bluuebunny/crossref_metadata_2025_split huggingface dataset:
NeuroXNet: Creating A Novel Deep Learning Architecture that Diagnoses Neurological Disorders, Finds New Blood Biomarkers, and Assesses Surgical, Drugs, and Radiation Treatment Plans Using Medical Imaging and Genomic Data
Authors: Mishra Vaibhav 
Published: December 2021

AbstractNeurodegenerative diseases and cancerous brain tumors cause millions of patients worldwide to be fatally ill and face cognitive impairment each year. Current diagnosis and treatment of these neurological conditions take many days, are sometimes inaccurate, and use invasive approaches that could endanger the patient’s life. Thus, this study’s purpose is the creation of a novel deep learning model called NeuroXNet, which uses MRI images and genomic data to diagnose both neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Mild Cognitive Impairment as well as cancerous brain tumors, including glioma, meningioma, and pituitary tumors. Moreover, the model helps find novel blood biomarkers of differentially expressed genes to aid in diagnosing the six neurological conditions. Furthermore, the model uses patient genomic data to give additional recommendations for treatment plans that include various treatment approaches, including surgical, radiation, and drugs for higher patient survival for each class of the disease. The NeuroXNet model achieves a training accuracy of 99.70%, a validation accuracy of 100%, and a test accuracy of 94.71% in multi-class classification of the six diseases and normal patients. Thus, NeuroXNet reduces the chances of misdiagnosis, helps give the best treatment options, and does so in a time/cost-efficient manner. Moreover, NeuroXNet efficiently diagnoses diseases and recommends treatment plans based on patient data using relatively few parameters causing it to be more cost and time-efficient in providing non-invasive approaches to diagnosis and treatment for neurological disorders than current procedures.
RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts
Authors: Ciscar Marina , Trinidad Eva M. , Perez-Montoyo Hector , Alsaleem Mansour , Jimenez-Santos Maria J. , Toss Michael , Sanz-Moreno Adrian , Vethencourt Andrea , Perez-Chacon Gema , Petit Anna , Soler-Monso Maria T. , Gomez-Miragaya Jorge , Gomez-Aleza Clara , Jimenez Maria , Dobrolecki Lacey E. , Lewis Michael T. , Bruna Alejandra , Mouron Silvana , Quintela-Fandino Miguel , Al-Shahrour Fatima , Martinez-Aranda Antonio , Sierra Angels , Green Andrew R. , Rakha Emad , Gonzalez-Suarez Eva 
Published: December 2021

AbstractDespite strong preclinical data, the therapeutic benefit of the RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated the prognostic value of RANK expression and its functionality in human BC. We analyzed RANK and RANKL expression in more than 1500 BC cases (777 being estrogen receptor-negative (ER-)) from four independent cohorts. We confirmed that RANK is more frequently expressed in ER- tumors, but it is also found in a subset of ER+ tumors. In ER- BC, RANK expression was independently associated with poor outcome, especially in postmenopausal patients and those who received adjuvant chemotherapy. Gene expression analyses unraveled distinct biology associated with RANK in relation to ER expression and menopause, and evidenced enhanced RANK activation in ER- postmenopausal tumors, together with regulation of metabolic pathways. Functional studies and transcriptomic analyses in ER- RANK+ patients-derived orthoxenografts demonstrated that activation of RANK signaling pathway promotes tumor cell proliferation and stemness, and regulates multiple biological processes including tumor immune surveillance and metabolism. Our results demonstrate that RANK expression is an independent poor prognosis biomarker in postmenopausal ER- BC patients and support the rational of using RANK pathway inhibitors in combination with chemotherapy in ER- BC.
ADAP’s intrinsically disordered region is an actin sponge regulating T cell motility
Authors: Dadwal Nirdosh , Degen Janine , Sticht Jana , Hilal Tarek , Wegner Tatjana , Reichardt Peter , Lyck Ruth , Abadier Michael , Hons Miroslav , Mix Charlie , Kuropka Benno , Stephanowitz Heike , Liu Fan , Schraven Burkhart , Wülfing Christoph , Kliche Stefanie , Freund Christian 
Published: December 2021

