bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of MIPs effects on a MAPS for electron ion collider in China
Authors: Cao B. , Jing L. , He R. , Yin R. , Huang J. , Liu N. , Niu X. , Fu F. , Han W. , Wang Y. , Zhao C.
Published: May 2023

The Monolithic Active Pixel Sensor (MAPS) is a good candidate for the inner
tracking system of the Electron–Ion Collider in China (EicC). Hence, a
MAPS with a pixel pitch of ∼30 µm is being designed. Two
130 nm CMOS processes have been proposed as candidates for this MAPS
design. The first one is a commercial standard twin-well low-resistivity
(<50 Ω cm−3) process, and the other
one is a quadruple-well high-resistivity (>1 kΩ cm−3)
process. A 3-dimensional TCAD model of the pixels has been established to
evaluate the Minimum Ionizing Particles (MIPs) induced charge collection in
these two processes. This paper will discuss the study of charge collection
efficiency, charge collection time, and charge sharing among pixels.
Correlation between thermal neutrons and soil moisture measured by ENDA
Authors: Yang F. , Ma X.-H. , Chen H.-K. , Chen T.-L. , Cui S.-W. , Danzengluobu  , Gao W. , Kuleshov D. , Kurinov K. , Li B.-B. , Liu M.-Y. , Liu Y. , Shchegolev O. , Stenkin Y. , Xiao D.-X. , Yin L.-Q. , Zhang L.-W.
Published: May 2023

Hadrons are the “skeleton” of extensive air shower (EAS). They possess favorable information concerning composition and energy of cosmic ray. Thermal neutrons generated by the EAS hadrons in the ground as well as charged particles in EAS front plane can be detected by Electron-Neutron detector (EN-detector). A prototype of EN-Detector Array (ENDA), ENDA-16 was built at Large High Altitude Air Shower Observatory (LHAASO) to test its performance of detection of cosmic ray composition and energy spectrum. It has been proved in former work that there is a decrease of thermal neutrons detected in rainy season. For quantitative evaluation of influence of soil moisture on thermal neutrons, at the center of ENDA-16, five soil moisture meters are installed to record soil moisture. Negative correlation between thermal neutron counting rate and soil moisture is obtained. Moreover, it is demonstrated that a soil depth 0.5 m over the soil moisture sensor is enough for monitoring negative correlation between thermal neutron counting rate and soil moisture. The results provide us a method to correct the experimental data during the rainy season so as to reduce systematic uncertainty of thermal neutron measurement in the ENDA experiment.
Recent advances in horizontal alveolar bone regeneration
Authors: Li Tiancheng , Zeng Xinyi , Zou Shujuan , Xu Yi , Duan Peipei
Published: May 2023

Alveolar bone loss is widespread in all age groups and remains a severe hazard to periodontal health. Horizontal alveolar bone loss is the pattern of bone loss more commonly seen in periodontitis. Until now, limited regenerative procedures have been applied to treating horizontal alveolar bone loss in periodontal clinics, making it the least predictable periodontal defect type. This article reviews the literature on recent advances in horizontal alveolar bone regeneration. The biomaterials and clinical and preclinical approaches tested for the regeneration of the horizontal type of alveolar bone are first discussed. Furthermore, current obstacles for horizontal alveolar bone regeneration and future directions in regenerative therapy are presented to provide new ideas for developing an effective multidisciplinary strategy to address the challenge of horizontal alveolar bone loss.
Plant resistance to pests and diseases: potency in coconut
Authors: Sivapragasam A. , Sathis Sri T.
Published: May 2023

Plant resistance to pests and diseases help avoid, tolerate or recover from an injury that would cause greater damage to plants of the same species under similar environmental conditions. In coconut, resistant traits are generally acquired traits against pests and diseases in conventional breeding programs and indirectly through the application of nutrients. The paper provides a list of existing resistant or tolerant coconut varieties reported against key pests and diseases. The use of resistant coconut varieties as part of the integrated pest management toolbox is considered to be an effective medium to long-term strategy. Thus, it is anticipated that resistant varieties will become increasingly important as a component of the IPM toolbox as we encounter invasive species and face the vagaries of climate change. This strategy may also be helpful for managing diseases caused by phytoplasmas. The paper alluded to a number of challenges faced in breeding resistant coconut varieties and the strategies for deploying them. The future projects interesting prospects for resistant variety development that are underpinned by the use of biotechnological tools such as Resistance Gene Analogues (RGAs) and Eco-TILLING and supported by advances in tissue culture and micropropagation that could be used to expedite conventional breeding programs.
Long-term analysis of indoor air quality and thermal comfort in a public school
Authors: Catalina T , Damian A , Vartires A , Niță M , Racovițeanu V
Published: May 2023

