bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience of induction of labour: a cross-sectional postnatal survey of women at UK maternity units
Authors: Harkness Mairi , Yuill Cassandra , Cheyne Helen , McCourt Christine , Black Mairead , Pasupathy Dharmintra , Sanders Julia , Heera Neelam , Wallace Chlorice , Stock Sarah Jane
Published: May 2023

Objectives

This study explored women’s views and experiences of key elements of the induction of labour (IOL) process, including at home or in hospital cervical ripening (CR).

Design

A questionnaire-based postnatal survey undertaken as part of the CHOICE Study process evaluation. The questionnaire was administered online and included fixed response and free-text options.

Setting

National Health Service maternity units in the UK.

Participants

309 women who had an IOL.

Outcome measures

The primary outcome measure was experience of IOL. Few women returned home during CR, meaning that statistical comparison between those who experienced home-based and hospital-based CR was not possible. Findings are reported as descriptive statistics with content analysis of women’s comments providing context.

Results

Information to support choice and understand what to expect about IOL is often inadequate or unavailable. Having IOL can create anxiety and remove options for birth that women had hoped would enhance their experience. Although it can provide a more comfortable environment, home CR is not always an acceptable solution. Women described maternity care negatively impacted by staffing shortages; delays to care sometimes led to unsafe situations. Women who had a positive experience of IOL described supportive interaction with staff as a significant contribution to that.

Conclusions

Women do not experience IOL as a benign and consequence free intervention. There is urgent need for research to better target IOL and optimise safety and experience for women and their babies. Relatively few women were offered CR at home and further research is needed on this experience.
Single-arm, open-labelled, safety and tolerability of intrabronchial and nebulised bacteriophage treatment in children with cystic fibrosis andPseudomonas aeruginosa
Authors: Singh Jagdev , Fitzgerald Dominic A , Jaffe Adam , Hunt Sharon , Barr Jeremy J , Iredell Jonathan , Selvadurai Hiran
Published: May 2023

Introduction

Cystic fibrosis (CF) is a multisystem condition that is complicated by recurrent pulmonary infections requiring aggressive antibiotic treatment. This predisposes the patient to complications such as sensorineural hearing loss, renal impairment, hypersensitivity and the development of antibiotic resistance.Pseudomonas aeruginosais one of the more common organisms which cause recurrent infections and result in greater morbidity and mortality in people living with CF. Bacteriophages have been identified as a potential alternative or adjunct to antibiotics. We hypothesise that bacteriophage therapy is a safe and well-tolerated treatment in children with CF infected withP. aeruginosainfection in their airways.

Methods

This single-arm, open-labelled, non-randomised trial will run for a maximum period of 36 months with up to 10 participants. Adolescents (≥12 years and <18 years of age) who continue to shedP.aeruginosa(within 3 months of enrolment) despite undergoing eradication therapy previously, will be considered for this trial. Non-genetically modified bacteriophages that have demonstrated obligate lytic activity against each of the study participants’P. aeruginosastrains will be selected and prepared according to a combination of established protocols (isolation, purification, sterility testing and packaging) to achieve close to good manufacturing practice recommendations. The selected bacteriophage will be administered endo-bronchially first under direct vision, followed by two times a day nebulisation for 7 days in addition to standard CF treatment (intravenous antibiotics, physiotherapy to be completed as inpatient for 10–14 days). Safety and tolerability will be defined as the absence of (1) fever above 38.5°C occurring within 1 hour of the administration of the nebulised bacteriophage, (2) a 10% decline in spirometry (forced expiratory volume in 1 s %) measured preadministration and postadministration of the first dose of nebulised bacteriophage. Clinical reviews including repeat sputum cultures and spirometry will be performed at 3, 6, 9 and 12 months following bacteriophage treatment.

Ethics and dissemination

Our clinical trial is conducted in accordance with (1) good clinical practice, (2) Australian legislation, (3) National Health and Medical Research Council guidelines for the ethical conduct of research.

Trial registration number

Australia and New Zealand Clinical Trial Registry (ACTRN12622000767707).
The Canadian Food Intake Screener for assessing alignment of adults’ dietary intake with the 2019 Canada’s Food Guide healthy food choices recommendations: scoring system and construct validity
Authors: Hutchinson Joy M. , Dodd Kevin W. , Guenther Patricia M. , Lamarche Benoit , Haines Jess , Wallace Angela , Perreault Maude , Williams Tabitha E. , Louzada Maria Laura da Costa , Jessri Mahsa , Lemieux Simone , Olstad Dana Lee , Prowse Rachel , Simpson Janis Randall , Vena Jennifer E. , Szajbely Kathleen , Kirkpatrick Sharon I.
Published: May 2023

