bluuebunny/crossref_metadata_2025 huggingface dataset:
Proactive community case management and child survival: protocol for a cluster randomised controlled trial
Authors: Whidden Caroline , Treleaven Emily , Liu Jenny , Padian Nancy , Poudiougou Belco , Bautista-Arredondo Sergio , Fay Michael P , Samaké Salif , Cissé Amadou B , Diakité Djoumé , Keita Youssouf , Johnson Ari D , Kayentao Kassoum
Published: April 2023

Introduction

Community health workers (CHWs)—shown to improve access to care and reduce maternal, newborn, and child morbidity and mortality—are re-emerging as a key strategy to achieve health-related Sustainable Development Goals (SDGs). However, recent evaluations of national programmes for CHW-led integrated community case management (iCCM) of common childhood illnesses have not found benefits on access to care and child mortality. Developing innovative ways to maximise the potential benefits of iCCM is critical to achieving the SDGs.

Methods and analysis

An unblinded, cluster randomised controlled trial in rural Mali aims to test the efficacy of the addition of door-to-door proactive case detection by CHWs compared with a conventional approach to iCCM service delivery in reducing under-five mortality. In the intervention arm, 69 village clusters will have CHWs who conduct daily proactive case-finding home visits and deliver doorstep counsel, care, referral and follow-up. In the control arm, 68 village clusters will have CHWs who provide the same services exclusively out of a fixed community health site. A baseline population census will be conducted of all people living in the study area. All women of reproductive age will be enrolled in the study and surveyed at baseline, 12, 24 and 36 months. The survey includes a life table tracking all live births and deaths occurring prior to enrolment through the 36 months of follow-up in order to measure the primary endpoint: under-five mortality, measured as deaths among children under 5 years of age per 1000 person-years at risk of mortality.

Ethics and dissemination

The trial has received ethical approval from the Ethics Committee of the Faculty of Medicine, Pharmacy and Dentistry, University of Bamako. The results will be disseminated through peer-reviewed publications, national and international conferences and workshops, and media outlets.

Trial registration number

NCT02694055; Pre-results.
Rituximab versus steroids and cyclophosphamide for the treatment of primary membranous nephropathy: protocol of a pilot randomised controlled trial
Authors: Scolari Francesco , Dallera Nadia , Gesualdo Loreto , Santoro Domenico , Pani Antonello , Santostefano Marisa , Feriozzi Sandro , Mani Laila-Yasmin , Boscutti Giuliano , Messa Piergiorgio , Magistroni Riccardo , Quaglia Marco , Ponticelli Claudio , Ravani Pietro
Published: April 2023

Introduction

Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%–50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend that initial therapy should consist of alternating steroids and an alkylating agent for 6 months. Recent observational studies showed that the anti-CD20 antibody rituximab may be effective in inducing remission. We designed a pilot multicentre randomised trial to inform the design of a larger trial testing the efficacy and safety of treatment with steroids and cyclophosphamide versus rituximab in patients with primary MN and heavy proteinuria (>3.5 g/24 hours).

Methods and analysis

This pilot, open-label, two-parallel-arm, randomised clinical trial will enrol 70 patients with primary MN and heavy proteinuria. Patients will be randomised in a 1:1 ratio to either the intervention arm (rituximab) or the active comparator arm (corticosteroid/alkylating-agent therapy). The study will provide estimates of the probability of complete remission of proteinuria and risk of serious side effects at 12 months to inform the design of a larger trial. We will also assess the recruitment potential of each participating centre to address study feasibility.

Ethics and dissemination

The trial received ethics approval from the local ethics boards. We will publish pilot data to inform the design of a larger clinical trial.

Trial registration numbers

NCT03018535; 2011-006115-59.
TurnerFertility trial: PROTOCOL for an observational cohort study to describe the efficacy of ovarian tissue cryopreservation for fertility preservation in females with Turner syndrome
Authors: Schleedoorn Myra , van der Velden Janielle , Braat Didi , Beerendonk Ina , van Golde Ron , Peek Ron , Fleischer Kathrin
Published: April 2023

Objective

To investigate the occurrence of live birth in women with Turner syndrome (TS) after ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood and to find reliable prognostic markers for estimating the ovarian reserve in girls with TS in the future.

Setting

An observational cohort study with long-term follow-up in a tertiary fertility clinic in the Netherlands. Patients recruitment between January 2018 and December 2021.

Participants

100 females aged 2 through 18 years with classical Turner (ie, 45,X0) or Turner variants (ie, 45,X mosaicism or structural anomalies). Girls with Y chromosomal content, minor X deletions with marginal impact on fertility, active HIV, hepatitis B or hepatitis C infection, and/or an absolute contra indication for surgery, anaesthesia or future pregnancy will be excluded.