The paper is focused on the investigation of the Indoor Air Quality (IAQ) in two classrooms from a thermal renovated school from Bucharest, related to indoor carbon dioxide (CO2), ozone (O3) concentrations or airborne particles (PM2.5), by using experimental data. The experimental campaign has been conducted over a long period (February-June 2022), allowing the study of indoor air quality under different weather data conditions. The results showed that the use of classroom ventilation is mandatory in order to reach a satisfactory degree of thermal comfort and indoor air quality and even the natural ventilation by windows opening remains a simply and useful tool to lower the indoor pollutant concentrations. However, if the target is to ensure permanent good indoor air quality in these learning spaces, a mechanical ventilation system is more adapted than the natural ventilation, due to the fact it is independent of the weather factors variation (outside temperature and wind velocity and direction).
Fish guidance system for a river water intake - experimental and numerical study
Authors: Danca Paul Alexandru , Simionescu Stefan-Mugur , Cîrciumaru Gabriela , Nistoran Daniela-Elena Gogoașe , Chihaia Rares Andrei , Babutanu Corina
Published: May 2023

Fish guidance systems associated to water intakes represent an important feature, mandatory to prevent fish from being accidentally drawn into artificial hydraulic facilities. Such systems are recommended for a proper integration of the water intake into the surrounding environment and contribute to reducing the impact on the environment. In this paper a prototype of fish guidance system which can be applied to river water intakes is presented and analysed. The fish are guided by means of an air bubbles curtain, which influence the flow of the water. This study was performed numerically in Fluent software and experimentally in laboratory conditions. Velocity distribution maps were achieved using Particle Image Velocimetry technique for two water flowrates. The results presented in the paper are a part of the recorded data, and have the purpose to validate the numerical model for the case without air bubbles curtain. A second purpose is to evaluate the changes caused by the bubbles curtain on the water velocity. The results obtained by numerical simulations are in good correlation with the experimental results performed using PIV technique and demonstrate that the fish guidance systems associated to water intakes can represent an efficient solution for fish protection in their natural environment.
Comparative analysis of significant wave height between satellite altimetry data and SWAN model simulations in the Black Sea basin
Authors: Luca E , Bandoc G , Degeratu M
Published: May 2023

Significant wave height (Hs) data are essential in different scientific studies regarding coastal and marine environments, coastal management, various economic activities nearshore and offshore, as well as in the use of marine renewable energy, oil and gas offshore platform operation and security, safety of personnel and equipment. The current paper presents an analysis of the significant wave height parameter for the particular case of the Black Sea basin. In order to achieve this analysis, satellite altimetry measurements from five different satellites taken from the IMOS (Integrated Marine Observing System) database were used and compared with the results of SWAN model simulations in order to assess the accuracy of simulated Hs values. The analysis was performed on data available for a period of 3 years, from 2018 to 2020. The comparison of the simulated significant wave height with data measured by altimetry satellites showed a good correlation of 0.8. The obtained results bring a contribution with regards to a better insight and knowledge into the characteristics of wind waves in the Black Sea.
Evaluation of CFD-predicted thermal comfort uncertainties based on a seated thermal manikin test case
Authors: Zasimova M A , Podmarkova A D , Ivanov N G , Marinova A A
Published: May 2023

The contribution presents the results of numerical simulation of 3D turbulent airflow and heat transfer around a seated thermal manikin in a model room with mixing ventilation. The main goal of the study is to evaluate the uncertainties caused by a CFD model. The room and the detailed thermal manikin geometry correspond to the experiment of P.V. Nielsen et al. (2007). The 3D computational model based on the RANS approach with the standard k-ε turbulence model is applied. The radiation effects are taken into account with the surface-to-surface radiation model. The study considers (1) the effect of the supply air flow rate variation and (2) the effect of the thermal manikin geometrical shape. For a particular parameters set, the results of numerical simulation are validated using the experimental data available (P.V. Nielsen et al.). The contribution is focused also on studying the effects of various heat transfer mechanisms on the airflow pattern and thermal comfort parameters: the baseline mixing ventilation scenario is compared with the buoyancy-dominated case.
Measuring the impact of academic literacy interventions: Refining an evaluation design through self-reflection and feedback
Authors: Fouché Ilse
Published: May 2023

