bluuebunny/crossref_metadata_2025 huggingface dataset:
Global challenges in access to diagnostics and treatment for neuroendocrine tumor (NET) patients
Authors: Dureja Sugandha , McDonnell Mark , Van Genechten Dirk , Bouvier Catherine , Kolarova Teodora , O'Toole Dermot , Singh Harjit , Chen Jie , Howe James , Singh Simron , Rodien‐Louw Christine , Leyden Simone , Gellerman Elyse , Herman Jackie , Pavel Marianne ,   International Neuroendocrine Cancer Alliance (INCA)
Published: May 2023

SCAN, an online survey, measured access to diagnosis, treatments and monitoring of neuroendocrine tumor (NET) patients globally. Between September and November 2019, NET patients and healthcare professionals (HCPs) completed an online, semi‐standardized survey with 54 patient questions and 33 HCP questions. A total of 2359 patients with NETs and 436 HCPs responded. Misdiagnosis was common (44% [1043/2359]). Mean time to diagnosis was 4.8 years (standard deviation [SD], 6.2). Compared with global figures (60% [1407/2359]), the availability of 68Ga‐DOTA positron emission tomography (PET)/computed tomography (CT) was significantly lower in Asia (45% [126/280]) and higher in Oceania (86% [171/200]). HCPs reported that 68Ga‐DOTA PET/CT was free/affordable to fewer patients in Emerging and Developing Economies (EDE) than Advanced Economies (AE; 17% [26/150] and 59% [84/142], respectively). Compared with global data (52% [1234/2359]), patient‐reported availability of peptide receptor radionuclide therapy (PRRT) was significantly lower in Asia (31% [88/280]) and higher in Oceania (61% [122/200]). Significant differences were observed in average annual NET specialist costs between AE and EDE ($1081 and $2915, respectively). Compared with AE, patients in EDE traveled further for NET specialists (1032 [SD, 1578] and 181 [SD, 496] km, respectively). Patients and HCPs both recommended referral to HCPs that were more knowledgeable in the field of NETs and had better access to NET experts/specialist centers. National care pathways, enhancing HCP NET knowledge and ensuring effective diagnostics and access to appropriate treatments are crucial to improving patient survival and NET care worldwide.
Toxic medications in Charcot–Marie–Tooth patients: A systematic review
Authors: Cavaletti Guido , Forsey Katherine , Alberti Paola
Published: May 2023

Background and Aims

Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot–Marie–Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence‐based updated recommendations on this clinically relevant topic.

Methods

A systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.

Results

The results of our systematic review provide evidence‐based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug‐related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.

Interpretation

It is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non‐oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.
Clinical features of a family with late‐onset distal hereditary motor neuropathy harboring p.Pro39Leu variant of HSPB1
Authors: Naruse Hiroya , Okubo So , Sudo Atsushi , Mitsui Jun , Mikata Takashi , Ishiura Hiroyuki , Morishita Shinichi , Tsuji Shoji , Toda Tatsushi
Published: May 2023

Background and Aims

Pathogenic variants of HSPB1, the gene encoding the small heat shock protein 27, have been reported to cause autosomal dominant distal hereditary motor neuropathy (dHMN) type II and autosomal dominant Charcot–Marie‐Tooth (CMT) disease with minimal sensory involvement (CMT2F). This study aimed to describe the clinical features of patients in a family with late‐onset dHMN carrying the Pro39Leu variant of HSPB1.

Methods

Whole‐exome sequence analysis identified a heterozygous pathogenic variant (Pro39Leu) of HSPB1 in the proband. The presence of the HSPB1 Pro39Leu variant in two affected individuals was confirmed using direct nucleotide sequence analysis.

Results

Both patients exhibited distal muscle weakness with lower extremity predominance and no obvious sensory deficits, leading to a clinical diagnosis of late‐onset dHMN. Nerve conduction studies (NCSs) revealed a subclinical complication of sensory disturbance in one of the patients. The clinical and electrophysiological findings of patients with the HSPB1 Pro39Leu variant in this study and previous reports are summarized.

Interpretation

This study suggests that the clinical spectrum of patients carrying HSPB1 Pro39Leu variants, especially the disease onset, might be broader than expected, and HSPB1 variants should be considered in patients diagnosed with late‐onset dHMN. Furthermore, patients with dHMN may have concomitant sensory deficits that should be evaluated using NCSs.
Neuroimaging meta‐analysis of brain mechanisms of the association between orofacial pain and mastication
Authors: Chen Ta‐Chung , Lin Chia‐Shu
Published: May 2023

Background

Temporomandibular disorders (TMD) are characterized by pain and impaired masticatory functions. The Integrated Pain Adaptation Model (IPAM) predicts that alterations in motor activity may be associated with increased pain in some individuals. The IPAM highlights the diversity of patients' responses to orofacial pain and suggests that such diversity is related to the sensorimotor network of the brain. It remains unclear whether the pattern of brain activation reflects the diversity of patients' responses underlying the association between mastication and orofacial pain.