AbstractIntrinsically disordered proteins (IDPs) play a vital role in biological processes that rely on transient molecular compartmentation1. In T cells, the dynamic switching between migration and adhesion mandates a high degree of plasticity in the interplay of adhesion and signaling molecules with the actin cytoskeleton2,3. Here, we show that the N-terminal intrinsically disordered region (IDR) of adhesion- and degranulation-promoting adapter protein (ADAP) acts as a multipronged scaffold for G- and F-actin, thereby promoting actin polymerization and bundling. Positively charged motifs, along a sequence of at least 200 amino acids, interact with both longitudinal sides of G-actin in a promiscuous manner. These polymorphic interactions with ADAP become constrained to one side once F-actin is formed. Actin polymerization by ADAP acts in synergy with a capping protein but competes with cofilin. In T cells, ablation of ADAP impairs adhesion and migration with a time-dependent reduction of the F-actin content in response to chemokine or T cell receptor (TCR) engagement. Our data suggest that IDR-assisted molecular crowding of actin above the critical concentration defines a new mechanism to regulate cytoskeletal dynamics. The principle of IDRs serving as molecular sponges to facilitate regulated self-assembly of filament-forming proteins might be a general phenomenon.
The barriers and facilitators of radical innovation implementation in secondary healthcare: a systematic review
Authors: Thijssen Salina V. , Jacobs Maria J.G. , Swart Rachelle R. , Heising Luca , Ou Carol X.J. , Roumen Cheryl 
Published: December 2021

PurposeThis study aimed to identify the barriers and facilitators related to the implementation of radical innovations in secondary healthcare.Design/methodology/approachA systematic review was conducted and presented in accordance with a PRISMA flowchart. The databases PubMed and Web of Science were searched for original publications in English between the 1st of January 2010 and 6th of November 2020. The level of radicalness was determined based on five characteristics of radical innovations. The level of evidence was classified according to the level of evidence scale of the University of Oxford. The Consolidated Framework for Implementation Research was used as a framework to classify the barriers and facilitators.FindingsBased on the inclusion and exclusion criteria, nine publications were included, concerning six technological, two organizational and one treatment innovation. The main barriers for radical innovation implementation in secondary healthcare were lack of human, material and financial resources, and lack of integration and organizational readiness. The main facilitators included a supportive culture, sufficient training, education and knowledge, and recognition of the expected added value.Originality/valueTo our knowledge, this is the first systematic review examining the barriers and facilitators of radical innovation implementation in secondary healthcare. To ease radical innovation implementation, alternative performance systems may be helpful, including the following prerequisites: (1) Money, (2) Added value, (3) Timely knowledge and integration, (4) Culture, and (5) Human resources (MATCH). This study highlights the need for more high-level evidence studies in this area.
A review on the identification of total productive maintenance critical success factors for effective implementation in the manufacturing sector
Authors: Chaurey Sudhir , Kalpande Shyamkumar D. , Gupta R.C. , Toke Lalit K. 
Published: December 2021

PurposeThe purpose of this paper is to carry out the literature search on manufacturing organizations and total productive maintenance (TPM). This research aims at studying TPM attributes and barriers in line with the TPM framework for effective implementation of TPM. This study identifies the barriers in TPM implementation and the critical success factors (CSFs) for effective TPM implementation.Design/methodology/approachIn this manuscript, the study of TPM in the manufacturing sector has been considered a broad area of the research and emphasis on the TPM literature review, which primarily relates to the contribution of manufacturing sector and employment availability. Next sections covers TPM history, importance, justification, pillars, obstacles and TPM implementation procedure and models. Thereafter author identified the gaps in existing literature.FindingsThe existing literature shows that very few TPM implementation models are available for the manufacturing sector. The study also found that there is no systematically conducted large-scale empirical research which deals with TPM implementation. In order to bridge this gap, an investigation into the successful implementation of TPM in is truly needed. The finding of the literature shows that there is a need of TPM model specially developed for the manufacturing sector. The identified critical factors derived from the extensive literature review help to overcome the barriers for effective TPM implementation.Research limitations/implicationsThis review study is limited to Indian manufacturing industries. The identified TPM CSFs are based on the TPM pillars and their sub-factors. This cross-sectional study was based on the existing TPM model.Practical implicationsThis paper can increase the significance of TPM strategy, which could help managers of organizations to have a better understanding of the benefits of implementing TPM and therefore enable patient satisfaction within their organizations.Originality/valueThe literature review covers methodical identification of TPM barriers and critical factors for maintenance performance improvements. It allows the practitioners to apply these identified CSFs for TPM implementation to achieve an improvement in industrial performance and competitiveness.
Spurring inclusive entrepreneurship and student development post-C19: synergies between research and business plan competitions
Authors: Gonzalez Laura 
Published: December 2021