This article, located in the discipline of academic literacy studies, draws upon the fields of critical realism, design research, and evaluation studies. It reports on the validation of a flexible evaluation design for assessing the impact of academic literacy interventions. The design was validated in two ways. Firstly, through a process of critical reflection, the researcher considers her own experience with applying the evaluation design to an academic literacy course; the weaknesses and limitations that emerged from this implementation are considered. Secondly, academic literacy specialists responsible for a wide variety of interventions in South Africa were consulted by means of a questionnaire containing both quantitative and qualitative questions. The purpose of this questionnaire was to determine to which extent the evaluation design could be applied to a variety of academic literacy interventions in various contexts. Recommendations regarding the refinement of the evaluation design are made, and a revised evaluation design is put forward.
Evaluating the effect of weekly patient-reported symptom monitoring on trial outcomes: results of the Eczema Monitoring Online randomized controlled trial
Authors: Baker Arabella , Mitchell Eleanor J , Partlett Christopher , Thomas Kim S
Published: May 2023

Background

Patient-reported outcome measures (PROMs) are commonly used in eczema clinical trials. Several trials have used PROMs weekly for symptom monitoring. However, the increased frequency of patient-reported symptom monitoring may prompt participants to enhance the self-management of eczema and increase standard topical treatment use that can lead to improvements in outcomes over time. This is concerning as weekly symptom monitoring may constitute an unplanned intervention, which may mask small treatment effects and make it difficult to identify changes in the eczema resulting from the treatment under investigation.

Objectives

To evaluate the effect of weekly patient-reported symptom monitoring on participants’ outcomes and to inform the design of future eczema trials.

Methods

This was an online parallel-group nonblinded randomized controlled trial. Parents/carers of children with eczema and young people and adults with eczema were recruited online, excluding people scoring < 3 points on the Patient Oriented Eczema Measure (POEM), to avoid floor effects. Electronic PROMs were used for data collection. Participants were allocated using online randomization (1 : 1) to weekly POEM for 7 weeks (intervention) or no POEM during this period (control). The primary outcome was change in eczema severity based on POEM scores, assessed at baseline and week 8. Secondary outcomes included change in standard topical treatment use and data completeness at follow-up. Analyses were conducted according to randomized groups in those with complete data at week 8.

Results

A total of 296 participants were randomized from 14 September 2021 to 16 January 2022 (71% female, 77% white, mean age 26.7 years). The follow-up completion rate was 81.7% [n = 242; intervention group, n = 118/147 (80.3%); control group n = 124/149 (83.2%)]. After adjusting for baseline disease severity and age, eczema severity improved in the intervention group (mean difference in POEM score –1.64, 95% confidence interval –2.91 to –0.38; P = 0.01). No between-group differences were noted in the use of standard topical treatments and data completeness at follow-up.

Conclusions

Weekly patient-reported symptom monitoring led to a small perceived improvement in eczema severity.
Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases
Authors: Kataoka Kozo , Takahashi Kanae , Takeuchi Jiro , Ito Kazuma , Beppu Naohito , Ceelen Wim , Kanemitsu Yukihide , Ajioka Yoichi , Endo Itaru , Hasegawa Kiyoshi , Takahashi Keiichi , Ikeda Masataka
Published: May 2023

Background

The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis.

Methods

Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005–2007 and 2013–2014). RFS, OS, and survival after recurrence were estimated using the Kaplan–Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated.

Results

A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06).

Conclusion

In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.
Become Something More
Authors: Runciman Brian
Published: May 2023

New BCS President Gillian Arnold spoke to Brian Runciman MBCS about her punk days, where she sees BCS going and the importance of volunteering.
BCS in the News: Policy and Impact
Authors: Penketh Claire
Published: May 2023

Across core policy areas such as diversity, education, AI and climate change, BCS’ focus on influencing IT’s defining debates continues to grow. Claire Penketh, Senior Press Officer, reports on BCS’ reach and reputation.
What Cyber Security Can Learn from Local Government
Authors: Richardson Dave
Published: May 2023

Dave Richardson MBCS, ICT and Digital Services Business Manager at Newark and Sherwood District Council, explains how local authorities can lead by example in tackling the information security challenge.
The WiFi Evil Twin
Authors: Abhishek Kumar
Published: May 2023

Kumar Abhishek, Senior Machine Learning Engineer for Expedia and a fraud detection expert, offers some advice about the risks of using public WiFi networks.
Open Source is Good for AI But, Is AI Good for Open Source?
Authors: Cooper Martin
Published: May 2023

Terence Eden CITP MBCS MIET, Chair of the BCS Open Source Specialist Group, takes Martin Cooper MBCS on a tour of the open source world and explains why writing software is both an art and a science.
Understanding the Global Chip Shortage
Authors: Cooper Martin
Published: May 2023