Objective

This meta‐analysis aims to compare the spatial pattern of brain activation, as the primary outcome of neuroimaging studies, between studies of mastication (i.e. Study 1: mastication of healthy adults) and studies of orofacial pain (i.e. Study 2: muscle pain in healthy adults and Study 3: noxious stimulation of the masticatory system in TMD patients).

Methods

Neuroimaging meta‐analyses were conducted for two groups of studies: (a) mastication of healthy adults (Study 1, 10 studies) and (b) orofacial pain (7 studies), including muscle pain in healthy adults (Study 2) and noxious stimulation of the masticatory system in TMD patients (Study 3). Consistent loci of brain activation were synthesized using Activation Likelihood Estimation (ALE) with an initial cluster‐forming threshold (p < .05) and a threshold of cluster size (p < .05, familywise error‐corrected).

Results

The orofacial pain studies have shown consistent activation in pain‐related regions, including the anterior cingulate cortex and the anterior insula (AIns). A conjunctional analysis of mastication and orofacial pain studies showed joint activation at the left AIns, the left primary motor cortex and the right primary somatosensory cortex.

Conclusion

The meta‐analytical evidence suggests that the AIns, as a key region in pain, interoception and salience processing, contributes to the pain‐mastication association. These findings reveal an additional neural mechanism of the diversity of patients' responses underlying the association between mastication and orofacial pain.
Consistency amongst pairs: How consistent are child co‐witnesses with one another?
Authors: Deck Sarah L. , Brubacher Sonja P. , Dickinson Jason J. , Powell Martine B.
Published: May 2023

Purpose

When multiple children are asked about the same event, the consistency of their reports may be used as a heuristic for credibility. Little research has considered how consistent child co‐witnesses are likely to be. In this study, we explored how likely child co‐witnesses were to report the same details from a mutually experienced event.

Methods

Pairs of children participated in an educational science event during which the target attempted to coax the children into breaking preestablished rules for the session (i.e., commit transgressions). Children were individually interviewed about their experience on two subsequent occasions.

Results

Co‐witnesses tended to be quite inconsistent: 32%–55% of all details recalled were only mentioned by one co‐witness. Various factors were associated with co‐witness consistency, including delay before the interview, centrality of details recalled, and children's age and forthcomingness.

Conclusions

The findings indicate that inconsistency between co‐witnesses reflects a natural memory phenomenon, and that practitioners should be cautious of using co‐witness consistency as an indicator of credibility.
Effects of the ridge‐and‐runnel system on macrofaunal spatial distribution on a macrotidal sandy beach in the Brazilian Amazon coast
Authors: Cardoso Edma Mayara Pereira , Petracco Marcelo , Santos Thuareag , Venekey Virag , Aviz Daiane
Published: May 2023

Ridge‐and‐runnel systems are common morphological features across the intertidal zone of dissipative macrotidal beaches. However, these systems have often been overlooked by macrofaunal zonation studies. The present study investigated the effects of this system on the spatial distribution of the macrofaunal community on an Amazonian macrotidal sandy beach. Samples (macrobenthos and sediments) were collected at seven equidistant levels (50 m apart) from the high tide water mark to the swash zone, in two different areas: (1) with and (2) without ridge‐and‐runnel systems. The results showed a significant increase in macrofaunal abundance and richness in area with runnels, associated with muddier sediment and higher organic content. The macrofauna in the runnels, both in upper‐intertidal and lower‐intertidal zones, had higher density and richness than that in the sandbars. There was no difference between tidal levels in area 2, although we observed an increasing tendency of abundance and richness towards the low tide line. Taxonomic composition and trophic groups also differed between areas, with predominance of species that are typical of sandy‐mud substrate and higher participation of nonselective deposit feeders in area 1. Predatory species typical of sandy substrates prevailed in area 2. These findings add knowledge to sandy beach ecology and indicate the importance of including aspects of habitat complexity in both across‐ and alongshore macrofaunal distribution studies.
Variations in mechanical stiffness alter microvascular sprouting and stability in a PEG hydrogel model of idiopathic pulmonary fibrosis
Authors: Leonard‐Duke Julie , Bruce Anthony C. , Peirce Shayn M. , Taite Lakeshia J.
Published: May 2023

Objective

Microvascular remodeling is governed by biomechanical and biochemical cues which are dysregulated in idiopathic pulmonary fibrosis. Understanding how these cues impact endothelial cell‐pericyte interactions necessitates a model system in which both variables can be independently and reproducibly modulated. In this study we develop a tunable hydrogel‐based angiogenesis assay to study how varying angiogenic growth factors and environmental stiffness affect sprouting and vessel organization.

Methods

Lungs harvested from mice were cut into 1 mm long segments then cultured on hydrogels having one of seven possible stiffness and growth factor combinations. Time course, brightfield, and immunofluorescence imaging were used to observe and quantify sprout formation.