The Canadian Food Intake Screener/Questionnaire court canadien sur les apports alimentaires was developed to rapidly assess alignment of adults’ dietary intake over the past month with the 2019 Canada’s Food Guide’s healthy food choices recommendations. From July to December 2021, adults ( n = 154) aged 18–65 years completed the screener and up to two 24 h dietary recalls. The screener scoring system was aligned with the Healthy Eating Food Index-2019 (HEFI-2019), to the extent possible. Analysis of variance compared screener scores among subgroups with known differences in diet quality. Using the recall data, the National Cancer Institute multivariate method was used to model HEFI-2019 components, with the screener score as a covariate, and the correlation coefficient between screener and total HEFI-2019 scores was estimated. The mean screener score was 35 points (SD = 4.7; maximum 65), ranging from 26 (1st percentile) to 45 (99th percentile). Differences in scores in hypothesized directions were evident by gender identity ( p = 0.06), perceived income adequacy ( p = 0.07), education ( p = 0.02), and smoking status ( p = 0.003). The correlation between screener and HEFI-2019 scores was 0.53 (SE = 0.12). The screener’s moderate construct validity supports its use for rapid assessment of alignment of adults’ intake with the healthy food choices recommendations when comprehensive dietary assessment is not possible.

Novelty

The Canadian Food Intake Screener was developed to rapidly assess alignment of dietary intake with the Canada’s Food Guide-2019 healthy food choices recommendations. Scoring is aligned with the Healthy Eating Food Index-2019 to the extent possible. Among a sample of adults, reasonable variation in screener scores was noted, mean screener scores differed between some subgroups with known differences in diet quality, and a moderate correlation between screener scores and total Healthy Eating Food Index-2019 scores based on repeat 24 h dietary recalls was observed. The Canadian Food Intake Screener has moderate construct validity for rapid assessment of overall alignment of adults’ dietary intake with the Canada’s Food Guide-2019 healthy food choices recommendations.
CPT-based design method for helical piles in sand
Authors: Bittar Eduardo , Lehane Barry M. , Blake Anthony , Richards David , White David , Mahdavi Sam , Cerfontaine Benjamin
Published: May 2023

Helical piles are used extensively for low and medium rise developments and are a popular foundation solution in cases where resistance to significant uplift loads is required. The ability to re-use helical piles and recent interest in their use as foundations in offshore wind and solar energy applications has renewed interest in improving existing design methods. This paper presents the results from field investigations in medium dense and dense sand that examine effects on the axial tension and compression capacity of varying the helix pitch, shaft diameter, advancement ratio and shaft tip geometry. The results from the 20 pile tests conducted (many of which included instrumentation) indicate low sensitivity to a range of the investigated parameters and a strong correlation of the capacity to the cone penetration test resistance. A design method based on these findings is proposed for typical helical pile geometries and is shown to provide predictions that are generally within 10 to 15% of the axial capacities reported for 30 other well documented pile tests reported in the literature. The method, referred to as UWASP-22, incorporates a simple means of estimating the load-displacement response of a helical pile as well as a formulation enabling prediction of the installation torque which is a common quality control measure for helical piles.
Phylogenomics of transcriptionally active AP2/ERF and bHLH transcription factors and study of their promoter regions in Nothapodytes nimmoniana (J.Graham) Mabb
Authors: Godbole Rucha C. , Kadam Swapnil B. , Pable Anupama A. , Singh Sudhir , Barvkar Vitthal T.
Published: May 2023

Nothapodytes nimmoniana is a medicinally important plant producing anticancer monoterpene indole alkaloid (MIA), camptothecin (CPT). The CPT is synthesised through the strictosidine intermediate following the MIA pathway; however, transcriptional regulation of CPT pathway is still elusive in N. nimmoniana. Biosynthesis of MIA is regulated by various transcription factors (TFs) belonging to AP2/ERF, bHLH, MYB, and WRKY families. The present study identified transcriptionally active full-length 105 AP2/ERF and 68 bHLH family TFs from the N. nimmoniana. AP2/ERF TFs were divided into three subfamilies along with a soloist, while bHLH TFs were divided into 10 subfamilies according to their phylogenetic similarities. Three group IXa ERFs, Nn-ERF22, Nn-ERF29, and Nn-ERF41, one subfamily IVa TF Nn-bHLH7, and three subfamilies IIIe Nn-bHLH33, Nn-bHLH51, and Nn-bHLH52 clustered with the TFs regulating alkaloid biosynthesis in Catharanthus roseus, tomato, tobacco, and Artemisia annua. Expression of these TFs in N. nimmoniana was higher in roots, which is a primary CPT accumulating tissue. Moreover, genome skimming approach was used to reconstruct the promoter regions of candidate ERF genes to identify the cis-regulatory elements. The presence of G-boxes and other jasmonic acid-responsive elements in the promoter suggests the regulation of ERFs by bHLHs. The present study effectively generated and used genomics resource for characterisation of regulatory TFs from non-model medicinal plant.
Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response
Authors: Jeon Youngsic , Kang Tae Kyeom , Lee Wook-Bin , Jung Sang Hoon , Kim Young-Joo
Published: May 2023