PurposeAcademic innovation strives to benefit from an ample talent pool, and entrepreneurship and research competitions constitute an integral part of the effort. This prompts discussions about how to optimize the impact of interdisciplinary learning, especially for less-traditional participants. The main purpose of this article is to describe how synergies between research and business plan competitions can facilitate inclusive engagement and enhanced development of transferable skills.Design/methodology/approachA case illustration addresses the following questions: (1) what skills can be enhanced through a single project toward parallel participation in research and business plan competitions? (2) How can synergies between research and business plan competitions support more inclusive student development? The case illustration outlines the process and outcomes of an initiative with three first-gen business students, two female and two international.FindingsThe case illustration describes how synergies and alignments of deadliness between research and business plan competitions enhanced the learning process by facilitating more opportunities to showcase learning and receive feedback. In addition, the parallel preparation facilitated student inclusion by providing purposeful authentic practice in a project envisioned by the students. As a result of the 2019 learning experience, students and their employers continue to value in 2021 the effective development of transferable skills.Originality/valuePrevious studies examine independently entrepreneurship initiatives, science technology engineering arts and mathematics (STEAM) initiatives, transferable skills and pedagogy that support inclusive education. This manuscript describes the option of synergies between research and entrepreneurship competitions to support more inclusive student development. In addition, it provides recommendations for impact when scaling-up synergies.
Assessment of non-linear behavior and ductility of reinforced concrete structures
Authors: Belhocine Malika , Bouafia Youcef , Kachi Mohand Said , Benyahi Karim 
Published: December 2021

Purpose
The calculation and design of the structures are carried out with the aim of obtaining a sufficiently ductile behavior to allow the structure to undergo displacements, without risk of sudden breaks or loss of stability. The purpose of this study is to develop and validate a computer program (Thin beam2), allowing the modeling and simulation of the nonlinear behavior of reinforced concrete elements, on the other part, it is estimating the local and global ductility of the sections or elements constituting these structures.

Design/methodology/approach
The authors present two nonlinear analysis methods to carry out a parametric study of the factors influencing the local and global ductility of reinforced concrete structures. The first consists in evaluating the nonlinear behavior at the level of the cross-section of the reinforced concrete elements used in the elaborate Sectenol 1 program, it allows us to have the local ductility. The second, allows us to evaluate the nonlinear behavior of the element used in the modified thin beam 2 program, it allows us to estimate the overall ductility of the element.

Findings
The validation results of the Thin beam2 program are very satisfactory, by conferring the analytic and experimental results obtained by various researchers and the parametric study shows that each factor such as the compressive strength of the concrete has a favorable effect on ductility. Conversely, the normal compression force and the high resistance of tensioned reinforcements adversely affect ductility.

Originality/value
The reliability of the two programs lies in obtaining the local and global ductility of reinforced concrete structures because the calculation and design of the structures are carried out with the aim of obtaining ductile behavior without risk of breakage and instability.
Bottom‐up effect of host protective symbionts on parasitoid diversity: Limited evidence from two field experiments
Authors: Narayan Karthik Sankar , Vorburger Christoph , Hafer‐Hahmann Nina 
Published: December 2021

Abstract

Protective symbionts can provide effective and specific protection to their hosts. This protection can differ between different symbiont strains with each strain providing protection against certain components of the parasite and pathogen community their host faces. Protective symbionts are especially well known from aphids where, among other functions, they provide protection against different parasitoid wasps. However, most of the evidence for this protection comes from laboratory experiments.

Our aim was to understand how consistent protection is across different symbiont strains under natural field conditions and whether symbiont diversity enhanced the species diversity of colonizing parasitoids, as could be expected from the specificity of their protection.

We used experimental colonies of the black bean aphid Aphis fabae to investigate symbiont‐conferred protection under natural field conditions over two seasons. Colonies differed only in their symbiont composition, carrying either no symbionts, a single strain of the protective symbiont Hamiltonella defensa, or a mixture of three H. defensa strains. These aphid colonies were exposed to natural parasitoid communities in the field. Subsequently, we determined the parasitoids hatched from each aphid colony.

The evidence for a protective effect of H. defensa was limited and inconsistent between years, and aphid colonies harbouring multiple symbiont strains did not support a more diverse parasitoid community. Instead, parasitoid diversity tended to be highest in the absence of H. defensa.

Symbiont‐conferred protection, although a strong and repeatable effect under laboratory conditions may not always cause the predicted bottom‐up effects under natural conditions in the field.
Best person or best mix? How public sector managers understand the merit principle
Authors: Foley Meraiah , Cooper Rae , Colley Linda , Williamson Sue 
Published: December 2021

AbstractAs public sector organisations around the world enact strategies to progress gender equality, managers are forced to navigate the apparent conflict between making employment decisions on individual‐level ‘merit’ and considering the collective constraints and disadvantage that occur along gender lines. In this paper, we investigate how managers’ understandings of merit contribute to this tension. Analysing data collected in focus groups with 273 mid‐level public sector managers in four Australian jurisdictions where efforts to promote gender equality were actively under way, we found that many managers adhered to a highly individualised understanding of merit which precluded them from considering gender or addressing gendered inequality in their employment decisions. Only a small proportion of managers who believed that creating a more representative bureaucracy was a legitimate public sector objective were able to justify considering a candidate's gender as a source of merit. We argue that public sector organisations seeking to promote gender equality should focus managers’ attention on the benefits of achieving a more representative bureaucracy and give managers greater normative and regulatory certainty about how to assess and apply merit in that context.
Noninvasive, visual examination for the presence of gunshot residue on human skin
Authors: Husak Jennifer 
Published: December 2021