Interventions

Ovarian cortical tissue will be harvested by performing a unilateral oophorectomy via laparoscopic approach. Ovarian cortex fragments will be prepared and cryopreserved. One fragment per patient will be used to determine follicular density by conventional histology, and to perform fluorescence in situ hybridisation analysis of ovarian cells. Routine chromosome analysis will be performed on both lymphocytes and buccal cells. A blood sample will be taken for hormonal analysis and all subjects will undergo a transabdominal ultrasound to determine the uterine and ovarian size. Patient characteristics, pregnancy rates and pregnancy outcomes will be collected from the patient’s medical record.

Ethics and dissemination

The study protocol has been approved by the Central Committee on Research Involving Human Subjects in November 2017 (CCMO NL57738.000.16).

Trial registration number

NCT03381300.
Testing a digital system that ranks the risk of unplanned intensive care unit admission in all ward patients: protocol for a prospective observational cohort study
Authors: Malycha James , Redfern Oliver C , Ludbrook Guy , Young Duncan , Watkinson Peter J
Published: April 2023

Introduction

Traditional early warning scores (EWSs) use vital sign derangements to detect clinical deterioration in patients treated on hospital wards. Combining vital signs with demographics and laboratory results improves EWS performance. We have developed the Hospital Alerting Via Electronic Noticeboard (HAVEN) system. HAVEN uses vital signs, as well as demographic, comorbidity and laboratory data from the electronic patient record, to quantify and rank the risk of unplanned admission to an intensive care unit (ICU) within 24 hours for all ward patients. The primary aim of this study is to find additional variables, potentially missed during development, which may improve HAVEN performance. These variables will be sought in the medical record of patients misclassified by the HAVEN risk score during testing.

Methods

This will be a prospective, observational, cohort study conducted at the John Radcliffe Hospital, part of the Oxford University Hospitals NHS Foundation Trust in the UK. Each day during the study periods, we will document all highly ranked patients (ie, those with the highest risk for unplanned ICU admission) identified by the HAVEN system. After 48 hours, we will review the progress of the identified patients. Patients who were subsequentlyadmittedto the ICU will be removed from the study (as they will have been correctly classified by HAVEN). Highly ranked patientsnot admittedto ICU will undergo a structured medical notes review. Additionally, at the end of the study periods, all patients who had an unplanned ICU admission but whom HAVENfailed to rank highlywill have a structured medical notes review. The review will identify candidate variables, likely associated with unplanned ICU admission, not included in the HAVEN risk score.

Ethics and dissemination

Approval has been granted for gathering the data used in this study from the South Central Oxford C Research Ethics Committee (16/SC/0264, 13 June 2016) and the Confidentiality Advisory Group (16/CAG/0066).

Discussion

Our study will use a clinical expert conducting a structured medical notes review to identify variables, associated with unplanned ICU admission, not included in the development of the HAVEN risk score. These variables will then be added to the risk score and evaluated for potential performance gain. To the best of our knowledge, this is the first study of this type. We anticipate that documenting the HAVEN development methods will assist other research groups developing similar technology.

Trial registration number

NCT12518261
Cohort profile: the Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort, a prospective preterm birth cohort in New York City
Authors: Stroustrup Annemarie , Bragg Jennifer B , Spear Emily A , Aguiar Andrea , Zimmerman Emily , Isler Joseph R , Busgang Stefanie A , Curtin Paul C , Gennings Chris , Andra Syam S , Arora Manish
Published: April 2023

Purpose

The Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) longitudinal preterm birth cohort studies the impact of the NICU exposome on early-life development. NICU-HEALTH collects multiple biospecimens, complex observational and survey data and comprehensive multisystem outcome assessments to allow measurement of the impact of modifiable environmental exposures during the preterm period on neurodevelopmental, pulmonary and growth outcomes.

Participants

Moderately preterm infants without genetic or congenital anomalies and their mothers are recruited from an urban academic medical centre level IV NICU in New York City, New York, USA. Recruitment began in 2011 and continues through multiple enrolment phases to the present with goal enrolment of 400 infants. Follow-up includes daily data collection throughout the NICU stay and six follow-up visits in the first 2 years. Study retention is 77% to date, with the oldest patients turning age 8 in 2019.

Findings to date

NICU-HEALTH has already contributed significantly to our understanding of phthalate exposure in the NICU. Phase I produced the first evidence of the clinical impact of phthalate exposure in the NICU population. Further study identified specific sources of exposure to clinically relevant phthalate mixtures in the NICU.

Future plans

Follow-up from age 3 to 12 is co-ordinated through integration with the Environmental Influences on Child Health Outcomes (ECHO) programme. The NICU-HEALTH cohort will generate a wealth of biomarker, clinical and outcome data from which future studies of the impact of early-life chemical and non-chemical environmental exposures can benefit. Findings from study of this cohort and other collaborating environmental health cohorts will likely translate into improvements in the hospital environment for infant development.