Gartner’s Gaurav Gupta and Kanishka Chauhan explore the global chip shortage’s origins and discuss future silicon supply trends. Martin Cooper MBCS asks the questions.
Making Retail Smarter with Digital Twins
Authors: Shekhawat Sandeep
Published: May 2023

Sandeep Shekhawat, Director of Engineering at Walmart Global Tech (USA), explores how a fusion of AI and IoT technologies enables retailers to design, test and deploy innovative new customer experiences.
How Business Analysis is Changing
Authors: Chung Kitty
Published: May 2023

Dr Kitty Hung PhD CITP FBCS, Principal Consultant at Atkins, discusses how major world events in 2022 have led to both challenges and opportunities for business analysts in 2023.
Optimization-Based Compressive Sensing for Image Compression and Recovery
Authors:   BCS
Published: May 2023

Sekar R and Ravi G author a paper called Taylor Sun Flower Optimization-Based Compressive Sensing for Image Compression and Recovery, which appears in the The Computer Journal (Volume 66, issue 4, April 2023)
Feasibility and Acceptability of a Classroom-Based Motivational Interviewing Intervention for Ninth-Grade Students at Risk for School Dropout
Authors: Iachini Aidyn L
Published: May 2023

The purpose of this mixed-methods study was to explore the feasibility, acceptability, and preliminary effectiveness of a Tier 2 classroom-based motivational interviewing (MI) intervention—the Aspire Group Intervention (AGI)—designed for ninth-grade students identified as being at high risk for school dropout. The nine-lesson AGI curriculum was grounded in self-determination theory and positive youth development, and aligned with the four processes that characterize MI (i.e., engaging, focusing, evoking, and planning). The intervention was implemented with 38 ninth-grade students in two classrooms in one southeastern high school. Data were collected through pre/post student surveys, implementation fidelity checklists, and teacher interviews. Results suggest students were satisfied and found the intervention helpful. Teachers were satisfied with the intervention overall but shared concerns regarding student engagement and group size due to classroom delivery of the intervention. Implementation data suggest that lessons were slightly longer than a class period and most activities were implemented as intended. The article concludes with a discussion of implications of this study for future refinement of the intervention, along with more general implications for school social work practice.
Digest: Complex dynamics of speciation and implications for macroevolutionary models
Authors: Ahmad-Gawel Miriam
Published: May 2023

What kinds of reproductive barriers are important for maintaining species integrity, and how are species boundaries preserved in the face of gene flow? Ivey et al. (2023) find little evidence for reproductive barriers and uncover a history of introgression between two incipient species of monkeyflower. These findings contribute to a growing body of work that calls for a reconsideration of how speciation dynamics are modeled at the macroevolutionary level.
Short-term fitness consequences of parasitism depend on host genotype and within-host parasite community
Authors: Sallinen Suvi , Laine Anna-Liisa
Published: May 2023

Multiparasite communities inhabiting individual hosts are common and often consist of parasites from multiple taxa. The effects of parasite community composition and complexity on host fitness are critical for understanding how host–parasite coevolution is affected by parasite diversity. To test how naturally occurring parasites affect host fitness of multiple host genotypes, we performed a common-garden experiment where we inoculated four genotypes of host plant Plantago lanceolata with six microbial parasite treatments: three single-parasite treatments, a fungal mixture, a viral mixture, and a cross-kingdom treatment. Seed production was affected by both host genotype and parasite treatment, and their interaction jointly determined the growth of the hosts. Fungal parasites had more consistent negative effects than viruses in both single- and mixed-parasite treatments. These results demonstrate that parasite communities have the potential to affect the evolution and ecology of host populations through their effects on host growth and reproduction. Moreover, the results highlight the importance of accounting for the diversity of parasites as well as host genotypes when aiming to predict the consequences of parasites for epidemics as the effects of multiparasitism are not necessarily additive of single-parasite effects, nor uniform across all host genotypes.
The Adaptive Evolution of Leuciscus waleckii in Lake Dali Nur and Convergent Evolution of Cypriniformes Fishes Inhabiting Extremely Alkaline Environments
Authors: Zhou Zhixiong , Yang Junyi , Lv Hongzao , Zhou Tao , Zhao Ji , Bai Huaqiang , Pu Fei , Xu Peng
Published: May 2023

Leuciscus waleckii is widely distributed in Northeast Asia and has high economic value. The population in Lake Dali Nur can adapt to extremely alkaline–saline water with bicarbonate over 50 mmol/L (pH 9.6), thus providing an exceptional model for exploring the mechanisms of adaptive evolution under extreme alkaline environments. Here, we assembled a high-quality chromosome-level reference genome for L. waleckii from Lake Dali Nur. Based on the resequencing of 85 individuals from divergent populations, the historical population size of L. waleckii in Lake Dali Nur dramatically expanded in a thousand years approximately 13,000 years ago and experienced a cliff recession in the process of adapting to the alkaline environment of Lake Dali Nur approximately 6,000 years ago. Genome scans between freshwater and alkaline populations further revealed the significant selective sweep regions from Lake Dali Nur, which harbor a set of candidate genes involved in hypoxia tolerance, ion transport, acid–base regulation, and nitrogen metabolism. 5 alkali population–specific nonsynonymous mutations were identified in CA15 gene copies. In addition, two sites with convergent amino acid mutation were detected in the RHCG-a gene among several alkali environment–adapted Cypriniformes fish. Our findings provide comprehensive insight into the genomic mechanisms of L. waleckii and reveal their adaptative evolution under extreme alkaline environments.
A Novel Serum Metabolomic Panel for the Diagnosis of Crohn’s Disease
Authors: Ma Ruiqi , Zhu Yijun , Li Xiaozhi , Hu Shixian , Zheng Danping , Xiong Shanshan , Xu Shu , Xiang Liyuan , Zhao Min , Tang Ce , Zeng Zhirong , Chen Minhu , Feng Rui
Published: May 2023

Background

A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn’s disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis.

Methods

Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet’s disease (n = 31).

Results

Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases.

Conclusions

The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.
Geometric Models for Algebraic Suspensions
Authors: Asok A , Dubouloz A , Østvær P A
Published: May 2023

We analyze the question of which motivic homotopy types admit smooth schemes as representatives. We show that given a pointed smooth affine scheme $X$ and an embedding into affine space, the affine deformation space of the embedding gives a model for the ${\mathbb P}^{1}$ suspension of $X$; we also analyze a host of variations on this observation. Our approach yields many examples of ${\mathbb A}^{1}$-$(n-1)$-connected smooth affine $2n$-folds and strictly quasi-affine ${\mathbb A}^{1}$-contractible smooth schemes.
Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study
Authors: Skarbinski Jacek , Nugent Joshua R , Wood Mariah S , Liu Liyan , Bullick Teal , Schapiro Jeffrey M , Arunleung Phacharee , Morales Christina , Amsden Laura B , Hsiao Crystal A , Wadford Debra A , Chai Shua J , Reingold Arthur , Wyman Stacia K
Published: May 2023

Background

The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection.

Methods

In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score.

Results

Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006.

Conclusions

Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.
Early mortality in patients with cancer treated with immune checkpoint inhibitors in routine practice
Authors: Raphael Jacques , Richard Lucie , Lam Melody , Blanchette Phillip , Leighl Natasha B , Rodrigues George , Trudeau Maureen , Krzyzanowska Monika K
Published: May 2023

Background

We sought to estimate the proportion of patients with cancer treated with immune checkpoint inhibitors (ICI) who die soon after starting ICI in the real world and examine factors associated with early mortality (EM).

Methods

We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada. EM was defined as death from any cause within 60 days of ICI initiation. Patients with melanoma, lung, bladder, head and neck, or kidney cancer treated with ICI between 2012 and 2020 were included.

Results

A total of 7126 patients treated with ICI were evaluated. Fifteen percent (1075 of 7126) died within 60 days of initiating ICI. The highest mortality was observed in patients with bladder and head and neck tumors (approximately 21% each). In multivariable analysis, previous hospital admission or emergency department visit, prior chemotherapy or radiation therapy, stage 4 disease at diagnosis, lower hemoglobin, higher white blood cell count, and higher symptom burden were associated with higher risk of EM. Conversely, patients with lung and kidney cancer (compared with melanoma), lower neutrophil to lymphocytes ratio, and with higher body mass index were less likely to die within 60 days post ICI initiation. In a sensitivity analysis, 30-day and 90-day mortality were 7% (519 of 7126) and 22% (1582 of 7126), respectively, with comparable clinical factors associated with EM identified.