Results

Our assay was able to support angiogenesis in a comparable manner to Matrigel in soft 2 kPa gels while enabling tunability to study the effects of stiffness on sprout formation. Matrigel and 2 kPa groups contained significantly more samples with sprouts when compared to the stiffer 10 and 20 kPa gels. Growth factor treatment did not have as obvious an effect, although the 20 kPa PDGF + FGF‐treated group had significantly longer vessels than the vascular endothelial growth factor‐treated group.

Conclusions

We have developed a novel, tunable hydrogel assay for the creation of lung explant vessel organoids which can be modulated to study the impact of specific environmental cues on vessel formation and maturation.
A critical examination of epistemological congruence between intersectionality and feminist poststructuralism: Toward an integrated framework for health research
Authors: Willett Andrea , Etowa Josephine
Published: May 2023

The theoretical perspectives of intersectionality and poststructuralism have contributed meaningfully to advancing issues of social injustice within the realm of women's health research. However, the question of whether the two approaches are epistemologically commensurate has been at the heart of a polarized debate within third‐ and fourth‐wave feminist literature in recent years. In this paper, we draw on the extant literature to explore existing dilemmas within this debate and critically reflect on points of epistemological tension and congruence between the two perspectives. It will be demonstrated that intersectionality and poststructuralism, especially feminist poststructuralism, represent concordant theoretical perspectives and a synthesized theoretical framework for application in qualitative research into women's health will be proposed. We argue that an intersectional feminist poststructuralist framework contributes to a deepened analysis of women's disparate healthcare experiences, and the social mechanisms, power relations, and discourses that mediate these experiences, while offering avenues for advocacy and political praxis on a multitude of levels.
Physicians and nurses view on their roles in communication and collaboration with families: A qualitative study
Authors: Woldring Josien M. , Gans Rijk O. B. , Paans Wolter , Luttik Marie Louise
Published: May 2023

Background

Families are introduced as new partners in interprofessional communication and collaboration during hospitalisation of an adult patient. Their introduction into the healthcare team has consequences for the roles and responsibilities of all healthcare professionals. Role clarification is thus needed to create optimal communication and collaboration with families.

Aim

To gain insight into how physicians and nurses view their own roles and each other's roles in communication and collaboration with families in the care of adult patients.

Methods

A qualitative interpretive interview design was used. Fourteen semi‐structured interviews, with seven physicians and seven nurses, were conducted. Data were analysed according to the steps of thematic analysis. For the study design and analysis of the results, the guidelines of the consolidated criteria for reporting qualitative studies (COREQ) were followed. The ethical committee of the University Medical Center Groningen approved the study protocol (research number 202100640).

Findings

Thematic analysis resulted in three themes, each consisting of two or three code groups. Two themes “building a relationship” and “sharing information” were described as roles that both nurses and physicians share regarding communication and collaboration with families. The role expectations differed between physicians and nurses, but these differences were not discussed with each other. The theme “providing support to family” was regarded a nurse‐specific role by both professions.

Conclusion

Physicians and nurses see a role for themselves and each other in communication and collaboration with families. However, the division of roles and expectations thereof are different, overlapping, and unclear. To optimise the role and position of family during hospital care, clarification and division of the roles between physicians and nurses in this partnership is necessary.
The RLCK subfamily VII‐4 controls pattern‐triggered immunity and basal resistance to bacterial and fungal pathogens in rice
Authors: Jalilian Ahmad , Bagheri Abdolreza , Chalvon Véronique , Meusnier Isabelle , Kroj Thomas , Kakhki Amin Mirshamsi
Published: May 2023

Receptor‐like cytoplasmic kinases (RLCKs) mediate the intracellular signaling downstream of pattern‐recognition receptors (PRRs). Several RLCKs from subfamily VII of rice (Oryza sativa) have important roles in plant immunity, but the role of RLCK VII‐4 in pattern‐triggered immune (PTI) signaling and resistance to pathogens has not yet been investigated. Here, we generated by multiplex clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9‐mediated genome editing rice sextuple mutant lines where the entire RLCK VII‐4 subfamily is inactivated and then analyzed the resulting lines for their response to chitin and flg22 and for their immunity to Xanthomonas oryzae pv. oryzae (Xoo) and Magnaporthe oryzae. Analysis of the rlckvii‐4 mutants revealed that they have an impaired reactive oxygen system burst and reduced defense gene expression in response to flg22 and chitin. This indicates that members of the rice RLCK VII‐4 subfamily are required for immune signaling downstream of multiple PRRs. Furthermore, we found that the rice RLCK VII‐4 subfamily is important for chitin‐induced callose deposition and mitogen‐activated protein kinase activation and that it is crucial for basal resistance against Xoo and M. oryzae pathogens. This establishes that the RLCK VII‐4 subfamily has critical functions in the regulation of multiple PTI pathways in rice and opens the way for deciphering the precise role of its members in the control of rice PTI.
Xenotransplantation literature update March 2021–March 2023
Authors: Kamberi Shani , Meier Raphael P.H.
Published: May 2023