Trial registration numbers

This observational cohort is registered with ClinicalTrials.gov (NCT01420029andNCT01963065).
Oral switch versus standard intravenous antibiotic therapy in left-sided endocarditis due to susceptible staphylococci, streptococci or enterococci (RODEO): a protocol for two open-label randomised controlled trials
Authors: Lemaignen Adrien , Bernard Louis , Tattevin Pierre , Bru Jean-Pierre , Duval Xavier , Hoen Bruno , Brunet-Houdard Solène , Mainardi Jean-Luc , Caille Agnes
Published: April 2023

Introduction

Left-sided infective endocarditis (IE) is a serious infection with a heavy burden for patients and healthcare system. Oral switch after initial intravenous antibiotic therapy may reduce costs and improve patients’ discomfort without increasing unfavourable outcomes. We describe the methodology of two simultaneously conducted open-label randomised trials aiming to assess non-inferiority of oral switch as compared with entirely intravenous antibiotic therapy for the treatment of left-sided IE.

Methods and analysis

Two simultaneous multicentre open-label prospective randomised trials assessing non-inferiority of oral switch during antibiotic treatment as compared with entirely intravenous therapy in patients with left-sided IE are ongoing. One trial is dedicated to left-sided IE caused by multisusceptible staphylococci (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques (RODEO)-1) and the other is dedicated to left-sided IE caused by susceptible streptococci or enterococci (RODEO-2). It is planned to randomise 324 patients in each trial after an initial course of at least 10 days of intravenous antibiotic therapy either to continue intravenous antibiotic therapy or to switch to oral antibiotic therapy. The primary outcome is treatment failure within 3 months after the end of antibiotic treatment, a composite outcome defined by all-cause death and/or symptomatic embolic events and/or unplanned valvular surgery and/or microbiological relapse (with the primary pathogen). Secondary outcomes include patient quality of life, echocardiographic outcome, costs and efficiency associated with IE care. Statistical analysis will be performed with a non-inferiority margin of 10% and a one-sided 2.5% type I error.

Ethics and dissemination

Written informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS-Region Centre-Ouest 1, 2015-R26, 23 February 2016). Study findings will be published in peer-reviewed journals and disseminated through presentation at relevant national and international conferences.

Trial registration number

EudraCT Number: 2015-002371-16 andNCT02701608NCT02701595.
Assessment of the impact of a new sequential approach to antimicrobial use in young febrile children in the emergency department (DIAFEVERCHILD): a French prospective multicentric controlled, open, cluster-randomised, parallel-group study protocol
Authors: Hubert Gaelle , Launay Elise , Feildel Fournial Cécile , Chauvire-Drouard Anne , Lorton Fleur , Tavernier Elsa , Giraudeau Bruno , Gras Le Guen Christele
Published: April 2023

Introduction

Fever is one of the most common reasons for consultation in the paediatric emergency department (ED). Because of fear of bacterial infection in parents and caregivers, clinicians often overprescribe laboratory tests and empirical antibiotic treatment. The aims of this study are to demonstrate that using a procalcitonin (PCT) rapid test-based prediction rule (1) would not be inferior to usual practice in terms of morbidity and mortality (non-inferiority objective) and (2) would result in a significant reduction in antibiotic use (superiority objective).

Methods and analysis

This prospective multicentric cluster-randomised study aims to include 7245 febrile children aged 6 days to 3 years with a diagnosis of fever without source in 26 participating EDs in France and Switzerland during a 24-month period. During first period, all children will receive usual care. In a second period, a point-of-care PCT-based algorithm will be used in half of the clusters. The primary endpoints collected on day 15 after ED consultation will be a composite outcome of death or intensive care unit admission for any reason, disease-specific complications, diagnosis of bacterial infection after discharge from the ED for the non-inferiority objective and proportion of children with antibiotic treatment administered for the superiority objective. The endpoints will be compared between the two groups (experimental and control) by using a mixed logistic regression model adjusted on clustering of participants within centres and period within centres.

Discussion

If the algorithm is validated, a new strategy will be discussed with medical societies to safely manage fever in young children without the need for invasive procedures for microbiological testing or empirical antibiotics.

Ethics and dissemination

This study was submitted to an independent ethics committee on 17 May 2018 (no. 2018-A00252-53). Results will be submitted to international peer-reviewed journals and presented at international conferences.

Trial registration number

NCT03607162.
Economic evaluation protocol of a short, all-oral bedaquiline-containing regimen for the treatment of rifampicin-resistant tuberculosis from the STREAM trial
Authors: Rosu Laura , Madan Jason , Worrall Eve , Tomeny Ewan , Squire Bertel
Published: April 2023

Introduction

A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9–11-month MDR-TB treatment regimens.

Methods and analysis

Health system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using ‘bottom-up’ and ‘top-down’ costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost–utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial.

Ethics and dissemination

The study has been evaluated and approved by the Ethics Advisory Group of theInternational Union Against Tuberculosis and Lung Diseaseand also approved by ethics committees in all participating countries. All participants have provided written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal.