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset (n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response‐related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response‐related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.
Applications of Robust Methods in Spatial Analysis
Authors: Selvaratnam Selvakkadunko
Published: May 2023

Spatial data analysis provides valuable information to the government as well as companies. The rapid improvement of modern technology with a geographic information system (GIS) can lead to the collection and storage of more spatial data. We developed algorithms to choose optimal locations from those permanently in a space for an efficient spatial data analysis. Distances between neighboring permanent locations are not necessary to be equispaced distances. Robust and sequential methods were used to develop algorithms for design construction. The constructed designs are robust against misspecified regression responses and variance/covariance structures of responses. The proposed method can be extended for future works of image analysis which includes 3 dimensional image analysis.
Surface Temperature Influences the Population of Limnothrissa miodon in Lake Kariba
Authors: Mutasa Farikayi K. , Jones Brian , Tendaupenyu Itai H. , Nhiwatiwa Tamuka , Ndebele-Murisa Mzime R.
Published: May 2023

Global warming is a serious world problem where earth’s temperature has been reported to increase over the years; the aquatic ecosystems are also not the exceptions. But, the effects of this phenomenon on the aquatic ecosystems are not well understood. This study aims to understand the influence of surface temperature on the population density of Limnothrissa miodon in Lake Kariba. We constructed a mathematical model on the population dynamics of Limnothrissa miodon with nutrients, phytoplankton, zooplankton, and Hydrocynus vittatus. Lake surface water temperature was modelled by a cosine function, and the parameters were estimated from data fitting. Numerical simulations were used to determine the stability of the nonautonomous model. Numerical simulation results of the nonautonomous model showed a stable periodic orbit for varying initial conditions, and therefore, instability. Numerical techniques were used to investigate the influence of surface water temperature on Limnothrissa miodon. Results from the model with fitted lake surface water temperature data showed that a shift in the optimal temperature for phytoplankton growth from

25

°

C to

34

°

C, corresponding to dominance of Cyanophyceae over Chlorophyceae, resulted in a decline in the population density of Limnothrissa miodon. Numerical results showed that the population density of Limnothrissa miodon declines after an optimum temperature of

30

°

C for phytoplankton growth. Numerical simulation results suggested that warming of the lake may lead to a decline in Limnothrissa miodon population density in Lake Kariba.
Acceleration-Based Design Procedure for Sloped Rolling-Type Bearings with an Added Rotational Inerter
Authors: Lai Yi-An , Wang Shiang-Jung , Hsu Ting-Yu
Published: May 2023

This research numerically investigates the mechanical behavior of sloped rolling-type bearings equipped with an inerter. After deriving equations of motion, the mechanical behavior, under harmonic excitation, of a sloped rolling-type bearing with its inherent rotational mass (i.e., considering the inertial and restoring forces generated by the existing roller) and one with an added rotational inerter is numerically analyzed. It is demonstrated that the latter is mechanically different from the former and, more importantly, the latter is more effective at controlling acceleration and displacement responses and practically more feasible. The acceleration control performance designed for sloped rolling-type bearings that ignore the inherent rotational mass can basically be retained when adding a rotational inerter if a suitable inertance-to-mass ratio can first be determined based on a specific acceleration target. Precisely stated, retaining the unique mechanical feature of sloped rolling-type bearings under harmonic excitation (i.e., the maximum transmitted acceleration is irrelevant to the external disturbance) is the optimum design objective in this study. Parametric and numerical analyses show that the peak acceleration responses of sloped rolling-type bearings with an added rotational inerter whose inertance-to-mass ratio is determined based on the optimum objective are less dependent on having a sufficiently large harmonic excitation period (i.e., on having the roller in motion within the sloped rolling range). In addition, the peak displacement responses under harmonic excitation can be effectively reduced compared with sloped rolling-type bearings that only consider the inherent rotational mass (i.e., without an added rotational inerter). Similar tendencies are seen when the sloped rolling-type bearings are subjected to ground motion records including far-field and pulse-like near-fault ones. Regardless of the ground motion considered in this study, the sloped rolling-type bearings with an added rotational inerter designed based on the optimum objective show steady displacement reduction. Finally, a simple, practical, and acceleration-based procedure is proposed for designing sloped rolling-type bearings equipped with added rotational inerters based on observations from the parametric and numerical analyses.
[Retracted] Smart Grid Security Based on Blockchain with Industrial Fault Detection Using Wireless Sensor Network and Deep Learning Techniques
Authors: Kandasamy Manivel , Anto S. , Baranitharan K. , Rastogi Ravi , Satwik Gunda , Sampathkumar A.
Published: May 2023