Conclusions

EM is common among patients treated with ICI in the real-world setting and is associated with several patient and tumor characteristics. Development of a validated tool to predict EM may facilitate better patient selection for treatment with ICI in routine practice.
What Kind of Weapon Is Education? Teleological Violence, Local Integration, and Refugee Education in Northern Ethiopia
Authors: Poole Amanda , Riggan Jennifer
Published: May 2023

Why does education damage refugees? To understand this, we need to ask how education frames refugees’ thinking about their future, specifically related to questions of waiting in the camp or migrating through dangerous, irregular channels. Between 2016 and 2019, Ethiopia was at the forefront of trends in migration policy that prioritized education as part of a global strategy to prevent irregular, northward migration. However, despite increased educational opportunities, refugees rejected schooling as they weighed the decision to migrate onwards, citing a sharp disconnect between aspirations connected to schooling and the constraints on professional and personal progress that they face in hosting states. Drawing on long-term, multi-sited, ethnographic research on temporal violence, and temporal agency among Eritrean refugees in Ethiopia, we develop the concept of teleological violence to describe the harm generated by this disconnect, as risky secondary migration may come to seem like the only path toward a desired future.
Identifying irregular activity sequences: an application to passive household monitoring
Authors: Gillam Jess , Killick Rebecca , Taylor Simon , Heal Jack , Norwood Ben
Published: May 2023

Approximately one in five people will live to see their 100th birthday due to advancements in modern medicine and other factors. Over 65’s constitute 42% of elective admissions and 43% of emergency admissions to hospitals. Increasingly, people are turning to technology to help improve health and care of the elderly. There is mixed evidence of the success of wearables in older populations with a key barrier being adoption. In contrast, passive sensors such as infra-red motion and plug sensors have had more success. These passive sensors give us a sequence of categorical “trigger” events throughout the day. This paper proposes a method for detecting subtle changes in sequences while taking account of the natural day-to-day variability and differing numbers of “trigger” events per day.
PIN structures shed light on their mechanism of auxin efflux
Authors: Joshi Chitra , Napier Richard
Published: May 2023

Polar auxin transport is a quintessential feature of higher plant physiology and it has been known for many years that some of the primary drivers of polar auxin transport are the PIN-formed (PIN) auxin efflux proteins. Formative research established many key biochemical features of the transport system and discovered inhibitors such as 1-naphthylphthalamic acid (NPA), but the mechanism of action of PINs has remained elusive. This changed in 2022 with the publication of high-resolution structures of the membrane-spanning domains of three PIN proteins. The atomic structures and associated activity assays reveal that PINs use an elevator mechanism to transport auxin anions out of the cell. NPA was shown to be a competitive inhibitor that traps PINs in their inward-open conformation. The secrets of the hydrophilic cytoplasmic loop of PIN proteins remain to be discovered.
Addressing uncertainties in correlative imaging of exogenous particles with the tissue microanatomy with synchronous imaging strategies
Authors: Morrell Alexander P , Martin Richard A , Roberts Helen M , Castillo-Michel Hiram , Mosselmans J Frederick W , Geraki Kalotina , Warfield Adrian T , Lingor Paul , Qayyum Wasif , Graf Daniel , Febbraio Maria , Addison Owen
Published: May 2023

Exposure to exogenous particles is of increasing concern to human health. Characterizing the concentrations, chemical species, distribution, and involvement of the stimulus with the tissue microanatomy is essential in understanding the associated biological response. However, no single imaging technique can interrogate all these features at once, which confounds and limits correlative analyses. Developments of synchronous imaging strategies, allowing multiple features to be identified simultaneously, are essential to assess spatial relationships between these key features with greater confidence. Here, we present data to first highlight complications of correlative analysis between the tissue microanatomy and elemental composition associated with imaging serial tissue sections. This is achieved by assessing both the cellular and elemental distributions in three-dimensional space using optical microscopy on serial sections and confocal X-ray fluorescence spectroscopy on bulk samples, respectively. We propose a new imaging strategy using lanthanide-tagged antibodies with X-ray fluorescence spectroscopy. Using simulations, a series of lanthanide tags were identified as candidate labels for scenarios where tissue sections are imaged. The feasibility and value of the proposed approach are shown where an exposure of Ti was identified concurrently with CD45 positive cells at sub-cellular resolutions. Significant heterogeneity in the distribution of exogenous particles and cells can be present between immediately adjacent serial sections showing a clear need of synchronous imaging methods. The proposed approach enables elemental compositions to be correlated with the tissue microanatomy in a highly multiplexed and non-destructive manner at high spatial resolutions with the opportunity for subsequent guided analysis.
Accurate quantification of DNA using on-site PCR (osPCR) by characterizing DNA amplification at single-molecule resolution
Authors: Ding Ruihua , Liu Liying , Zhang Jiali , Lv Pengxiao , Zhou Lin , Zhang Tinglu , Li Shenwei , Zhao Ran , Yang Zhuo , Xiong Peng , Chen Hu , Wang Wei , Wang Hualiang , Tian Zhengan , Liu Bo , Chen Chang
Published: May 2023

