the Hannover Airport, Germany, is assessed. For this purpose, a comparative study of the air traffic noise in the years 2019 and 2020 is conducted by means of publicly available measurement data and computational simulations. Based on environmental noise directives defined by the responsible German authorities, the comparative study is conducted in terms of A-weighted equivalent sound pressure level metrics computed for the six months of the forecast years with the largest number of flights. In comparison with the year of 2019, the measurement data indicates that the LA,eq,day, LA,eq,night, and Lden were reduced in average by 2.4, 4.2, and 3.7 dBA, respectively, in the year 2020. Furthermore, the results based on the computational simulations show that the isocontour areas of the LA,eq,day=60 dBA and LA,eq,night=55 dBA noise protection zones defined by the German federal government were reduced by ≈40.29% and ≈54.08%, respectively, in the year of 2020.
Is speech intelligibility what speech intelligibility tests test?
Authors: Beechey Timothy
Published: September 2022

Natural, conversational speech signals contain sources of symbolic and iconic information, both of which are necessary for the full understanding of speech. But speech intelligibility tests, which are generally derived from written language, present only symbolic information sources, including lexical semantics and syntactic structures. Speech intelligibility tests exclude almost all sources of information about talkers, including their communicative intentions and their cognitive states and processes. There is no reason to suspect that either hearing impairment or noise selectively affect perception of only symbolic information. We must therefore conclude that diagnosis of good or poor speech intelligibility on the basis of standard speech tests is based on measurement of only a fraction of the task of speech perception. This paper presents a descriptive comparison of information sources present in three widely used speech intelligibility tests and spontaneous, conversational speech elicited using a referential communication task. The aim of this comparison is to draw attention to the differences in not just the signals, but the tasks of listeners perceiving these different speech signals and to highlight the implications of these differences for the interpretation and generalizability of speech intelligibility test results.
The importance of sound to the Atlantic cod, Gadus morhua, and the Atlantic haddock, Melanogrammus aeglefinus
Authors: Hawkins Anthony
Published: September 2022

The gadoid fishes, including the Atlantic cod and haddock, are currently being exploited close to their safe biological limits, requiring restrictions upon the human activities that may harm them. This has prompted interest in the biology of such fishes. Studies of the cod and haddock have shown highly complex behavior, involving prolonged and energetic visual and acoustic displays. Different sounds are produced in different behavioral contexts and are emitted almost continuously by cod and haddock, especially throughout the spawning season (February to May). The distinctive characteristics of these sounds make it possible to locate spawning cod and haddock at their marine spawning grounds. Human activities in these areas may affect their spawning adversely and have deleterious effects upon their stocks. Man-made sounds in water do have an adverse effect upon cod and haddock, and other fishes. Listening for the cod and haddock sounds provides a reliable, non-invasive technique for detecting their locations, and especially their spawning areas, and enables them to be protected well.
Molecular beam homoepitaxy of N-polar AlN: Enabling role of aluminum-assisted surface cleaning
Authors: Zhang Zexuan , Hayashi Yusuke , Tohei Tetsuya , Sakai Akira , Protasenko Vladimir , Singhal Jashan , Miyake Hideto , Xing Huili Grace , Jena Debdeep , Cho YongJin
Published: September 2022