Trial registration number

NCT18148631.
Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases
Authors: Yang Annie , Zhang Zhifang , Chaurasiya Shyambabu , Park Anthony K , Jung Audrey , Lu Jianming , Kim Sang-In , Priceman Saul , Fong Yuman , Woo Yanghee
Published: April 2023

Background

Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) and triple-negative breast cancer (NCT05081492). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM).

Methods

We infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×105pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging.

Results

CF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×105pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01).

Conclusions

Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
Double Color Image Visual Encryption Based on Digital Chaos and Compressed Sensing
Authors: Sun Yuxuan , Cao Lvchen , Zhang Wanjun
Published: April 2023

Image encryption is an effective way to protect images in secure transmission or storage. In this paper, we propose a novel double color image visual encryption algorithm based on the improved Chebyshev map (ICM) and compressed sensing. Firstly, a new nonlinear term is introduced into the classical one-dimensional Chebyshev map, and then the ICM is used to generate the secret code stream for the encryption algorithm. Next, the key-controlled sensing measurement matrices are constructed through the ICM, and they are used to compress the integer wavelet coefficients of two plain images. Subsequently, the compressed images are dislocated by dislocation matrices and diffused by an ICM-generated diffusion matrix, respectively. Finally, the encrypted images are embedded into the carrier image using the least significant bit embedding algorithm. Experimental results demonstrate that the proposed method has good visual safety, large key space, and high key sensitivity.
Study of Effort Calculation and Estimation in Open Source Projects
Authors: Sone Hironobu , Tamura Yoshinobu , Yamada Shigeru
Published: April 2023

It is important to carefully monitor the development status of an open source projects because of the large number of people involved in the projects. One of the methods for evaluating project stability is earned value management (EVM), applying EVM to projects requires time-series effort data. However, there are few researches on the calculation of time-series effort data for open source projects, because open source projects do not manage effort as a whole. In this research, we have examined the validity of the calculation method and results of the time-series effort data in the open source projects. In addition, we have verified similarity of proprietary software development projects to open source projects in terms of effort. In particular, the similarity between open source projects and proprietary software development projects is verified by applying the effort data of open source projects to the software reliability growth model (SRGM).
Containers for Specification in SPARK
Authors: Dross Claire
Published: April 2023

The SPARK tool analyzes Ada programs statically. It can be used to verify both that a program is free from runtime exceptions and that it conforms to a specification expressed through contracts. To facilitate dynamic analysis, Ada contracts are regular expressions which can be evaluated at execution. As a result, the annotation language of the SPARK tool is restricted to executable constructs. In this context, high-level concepts necessary for specification by contracts need to be supplied as libraries. For example, the latest version of the Ada language introduces unbounded integers and rational numbers to the standard library. In this article, we present the functional containers library which provides collections suitable for use in specification. We explain how they can be used to specify and verify complex programs through concrete examples that have been developed over many years.
Correctness-by-Construction
Authors: Bordis Tabea , Runge Tobias , Kittelmann Alexander , Schaefer Ina
Published: April 2023

Correctness-by-Construction (CbC) is an incremental software development technique in the field of formal methods to create functionally correct programs guided by a specification. In contrast to post-hoc verification, where the specification and verification take part after implementing a program, with CbC the specification is defined first, and then the program is successively created using a small set of refinement rules that define side conditions preserving the correctness of the program. This specification-first, refinement-based approach as pursued by CbC has the advantage that errors are likely to be detected earlier in the design process and can be tracked more easily. Even though the idea of CbC emerged over 40 years ago, CbC is not widespread and is mostly used to create small algorithms.We believe in the idea of CbC and envision a scaled CbC approach that contributes to solving problems of modern software verification. In this short paper, we give an overview of our research regarding CbC in four different lines of research. For all of them, we provide tool support for building the CorC ecosystem that even further enables CbC-based development for different fields of application and size of software systems. Furthermore, we give an outlook on future work that extends on our concepts for CbC.
Achieving 100% availability
Authors: Ausden Howard
Published: April 2023

Fault tolerance is a key requirement for En Route Automation Modernization (ERAM), the FAA's system that manages En Route air traffic over the USA. A system failure could lead to hundreds of flights being delayed or cancelled. Using experience from earlier systems a set of techniques were built into ERAM at inception, including a hot standby copy of each executable and the latest state checkpointed in disk files. As the system matured through formal testing and operational experience at the first sites (2010 - 2015), the goal of 100% availability was not achieved so additional techniques were added. These included exception safety, runaway process protection, and proactive monitoring of the system to detect defects and often resolve them without the air traffic controllers being aware. With the implementation of these additional techniques the FAA has measured ERAM as 100% available from October 2016 at all 20 operational sites. Software fault tolerance techniques have been well documented [2]; this extended abstract describes the specific techniques that have led to ERAM achieving continuous 24x7 availability for 6 years.
MORPHEMIC - Optimization of the Deployment and Life-cycle Management of Data-intensive Applications in the Cloud Computing Continuum
Authors: Bagnato Alessandra , Krasnodebska Józefina
Published: April 2023

In their Cloud strategy companies are choosing more and more multi-cloud computing giving them the opportunity to distribute its assets, redundancies, software, applications, and anything it deems worthy not only on one Cloud-hosting environment, but rather across several. The model of using multiple Cloud services to host the business's functions and features has a list of advantages that can provide security, flexibility, cost-effectiveness and more to increase business's efficiency and ensure it stays up and running 24 hours a day. The paper presents the MORPHEMIC H2020 project and its unique way of adapting and optimising Cloud computing applications. The Morphemic project covers several features from modelling cross-cloud applications, continuous and autonomous optimization and deployment and providing access to several cloud capabilities for data intensive applications. The outcome of the project will be implemented in the form of an open-source platform covering all the data intensive applications deployment phases starting from modelling, through profiling, optimization, runtime reconfiguration and monitoring.
Targeting Aminoacyl tRNA Synthetases for Antimalarial Drug Development
Authors: Xie Stanley C. , Griffin Michael D.W. , Winzeler Elizabeth A. , Ribas de Pouplana Lluis , Tilley Leann
Published: April 2023

Infections caused by malaria parasites place an enormous burden on the world's poorest communities. Breakthrough drugs with novel mechanisms of action are urgently needed. As an organism that undergoes rapid growth and division, the malaria parasite Plasmodium falciparum is highly reliant on protein synthesis, which in turn requires aminoacyl-tRNA synthetases (aaRSs) to charge tRNAs with their corresponding amino acid. Protein translation is required at all stages of the parasite life cycle; thus, aaRS inhibitors have the potential for whole-of-life-cycle antimalarial activity. This review focuses on efforts to identify potent plasmodium-specific aaRS inhibitors using phenotypic screening, target validation, and structure-guided drug design. Recent work reveals that aaRSs are susceptible targets for a class of AMP-mimicking nucleoside sulfamates that target the enzymes via a novel reaction hijacking mechanism. This finding opens up the possibility of generating bespoke inhibitors of different aaRSs, providing new drug leads.
The Shear Force Law: A Guide to Modeling CMP Removal Rates
Authors: Borucki L. , Sampurno Y. , Philipossian A.
Published: April 2023

A new theory is presented that generalizes the classical version of Preston’s Law in chemical-mechanical planarization (CMP). The approach is motivated by removal rate data that cannot be explained by the classical version. The theory begins by observing that when removal rates are plotted against the measured wafer frictional shear force, the data often lie on or near half-lines that emanate from a common intercept on the removal rate axis. The half-lines have slopes that are indexed by polishing speed. While the common intercept might be interpreted as a static etch rate, evidence suggests that it may be due mainly to compliant pad fragments generated by conditioning. An extension of the new model outside of the experimental design using a Stribeck curve is found to explain the puzzling non-Prestonian removal rate trends. It also suggests an explanation for some frequently observed removal rate pressure thresholds. Finally, the new theory predicts that it is possible to scale the pressure and speed in CMP to obtain a desired scaling of the removal rate without changing the friction coefficient. The approach has been successfully applied to several recent metal and dielectric polishing processes that use a variety of consumables.
Discovering New Prognostic Features for the Harmonic Reducer in Remaining Useful Life Prediction
Authors: Wu Jin , Jiang Lulu , Li Jinfu , Zhu Yaqiao , Wang Jia
Published: April 2023

Vibration and current signals are widely used in fault diagnosis and life prediction of electromechanical transmission systems. However, due to the complex working environment of harmonic reducer in the industrial robot, using a single signal for failure analysis or life prediction may risk to false alarming due to lacking of fault information. In the early operation stage of equipment, fault information contained in the signal is too weak to be extracted. In addition, there is certain correlation among the features, which can lead to meaningless superposition of the calculation process. Therefore, a new health index construction method is proposed integrating the current signal and vibration signal and reducing the redundancy among the features in multidomains and can effectively enhance the fault information. In addition, in view of the local optimum and slow speed caused by the random initialization of the network model, an improved life prediction method is proposed to optimize BP neural network to improve the prediction performance. The proposed method is verified by the test data of the harmonic reducer. Results show that the proposed method can predict the remaining useful life of the harmonic reducer more accurately and effectively.
Deep Reinforcement Learning‐Based UAV Path Planning for Energy‐Efficient Multitier Cooperative Computing in Wireless Sensor Networks
Authors: Guo Zhihui , Chen Hongbin , Li Shichao
Published: April 2023