Low‐cost monitoring and automation solutions for smart grids have been made viable by recent advancements in embedded systems and wireless sensor networks (W.S.N.s). A well‐designed smart network of subsystems and metasystems known as a “smart grid” is aimed at enhancing the conventional power grid’s efficiency and guaranteeing dependable energy delivery. A smart grid (S.G.) requires two‐way communication between utility providers and end users in order to accomplish its aims. This research proposes a novel technique in enhancing the smart grid security and industry fault detection using a wireless sensor network with deep learning architectures. The smart grid network security has been enhanced using a blockchain‐based smart grid node routing protocol with IoT module. The industrial analysis has been carried out based on monitoring for fault detection in a network using Q‐learning‐based transfer convolutional network. The experimental analysis has been carried out in terms of bit error rate, end‐end delay, throughput rate, spectral efficiency, accuracy, M.A.P., and RMSE. The proposed technique attained bit error rate of 65%, end‐end delay of 57%, throughput rate of 97%, spectral efficiency of 93%, accuracy of 95%, M.A.P. of 55%, and RMSE of 75%. This proposed paradigm is advantageous for the operation of smart grids for increased security and industrial fault detection across the network because security is the biggest barrier in smart grid implementation.
Two-Dimensional Hexagonal Structure of Boron Nitride Nanotubes and BNNT-Induced Phase Transition of Block Copolymer in BNNT/Block Copolymer Complex for Energy Harvesting
Authors: Jeon Sang-Woo , Yoo Heeil , Moon Se Youn , Kim Tae-Hwan
Published: May 2023

Since boron nitride nanotubes (BNNTs) were first manufactured, they have gained considerable attention for their wide-scale application as reinforcing composites, piezoelectric materials, electrical insulating materials, thermal conductors, and neutron shielding materials because of their excellent mechanical, electrical, thermal, and neutron absorption properties. Despite the remarkable properties and broad application scope of BNNTs, their use has been limited because of their ineffective structural control due to the presence of one-dimensional nanoparticles. To overcome this limitation, we investigated an approach for the collective self-assembly of BNNTs by using block copolymers (Pluronic P65 and Pluronic P85) as a template and studied the BNNT-induced phase behavior of the block copolymer. For homogenous mixtures of BNNTs and block copolymers, the BNNTs were encapsulated by the in situ polymerization of surfactants (p-BNNTs), where their overall structures were confirmed by small-angle neutron scattering (SANS) and atomic force microscopy (AFM) measurements. The p-BNNTs were mixed with the block copolymers (at 50%, Pluronic P65 or Pluronic P85) by centrifugation in alternative directions to form homogeneously mixed complexes. Polarized optical microscopy (POM) and small-angle X-ray scattering (SAXS) measurements confirmed a two-dimensional hexagonal structure of the BNNTs in the block copolymer matrix that self-assembled upon heating, which can give a possibility of being used as effective piezoelectric materials for energy harvesting. Moreover, upon the addition of BNNTs, the phase behavior of the block copolymer can be controlled, allowing the formation of hexagonal, face-centered cubic, and body-centered cubic structures depending on the BNNT concentration and temperature. This study provides a new and simple method to control the collective BNNT structure.
Exact Nonlinear Spectral Analysis of Nonsmooth WENO-JS Solutions
Authors: Kasem Tamer H. M. A.
Published: May 2023

The fifth-order accurate Weighted Essentially Nonoscillatory space discretization developed by Jiang and Shu (WENO-JS) is studied theoretically. An exact Nonlinear Spectral Method (NSM) is developed based on an innovative yet simple methodology. The NSM explains the behaviour of nonsmooth solutions because it is valid for arbitrary modified wave numbers (MWN). The NSM clarifies the effects of the time integration methods and the Courant number. The mode isolation assumption, extensively used to analyse WENO-JS, is elucidated, and several novel findings are presented. The improved performance of the combination of WENO-JS with the forward Euler time integration method, compared to the Linear Fifth-Order Upwind discretization, is illustrated. The overdamping of the combination of WENO-JS with the popular third-order total variation diminishing Runge-Kutta method is discovered. Thus, the NSM covers several gaps in the current literature.
Analysing WAHIS Animal Health Immediate Notifications to Understand Global Reporting Trends and Measure Early Warning Capacities (2005–2021)
Authors: Lin Shu-Yu , Beltran-Alcrudo Daniel , Awada Lina , Hamilton-West Christopher , Lavarello Schettini Andrea , Cáceres Paula , Tizzani Paolo , Allepuz Alberto , Casal Jordi
Published: May 2023

The World Animal Health Information System (WAHIS) from the World Organization for Animal Health (WOAH) is an online reporting system, essential for ensuring the transparency and accuracy of global animal health. One of the WOAH’s objectives is to disseminate timely notifications to support countries’ efforts to prevent and control the spread of animal diseases. This paper describes the 3,263 exceptional events notified through immediate notifications sent to WOAH from 2005 to February 2021 and their distribution in time and space and by disease. To evaluate the timeliness of reporting, we defined and analysed two periods: the confirmation period (CT), which is the time interval between the disease onset date and the confirmation date, and the notification period (NT), defined as the interval between the disease confirmation and the date of reporting to WOAH. The results showed that (1) the number of events increased over the analysis period; (2) the events were mainly reported for domestic animals and the data provided for wildlife were limited; (3) the official source of disease introduction was often unknown when the event was reported; and (4) the global median CT value was 5 days while the global median NT value was 4 days, with a decreasing trend in both cases over the study period. Divergences were found across world regions and country income categories. This analysis provides interesting insights into the early detection capabilities and transparency of countries, globally and over time.
Remarks on the Periodic Conformable Sturm–Liouville Problems
Authors: Wang Wei-Chuan
Published: May 2023