Despite the need in various applications, accurate quantification of nucleic acids still remains a challenge. The widely-used qPCR has reduced accuracy at ultralow template concentration and is susceptible to nonspecific amplifications. The more recently developed dPCR is costly and cannot handle high-concentration samples. We combine the strengths of qPCR and dPCR by performing PCR in silicon-based microfluidic chips and demonstrate high quantification accuracy in a large concentration range. Importantly, at low template concentration, we observe on-site PCR (osPCR), where only certain sites of the channel show amplification. The sites have almost identical ct values, showing osPCR is a quasi-single molecule phenomenon. Using osPCR, we can measure both the ct values and the absolute concentration of templates in the same reaction. Additionally, osPCR enables identification of each template molecule, allowing removal of nonspecific amplification during quantification and greatly improving quantification accuracy. We develop sectioning algorithm that improves the signal amplitude and demonstrate improved detection of COVID in patient samples.
Individual and Conjoint Factors Associated With Beliefs About the Harmfulness of Nicotine Replacement Therapies Relative to Combustible Cigarettes Among People Who Smoke: Findings From the 2020 ITC Four Country Smoking and Vaping Survey
Authors: Yong Hua-Hie , Karmakar Chandan , Motin Mohammod Abdul , Borland Ron , Cummings K Michael , Gravely Shannon , Fong Geoffrey T
Published: May 2023

Introduction

This study examined individual and conjoint factors associated with beliefs about the harmfulness of nicotine replacement therapies (NRTs) relative to combustible cigarettes (CCs).

Aims and Methods

Data analyzed came from 8642 adults (≥18 years) who smoked daily/weekly and participated in the 2020 ITC Four Country Smoking and Vaping Survey in Australia (n = 1213), Canada (n = 2633), England (n = 3057), and United States (n = 1739). Respondents were asked: “Compared to smoking cigarettes, how harmful do you think nicotine replacement products are?” Responses were dichotomized into “much less” versus otherwise for analysis using multivariable logistic regression models, complemented by decision-tree analysis to identify conjoint factors.

Results

Percentages believing that NRTs are much less harmful than CCs were 29.7% (95% CI = 26.2% to 33.5%) in Australia, 27.4% (95% CI = 25.1% to 29.8%) in England, 26.4% (95% CI = 24.4% to 28.4%) in Canada, and 21.7% (95% CI = 19.2% to 24.3%) in the United States. Across all countries, believing nicotine is not at all/slightly harmful to health (aOR = 1.53–2.27), endorsing nicotine vaping products (NVPs) as less harmful than CCs (much less harmful: aOR = 7.24–14.27; somewhat less harmful: aOR = 1.97–3.23), and possessing higher knowledge of smoking harms (aOR = 1.23–1.88) were individual factors associated with increased odds of believing NRTs are much less harmful than CCs. With some country variations, these nicotine-related measures also interacted with each other and sociodemographic variables to serve as conjoint factors associated with the likelihood of accurate NRT relative harm belief.

Conclusions

Many people who regularly smoke cigarettes are unaware that NRTs are much less harmful than cigarettes. Additionally, beliefs about NRTs relative harmfulness appear to be influenced by both individual and conjoint factors.

Implications

This study demonstrates that despite past efforts to educate people who smoke about the harms of NRTs relative to CCs, misperceptions around the relative harmfulness of NRTs remain substantial. In all four studied countries, subgroups of people who smoke regularly who are misinformed about the relative harmfulness of NRTs, and who may be reluctant to use NRTs for smoking cessation can be reliably identified for corrective interventions based on their understanding of the harms related to nicotine, NVPs and smoking along with sociodemographic markers. The identified subgroup information can be used to prioritize and inform the development of effective interventions to specifically address the gaps in knowledge and understanding of the various subgroups identified. Our results suggest these may need to be tailored for each country.
Comparative Genomic Landscape of Urothelial Carcinoma of the Bladder Among Patients of East and South Asian Genomic Ancestry
Authors: Peak Taylor , Spiess Philippe E , Li Roger , Grivas Petros , Necchi Andrea , Pavlick Dean , Huang Richard S P , Lin Douglas , Danziger Natalie , Jacob Joseph M , Bratslavsky Gennady , Ross Jeffrey S
Published: May 2023

Background

Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort.

Methods

Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a 324-gene hybrid-capture-based method which also calculates tumor mutational burden (TMB) and determines microsatellite status (MSI).