Benefiting from the progress of microelectromechanical system (MEMS) technology, wireless sensor networks (WSNs) can run a large number of complex applications. One of the most critical challenges for complex WSN applications is the huge computing demands and limited battery energy without any replenishment. The recent development of UAV‐assisted cooperative computing technology provides a promising solution to overcome these shortcomings. This paper addresses a three‐tier WSN model for UAV‐assisted cooperative computing, which includes several sensor nodes, a moving UAV equipped with computing resources, and a sink node (SN). Computation tasks arrive randomly at each sensor node, and the UAV moves around above the sensor nodes and provides computing services. The sensor nodes can process the computation tasks locally or cooperate with the UAV or SN for computing. In a life cycle of the UAV, we aim to maximize the energy efficiency of cooperative computing by optimizing the UAV path planning on the constraints of node energy consumption and task deadline. To adapt to the time‐varying indeterminate environment, a deep Q network‐ (DQN‐) based path planning algorithm is proposed. Simulation studies show that the performance of the proposed algorithm is better than the competitive algorithms, significantly improves the energy efficiency of cooperative computing, and achieves energy consumption balance.
Influence of Oral Supplementation of Vitamins A and E on the Effectiveness of Vitiligo Treatment
Authors: Nowowiejska Laura , Marek-Józefowicz Luiza , Szewczyk-Golec Karolina , Woźniak Alina , Basałygo Magdalena , Zegarska Barbara , Jankowski Marek , Niezgoda Anna , Tadrowski Tadeusz , Czajkowski Rafał
Published: April 2023

Oxidative stress plays an important role in the development of vitiligo. The aim of our study was to assess the effect of oral vitamin supplementation with antioxidant activity on the effectiveness of the vitiligo treatment. The study group consisted of 46 patients suffering from nonsegmental vitiligo for over a year. Before and after the therapy, the clinical advancement of the disease (VASI) and impairment of quality of life (DLQI) were assessed in all patients, and the activities of selected antioxidant enzymes (SOD, CAT, and GPx), lipid peroxidation products (MDA), and vitamins A and E were determined. Each patient was randomly assigned to one of three therapeutic groups: FOTO (UVB therapy at 311 nm, 3x a week for 4 months), WIT (oral antioxidant supplementation‐vitamin A + E at a dose of 5000 IU of retinol and 400 mg of tocopherol), and FOTO + WIT (combination therapy). After the treatment, an increase in all antioxidant enzymes and a decrease in the concentration of malondialdehyde in patients were noted, regardless of the therapeutic method used. The greatest improvement in the repigmentation of skin lesions was achieved in patients treated with combined therapy (VASI −6.95 ± 4.69, p < 0.01, DLQI −1.90 ± 2.77, p = 0.011). The burden of patients with risk factors for oxidative stress turned out to be associated with a greater severity of the disease process, and a longer period of disease was positively correlated with a reduction in the quality of life in patients.
Healing of Large Endodontic Lesions Using Long-Term Application of a New Combination of Triple Antibiotics: A Series of Cases
Authors: Asgary Saeed , Parhizkar Ardavan
Published: April 2023

Apical periodontitis (AP) is defined as an inflammatory and destructive reaction of periapical tissues and a consequence of bacterial invasion to the dental pulp and root canal system. To avoid possible complications and undesirable repercussions of the surgical treatment of large AP, more conservative non-surgical approaches are endorsed. In the presented hopeless cases, a newly introduced modified combination of triple antibiotics, that is Penicillin G, metronidazole, and ciprofloxacin (PMC), was used as a long-term intracanal medication in the non-surgical endodontic retreatments of large AP. In the course of 10-month to 3-year follow-up, the large periapical lesions completely disappeared, and thorough bone healing was evident. Additionally, complete functionality of the involved teeth as well as other favourable treatment outcomes of the addressed cases showed that the long-term use of PMC, as a modified combination of antibiotics, in non-surgical endodontic retreatments may successfully resolve large AP. However, further investigations and well-designed controlled clinical trials are recommended.
Data from Diet Quality and All-Cause Mortality in Women with Breast Cancer from the Breast Cancer Family Registry
Authors: Haslam Danielle E. , John Esther M. , Knight Julia A. , Li Zhongyu , Buys Saundra S. , Andrulis Irene L. , Daly Mary B. , Genkinger Jeanine M. , Terry Mary Beth , Zhang Fang Fang
Published: April 2023