The conformable Sturm–Liouville problem (CSLP),

−

x

1
−
α

p

x

x

1
−
α

y

′

x

′

=

λ
ρ

x

−
q

x

y

x

, for

0
<
α
≤
1

, is studied under some certain conditions on the coefficients

p

,

ρ

, and

q

. According to an interesting idea proposed by P. Binding and H. Volkmer [Binding et al., 2012, Binding et al., 2013], we will derive how to reduce the periodic or antiperiodic (CSLP) to an analysis of the Prüfer angle. The eigenvalue interlacing property related to (CSLP) will be given.
Isolation and Pathogenicity Analysis of a Novel Orthoreovirus Caused the Outbreak of Duck Viral Arthritis in China
Authors: Li Bing , Jiang Xiaoning , Zhang Shuai , Wang Qianqian , Cui Yitong , Wu Qiong , Jia Wensha , Zhang Jie , Diao Youxiang , Tang Yi
Published: May 2023

Novel duck orthoreovirus can infect various hosts, mainly causing spleen necrosis and hemorrhagic necrotizing hepatitis, leading to immunosuppression and growth impairment. Infectious diseases characterized by swollen hock joints, movement disorders, and impaired growths have recently occurred in significant duck breeding areas in China. Infected ducks from Shandong Province were selected, and N-DRV-LY20 was isolated from the swollen joints. Next-generation sequencing (NGS) of N-DRV-LY20 and homology analysis showed that all ten fragments had the highest homology to N-DRV and the closest affinity to Duck/N-DRV-XT18/China/2018. After artificial inoculation with N-DRV-LY20 virus solution, Cherry Valley ducks showed the same symptoms of leg swelling and hock joint deformation, which were not explored in previous studies. A long history of evolution has led to significant variation in DRV and altered its pathogenicity. In this study, we confirmed the ability of N-DRV to cause viral arthritis in ducks and clarified this isolate’s genetic characteristics and level of variation, providing a basis for the control and variation detection of N-DRV.
DeepDefense: A Steganalysis-Based Backdoor Detecting and Mitigating Protocol in Deep Neural Networks for AI Security
Authors: Zhang Lei , Peng Ya , Wei Lifei , Chen Congcong , Zhang Xiaoyu
Published: May 2023

Backdoor attacks have been recognized as a major AI security threat in deep neural networks (DNNs) recently. The attackers inject backdoors into DNNs during the model training such as federated learning. The infected model behaves normally on the clean samples in AI applications while the backdoors are only activated by the predefined triggers and resulted in the specified results. Most of the existing defensing approaches assume that the trigger settings on different poisoned samples are visible and identical just like a white square in the corner of the image. Besides, the sample-specific triggers are always invisible and difficult to detect in DNNs, which also becomes a great challenge against the existing defensing protocols. In this paper, to address the above problems, we propose a backdoor detecting and mitigating protocol based on a wider separate-then-reunion network (WISERNet) equipped with a cryptographic deep steganalyzer for color images, which detects the backdoors hiding behind the poisoned samples even if the embedding algorithm is unknown and further feeds the poisoned samples into the infected model for backdoor unlearning and mitigation. The experimental results show that our work performs better in the backdoor defensing effect compared to state-of-the-art backdoor defensing methods such as fine-pruning and ABL against three typical backdoor attacks. Our protocol reduces the attack success rate close to 0% on the test data and slightly decreases the classification accuracy on the clean samples within 3%.
PTTG1 Reprograms Asparagine Metabolism to Promote Hepatocellular Carcinoma Progression
Authors: Zhou Qi , Li Leijia , Sha Feifei , Lei Yiming , Tian Xuan , Chen Lingjun , Chen Yan , Liu Huiling , Guo Yunwei
Published: May 2023

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a poor prognosis. Pituitary tumor transforming gene 1 (PTTG1) is highly expressed in HCC, suggesting it could play an important role in hepatocellular carcinogenesis. Here, we evaluated the impact of PTTG1 deficiency on HCC development using a diethylnitrosamine (DEN)-induced HCC mouse model and a hepatitis B virus (HBV) regulatory X protein (HBx)–induced spontaneous HCC mouse model. PTTG1 deficiency significantly suppressed DEN- and HBx-induced hepatocellular carcinogenesis. Mechanistically, PTTG1 promoted asparagine synthetase (ASNS) transcription by binding to its promoter, and asparagine (Asn) levels were correspondingly increased. The elevated levels of Asn subsequently activated the mTOR pathway to facilitate HCC progression. In addition, asparaginase treatment reversed the proliferation induced by PTTG1 overexpression. Furthermore, HBx promoted ASNS and Asn metabolism by upregulating PTTG1 expression. Overall, PTTG1 is involved in the reprogramming of Asn metabolism to promote HCC progression and may serve as a therapeutic and diagnostic target for HCC.