Results

Of the cohort, 7447 (85.3%) were EUR, 541 (6.2%) were AFR, 461 (5.3%) were of AMR, 74 (0.85%) were SAS, and 205 (2.3%) were EAS. When compared with EUR, TERT GAs were less frequent in SAS (58.1% vs. 73.6%; P = .06). When compared with non-SAS, SAS had less frequent GAs in FGFR3 (9.5% vs. 18.5%, P = .25). TERT promoter mutations were significantly less frequent in EAS compared to non-EAS (54.1% vs. 72.9%; P < .001). When compared with the non-EAS, PIK3CA alterations were significantly less common in EAS (12.7% vs. 22.1%, P = .005). The mean TMB was significantly lower in EAS vs. non-EAS (8.53 vs. 10.02; P = .05).

Conclusions

The results from this comprehensive genomic analysis of UCB provide important insight into the possible differences in the genomic landscape in a population level. These hypothesis-generating findings require external validation and should support the inclusion of more diverse patient populations in clinical trials.
Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: the role of imaging in a prospective observational study
Authors: Muratore Francesco , Marvisi Chiara , Cassone Giulia , Boiardi Luigi , Mancuso Pamela , Besutti Giulia , Spaggiari Lucia , Casali Massimiliano , Croci Stefania , Versari Annibale , Giorgi Rossi Paolo , Catanoso Mariagrazia , Costantini Massimo , Galli Elena , Salvarani Carlo
Published: May 2023

Objectives

To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA).

Methods

In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52.

Results

A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions –8.6 (–11.5 to –5.7) and –10.4 (–13.6 to –7.2), P = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31–78) and 8/17 (47%, 95% CI 23–72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52.

Conclusion

TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909.
Per- and polyfluoroalkyl substances (PFAS) in mixtures show additive effects on transcriptomic points of departure in human liver spheroids
Authors: Addicks Gregory C , Rowan-Carroll Andrea , Reardon Anthony J F , Leingartner Karen , Williams Andrew , Meier Matthew J , Moffat Ivy , Carrier Richard , Lorusso Luigi , Wetmore Barbara A , Yauk Carole L , Atlas Ella
Published: May 2023

Per- and polyfluoroalkyl substances (PFAS) are a wide range of chemicals that are used in a variety of consumer and industrial products leading to direct human exposure. Many PFAS are chemically nonreactive and persistent in the environment, resulting in additional exposure from water, soil, and dietary intake. While some PFAS have documented negative health effects, data on simultaneous exposures to multiple PFAS (PFAS mixtures) are inadequate for making informed decisions for risk assessment. The current study leverages data from previous work in our group using Templated Oligo-Sequencing (TempO-Seq) for high-throughput transcriptomic analysis of PFAS-exposed primary human liver cell spheroids; herein, we determine the transcriptomic potency of PFAS in mixtures. Gene expression data from single PFAS and mixture exposures of liver cell spheroids were subject to benchmark concentration (BMC) analysis. We used the 25th lowest gene BMC as the point of departure to compare the potencies of single PFAS to PFAS mixtures of varying complexity and composition. Specifically, the empirical potency of 8 PFAS mixtures were compared to predicted mixture potencies calculated using the principal of concentration addition (ie, dose addition) in which mixture component potencies are summed by proportion to predict mixture potency. In this study, for most mixtures, empirical mixture potencies were comparable to potencies calculated through concentration addition. This work supports that the effects of PFAS mixtures on gene expression largely follow the concentration addition predicted response and suggests that effects of these individual PFAS in mixtures are not strongly synergistic or antagonistic.
The Effects of Community Health Worker Visits and Primary Care Subsidies on Health Behavior and Health Outcomes for Children in Urban Mali
Authors: Dean Mark , Sautmann Anja
Published: May 2023

Subsidized primary care and community health worker (CHW) visits are important demand-side policies in the effort to achieve universal health care for children aged under 5. Causal evidence on the interaction between these policies is still sparse. This paper reports the effects on diarrhea prevention, curative care, and incidence as well as anthropometrics for 1,649 children from a randomized controlled trial in Bamako that cross-randomized CHW visits and access to free health care. CHW visits improve prevention and subsidies increase the use of curative care for acute illness, with some indication of positive interaction effects. There is no evidence of moral hazard, such as reduced preventive care among families receiving the subsidy. Although there are no significant improvements in malnutrition, diarrhea incidence is reduced by over 70 percent in the group that receives both subsidies and CHWs. Positive effects are concentrated among children under age 2.