After a significant hiatus imposed by the COVID‐19 pandemic, we hereby restart Xenotransplantation literature updates. With the recently performed clinical xenotransplantation cases and the much‐heightened interest in the field, we have determined that this is an optimal time to reinstate this section. There has been an invigorated focus on unique challenges posed by pig‐to‐human xenotransplantation, and specific attention will be given to this aspect. In this issue, we aimed to cover the gap and compiled the most relevant publications from March 2021 to March 2023.
Enhancing the Developer Experience (DX) in Docker Supported Projects
Authors: Ghazali Masitah , Hidayat Alfian Naufal Ravi
Published: May 2023

Docker is undeniably powerful and revolutionary in how containerized system development is developed today, but it is apparent that the learning curve for it should be addressed, as it typically is complex at times, especially for beginners. One of the fundamental tasks in a Docker workflow is Dockerfile configurations, which at times require ample time to study and observe for attaining the best practices, even the appropriate result. This issue undeniably affects the developer experience. Developer Experience (DX), being a derived field from User Experience (UX) that has been getting traction for the past few years concerns developers’ innate ability to perceive tasks as enjoyable, painful, or perhaps some other sets of emotions. The goal of DX is to evaluate all those factors in order to improve the software development experience, which consequently affects how the project is delivered. In resonance with that, this work aims to enhance the DX by way of proposing and incorporating supporting interaction tools, both based on CLI and GUI as the interface type, with two different permutations: CLI and GUI. The DX of both has to be evaluated by the experts, who are of experienced developers, regardless of whether they have knowledge of Docker or not. The method to test and evaluate two different solutions is conducted qualitatively, with each respondent having a different order of evaluating the two solutions. The qualitative data is thematically analyzed, resulting in GUI being the best option among the two. The contribution of this research is the design guidelines for GUI and CLI-based tools development that enhance the Developer Experience (DX) in the scaffolding of Dockerfile and docker-compose.yml for projects that use Docker.
Desenvolvimento Sustentável e a Inteligência Artificial no Âmbito do Poder Judiciário
Authors: De Lima Andrade Matheus , Alcântara Machado Carlos Augusto , Maia Rebouças Gabriela
Published: May 2023

O artigo se propõe a discutir a Inteligência Artificial (IA) e a sua implicação para o Desenvolvimento Sustentável, com enfoque na utilização de aplicações de IA no âmbito do Poder Judiciário e à luz dos Objetivos de Desenvolvimento Sustentável (ODS) da Agenda 2030. Nesse sentido, busca situar as inovações tecnológicas e a Justiça no compromisso firmado pelas metas inerentes ao projeto global de desenvolvimento. Com suporte metodológico no levantamento documental e bibliográfico, empreendeu-se uma análise qualitativa para, no primeiro capítulo, examinar o conceito e o processo evolutivo do desenvolvimento sustentável; no segundo capítulo, analisar a IA e sua relação com o desenvolvimento sustentável a partir dos objetivos que compõem a Agenda 2030; e, por fim, discutir a implementação de IA na esfera de atuação da Justiça e os seus avanços e desafios em atendimento aos ODS, com enfoque no exemplo do Poder Judiciário brasileiro, concluindo que as aplicações de IA podem auxiliar o Poder Judiciário a exercer o seu protagonismo no ODS 16, mas que requerem preocupação e um maior esforço por uma agenda regulatória.
A Lei n. 12.711/2012 e Ações Afirmativas de Acesso ao Ensino Superior de Negros e Não-Negros
Authors: Ferreira Vieira Enilton , Lino Videira Piedade , Serrao Custodio Elivaldo
Published: May 2023

O presente artigo tem por objetivo analisar a implementação da Lei n. 12.711/2012, que trata da Política de Ações Afirmativas no que tange à sua aplicabilidade, entraves e seus limites. Trata-se de uma pesquisa qualitativa bibliográfica a partir dos estudos de Minayo (2008), apoiada na Teoria Crítica da Raça (TCR) e pelo referencial teórico de intelectuais negras e negros que estudam a temática racial. O método eleito para a análise de dados articula hermenêutica e dialética que nos permitiu tanto interpretar os sentidos dos discursos elaborados (hermenêutica), quanto lhes compreender os sentidos através da contradição, do contexto histórico e social em que foram constituídos (dialética). Os resultados apontam para uma postura institucional refratária à adoção das ações afirmativas no âmbito das políticas públicas educacionais, ao mesmo tempo, essas instituições desconhecem e/ou resistem em compreender os processos históricos e sociais que precederam sua criação, bem como mensurar sua importância para a educação da população negra, da sociedade brasileira e da própria Universidade. Os dados revelam ainda indícios de incipientes controles administrativos. Os controles sociais da Política indicam baixa aproximação entre a Instituição e a comunidade a qual se encontra inserida, sobretudo com o Movimento Negro Brasileiro.
Proteção do Direito à Educação Inclusiva das Crianças e Adolescentes Venezuelanos Beneficiários da Interiorização em Dourados - MS
Authors: Zanoni da Silva Joâo Lucas , Zanoni da Silva Ana Maria
Published: May 2023

O município de Dourados, situado no estado de Mato Grosso do Sul, é o quarto maior receptor de imigrantes venezuelanos interiorizados pela Operação Acolhida. Até dezembro de 2022 já haviam sido interiorizadas 3.591 pessoas nessa localidade, entre as quais existe uma parcela significativa de crianças e adolescentes em idade escolar que vem enfrentando obstáculos à realização de matrículas nas escolas públicas e na permanência no ambiente escolar. Nesse sentido, esta pesquisa objetivará analisar o direito humano e fundamental à educação, sob a perspectiva inclusiva, e as políticas públicas implementadas na referida localidade para assegurar o acesso e a permanência das crianças e adolescentes venezuelanos no ensino fundamental e médio, com vistas à sua integração local. Para tanto, se utiliza o método dedutivo, em uma abordagem qualitativa, numa pesquisa básica de referencial bibliográfico e documental. Por derradeiro, assevera-se que a política pública de permanência e acesso nas instituições de ensino estaduais e municipais de Dourados não considera as necessidades educacionais especiais dos imigrantes e refugiados venezuelanos, razão pela qual é necessária a interlocução o intercâmbio de informações entre as autoridades públicas dos três níveis federativos de governo.
Positive scalar curvature and homology cobordism invariants
Authors: Konno Hokuto , Taniguchi Masaki
Published: May 2023

We give an obstruction to positive scalar curvature metrics on 4‐manifolds with the homology described in terms of homology cobordism invariants from Seiberg–Witten theory. The main tool of the proof is a relative Bauer–Furuta‐type invariant on a periodic‐end 4‐manifold.
A Novel Approach to Line Clipping Against a Rectangular Window
Authors: Yu H. Y. , He Y. J. , Zhang W. J.
Published: May 2023

Line clipping against a rectangular window is a fundamental problem in computer graphics. A robust and fast algorithm is needed not only for the traditional graphics pipeline but also for new applications, including web maps, nanomaterials, and sensor measurements. In this paper, we present a novel approach, which is based on the idea of combining the geometric and algebraic approaches. In particular, the proposed approach first decomposes a 2D line clipping problem into a set of 1D clipping problems, and then solves the 1D clipping problem by the comparison (i.e., >, <, and =) operation on the coordinate value of the projected points on one dimension only. Both theoretical analysis and experimental tests were conducted to demonstrate the improved robustness (for degenerated cases) and computational efficiency of the proposed approach.
Hierarchical Automatic Multilayer Power Plane Generation With Genetic Optimization and Multilayer Perceptron
Authors: Liao Haiguang , Patil Vinay , Dong Xuliang , Shanbhag Devika , Fallon Elias , Hogan Taylor , Spasojevic Mirko , Burak Kara Levent
Published: May 2023

We present an automatic multilayer power plane generation method to accelerate the design of printed circuit boards (PCB). In PCB design, while automatic solvers have been developed to predict important indicators such as the IR-drop, power integrity, and signal integrity, the generation of the power plane itself still largely relies on laborious manual methods. Our automatic power plane generation approach is based on genetic optimization combined with a multilayer perceptron (MLP) and is able to automatically generate power planes across a diverse set of problems with varying levels of difficulty. Our method GOMLP consists of an outer loop genetic optimizer (GO) and an inner loop MLP that generate power planes automatically. The critical elements of our approach include contour detection, feature expansion, and a distance measure to enable island-minimizing complex power plane generation. We compare our approach to a baseline solution based on A*. The A* method consisting of a sequential island generation and merging process which can produce less than ideal solutions. Our experimental results show that on single layer power plane problems, our method outperforms A* in 71% of the problems with varying levels of board layout difficulty. We further describe H-GOMLP, which extends GOMLP to multilayer power plane problems using hierarchical clustering and net similarities based on the Hausdorff distance.
Root-knot nematode modulates plant CLE3-CLV1 signaling as a long-distance signal for successful infection
Authors: Nakagami Satoru , Notaguchi Michitaka , Kondo Tatsuhiko , Okamoto Satoru , Ida Takanori , Sato Yoshikatsu , Higashiyama Tetsuya , Tsai Allen Yi-Lun , Ishida Takashi , Sawa Shinichiro
Published: June 2023

Plants use many long-distance and systemic signals to modulate growth and development, as well as respond to biotic and abiotic stresses. Parasitic nematodes infect host plant roots and cause severe damage to crop plants. However, the molecular mechanisms that regulate parasitic nematode infections are still unknown. Here, we show that plant parasitic root-knot nematodes (RKNs),
Meloidogyne incognita
, modulate the host CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE)–CLV1 signaling module to promote the infection progression. Plants deficient in the
CLE
signaling pathway show enhanced RKN resistance, whereas
CLE
overexpression leads to increased susceptibility toward RKN. Grafting analysis shows that
CLV1
expression in the shoot alone is sufficient to positively regulate RKN infection. Together with results from the split-root culture system, infection assays, and CLE3-CLV1 binding assays, we conclude that mobile root-derived CLE signals are perceived by CLV1 in the shoot, which subsequently produce systemic signals to promote gall formation and RKN reproduction.
Achieving ideal transistor characteristics in conjugated polymer semiconductors
Authors: Xiao Mingfei , Ren Xinglong , Ji Kangyu , Chung Sein , Shi Xiaoyu , Han Jie , Yao Zefan , Tao Xudong , Zelewski Szymon J. , Nikolka Mark , Zhang Youcheng , Zhang Zhilong , Wang Zichen , Jay Nathan , Jacobs Ian , Wu Weijing , Yu Han , Abdul Samad Yarjan , Stranks Samuel D. , Kang Boseok , Cho Kilwon , Xie Jin , Yan He , Chen Shangshang , Sirringhaus Henning
Published: June 2023

Organic thin-film transistors (OTFTs) with ideal behavior are highly desired, because nonideal devices may overestimate the intrinsic property and yield inferior performance in applications. In reality, most polymer OTFTs reported in the literature do not exhibit ideal characteristics. Supported by a structure-property relationship study of several low-disorder conjugated polymers, here, we present an empirical selection rule for polymer candidates for textbook-like OTFTs with high reliability factors (100% for ideal transistors). The successful candidates should have low energetic disorder along their backbones and form thin films with spatially uniform energetic landscapes. We demonstrate that these requirements are satisfied in the semicrystalline polymer PffBT4T-2DT, which exhibits a reliability factor (~100%) that is exceptionally high for polymer devices, rendering it an ideal candidate for OTFT applications. Our findings broaden the selection of polymer semiconductors with textbook-like OTFT characteristics and would shed light upon the molecular design criteria for next-generation polymer semiconductors.
Whole-Genome Subtyping Reveals Population Structure and Host Adaptation of Salmonella Typhimurium from Wild Birds
Authors: Fu Yezhi , M’ikanatha Nkuchia M. , Dudley Edward G.
Published: May 2023

Within-host evolution of bacterial pathogens can lead to host-associated variants of the same species or serovar. Identification and characterization of closely related variants from diverse host species are crucial to public health and host-pathogen adaptation research.
An Integrated Approach to Teaching Cell Staining
Authors: Lal Archana , Vanniasinkam Thiru
Published: May 2023

Active learning has been shown to improve student outcomes across a range of science, technology, engineering, and math (STEM) disciplines. In addition, active learning with an interdisciplinary focus in the classroom is beneficial for students to pursue health and allied health careers.
Hadean tectonics: Insights from machine learning
Authors: Chen Guoxiong , Kusky Timothy , Luo Lei , Li Quanke , Cheng Qiuming
Published: May 2023

The tectonic affiliations and magma compositions that formed Earth’s earliest crusts remain hotly debated. Previous efforts toward this goal have relied heavily on determining the provenance of Hadean zircons using low-dimensional discriminant diagrams developed from Phanerozoic samples, which are inadequate for capturing systematic differences without considering secular changes in zircon composition. Here, we developed high-dimensional machine learning (ML) approaches using zircon chemistry data (spanning 19 elements over 4.0 b.y.) to characterize zircons that crystallized in some typical tectonic settings (e.g., arcs, plume-related hotspots, and rifts) and from either igneous (I-type) or sedimentary (S-type) magmas. The proposed ML method, from a nonuniformitarian perspective, identifies the tectonic settings and granitoid types of given zircons (from Archean to Phanerozoic) at a higher prediction accuracy of >89% compared to ∼66%–82% for traditional discriminant diagrams (e.g., U/Yb vs. Y and rare earth elements (REE) + Y vs. P). The ML-based discriminators depend on the systematic differences in zircon chemistry, notably, significant differences in U, Th, and heavy REE for tectonic settings, and P and Hf for I- and S-type magmas. Application of the trained ML models to Hadean zircons from Jack Hills, Australia, suggests that these zircons were mainly crystallized in continental arc–forming magmas (90%) with 45% belonging to S-type melts. This result provides clear evidence of sediment recycling associated with subduction activity in the Hadean.
Protective equipment in youth ice hockey: are mouthguards and helmet age relevant to concussion risk?concussionfor mouthguard wearers
Authors: Kolstad Ash T , Eliason Paul H , Galarneau Jean-Michel , Black Amanda Marie , Hagel Brent E , Emery Carolyn A
Published: May 2023

Objectives

To compare the incidence rates and odds of concussion between youth ice hockey players based on mouthguard use and helmet age.

Materials and methods

Within a 5-year longitudinal cohort (2013/2014 to 2017/2018) of male and female ice hockey players (ages 11–18; n=3330 players) in Alberta (Canada), we analysed the relationship of equipment and concussion in both a prospective cohort and nested case (concussion) control (acute musculoskeletal injury) approach. The prospective cohort included baseline assessments documenting reported mouthguard use (yes/sometimes, no use), helmet age (newer/<2 years old, older/≥2 years old) and important covariables (weight, level of play, position of play, concussion history, body checking policy), with weekly player participation throughout the season. The nested case–control component used injury reports to document equipment (mouthguard use, helmet age) and other information (eg, mechanism and type of injury) for the injury event. Multivariable mixed effects negative binomial regression (prospective cohort, incidence rate ratios (IRRs)) and multivariable mixed effects logistic regression (nested case–control, odds ratios (OR)) examined the association between equipment and concussion.

Results

Players who reported wearing a mouthguard had a 28% lower concussion rate (IRR=0.72, 95% CI 0.56 to 0.93) and 57% lower odds of concussion (OR=0.43, 95% CI 0.27 to 0.70) compared with non-wearers. There were no associations in the concussion rate (IRR=0.95, 95% CI 0.77 to 1.18) and odds (OR=1.16, 95% CI 0.73 to 1.86) between newer and older helmets.

Conclusions

Wearing a mouthguard was associated with a lower concussion rate and odds. Policy mandating use should be considered in youth ice hockey. More research is needed to identify other helmet characteristics (eg, quality, fit) that could lower concussion risk.
Advances in systemic therapies for triple negative breast cancer
Authors: Leon-Ferre Roberto A , Goetz Matthew P
Published: May 2023

Triple negative breast cancer (TNBC) continues to be the subtype of breast cancer with the highest rates of recurrence and mortality. The lack of expression of targetable proteins such as the estrogen receptor and absence of HER2 amplification have made relying on cytotoxic chemotherapy necessary for decades. In the operable setting, efforts to improve outcomes have focused on escalation of systemic therapy and a shift toward preoperative delivery followed by a response adapted approach to postoperative systemic therapy. An improved understanding of tumor biology has resulted in the identification of subsets of patients with specific molecular features, leading to testing and approval of multiple new targeted therapies for this disease. Furthermore, advances in drug development have led to the approval of antibody-drug conjugates that are redefining classification schemes for breast cancer. This review focuses on the modern management of TNBC, with particular focus on recent updates in the treatment of operable disease, and an overview of the most recent promising advances in the therapeutic landscape of metastatic disease. It discusses the practical challenges and unanswered questions resulting from the approval of neoadjuvant immunotherapy and shares an approach in the clinic on topics for which evidence is lacking. In addition, it provides a glimpse into the future, highlighting challenges and opportunities for biomarker based right-sizing of preoperative therapy, refining evaluation of response to preoperative therapy after surgery, early diagnosis and detection of relapse, and areas of needed research for metastatic TNBC.
Finding undiagnosed patients with hepatitis C virus: an application of machine learning to US ambulatory electronic medical records
Authors: Rigg John , Doyle Orla , McDonogh Niamh , Leavitt Nadea , Ali Rehan , Son Annie , Kreter Bruce
Published: May 2023

Aims

To develop and validate a machine learning (ML) algorithm to identify undiagnosed hepatitis C virus (HCV) patients, in order to facilitate prioritisation of patients for targeted HCV screening.

Methods

This retrospective study used ambulatory electronic medical records (EMR) from January 2015 to February 2020. A Gradient Boosting Trees algorithm was trained using patient records to predict initial HCV diagnosis and was validated on a temporally independent held-out cross-section of the data. The fold improvement in precision (proportion of patients identified by the algorithm who are HCV positive) over universal screening was examined and compared with risk-based screening.

Results

21 508 positive (HCV diagnosed) and 28.2M unlabelled (lacking evidence of HCV diagnosis) patients met the inclusion criteria for the study. After down-sampling unlabelled patients to aid the algorithm’s learning process, 16.2M unlabelled patients entered the analysis. Performance of the algorithm was compared with universal screening on the held-out cross-section, which had an incidence of HCV diagnoses of 0.02%. The algorithm achieved a 101.0 ×, 18.0 × and 5.1 × fold improvement in precision over universal screening at 5%, 20% and 50% levels of recall. When compared with risk-based screening, the algorithm required fewer patients to be screened and improved precision.

Conclusions

This study presents strong evidence towards the use of ML on EMR data for the prioritisation of patients for targeted HCV testing with potential to improve efficiency of resource utilisation, thereby reducing the workload for clinicians and saving healthcare costs. A prospective interventional study would allow for further validation before use in a clinical setting.
Organizational and health professional readiness for the implementation of electronic medical record system: an implication for the current EMR implementation in northwest Ethiopia
Authors: Yilma Tesfahun Melese , Tilahun Binyam , Mamuye Adane , Kerie Hailemariam , Nurhussien Fedlu , Zemen Endalkachew , Mebratu Aragaw , Abebaw Tewodros , Gebeyehu Henok , Abay Sefiw , Sisay Girma , Getachew Redet , Zemene Wondewossen , Tesfaye Selamsew , Tegegne Masresha Derese
Published: May 2023

Objective

The WHO developed a manual outlining the preliminary organizational and health professionals’ readiness to implement electronic medical records (EMR). On the other hand, the readiness assessment in Ethiopia only includes the evaluation of health professionals, leaving out organisational readiness components. As a result, this research aimed to determine health professionals’ and organizational readiness to implement EMR at a specialized teaching hospital.

Methods

An institutional-based cross-sectional study design was conducted among 423 health professionals and 54 managers. Self-administered and pretested questionnaires were used to collect data. Binary logistic regression analysis was used to identify factors associated with health professionals’ readiness for EMR implementation. An OR with a 95% CI and p<0.05 was used to determine the strength of the association and the statistical significance, respectively.

Results

In this study, 53.7% management capacity, 33.3% finance and budget capacity, 42.6% operational capacity, 37.0% technology capability and 53.7% organisational alignment among the five dimensions evaluated to assess an organisation’s readiness to implement an EMR system. Of 411 health professionals in this study, 173 (42.1%) with (95 CI 37.3% to 46.8%) were ready to implement an EMR system at the hospital. Sex (AOR 2.69, 95% CI 1.73 to 4.18), basic computer training (AOR 1.59, 95% CI 1.02 to 2.46), knowledge of EMR (AOR 1.88, 95% CI 1.19 to 2.97) and attitudes towards EMR (AOR 1.65, 95% CI 1.05 to 2.59) were significantly associated with health professionals’ readiness towards EMR system implementation.

Conclusions

Findings showed that most dimensions of organizational readiness for EMR implementation were below 50%. This study also revealed a lower level of EMR implementation readiness among health professionals compared with previous research studies’ results. To improve organisational readiness to implement an electronic medical record system, a focus on management capability, financial and budget capability, operational capability, technical capability and organisational alignment was crucial. Likewise, having basic computer training, giving special attention to female health professionals and improving health professionals’ knowledge of and attitudes towards EMR could help improve the readiness level of health professionals for implementing an EMR system.
Dynamic treatment regimes (DTRs) to study treatment sequencing in oncology: a scoping review protocol
Authors: Esteves Susana , Alves João Miguel , Rodrigues Pedro Pereira , Gomes da Silva Maria
Published: May 2023

Introduction

The rapid evolution of the therapeutic landscape in oncology poses challenges to optimal treatment sequencing. Evidence for clinical decision-making is often limited to studies focused on treatment evaluation at a single decision point, with limited capability of identifying delayed effects of prior treatment decisions on the efficacy and feasibility of future treatments. There is a growing interest in dynamic treatment regimes (DTRs) evaluation as it provides guidance on treatment individualisation based on evolving treatment and patient characteristics. In this scoping review we aim to systematically map how and to what extent DTRs have been evaluated in clinical studies to generate evidence for clinical decision-making in oncology.

Methods and analysis

We will do a systematic literature search in MEDLINE (PubMed), Web of Science, Scopus and WHO international clinical trials registry platform to identify clinical studies (including protocols of ongoing studies), with either experimental or observational design, that aim to answer a clinical question and explore treatment sequencing issues in oncology using the concept of DTR. Data extraction will comprise information concerning cancer disease, clinical setting, treatments, tailoring variables, decision rules, decision points and outcomes, type of data, study design and statistical methods used for DTR evaluation. The review will be conducted according to Joanna Briggs Institute Reviewer’s manual for scoping reviews. No patients will be involved.

Ethics and dissemination

Ethics committee approval is not required as this scoping review will undertake secondary analysis of published literature. Results will be disseminated through a peer-reviewed scientific journal and presented in relevant conferences. This scoping review will provide a better understanding of the methods used to generate evidence on treatment sequencing in oncology and will contribute to the identification of knowledge and methodological gaps that should be addressed.
Evaluating the clinical effectiveness of the NHS Health Check programme: a prospective analysis in the Genetics and Vascular Health Check (GENVASC) study
Authors: Debiec Radoslaw , Lawday Daniel , Bountziouka Vasiliki , Beeston Emma , Greengrass Chris , Bramley Richard , Sehmi Sue , Kharodia Shireen , Newton Michelle , Marshall Andrea , Krzeminski Andre , Zafar Azhar , Chahal Anuj , Heer Amardeep , Khunti Kamlesh , Joshi Nitin , Lakhani Mayur , Farooqi Azhar , Patel Riyaz , Samani Nilesh J
Published: May 2023

Objective

The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme—National Health Service Health Check (NHSHC) in reduction of CVD risk.

Design

Prospective cohort study.

Setting

147 primary care practices in Leicestershire and Northamptonshire in England, UK.

Participants

27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data.

Outcome measures

The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up.

Results

At recruitment, 18% of participants had high CVD risk (10%–20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI −0.34 to −0.41) and 1.71 mmol/L (−1.48 to −1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (−2.3 to −3.7), 15.7 mm Hg (−14.1 to −17.5) and 33.4 mm Hg (−29.4 to −37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment.

Conclusions

Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme.

Trial registration number

NCT04417387.