N-polar aluminum nitride (AlN) is an important building block for next-generation high-power radio frequency electronics. We report successful homoepitaxial growth of N-polar AlN by molecular beam epitaxy (MBE) on large-area, cost-effective N-polar AlN templates. Direct growth without any in situ surface cleaning leads to films with inverted Al polarity. It is found that Al-assisted cleaning before growth enables the epitaxial film to maintain N-polarity. The grown N-polar AlN epilayer with its smooth, pit-free surface duplicates the structural quality of the substrate, as evidenced by a clean and smooth growth interface with no noticeable extended defects generation. Near band-edge photoluminescence peaks are observed at room temperature on samples with MBE-grown layers but not on the bare AlN templates, implying the suppression of nonradiative recombination centers in the epitaxial N-polar AlN.
Susceptibilities of Ugandan Plasmodium falciparum Isolates to Proteasome Inhibitors
Authors: Garg Shreeya , Kreutzfeld Oriana , Chelebieva Sevil , Tumwebaze Patrick K. , Byaruhanga Oswald , Okitwi Martin , Orena Stephen , Katairo Thomas , Nsobya Samuel L. , Conrad Melissa D. , Aydemir Ozkan , Legac Jennifer , Gould Alexandra E. , Bayles Brett R. , Bailey Jeffrey A. , Duffey Maelle , Lin Gang , Kirkman Laura A. , Cooper Roland A. , Rosenthal Philip J.
Published: September 2022

The proteasome is a promising target for antimalarial chemotherapy. We assessed
ex vivo
susceptibilities of fresh
Plasmodium falciparum
isolates from eastern Uganda to seven proteasome inhibitors: two asparagine ethylenediamines, two macrocyclic peptides, and three peptide boronates; five had median IC
50
values <100 nM.
Effects of Nutrient Level and Growth Rate on the Conjugation Process That Transfers Mobile Antibiotic Resistance Genes in Continuous Cultures
Authors: Shafieifini Mohammadreza , Sun Yuepeng , Staley Zachery R. , Riethoven Jean-Jack , Li Xu
Published: September 2022

WWTPs have been regarded as an important hot spot of ARGs. The discharge point of WWTP effluent, where ARGs may be horizontally transferred from bacteria of treated wastewater to bacteria of receiving water, is an important interface between the human-dominated ecosystem and the natural environment.
GpsB Promotes PASTA Kinase Signaling and Cephalosporin Resistance in
Enterococcus faecalis
Authors: Minton Nicole E. , Djorić Dušanka , Little Jaime , Kristich Christopher J.
Published: September 2022

Enterococci are opportunistic pathogens that can cause severe bacterial infections. Treatment of these infections is challenging because enterococci possess intrinsic and acquired resistance to commonly used antibiotics.
Persistence of Rare Salmonella Typhi Genotypes Susceptible to First-Line Antibiotics in the Remote Islands of Samoa
Authors: Sikorski Michael J. , Hazen Tracy H. , Desai Sachin N. , Nimarota-Brown Susana , Tupua Siaosi , Sialeipata Michelle , Rambocus Savitra , Ingle Danielle J. , Duchene Sebastian , Ballard Susan A. , Valcanis Mary , Zufan Sara , Ma Jianguo , Sahl Jason W. , Maes Mailis , Dougan Gordon , Thomsen Robert E. , Robins-Browne Roy M. , Howden Benjamin P. , Naseri Take K. , Levine Myron M. , Rasko David A.
Published: September 2022

In this study, we used whole genome sequencing and comparative genomics analyses to characterize the population structure, evolutionary origins, and genomic features of
S.
Typhi associated with decades of endemic typhoid fever in Samoa.
Central Sugar Metabolism and the Cell Wall
Authors: Yaakoub Hajar , Latgé Jean-Paul , Papon Nicolas
Published: September 2022

The human opportunistic pathogen
Aspergillus fumigatus
is recognized for its versatile cell wall when it comes to remodeling its components in adaptation to external threats, and this remodeling renders it refractory to antifungals targeting cell wall biosynthesis. A specific role for general sugar metabolism in the regulation of the synthesis of cell wall polymers has been previously demonstrated.
Complete Genome Sequence of Methanofollis aquaemaris BCRC 16166
T
, Isolated from a Marine Aquaculture Fishpond
Authors: Chen Sheng-Chung , Lai Shu-Jung , You Yi-Ting , Shih Chao-Jen , Wu Yen-Chi , Wu Chih-Hung , Liao Ching-Hua
Published: September 2022