Significance:

PTTG1 is upregulated in hepatocellular carcinoma and increases asparagine production to stimulate mTOR activity and promote tumor progression.
Medical Financial Hardship and Food Security among Cancer Survivors in the United States
Authors: Hallgren Emily , Narcisse Marie-Rachelle , Andersen Jennifer A. , Willis Don E. , Thompson Tess , Bryant-Smith Gwendolyn , McElfish Pearl A.
Published: May 2023

Background:

Some cancer survivors experience medical financial hardship, which may reduce their food security. The purpose of this study was to explore whether medical financial hardship is related to food security among cancer survivors.

Methods:

The study was based on cross-sectional data from the 2020 National Health Interview Survey. We used ordinal logistic regression to examine the relationship between material, psychological, and behavioral medical financial hardships and household food security (i.e., high, marginal, low, or very low) among individuals ages ≥18 years who reported a cancer diagnosis from a health professional (N = 4,130).

Results:

The majority of the sample reported high household food security (88.5%), with 4.8% reporting marginal, 3.6% reporting low, and 3.1% reporting very low household food security. In the adjusted model, the odds of being in a lower food security category were higher for cancer survivors who had problems paying or were unable to pay their medical bills compared with those who did not [OR, 1.73; 95% confidence interval (CI), 1.06–2.82, P = 0.027], who were very worried about paying their medical bills compared with those who were not at all worried (OR, 2.88; 95% CI, 1.64–5.07; P < 0.001), and who delayed medical care due to cost compared with those who did not (OR, 2.56; 95% CI, 1.29–5.09; P = 0.007).

Conclusions:

Food insecurity is rare among cancer survivors. However, medical financial hardship is associated with an increased risk of lower household food security among cancer survivors.

Impact:

A minority of cancer survivors experience medical financial hardship and food insecurity; social needs screenings should be conducted.
Cancer InFocus: Tools for Cancer Center Catchment Area Geographic Data Collection and Visualization
Authors: Burus Justin Todd , Park Lee , McAfee Caree R. , Wilhite Natalie P. , Hull Pamela C.
Published: May 2023

Background:

The NCI added Community Outreach and Engagement (COE) requirements for NCI-designated cancer centers in 2017, including the charge of characterizing the cancer burden in the geographic area served by their center (i.e., catchment area). Doing so helps cancer centers better identify needs and areas of inequality in their populations to guide research and outreach. To accomplish this, current and comprehensive data must be gathered from multiple sources and analyzed by the COE—a task that is tedious and inefficient. In this paper we present an efficient solution, known as Cancer InFocus, to collecting and visualizing quantitative data that we have generalized for use by other cancer centers on their catchment areas.

Methods:

Cancer InFocus utilizes open source programming languages and modern data collection techniques to gather and transform publicly-available data from various sources for use in specific geographic contexts.

Results:

Cancer InFocus delivers a choice of two routes for creating interactive online mapping applications that visualize cancer incidence and mortality rates, along with relevant social determinant and risk factor variables, at various geographic levels for a defined cancer center catchment area.

Conclusions:

Generalized software has been produced to collect and visualize data on any set of U.S. counties, which can be automated to continue providing the most up-to-date data.

Impact:

Cancer InFocus provides tools for cancer centers to accomplish the critical task of maintaining current and comprehensive catchment area data. The open source format will facilitate future enhancements through user collaboration.
Data from Adjuvant Nivolumab Versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results From CheckMate 238
Authors: Larkin James , Del Vecchio Michele , Mandala Mario , Gogas Helen , Arance Ana M. , Dalle Stephane , Cowey Charles Lance. , Schenker Michael , Grob Jean-Jacques , Chiarion-Sileni Vanna , Marquez-Rodas Ivan , Butler Marcus O. , Di Giacomo Anna Maria , Middleton Mark R. , Lutzky Jose , de la Cruz-Merino Luis , Arenberger Petr , Atkinson Victoria , Hill Andrew G. , Fecher Leslie A. , Millward Michael , Nathan Paul D. , Khushalani Nikhil I. , Queirolo Paola , Ritchings Corey , Lobo Maurice , Askelson Margarita , Tang Hao , Dolfi Sonia , Ascierto Paolo A. , Weber Jeffrey
Published: May 2023

Abstract
Purpose: In the phase III CheckMate 238 study, adjuvant nivolumab (NIVO) significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab (IPI) in patients with resected stage IIIB–C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings. Patients and Methods: Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline PD-L1 expression and received NIVO 3 mg/kg every 2 weeks or IPI 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. Results: At a minimum follow-up of 62 months, RFS with NIVO remained superior to IPI (HR 0.72; 95% CI, 0.60–0.86; 5-year rates of 50% versus 39%). 5-year DMFS rates were 58% with NIVO versus 51% with IPI. Five-year OS rates were 76% with NIVO and 72% with IPI (75% data maturity: 228 of 302 planned events). Higher levels of TMB, tumor PD-L1, intratumoral CD8+ T cells and interferon-gamma–associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both NIVO and IPI, albeit with limited clinically meaningful predictive value. Conclusion: NIVO is a proven adjuvant treatment for resected melanoma at high-risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with IPI and high OS rates. Identification of additional biomarkers are needed to better predict treatment outcome.
Taming Glioblastoma in “Real Time”: Integrating Multimodal Advanced Neuroimaging/AI Tools Towards Creating a Robust and Therapy Agnostic Model for Response Assessment in Neuro-Oncology
Authors: de Godoy Laiz Laura , Chawla Sanjeev , Brem Steven , Mohan Suyash
Published: May 2023

The highly aggressive nature of glioblastoma carries a dismal prognosis despite aggressive multimodal therapy. Alternative treatment regimens, such as immunotherapies, are known to intensify the inflammatory response in the treatment field. Follow-up imaging in these scenarios often mimics disease progression on conventional MRI, making accurate evaluation extremely challenging. To this end, revised criteria for assessment of treatment response in high-grade gliomas were successfully proposed by the RANO Working Group to distinguish pseudoprogression from true progression, with intrinsic constraints related to the postcontrast T1-weighted MRI sequence. To address these existing limitations, our group proposes a more objective and quantifiable “treatment agnostic” model, integrating into the RANO criteria advanced multimodal neuroimaging techniques, such as diffusion tensor imaging (DTI), dynamic susceptibility contrast-perfusion weighted imaging (DSC-PWI), dynamic contrast enhanced (DCE)-MRI, MR spectroscopy, and amino acid-based positron emission tomography (PET) imaging tracers, along with artificial intelligence (AI) tools (radiomics, radiogenomics, and radiopathomics) and molecular information to address this complex issue of treatment-related changes versus tumor progression in “real-time”, particularly in the early posttreatment window. Our perspective delineates the potential of incorporating multimodal neuroimaging techniques to improve consistency and automation for the assessment of early treatment response in neuro-oncology.
Phase I Study of SYNB1891, an Engineered E. coli Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies
Authors: Luke Jason J. , Piha-Paul Sarina A. , Medina Theresa , Verschraegen Claire F. , Varterasian Mary , Brennan Aoife M. , Riese Richard J. , Sokolovska Anna , Strauss James , Hava David L. , Janku Filip
Published: May 2023

Purpose:

SYNB1891 is a live, modified strain of the probiotic Escherichia coli Nissle 1917 (EcN) engineered to produce cyclic dinucleotides under hypoxia, leading to STimulator of INterferon Genes (STING) activation in phagocytic antigen-presenting cells in tumors and activating complementary innate immune pathways.

Patients and Methods:

This first-in-human study (NCT04167137) enrolled participants with refractory advanced cancers to receive repeat intratumoral injections of SYNB1891 either alone or in combination with atezolizumab, with the primary objective of evaluating the safety and tolerability of both regimens.

Results:

Twenty-four participants received monotherapy across six cohorts, and 8 participants received combination therapy in two cohorts. Five cytokine release syndrome events occurred with monotherapy, including one that met the criteria for dose-limiting toxicity at the highest dose; no other SYNB1891-related serious adverse events occurred, and no SYNB1891-related infections were observed. SYNB1891 was not detected in the blood at 6 or 24 hours after the first intratumoral dose or in tumor tissue 7 days following the first dose. Treatment with SYNB1891 resulted in activation of the STING pathway and target engagement as assessed by upregulation of IFN-stimulated genes, chemokines/cytokines, and T-cell response genes in core biopsies obtained predose and 7 days following the third weekly dose. In addition, a dose-related increase in serum cytokines was observed, as well as stable disease in 4 participants refractory to prior PD-1/L1 antibodies.

Conclusions:

Repeat intratumoral injection of SYNB1891 as monotherapy and in combination with atezolizumab was safe and well tolerated, and evidence of STING pathway target engagement was observed.
Data from Dynamic intestinal stem cell plasticity and lineage remodeling by a nutritional environment relevant to human risk for tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: May 2023

Abstract
NWD1, a purified diet establishing mouse exposure to key nutrients recapitulating levels that increase human risk for intestinal cancer, reproducibly causes mouse sporadic intestinal and colonic tumors reflecting human etiology, incidence, frequency and lag with developmental age. Complex NWD1 stem cell and lineage reprogramming was deconvolved by bulk and scRNAseq, scATACseq, functional genomics and imaging. NWD1 extensively, rapidly, and reversibly, reprogrammed Lgr5hi stem cells, epigenetically down-regulating Ppargc1a expression, altering mitochondrial structure and function. This suppressed Lgr5hi stem cell functions and developmental maturation of Lgr5hi cell progeny as cells progressed through progenitor cell compartments, recapitulated by Ppargc1a genetic inactivation in Lgr5hi cells in vivo. Mobilized Bmi1+, Ascl2hi cells adapted lineages to the nutritional environment and elevated antigen processing and presentation pathways, especially in mature enterocytes, causing chronic, pro-tumorigenic low-level inflammation. There were multiple parallels between NWD1 remodeling of stem cells and lineages with pathogenic mechanisms in human inflammatory bowel disease, also pro-tumorigenic. Moreover, the shift to alternate stem cells reflects that the balance between Lgr5 positive and negative stem cells in supporting human colon tumors is determined by environmental influences. Stem cell and lineage plasticity in response to nutrients supports historic concepts of homeostasis as a continual adaptation to environment, with the human mucosa likely in constant flux in response to changing nutrient exposures.
Implications: Although oncogenic mutations provide a competitive advantage to intestinal epithelial cells in clonal expansion, the competition is on a playing field dynamically sculpted by the nutritional environment, influencing which cells dominate in mucosal maintenance and tumorigenesis.
Data from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas
Published: May 2023

Abstract
The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based “Mediators of apoptosis combinatorial score” (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN.
Significance:
Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making.
“Nenhum lugar é um deserto”: Dois museus de Álvaro Siza
Authors: Moreira Fernando Diniz , Medeiros Julia Silva de
Published: May 2023

Ancorado em uma abordagem fenomenológica da arquitetura, este artigo analisa dois museus projetados por Álvaro Siza, buscando explicitar como estratégias projetuais podem contribuir positivamente para a relação entre os museus contemporâneos e a cidade.  Siza foi escolhido pela sensível e criteriosa maneira que insere seus edifícios em situações urbanas complexas que articulam tecidos históricos, paisagens naturais e vestígios antigos de ocupação humana. A análise busca revelar como esses museus adquirem significado pela maneira como experienciamos seus espaços, através do arranjo de percursos, do manejo da luz, materiais e processos construtivos e da relação estabelecida com o sítio, a topografia e o território.
Um paradigma inalcançável: o masculino e as masculiniadades em Livro de uma sogra (1895)
Authors: Pereira Edson Salviano Nery , Lugarinho Mário César
Published: May 2023

Neste artigo investigamos as proposições para o masculino e o exercício das masculinidades em Livro de uma sogra, de Aluísio Azevedo (1895). Considerando o teor carnavalizante dessa obra, interessa-nos observar o modo como, ao dar voz a uma narradora, a sogra, a obra promove certos tensionamentos nos modelos de masculinidade, reafirmando, por fim, o caráter idealizado, móvel e inalcançável da masculinidade paradigmática.
Diffusion-Derived Vessel Density Computed From a Simplified Intravoxel Incoherent Motion Imaging Protocol in Pregnancies Complicated by Early Preeclampsia: A Novel Biomarker of Placental Dysfunction
Authors: He Junshen , Chen Chunlin , Xu Liqun , Xiao Benheng , Chen Zhao , Wen Ting , Wáng Yì Xiáng J. , Liu Ping
Published: May 2023

BACKGROUND:

Early preeclampsia is associated with significant placental hypoperfusion. We explore the diagnostic value of placental diffusion-derived vessel density (DDVD), a biomarker derived from diffusion-weighted magnetic resonance imaging, which measures in vivo vessel microperfusion, in the differential diagnosis of normal and early preeclampsia pregnancies.

METHODS:

This was a prospective study involving 29 controls and 17 singleton pregnancies affected by early preeclampsia. Nineteen pregnancies from 28 to 34 weeks of gestational age were included from the normal group for a comparison with the early preeclampsia group. Using a 3.0 T magnetic resonance imaging scanner, diffusion-weighted images were obtained with the diffusion weighting
b
values of 0, 20, and 40 s/mm
2
. DDVD
mean
was the mean of DDVD
b0b20
and DDVD
b0b40
, while DDVD
b0b20
and DDVD
b0b40
refer to the diffusion-derived vessel density values computed from
b
=0 and 20 s/mm
2
images, and from
b
=0 and 40 s/mm
2
images, respectively. The correlation between DDVD
mean
and gestational age was examined using a linear regression model. The area under the curve of the DDVD
mean
for early preeclampsia pregnancies detection was calculated by the receiver operating characteristic analysis.

RESULTS:

As gestational age increased, DDVD
mean
linearly decreased. DDVD
mean
was significantly decreased in the early preeclampsia pregnancies compared with the normal pregnancies (52.72±46.73 versus 213.34±93.50 au/pixel;
P
<0.001). The area under the curve (DDVD
mean
) for discriminating between normal and early preeclampsia pregnancies regardless of fetal growth restriction was 0.954, and the area under the curve was 1.000 when early preeclampsia pregnancies without fetal growth restriction were excluded.

CONCLUSIONS:

DDVD
mean
, an in vivo vessel microperfusion measure, allowed total separation of normal and early preeclampsia pregnancies.