AbstractBackground:
The impact of diet on breast cancer survival remains inconclusive. We assessed associations of all-cause mortality with adherence to the four diet quality indices: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH).
Methods:
Dietary intake data were evaluated for 6,157 North American women enrolled in the Breast Cancer Family Registry who had been diagnosed with invasive breast cancer from 1993 to 2011 and were followed through 2018. Pre-diagnosis (n = 4,557) or post-diagnosis (n = 1,600) dietary intake was estimated through a food frequency questionnaire. During a median follow-up time of 11.3 years, 1,265 deaths occurred. Cox proportional hazards models were used to estimate multivariable-adjusted HR and 95% confidence intervals (CI).
Results:
Women in the highest versus lowest quartile of adherence to the HEI-2015, AHEI, aMED, and DASH indices had a lower risk of all-cause mortality. HR (95% CI) were 0.88 (0.74–1.04; Ptrend = 0.12) for HEI-2015; 0.82 (0.69–0.97; Ptrend = 0.02) for AHEI; 0.73 (0.59–0.92; Ptrend = 0.02) for aMED; and 0.78 (0.65–0.94; Ptrend = 0.006) for DASH. In subgroup analyses, the associations with higher adherence to the four indices were similar for pre- or post-diagnosis dietary intake and were confined to women with a body mass index <25 kg/m2 and women with hormone receptor positive tumors.
Conclusions:
Higher adherence to the HEI-2015, AHEI, aMED, and DASH indices was associated with lower mortality among women with breast cancer.
Impact:
Adherence to a healthy diet may improve survival of women with breast cancer.
Supplementary Figure S3 from Analysis of DNA Repair–Related Genes in Breast Cancer Reveals CUL4A Ubiquitin Ligase as a Novel Biomarker of Trabectedin Response
Authors: García María J. , Saucedo-Cuevas Laura Paula , Muñoz-Repeto Iván , Fernández Victoria , Robles María J. , Domingo Samuel , Palacios José , Aracil Miguel , Nieto Antonio , Tercero Juan Carlos , Benítez Javier
Published: April 2023

PDF file - 2 MB, CUL4A mRNA and protein expression in cell lines
Supplementary Fig. S4 from Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells
Authors: Tani Tetsuo , Yasuda Hiroyuki , Hamamoto Junko , Kuroda Aoi , Arai Daisuke , Ishioka Kota , Ohgino Keiko , Miyawaki Masayoshi , Kawada Ichiro , Naoki Katsuhiko , Hayashi Yuichiro , Betsuyaku Tomoko , Soejima Kenzo
Published: April 2023

Inhibition of downstream signals by combination treatment
Supplementary Fig. S1 from Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells
Authors: Tani Tetsuo , Yasuda Hiroyuki , Hamamoto Junko , Kuroda Aoi , Arai Daisuke , Ishioka Kota , Ohgino Keiko , Miyawaki Masayoshi , Kawada Ichiro , Naoki Katsuhiko , Hayashi Yuichiro , Betsuyaku Tomoko , Soejima Kenzo
Published: April 2023

Irreversible resistance of H3122-AR cells to alectinib
Supplementary Table 2 from Identification of Preferred Chemotherapeutics for Combining with a CHK1 Inhibitor
Authors: Xiao Yang , Ramiscal Judi , Kowanetz Kaska , Del Nagro Christopher , Malek Shiva , Evangelista Marie , Blackwood Elizabeth , Jackson Peter K. , O'Brien Thomas
Published: April 2023

PDF - 42KB, Bliss scores associated with combining each indicated agent with either GNE-783 or AZD-7762 in HT29 cells.
Supplementary Methods from HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation
Authors: Efimova Elena V. , Ricco Natalia , Labay Edwardine , Mauceri Helena J. , Flor Amy C. , Ramamurthy Aishwarya , Sutton Harold G. , Weichselbaum Ralph R. , Kron Stephen J.
Published: April 2023

Supplementary Methods
Supplementary Table 1 from Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages
Authors: Iwanowycz Stephen , Wang Junfeng , Hodge Johnie , Wang Yuzhen , Yu Fang , Fan Daping
Published: April 2023

Primers used for qPCR
Supplementary Figure S2 from Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer
Authors: Grüner Barbara M. , Winkelmann Isabel , Feuchtinger Annette , Sun Na , Balluff Benjamin , Teichmann Nicole , Herner Alexander , Kalideris Evdokia , Steiger Katja , Braren Rickmer , Aichler Michaela , Esposito Irene , Schmid Roland M. , Walch Axel , Siveke Jens T.
Published: April 2023

Supplementary Figure S2. This supplementary figure depicts the non-correlation of average erlotinib peak intensities with survival or tumor grading or overall morphological feature
Supplemental Figure 4: UAB30 decreased migration. from Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies
Authors: Waters Alicia M. , Stewart Jerry E. , Atigadda Venkatram R. , Mroczek-Musulman Elizabeth , Muccio Donald D. , Grubbs Clinton J. , Beierle Elizabeth A.
Published: April 2023

G401 and HuH6 cells were plated and once they reached near confluence, a 20µL pipette was utilized to create a standard scratch on the plates. A The area of the scratch was quantified by measuring the pixel count of the scratched area and comparing it to time zero. Data were reported as percentage of scratch area closed after 24 hrs. Both cell lines showed a significant decrease in the ability to migrate following UAB30. B Representative photographs of the G401 (upper panel) and the HuH6 (lower panel) migration inserts. UAB30 treatment decreased the number of cells migrating through the membrane. There was a For the HuH6 cell lines, dashed lines represent distance of original scratch, solid lines the distance remaining after 24 hrs.
Figure S4 from A Short SOX9 Peptide Mimics SOX9 Tumor Suppressor Activity and Is Sufficient to Inhibit Colon Cancer Cell Growth
Authors: Blache Philippe , Canterel-Thouennon Lucile , Busson Muriel , Verdié Pascal , Subra Gilles , Ychou Marc , Prévostel Corinne
Published: April 2023

Crystal violet assay (n = 6) at day 11 post-seeding demonstrates that the removal of one or both NLS sequences in S9pep decreases S9pep inhibitory effect on DLD-1 cell growth.
Figure S9 from Characterization of 7A5: A Human CD137 (4-1BB) Receptor Binding Monoclonal Antibody with Differential Agonist Properties That Promotes Antitumor Immunity
Authors: Kotanides Helen , Sattler Rose Marie , Lebron Maria B. , Carpenito Carmine , Shen Juqun , Li Jingxing , Surguladze David , Haidar Jaafar N. , Burns Colleen , Shen Leyi , Inigo Ivan , Pennello Anthony L. , Forest Amelie , Chen Xinlei , Chin Darin , Sonyi Andreas , Topper Michael , Boucher Lauren , Sharma Prachi , Zhang Yiwei , Burtrum Douglas , Novosiadly Ruslan D. , Ludwig Dale L. , Plowman Gregory D. , Kalos Michael
Published: April 2023

Figure S9 shows antitumor efficacy of combination therapy in the L55 NSCLC tumor xenograft model
Figure S6 from Site-Specific PEGylation of Anti-Mesothelin Recombinant Immunotoxins Increases Half-life and Antitumor Activity
Authors: Zheng Zeliang , Okada Ryuhei , Kobayashi Hisataka , Nagaya Tadanobu , Wei Junxia , Zhou Qi , Lee Fred , Bera Tapan K. , Gao Yun , Kuhlman William , Tai Chin-Hsien , Pastan Ira
Published: April 2023

Mouse weight after treatment with PEGylated RITs
Supplementary Data from Effect of Modulating FcRn Binding on Direct and Pretargeted Tumor Uptake of Full-length Antibodies
Authors: Nazarova Lidia , Rafidi Hanine , Mandikian Danielle , Ferl Gregory Z. , Koerber James T. , Davies Christopher W. , Ulufatu Sheila , Ho Jason , Lau Jeffrey , Yu Shang-Fan , Ernst James , Sadowsky Jack D. , Boswell C. Andrew
Published: April 2023

Supplementary methods (S1-S4), Supplementary tables (1-4) and Supplementary Figures (1-5)
Data from Bepotastine Sensitizes Ovarian Cancer to PARP Inhibitors through Suppressing NF-κB–Triggered SASP in Cancer-Associated Fibroblasts
Authors: Jin Ping , Li Xin , Xia Yu , Li Huayi , Li Xiaoting , Yang Zong-Yuan , Wang Zhen , Xu Cheng , Fang Tian , Zhou Dongchen , Xiong Xiaoming , Wang Si-Yuan , Xu Sen , Gao Qinglei
Published: April 2023

Abstract
Therapy-induced senescence (TIS) is common in tumor cells treated with PARP inhibitors (PARPis) and can serve as a promising target for improving PARPi efficacy. However, whether stromal components within the tumor microenvironment undergo TIS caused by PARPis and contribute to consequential treatment failure remain unclear. We previously revealed that PARPis triggered a senescence-like secretory phenotype in stromal fibroblasts. Here, we further explored PARPi-induced senescence in the stroma, its contribution to PARPi resistance, and opportunities to leverage stromal TIS for improved PARPi sensitivity. In this study, we demonstrated that tumor tissues from patients treated with neoadjuvant PARPis showed a significant senescence-like phenotype in the stroma. Moreover, PARPi-induced senescent cancer-associated fibroblasts (CAFs) displayed a senescence-associated secretory phenotype (SASP) profile that was sufficient to induce tumor resistance to PARPis in both homologous recombination–deficient (HRD) and –proficient ovarian cancer cells. Using the GLAD4U database, we found that bepotastine, an approved H1-antihistamine, inhibited the SASP of PARPi-primed CAFs at clinical serum concentrations. We further demonstrated that bepotastine attenuated fibroblast-facilitated tumor resistance to PARPis in three-dimensional organotypic cultures and HRD-positive patient-derived xenograft models. Mechanistically, bepotastine suppressed PARPi-triggered SASP by inhibiting NF-κB signaling independent of the histamine H1 receptor. Taken together, our results highlight the importance of stromal TIS and SASP in PARPi resistance, and targeting SASP with bepotastine may be a promising therapeutic option for improving PARPi sensitivity in ovarian cancer.