The hydrogenotrophic methanogen
Methanofollis aquaemaris
BCRC 16166
T
(= N2F9704
T
= DSM 14661
T
) was isolated from a marine aquaculture fishpond near Wang-gong (Taiwan, Republic of China). The genome of strain BCRC 16166
T
was selected for sequencing in order to provide further information about the species delineation and its infected virus.
A Serotype-Specific and Multiplex PCR Method for Whole-Genome Sequencing of Dengue Virus Directly from Clinical Samples
Authors: Su Wenzhe , Jiang Liyun , Lu Weizhi , Xie Huaping , Cao Yimin , Di Biao , Li Yan , Nie Kai , Wang Huanyu , Zhang Zhoubin , Xu Songtao
Published: September 2022

Dengue virus (DENV) is becoming the most globally prevalent arbovirus. The number of people living under the threat of DENV is increasing year by year.
Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis
Authors: Armbruster Catherine R. , Li Kelvin , Kiedrowski Megan R. , Zemke Anna C. , Melvin Jeffrey A. , Moore John , Atteih Samar , Fitch Adam C. , DuPont Matthew , Manko Christopher D. , Weaver Madison L. , Gaston Jordon R. , Alcorn John F. , Morris Alison , Methé Barbara A. , Lee Stella E. , Bomberger Jennifer M.
Published: September 2022

Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures.
A Coccidia-Specific Phosphate Transporter Is Essential for the Growth of Toxoplasma gondii Parasites
Authors: Cui Jianmin , Yang Xuke , Yang Jichao , Jia Ruilian , Feng Yaoyu , Shen Bang
Published: September 2022

To grow and survive within host cells,
Toxoplasma
must scavenge necessary nutrients from hosts to support its parasitism. Transporters located in the plasma membrane of the parasites play critical roles in nutrient acquisition.
Toxoplasma
encodes a large number of transporters, but so far, only a few have been characterized.
Analysis of a Cell Wall Mutant Highlights Rho-Dependent Genome Amplification Events in Staphylococcus aureus
Authors: Portela Raquel , A. Faria Nuno , Mwangi Michael , Miragaia Maria , de Lencastre Hermínia , Tomasz Alexander , Gonçalves Sobral Rita
Published: September 2022

The cell wall of bacteria, namely, peptidoglycan, is the target of several antibiotic classes such as β-lactams.
Staphylococcus aureus
is well known for its capacity to adapt to antibiotic stress and develop resistance strategies, namely, to β-lactams. In this context, the construction of cell wall mutants provides useful models to study the development of such resistance mechanisms.
Expression of Ki67 as detected by MIB-1 and its association with histopathological high-risk factors among patients with retinoblastoma tumour: a cross-sectional study
Authors: Vuhahula Edda AM , Jumanne Shakilu , Yahaya James
Published: September 2022

Objectives

This study aims to investigate the expression of Ki67 in formalin-fixed paraffin-embedded tissue blocks from patients with a diagnosis of retinoblastoma tumour (RbT) as well as determining its association with histopathological high-risk factors (HHRFs).

Methods and analysis

Retrospectively, a total of 194 eyeball specimens from 163 children with RbT were reviewed at Muhimbili National Hospital between 2009 and 2013. Immunohistochemical expression of Ki67 using MIB-1 antibody (Abcam, batch ab93680, Cambridge, UK) was determined and correlated with the conventional HHRFs. The predictors of Ki67 expression were determined using binary logistic regression model in multivariate analysis. A two-tailed p<0.05 was considered statistically significant.

Results

Majority (67.5%) of the patients had leukocoria and extraocular disease was found in 20.9% of all the patients. High expression of Ki67 was present in 63.8% of the 80 eyeballs that were tested. Massive choroidal invasion (adjusted OR (AOR)=9.32, 95% CI=2.82 to 10.89), positive retrolaminar optic nerve invasion (AOR=3.01, 95% CI=4.43 to 9.11), positive surgical margin (AOR=7.10, 95% CI=1.63 to 11.40) and pT4 (AOR=7.49, 95% CI=0.12 to 0.89) were the potential HHRFs that were associated with Ki67 overexpression.

Conclusion

Overexpression of Ki67 may be of prognostic value for patients with RbT as it has been shown in the present study that high expression was common in tumours with massive choroidal invasion, positive retrolaminar optic nerve invasion, positive surgical margin and advanced tumour stage, which are the conventional HHRFs associated with prognosis of RbT.
Impact of workflow interruptions on baseline activities of the doctors working in the emergency department
Authors: Mobeen Asyia , Shafiq Muhammad , Aziz Muhammad Haris , Mohsin Muhammad Junaid
Published: September 2022

Background

Workflow interruptions are common in the emergency department (ED) of the hospitals for physicians, leading to an increased risk of errors.

Purpose

This study aims to understand the baseline activities of the ED doctors and how these are affected by workflow interruptions.

Methods

The study was conducted in two phases to collect the doctor’s perspective (through questionnaire survey) and observer’s perspective (through workflow observation study) about ED doctors’ baseline activities and workflow interruptions. Two different perspectives were obtained to make the insights clearer and more valuable. The point of view of the 223 doctors working in ED of the hospitals was recorded through a questionnaire survey. In the second phase, the observer’s point of view (authors) was obtained through a workflow observation study, and 13 doctors were observed for 160 hours.

Results

Direct communication with patients (37.1%) and ‘documentation and prescription’ (22.7%) were found to be the most frequent activities. The most common interruptions were visual and auditory distractions, rumination (mind-wandering) and intrusion (by co-workers). Also, the time consumed on indirect patient care (6.6%) was higher than direct patient care (4. 2%). Interruptions increase the chances of errors by making it hard for a doctor to resume a primary task after facing interruptions.

Conclusion

Interruptions increase the chances of errors and make it difficult for the doctors to resume primary tasks (after facing such incidents).
PD-1 inhibitor plus chemotherapy versus bevacizumab plus chemotherapy in patients with advanced non-squamous non-small-cell lung cancer: a pooled analysis of three randomised trials
Authors: Meng Xiangjiao , Chen Yu , Xing Ligang , Liu Xinchao , Zhao Kaikai , Jiang Liyang , Zhang Li , Zhou Caicun , Yu Jinming
Published: September 2022

Background

To date, none of randomised trials aim to compare the efficacy of programmed death 1 (PD-1) inhibitor plus chemotherapy and bevacizumab plus chemotherapy as first-line treatment for non-squamous non-small-cell lung cancer (NSCLC). This analysis pooled prospective data to compare the survival benefits of the two regimens for advanced NSCLC without targetable genetic mutations.

Methods

Data were pooled from three randomised phase III clinical trials:NCT03607539,NCT03134872andNCT02954172. 466 patients received PD-1 inhibitor (200 mg) plus pemetrexed (500 mg/m²) and platinum (cisplatin 75 mg/m2or carboplatin area under the curve (AUC) 5 mg/mL/min), while 432 patients received bevacizumab (15 mg/kg) plus paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/mL/min). Propensity score matching in a 1:1 ratio was performed to balance baseline characteristics of the two arms. The endpoints of this analysis were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR).

Results

In total, 375 patients in each arm were matched. With a median follow-up of 23 months (IQR 21–26), results showed that median PFS was significantly prolonged in the PD-1 inhibitor arm than in the bevacizumab arm (10.1 vs 7.4 months; HR 0.62, 95% CI 0.52 to 0.73, p<0.001). Improved OS was also demonstrated in the PD-1 inhibitor arm (27.9 vs 20.2 months; HR 0.75 95% CI 0.61 to 0.91, p=0.004). ORR in the PD-1 inhibitor arm was 56.8%, while that in the bevacizumab arm was 45.1%. However, exploratory subgroup analysis indicated that median PFS and median OS of the two arms were comparable in patients with negative programmed death ligand 1 expression or in patients aged ≥65 years old.

Conclusions

PD-1 inhibitor plus chemotherapy was associated with significant survival benefits compared with bevacizumab plus chemotherapy in patients with advanced non-squamous NSCLC, which provides evidence support to guide clinical practice. Nonetheless, the comparative survival outcomes in several subgroups indicated that bevacizumab plus chemotherapy still mattered.
Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest
Authors: Linde Louise , Mørk Sivagowry Rasalingam , Gregers Emilie , Andreasen Jo Bønding , Lassen Jens Flensted , Ravn Hanne Berg , Schmidt Henrik , Riber Lars Peter , Thomassen Sisse Anette , Laugesen Helle , Eiskjær Hans , Terkelsen Christian Juhl , Christensen Steffen , Tang Mariann , Moeller-Soerensen Hasse , Holmvang Lene , Kjaergaard Jesper , Hassager Christian , Moller Jacob Eifer
Published: September 2022

Objective

To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some.

Methods

Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge.

Results

Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group.

Conclusions

In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.
Evaluation of road safety policies and their enforcement in Mexico City, 2015–2019: an interrupted time-series study
Authors: Quintero Valverde Carolina , Perez-Ferrer Carolina , Chías Becerril Luis , Martínez Santiago Armando , Reséndiz Lopez Héctor , Prado Galbarro Javier , Quistberg D. Alex , Diez Roux Ana V , Barrientos-Gutierrez Tonatiuh
Published: September 2022

Background

Mexico City approved new road safety policies in 2015, which included lower speed limits and higher fines for traffic offences. In 2019, economic fines were replaced by a point penalty system among other changes. This study evaluates these policies on road traffic collisions, injuries and deaths.

Methods

Collisions data came from insurance collision claims (January 2015 to December 2019) and road traffic deaths from vital registrations (January 2013 to December 2019). We conducted an interrupted time series analysis for each outcome using negative binomial regression models with an offset of insured vehicles (collisions) or total population (deaths). Then, we classified the 16 municipalities in the city into enforcement and no-enforcement groups based on presence or absence of automated traffic enforcement devices and conducted a controlled interrupted time series analysis.

Results

The 2015 road safety policies had no effect on total collisions and collisions resulting in injury but were associated with a 0.2% (95% CI −0.3 to 0.0) decline in the mortality trend. The 2019 policies had no effect on total collisions but were associated with a 1.5% increase in the trend of collisions resulting in injuries and with a 2.7% (95% CI 1.0 to 4.5) increase in the mortality trend. Postpolicy trends in enforcement versus no-enforcement municipalities were not significantly different.

Conclusion

Policies that included high economic penalties for speeding and dangerous behaviours were effective in decreasing traffic mortality while removing economic penalties and replacing them with a point penalty system were associated with an increase in collisions, resulting in injury and mortality.
Prenatal and postnatal correlates of moderate-to-vigorous physical activity in midlife: evidence from the 1970 British Cohort Study
Authors: Blodgett Joanna M , Norris Thomas , Stamatakis Emmanuel , O'Donovan Gary , Pinto Pereira Snehal M , Hamer Mark
Published: September 2022

Background

It is hypothesised that lifelong physical activity behaviours are established in early life, however there is minimal, and contradictory, evidence examining prenatal and postnatal factors in relation to adulthood physical activity. We investigated associations between prospectively ascertained prenatal/postnatal factors and device-measured moderate-to-vigorous physical activity (MVPA) in midlife.

Methods

Analyses included 5011 participants from the 1970 British Cohort Study, a birth cohort study of individuals born within the same week. At birth, the following factors were ascertained: socioeconomic position (SEP), maternal age, number of previous pregnancies, maternal smoking, maternal diabetes, gestational age, birth weight, breastfeeding status and infant health concerns. MVPA was captured at age 46 with a thigh-worn accelerometer device following a 24-hour protocol over 7 days.

Results

In sex-adjusted models, lower SEP (−6.7 min/day (95% CI: −9.0 to –4.4) in those with a partly or unskilled paternal occupation), younger maternal age (0.4 min/day (0.2 to 0.5) per additional year of maternal age), maternal smoking during pregnancy (−2.5 min/day (−4.0 to –1.0)) and post-term gestational age (−7.4 min/day (−11.5 to –3.4); boys only) were associated with lower MVPA at age 46. In the mutually adjusted model, associations did not change but there was some evidence that birth weight may also be associated with MVPA levels.

Conclusions

SEP, maternal age, maternal smoking, post-term birth in boys and birth weight were associated with MVPA in midlife, indicating that midlife physical activity behaviours may be partially established at birth. Early interventions in disadvantaged environments may have a positive impact on physical activity throughout the life course.
LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization
Authors: Hu Jinyang , Dong Feng , He You , Xia Xianyou , Cheng Fangling , Chen Sui , Hou Xiaoshuang , Zhang Po , Liu Guohao , Li Ying , Gao Qian , Dong Minhai , Li Ting , Li Wei , Xiao Qungen , Li Xiaopeng , Yu Xingjiang , Xi Guifa , Guo Dongsheng , Wu Xudong , Wang Baofeng
Published: September 2022

Background

Glioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tumor-associated microglia/macrophages (TAMs).

Results

High level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor prognosis in GBM patients. LRIG2/sLRIGs promotes CD47 expression and facilitates TAM recruitment. Blockade of CD47–SIRPα interactions and inhibition of sLRIG2 secretion synergistically suppress GBM progression in an orthotropic murine GBM model.

Conclusions

GBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM.
Exceptional response to PD-1 inhibition immunotherapy in advanced metastatic osteosarcoma with tumor site infection
Authors: Li Meng , Bao Qiyuan , Zhang Zhusheng , Wang Beichen , Liu Zhuochao , Wen Junxiang , Wan Rong , Shen Yuhui , Zhang Weibin
Published: September 2022

Recent clinical trials have demonstrated a lack of activity of immune checkpoint inhibitors (ICIs) against osteosarcoma. Previous clinical observations have demonstrated a potential immune-stimulatory effect of tumor site infection for osteosarcoma patients. However, whether such infection could augment the efficacy of immunotherapy such as ICIs is currently unknown. Here we report a case of a heavily pretreated 14-year-old boy with pulmonary metastatic osteosarcoma, who has suffered from multiple wound infections and thoracic empyema after previous metastasectomy. Despite the ongoing tumor site infection, the patient had a rapid and durable (11 months) remission of the metastatic lesions after the administration of the Programmed cell death-1(PD-1) inhibitor camrelizumab. No serious ICI-related toxicities or worsening of the infection were noticed during the treatment. Correlative analysis suggested that intratumoral CD8+ T cell infiltration, Programmed death-ligand 1(PD-L1) expression and IFN-γ expression were increased in the tumor microenvironment postinfection versus preinfection. Furthermore, using RNA-seq gene expression analysis, we found a variety of checkpoint targets were also upregulated such asCD200,TIGIT,LAG3, etc. Our report supports the hypothesis of tumor site infection as a potential synergistic mechanism in the tumor microenvironment for ICI immunotherapy.
N-cadherin protects oral cancer cells from NK cell killing in the circulation by inducing NK cell functional exhaustion via the KLRG1 receptor
Authors: Lou Chao , Wu Kailiu , Shi Jianbo , Dai Zhenlin , Xu Qin
Published: September 2022

Background

Circulating tumor cells (CTCs) can survive in the circulation and return to primary tumors through a self-seeding process. However, the mechanisms underlying CTCs escape from natural killer (NK) cell-mediated immune surveillance remain unclear.

Method

Self-seeded tumor cells were isolated and characterized using a modified contralateral seeding model. A comparison of transcriptional profiles was performed between the parental cells and self-seeded cells. The molecular mechanism of self-seeded tumor cells escaping from NK cell was demonstrated through in vitro experiments and verified in a CTC-mimicking in vivo model. Then, the expression level of key protein mediating CTCs immune escape was detected in 24 paired primary and recurrent tumor samples of patients with oral cancer by the immunohistochemical method.

Result

Self-seeded cells displayed resistance to NK cell-mediated lysis and a higher tumor seeding ability than their parental cells. Elevated expression levels of the CDH2 gene and its protein product, N-cadherin were found in self-seeded cells. NK cells secreted cytokines, and fluid shear stress facilitated N-cadherin release by promoting A disintegrin and metalloprotease 10 (ADAM10) translation or converting the precursor ADAM10 to the mature form. Soluble N-cadherin triggered NK cell functional exhaustion by interacting with the killer cell lectin-like receptor subfamily G member 1 (KLRG1) receptor and therefore protected tumor cells from NK cell killing in the circulation. In vivo experimental results showed that overexpression of N-cadherin promoted tumor self-seeding and facilitated the survival of CTCs. Compared with primary tumors, N-cadherin expression was significantly increased in matched recurrent tumor tissues.

Conclusion

Together, our findings illustrate an unknown mechanism by which CTCs evaded NK cell-mediated immune surveillance, and indicate that targeting N-cadherin is an effective strategy to prevent CTCs from homing to primary tumor.
COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis
Authors: Holmstroem Rikke Boedker , Nielsen Ole Haagen , Jacobsen Søren , Riis Lene Buhl , Theile Susann , Bjerrum Jacob Tveiten , Vilmann Peter , Johansen Julia Sidenius , Boisen Mogens Karsbøl , Eefsen Rikke Helene Løvendahl , Marie Svane Inge , Nielsen Dorte Lisbet , Chen Inna Markovna
Published: September 2022

Background

Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis.

Patients and methods

Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40.

Results

Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3–4 treatment-related adverse events, which were manageable and reversible.

Conclusions

Tocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events.

Trial registration number

NCT03601611.
Thiamine deficiency: a commonly unrecognised but easily treatable condition
Authors: Schostak Tritia , San Millan Iňigo , Jani Alkesh , Johnson Richard Joseph
Published: September 2022

Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.
Does gender influence outcome measures similarly in patients with spondyloarthritis? Results from the ASAS-perSpA study
Authors: Benavent Diego , Capelusnik Dafne , Ramiro Sofia , Molto Anna , López-Medina Clementina , Dougados Maxime , Navarro-Compán Victoria
Published: September 2022

Objectives

To investigate the influence of gender on disease outcomes in patients with spondyloarthritis (SpA), including across SpA subtypes.

Methods

Data from 4185 patients of 23 countries with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or psoriatic arthritis (PsA) from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study were analysed. Associations between gender and disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), C-reactive protein (CRP)), function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and overall health (ASAS Health Index (ASAS HI), European Quality of Life Five Dimension (EQ-5D)) outcomes were investigated. Multilevel multivariable linear mixed models adjusted for relevant confounders (and stratified by disease subtype in case of a relevant interaction) were used.

Results

In total, 65%, 10% and 25% of patients had axSpA, pSpA and PsA, respectively. axSpA was more frequent in males (68%), whereas pSpA and PsA were more frequent in females (53% and 52%, respectively). A significant interaction between gender and disease subtype was found for ASDAS, BASDAI and BASFI. While being female independently contributed to higher BASDAI across the three disease subtypes (with varying magnitude), female gender was only associated with higher ASDAS in pSpA (β (95% CI): 0.36 (0.15 to 0.58)) and PsA (0.25 (0.12 to 0.38)) but not in axSpA (0.016 (−0.07 to 0.11)). No associations were observed between gender and CRP levels. Female gender was associated with higher ASAS HI and EQ-5D, without differences across disease subtype.

Conclusion

Female gender is associated with less favourable outcome measures across the SpA spectrum. However, while female gender influences BASDAI across the three subtypes, ASDAS is associated with gender only in pSpA and PsA but not in axSpA. Therefore, ASDAS is an appropriate instrument both for females and males with axSpA.