bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
Authors: Elía Andrés , Saldain Leo , Vanzulli Silvia I. , Helguero Luisa A. , Lamb Caroline A. , Fabris Victoria , Pataccini Gabriela , Martínez-Vazquez Paula , Burruchaga Javier , Caillet-Bois Ines , Spengler Eunice , Acosta Haab Gabriela , Liguori Marcos , Castets Alejandra , Lovisi Silvia , Abascal María F. , Novaro Virginia , Sánchez Jana , Muñoz Javier , Belizán José M. , Abba Martín C. , Gass Hugo , Rojas Paola , Lanari Claudia 
Published: October 2022

AbstractPurpose:Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844).Patients and Methods:Twenty patients with luminal breast carcinomas with PRA/PRB &gt; 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment.Results:A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions:Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients.See related commentary by Ronchi and Brisken, p. 833
Preclinical Study of a Biparatopic METxMET Antibody–Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC
Authors: Oh Seung Yeon , Lee You Won , Lee Eun Ji , Kim Jae Hwan , Park YoungJoon , Heo Seong Gu , Yu Mi Ra , Hong Min Hee , DaSilva John , Daly Christopher , Cho Byoung Chul , Lim Sun Min , Yun Mi Ran 
Published: October 2022

Abstract

Purpose:
MET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non–small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody–drug conjugate targeting MET in MET-driven patient-derived models.

Experimental Design:
Patient-derived organoids, patient-derived cells, or ATCC cell lines were used to investigate the in vitro/in vivo activity of REGN5093-M114.

Results:
REGN5093-M114 exhibited significant antitumor efficacy compared with MET TKI or unconjugated METxMET biparatopic antibody (REGN5093). Regardless of MET gene copy number, MET-overexpressed TKI-naïve EGFR-mutant NSCLC cells responded to REGN5093-M114 treatment. Cell surface MET expression had the most predictive power in determining the efficacy of REGN5093-M114. REGN5093-M114 potently reduced tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation after progression on prior osimertinib and savolitinib treatment.

Conclusions:
Altogether, REGN5093-M114 is a promising candidate to overcome the challenges facing functional MET pathway blockade.
ONCOS-102: A Step Forward or Sideways?
Authors: Levi Shoshana T. , Boland Genevieve M. 
Published: October 2022

SummaryTreatment of anti–PD-1 refractory melanoma remains a challenge. Intratumoral injection of ONCOS-102, a chimeric oncolytic adenovirus expressing GMCSF, into anti–PD-1–resistant melanoma with administration of pembrolizumab was safe and effective. Response to therapy was associated with increased lymphocyte infiltration and expression of cytotoxicity and costimulatory genes.See related article by Shoushtari et al., p. 100
Distributed power flow controller based on fuzzy-logic controller for solar-wind energy hybrid system
Authors: Sree Vemuri Sowmya , Rao Coppisetty Srinivasa 
Published: October 2022

The demand of electricity globally led to the concept of renewable energy resources for power generation that are eco-friendly and freely available from nature. The solar photovoltaic systems and wind-based power generators are considered as primary renewable resources and are called as Distributed Generation units as they are scattered in nature. These are operated with bidirectional converters by providing auxiliary services at grid side and load side in either mode of microgrid operation. Besides, the DC power generation units’ integration gets converted into AC system by means of inverters. These types of systems not only increase voltage and current harmonics, power frequency deviations but also drive the distribution system to risky operating zone. This emphasizes the stipulation of advanced control schemes for microgrid architecture. Consequently, power electronic converters introduce harmonics in the system and affect the system performance. To report these expanded issues, the authors recognized an advanced custom power device entitled distributed power flow controller. The proposed hybrid solar-wind energy system is first studied with a distributed power-flow controller. Later the system is examined by replacing proportional integral controller with fuzzy logic controller (FLC) for shunt control of distributed power-flow controller. To validate the investigations, MATLAB/Simulink software is used.
An efficient MPPT based photovoltaic control model considering environmental parameters
Authors: Zeynal Hossein , Zakaria Zuhaina , Pourveis Bahareh 
Published: October 2022

<span>This paper presents an efficient way for maximum power point tracking (MPPT) in photovoltaic (PV) system. MPPT is one of the crucial issues when working with PV system as well as the grid. To gain the highest efficiency for PV system the maximum power has to be generated continuously. The proposed MPPT method allows PV system to have real-time maximum power all the time with high accuracy and less fluctuations. As of the developed PV system control model presented in this work, an efficient MPP can be realized taking into account changes in irradiation level and temperature which are the thorny issues for other contender algorithms. To validate the model, results obtained from the proposed algorithm is compared with incremental conductance (IC) which is a universally accepted MPPT method. The simulation results exhibited that the developed model outperforms IC method in terms of accuracy of MPP and stability of the output in presence of variable irradiations and temperature. Based on the simulation results, the proposed algorithm is suitable for practical and real-time applications with promising results in terms of solution accuracy and execution. The model is implemented in MATLAB/Simulink.</span>
The Music of Heart Rate Variability
Authors: Schuller Jan C. , Göhle Ulf Henrik 
Published: October 2022

AbstractThe variability of the heart rate reflects the regulatory status of the autonomous nervous system. For analytic purposes accessible to laypersons, the authors developed methods to transform heart rate variability into acoustical information, through either direct sound synthesis or the production of MIDI files (musical instrument digital interface) to trigger other devices. The authors describe the methods and some results and discuss applications for analytical and artistic purposes, such as music composition and biofeedback. The resulting “music” is complex and rhythmic and often has unexpected and interesting implied harmony.
Evolution of Convective Energy and Inhibition before Instances of Large CAPE
Authors: Tuckman Philip , Agard Vince , Emanuel Kerry 
Published: October 2022

Abstract
We analyze the evolution of convective available potential energy (CAPE) and convective inhibition (CIN) in the days leading up to episodes of high CAPE in North America. The widely accepted theory for CAPE buildup, known as the advection hypothesis, states that high moist static energy (MSE) parcels of air moving north from the Gulf of Mexico become trapped under warm but dry parcels moving east from over elevated dry terrain. If and when the resulting CIN erodes, severe convection can occur due to the large energy difference between the boundary layer parcels and cool air aloft. However, our results, obtained via backward Lagrangian tracking of parcels at locations of peak CAPE, show that large values of CAPE are generated mainly via boundary layer moistening in the days leading up to the time of peak CAPE, and that a large portion of this moisture buildup happens on the day of peak CAPE. On the other hand, the free-tropospheric temperature above these tracked parcels rarely changes significantly over the days leading up to such occurrences. In addition, the CIN that allows for this buildup of CAPE arises mostly from unusually strong boundary layer cooling the night before peak CAPE, and has a contribution from differential advection of unusually warm air above the boundary layer to form a capping inversion. These results have important implications for the climatology of severe convective events, as it emphasizes the role of surface properties and their gradients in the frequency and intensity of high CAPE occurrences.

Significance Statement
Severe convective events, such as thunderstorms, tornadoes, and hail storms, are among the most deadly and destructive weather systems. Although forecasters are quite good at predicting the probability of these events a few days in advance, there is currently no reliable seasonal prediction method of severe convection. We show that the buildup of energy for severe convection relies on both strong surface evaporation during the day of peak energy and anomalous cooling the night before. This progress represents a step toward understanding what controls the frequency of severe convective events on seasonal and longer time scales, including the effect of greenhouse gas–induced climate change.
Role of C-Reactive Protein, White Blood Cell Counts, and Serum Glucose Levels as Early Predictors of Infectious Complications After Laparoscopic Colorectal Surgery for Colorectal Cancer
Authors: Park Byung-Soo , Cho Sung Hwan , Lee Si Hak , Son Gyung Mo , Kim Hyun Sung 
Published: October 2022

Background The early detection of infectious complications of colorectal surgery leads to better patient outcomes. This study aimed to assess the role of C-reactive protein (CRP), white blood cell count (WBC), and serum glucose in the early prediction of infectious complications of laparoscopic colorectal surgery. Methods Patients who underwent laparoscopic colorectal surgery were included and stratified into two groups: infectious complication (IC) or no infectious complication (non-IC). Serum levels were measured on postoperative days (PODs) 2 and 4. Results Analysis of 224 patients (IC group: 27, Non-IC group: 197) revealed higher CRP levels in IC group on POD 2 ( P = .001). On POD 4, CRP levels and WBC counts were higher in IC group ( P<.001, P = .011, respectively). The area under the curve (AUC) of the receiver operating characteristic (ROC) for CRP on PODs 2 and 4 were .743 and .907, respectively, and for WBC on POD 4 was .687. The cut-offs of CRP on PODs 2 and 4 were 156.2 mg/L and 91.3 mg/L, respectively; the cut-off of WBC was 7,220 cells/mm3. Sensitivity of CRP level ≥91.3 mg/L or WBC count ≥7,220 cells/mm3 was 96.3%; (cf. 88.9% for CRP alone), and specificity of CRP level ≥91.3 mg/L and WBC count ≥7,220 cells/mm3 was 93.4% (cf. 82.2% for CRP alone). Discussion The CRP level on postoperative day (POD) 2 and the combined CRP and WBC on POD 4 were meaningful in predicting infectious complications after laparoscopic colorectal surgery. However, serum glucose levels had a low predictive value for infectious complications.
A task service and a talking service: A qualitative exploration of bereaved family perceptions of community nursing care at the end of life
Authors: Robinson Jackie , Goodwin Hetty , Williams Lisa , Anderson Natalie , Parr Jenny , Irwin Rebekah , Gott Merryn 
Published: October 2022

Background: Greater emphasis on community-based care at the end of life is supported by the premise that most people want to be cared for and die at home. As such, it is important to understand the current state of palliative care nursing within an integrated generalist-specialist model of care in the community. Aim: To explore bereaved family perceptions and experiences of community nursing at the end of life, with a particular focus on service integration. Design: A qualitative study design using semi-structured telephone interviews with bereaved family. A critical realist framework was used to inform the analysis of interview data and thematic analysis of data was used to identify key themes. Setting/participants: Participants were the family carers of patients who had died within the catchment area of two large District Health Boards in Auckland, New Zealand. Results: Twenty-three participants were interviewed. Participants described their experiences of community nursing in terms of the service they provided. Hospice nursing roles were described in terms of a “talking service” and District Nursing as a “task service.” There was minimal expectation of the general practice nurse in terms of palliative care support and little evidence of service integration. Conclusion: Findings from this study support the need for a new integrated model of palliative care nursing which utilizes the unique skill set of nurses working across all community care settings including general practice, hospice and district nursing services. Accommodating different models of nursing care which can be responsive to patient need rather than limited to a defined service delivery model.
Continuum robot state estimation using Gaussian process regression on SE(3)
Authors: Lilge Sven , Barfoot Timothy D. , Burgner-Kahrs Jessica 
Published: October 2022

Continuum robots have the potential to enable new applications in medicine, inspection, and countless other areas due to their unique shape, compliance, and size. Excellent progress has been made in the mechanical design and dynamic modeling of continuum robots, to the point that there are some canonical designs, although new concepts continue to be explored. In this paper, we turn to the problem of state estimation for continuum robots that can been modeled with the common Cosserat rod model. Sensing for continuum robots might comprise external camera observations, embedded tracking coils, or strain gauges. We repurpose a Gaussian process (GP) regression approach to state estimation, initially developed for continuous-time trajectory estimation in SE(3). In our case, the continuous variable is not time but arclength and we show how to estimate the continuous shape (and strain) of the robot (along with associated uncertainties) given discrete, noisy measurements of both pose and strain along the length. We demonstrate our approach quantitatively through simulations as well as through experiments. Our evaluations show that accurate and continuous estimates of a continuum robot’s shape can be achieved, resulting in average end-effector errors between the estimated and ground truth shape as low as 3.5 mm and 0.016° in simulation or 3.3 mm and 0.035° for unloaded configurations and 6.2 mm and 0.041° for loaded ones during experiments, when using discrete pose measurements.
Design and optimization of carbon fiber eight-wire lifter with exterior cladding structure
Authors: Zhang Yujiao , Zhou Jiyong , Huang Xiongfeng , Zhu Xinjun , Chen Zhiwei , Zhou Li 
Published: October 2022

The UHV eight-wire lifter is an important tool in frequent use for the construction and maintenance of UHV transmission lines, which is made of titanium alloy and weighs about 40 kg. Due to high-weight, the work efficiency is greatly reduced. In this paper, the design of a lightweight UHV eight-wire lifter is proposed by using carbon fiber cladding structure. The effects of three factors on the maximum load-bearing load of the carbon fiber exterior cladding structural member are excavated through the failed experiment of the carbon fiber exterior cladding tensile and shear test pieces and the finite element progressive damage numerical calculation. The orthogonal experiment is employed to obtain the optimal cladding structure of the eight-wire lifter with a carbon fiber exterior coating cladding. After that, carbon fiber eight-wire lifter is developed and subjected to mechanical tests. The test results show that the performance of carbon fiber eight-wire lifter meets the mechanical performance requirements of eight-wire lifter. Compared with the titanium alloy eight-wire lifter, the maximum load-bearing load of the carbon fiber eight-wire lifter is increased by 20.5%, and the weight is decreased by 37.5%.
Examining the Associations of and Interactions Between Intrapersonal and Perceived Environmental Factors With Objectively Assessed Physical Activity Among Rural Midwestern Adults, USA
Authors: Serrano Natalicio , Beck Alan , Salvo Deborah , Eyler Amy , Reis Rodrigo , Steensma Joseph T. , Gilbert Amanda , Brownson Ross C. 
Published: October 2022

Purpose We investigated associations of intrapersonal and environmental factors with objectively assessed weekly moderate to vigorous physical activity (MVPA) minutes, and their interactions in rural adults. Design Cross-sectional. Setting 14 rural towns participating in a multilevel intervention to promote physical activity. Sample Baseline data from 241 rural community members (19% losses due to missing data). Measures Self-reported demographics, behavioral factors, and neighborhood environment perceptions. Weekly MVPA minutes were assessed using accelerometry data. Analysis Generalized linear models using a negative binomial distribution examined associations of and interactions between intrapersonal and environmental correlates with weekly MVPA. Results Older age (β = −1.37; P= .025) and identifying as a woman (β = −.71; p= <.001) were inversely associated with MVPA. Self-efficacy (β = .34; p = <.001) and trail use (β = .44; P-value = .003) were directly associated with MVPA. Further, among women, perceived safety from traffic was inversely associated with MVPA (β = −.37; P = .003), while indoor recreational facility access was directly associated with MVPA (β = .24; P = .045). Conclusions Rural residents, especially women, face disproportionately lower MVPA levels. Improving recreational access and self-efficacy may be effective strategies for increasing MVPA.
Patterns of Lipid Lowering Therapy Use Among Older Adults in a Managed Care Advantage Plan in the United States
Authors: Vadhariya Aisha , Sharma Manvi , Abughosh Susan M. , Birtcher Kim K. , Chen Hua , Mohan Anjana , Johnson Michael L. 
Published: October 2022

Background: The prevalence of cardiovascular events is increasing. There are many new lipids lowering therapies available in recent years. Increased evidence through literature and guidelines suggests that the use of lipid lowering therapy (LLT) benefits patients who are at risk for cardiovascular events. Objective: The objective of this study was to describe the current LLT use as well as patterns of treatment modification among adults ≥ 65 years. Methods: A retrospective analysis of administrative claims data between January 2016 and May 2018 was conducted. Patients with a LLT refill and continuous enrollment during 1-year prior and 1-year follow-up were identified. The treatment episodes captured were interruption of therapy, intensity changes, dose changes, treatment augmentation, switching, and discontinuation. An analysis of treatment patterns among patients ≥75 years was also performed. Results: The study included 14,360 patients with a LLT of which 99% of patients were on statins as monotherapy or combination. Overall non-statin therapy use either as monotherapy or combination was 2.1%. There were significant differences among new initiators and existing users of therapy. Among prevalent users 57.4% had no changes in the follow-up period, 13.6% interrupted therapy, and 6.6% discontinued. Among new users, 47.9% patients had interrupted therapy, 25% had no changes, and 21.9% discontinued therapy. Conclusion: Most patients were on monotherapy and statins with low non-statin use. The new users among them were more likely to discontinue and interrupt therapy, highlighting the limitations and issues that older patients face that need to increase adherence.
Understanding nurses’ justification of restraint in a neurosurgical setting: A qualitative interview study
Authors: Guenna Holmgren Amina , von Vogelsang Ann-Christin , Lindblad Anna , Juth Niklas 
Published: October 2022

Background Despite its negative impact on patients and nurses, the use of restraint in somatic health care continues in many settings. Understanding the reasons and justifications for the use of restraint among nurses is crucial in order to manage this challenge. Aim To understand nurses’ justifications for restraint use in neurosurgical care. Research design A qualitative, descriptive design was used. Data were analysed with inductive qualitative content analysis. Participants and research context Semi-structured interviews with 15 nurses working in three neurosurgical departments in Sweden. Ethical considerations Approved by The Regional Ethics Committee, Stockholm, Sweden. Findings The analysis resulted in three categories. The category Patient factors influencing restraint use describes patient factors that trigger restraint, such as a diminished decision-making competence, restlessness, and need for invasive devices. The category Specific reasons for justifying restraint describes reasons for restraining patients, such as restraint being used for the sake of the patient or for the sake of others. The category General reasoning in justifying restraint describes how nurses reason when using restraint, and the decision to use restraint was often based on a consequentialist approach where the nurses’ weighed the pros and cons of different alternatives. Discussion Nurses with experience of restraint use were engaged in a constant process of justifying and balancing different options and actions. Restraint was considered legitimate if the benefit exceeded the suffering, but decisions on which restraint measures to use and when to use them depended on the values of the individual nurse. Conclusion How nurses reason when justifying restraint, why they use restraint, and who they use restraint on must be considered when creating programs and guidelines to reduce the use of restraint and to ensure that when it is used it is used carefully, appropriately, and with respect.