AbstractWhen a firearm is discharged, the highest concentration of gunshot residue (GSR) is located on a shooter's hands, forearms, and clothing. Currently, collecting GSR from an individual's hands is accomplished with a carbon disk that is submitted for confirmatory analysis in a forensic laboratory. Presumptive chemical tests can be performed in the field, but these tests consume a portion of the GSR particles leaving a reduced amount of evidence available to be collected and sent to a forensic laboratory. An abundance of research exists for detecting GSR particles instantly on different fabrics using an alternate light source (ALS). This study expanded on that research and developed a noninvasive, visual examination to detect GSR on a suspected shooter's hands without destroying or removing any particles prior to collection. The hands of individuals who recently discharged a firearm were examined under a light source between 475 and 530 nm and an infrared (IR) camera. The fluorescent particles observed on a shooter's hands under 520 nm were similar in size and appearance to GSR particles observed on fabrics under an ALS. The fluorescent particles were collected and analyzed for GSR, and the results indicated that GSR particles were present. More testing needs to be conducted to determine if the fluorescent particles observed are inorganic or organic GSR particles. There is also potential to detect GSR under IR light; however, more research needs to be conducted to determine the composition of the particles observed after image enhancement.
Hip and stifle joint anatomy of the Saimaa (Pusa hispida saimensis) and Baltic ringed seals (Pusa hispida botnica)
Authors: Laakkonen Juha , Vedrines Alixia 
Published: December 2021

AbstractThe anatomical architecture of the hip and stifle joints of the Saimaa ringed seal was determined by dissection to be similar to that of the Baltic ringed seal. There was no ligament of the femoral head in the hip joint. The lateral side of the stifle joint lacked a collateral ligament but the collateral ligament on the medial side was of considerable size. The medial meniscus was larger and thicker than the lateral meniscus. The asymmetrical anatomical architecture allows for much lateral movement during aquatic motion, but it is poorly adapted to terrestrial locomotion.
Validation of self‐reported medication use applying untargeted mass spectrometry‐based metabolomics techniques in the Rhineland study
Authors: Alaeddin Nersi , Stingl Julia C. , Breteler Monique M. B. , de Vries Folgerdiena M. 
Published: December 2021

AimsTo assess the validity of self‐reported continuous medication use with drug metabolites measured in plasma by using untargeted mass spectrometric techniques.MethodsIn a population‐based cohort in Bonn, Germany, we compared interview‐based, self‐reported medication intake with drug‐specific metabolites measured in plasma (based on participants who completed their study visits between March 2016 and February 2020). Analyses were done stratified by sex and age (<65 years vs ≥65 years). Cohen's kappa (κ) statistics with 95% confidence intervals (CI) were calculated.ResultsA total of 13 drugs used to treat hypertension, gout, diabetes, epilepsy and depression were analysed in a sample of 4386 individuals (mean age 55 years, 56.1% women). Eleven drugs showed almost perfect agreement (κ > 0.8), whereas sitagliptin and hydrochlorothiazide showed substantial (κ = 0.8, 95% CI 0.71–0.90) and moderate agreement (κ = 0.61, 95% CI 0.56–0.66), respectively. Frequency of use allowed sex‐ and age‐stratified analyses for eight and nine drugs, respectively. For five drugs, concordance tended to be higher for women than for men. For most drugs, concordance was higher among individuals aged ≥65 years than among individuals aged <65 years, but these age‐related differences were not statistically significant.ConclusionHigh concordance rates between self‐reported drug use and metabolites measured in plasma suggest that self‐reported drug use is reliable and accurate for assessing drug use.
Structure‐based survey of ligand binding in the human insulin receptor
Authors: Kumar Lokender , Vizgaudis Whitney , Klein‐Seetharaman Judith 
Published: December 2021

The insulin receptor is a membrane protein responsible for the regulation of nutrient balance; and therefore, it is an attractive target in the treatment of diabetes and metabolic syndrome. Pharmacology of the insulin receptor involves two distinct mechanisms: (1) activation of the receptor by insulin mimetics that bind in the extracellular domain and (2) inhibition of the receptor TK enzymatic activity in the cytoplasmic domain. While a complete structural picture of the full‐length receptor comprising the entire sequence covering extracellular, transmembrane, juxtamembrane and cytoplasmic domains is still elusive, recent progress through cryoelectron microscopy has made it possible to describe the initial insulin ligand binding events at atomistic detail. We utilize this opportunity to obtain structural insights into the pharmacology of the insulin receptor. To this end, we conducted a comprehensive docking study of known ligands to the new structures of the receptor. Through this approach, we provide an in‐depth, structure‐based review of human insulin receptor pharmacology in light of the new structures.LINKED ARTICLESThis article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc