bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naringenin relieves paclitaxel‐induced pain by suppressing calcitonin gene‐related peptide signalling and enhances the anti‐tumour action of paclitaxel
Authors: Pan Chen , Xu Yuhao , Jiang Zongsheng , Fan Chengjiang , Chi Zhexi , Zhang Yu , Miao Mengmeng , Ren Yuxuan , Wu Ziyi , Xu Linbin , Mei Changqing , Chen Qingge , Xi Yang , Chen Xiaowei 
Published: May 2024

Background and PurposeChemotherapy‐induced peripheral neuropathy (CIPN) commonly causes neuropathic pain, but its pathogenesis remains unclear, and effective therapies are lacking. Naringenin, a natural dihydroflavonoid compound, has anti‐inflammatory, anti‐nociceptive and anti‐tumour activities. However, the effects of naringenin on chemotherapy‐induced pain and chemotherapy effectiveness remain unexplored.Experimental ApproachFemale and male mouse models of chemotherapy‐induced pain were established using paclitaxel. Effects of naringenin were assessed on pain induced by paclitaxel or calcitonin gene‐related peptide (CGRP) and on CGRP expression in dorsal root ganglia (DRG) and spinal cord tissue. Additionally, we examined peripheral macrophage infiltration, glial activation, c‐fos expression, DRG neuron excitability, microglial M1/M2 polarization, and phosphorylation of spinal NF‐κB. Furthermore, we investigated the synergic effect and related mechanisms of naringenin and paclitaxel on cell survival of cancer cells in vitro.Key ResultsSystemic administration of naringenin attenuated paclitaxel‐induced pain in both sexes. Naringenin reduced paclitaxel‐enhanced CGRP expression in DRGs and the spinal cord, and alleviated CGRP‐induced pain in naïve mice of both sexes. Naringenin mitigated macrophage infiltration and reversed paclitaxel‐elevated c‐fos expression and DRG neuron excitability. Naringenin decreased spinal glial activation and NF‐κB phosphorylation in both sexes but influenced microglial M1/M2 polarization only in females. Co‐administration of naringenin with paclitaxel enhanced paclitaxel's anti‐tumour effect, impeded by an apoptosis inhibitor.Conclusion and ImplicationsNaringenin's anti‐nociceptive mechanism involves CGRP signalling and neuroimmunoregulation. Furthermore, naringenin facilitates paclitaxel's anti‐tumour action, possibly involving apoptosis. This study demonstrates naringenin's potential as a supplementary treatment in cancer therapy by mitigating side effects and potentiating efficacy of chemotherapy.
Use of neurological criteria to declare death in children
Authors: Graf William D. , Epstein Leon G. , Kirschen Matthew P. 
Published: May 2024

AbstractAccurate determination of death is a necessary responsibility of the medical profession. Brain death, or death by neurological criteria (DNC), can be legally declared after the determination of permanent loss of clinical brain function, including the capacity for consciousness, brainstem reflexes, and the ability to breathe spontaneously. Despite longstanding debates over the exact definition of brain death or DNC and how it is determined, most middle‐ and high‐income countries have compatible medical protocols and legal policies for brain death or DNC. This review summarizes the 2023 updated guidelines for brain death or DNC determination, which integrate adult and pediatric diagnostic criteria. We discuss the clinical challenges related to brain death or DNC determination in infants and young children. We emphasize that physicians must follow the standardized and meticulous evaluation processes outlined in these guidelines to reduce diagnostic error and ensure no false positive determinations. An essential component of the brain death or DNC evaluation is appropriate and transparent communication with families. Ongoing efforts to promote consistency and legal uniformity in the declaration of death are needed.What this paper adds

Sociocultural sensitivity and appropriate communication with families during the brain death or death by neurological criteria (DNC) evaluation are needed.
A key component of the brain death or DNC evaluation is appropriate and transparent communication with families.
Uniform international standards and consistent legal definitions for brain death or DNC declaration remain a necessary objective.
The role of financial investors in successful family‐firm takeovers: A configurational approach
Authors: Kammerlander Nadine , Kurta Elias , Heider Anne 
Published: May 2024

AbstractFamily firms increasingly opt for an external succession route and sell shares to financial investors. Yet, not all family‐firm takeovers by financial investors are financially successful. To date, however, we lack a nuanced understanding of the conditions under which financial investors' family‐firm takeovers will succeed financially. Our fsQCA study builds on 52 interviews to reveal the interplay of three typical levers that financial investors use (i.e., operational, strategic, and governance measures), the market situation, and investor type. We identify three distinct roles (i.e., incentivizers, optimizers, and adjacent investors) that financial investors take in successful family‐firm takeover cases. We situate our findings in the literature on resources and their orchestration to explain how investors create value in each of the identified paths, and we contribute to the literature on family‐firm succession and the interplay of family firms and financial investors.
Simultaneous Discovery–Invention in Corporate R&D: Lessons from the CRISPR Case
Authors: Plantec Quentin , Le Masson Pascal , Weil Benoît 
Published: May 2024

AbstractSome companies invest in fundamental research, but many struggle when developing novel in‐house scientific knowledge and integrating it into their new inventions. While the literature advocates revised approaches to better understand this phenomenon, we investigate the processes that lead to Simultaneous Discovery–Invention (SDI). By adopting an abductive process, we propose a model that highlights the mechanisms of SDI. Notably, we reveal that teams must preserve independence in creative exploration during scientific knowledge creation and invention generation while maintaining intensive original knowledge exchange among them. We also demonstrate that anomaly detection and peer validation mechanisms are mandatory for SDI. We evaluate our model with a case study in the food industry: the discovery that CRISPR–Cas9 is an adaptative defense immune system of bacteria and the associated innovations in this industry. Finally, we discuss the insights provided by our model and the implications of our case study.
Virulence is associated with daily rhythms in the within‐host replication of the malaria parasite Plasmodium chabaudi
Authors: Owolabi Alíz T. Y. , Schneider Petra , Reece Sarah E. 
Published: May 2024

AbstractMost malaria (Plasmodium spp.) parasite species undergo asexual replication synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite's rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes of Plasmodium; however, this variation is poorly understood. The theory predicts that virulence and IDC synchrony are negatively correlated, and we tested this hypothesis using two closely related genotypes of the rodent malaria model Plasmodium chabaudi that differ markedly in virulence. We also test the predictions that, in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness losses and so hosts benefit less from misalignment when infected with a virulent genotype. Our predictions are partially supported by results suggesting that the virulent parasite genotype is less synchronous in some circumstances and recovers faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule, and host rhythms and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.
Improving outcomes in equine skin cancer
Authors: Prange Timo 
Published: May 2024

SummarySkin diseases are an important health problem in horses, and the skin is the most common location for tumours. Equine sarcoids, melanomas and squamous cell carcinomas make up over 95% of cutaneous tumours, but information about the effective treatment of these common forms of skin cancer is limited. In the absence of reliable therapies for advanced cases, cancer screening, reliable diagnostics and early treatment become even more important.
Personal and organisational health literacy in the non‐specific symptom pathway for cancer: An ethnographic study
Authors: Black Georgia B. , Moreland Julie‐Ann , Fulop Naomi J. , Lyratzopoulos Georgios , Nicholson Brian D. , Whitaker Katriina L. 
Published: May 2024

AbstractIntroductionPeople being investigated for cancer face a wealth of complex information. Non‐specific symptom pathways (NSS) were implemented in the United Kingdom in 2017 to address the needs of patients experiencing symptoms such as weight loss, fatigue or general practitioner ‘gut feeling’, who did not have streamlined pathways for cancer investigation. This study aimed to explore the health literacy skills needed by patients being investigated for cancer in NSS pathways.MethodsThis study employed ethnographic methods across four hospitals in England, including interviews, patient shadowing and clinical care observations, to examine NSS pathways for cancer diagnosis. We recruited 27 patients who were shadowed and interviewed during their care. We also interviewed 27 professionals. The analysis focused on patient communication and understanding, drawing on the concepts of personal and organisational health literacy.ResultsOur analysis derived six themes highlighting the considerable informational demands of the NSS pathway. Patients were required to understand complex blood tests and investigations in primary care and often did not understand why they were referred. The NSS pathway itself was difficult to understand with only a minority of patients appreciating that multiple organs were being investigated for cancer. The process of progressing through the pathway was also difficult to understand, particularly around who was making decisions and what would happen next. The results of investigations were complex, often including incidental findings. Patients whose persistent symptoms were not explained were often unsure of what to do following discharge.ConclusionWe have identified several potential missed opportunities for organisations to support patient understanding of NSS pathways which could lead to inappropriate help‐seeking post‐discharge. Patients' difficulties in comprehending previous investigations and findings could result in delays, overtesting or inadequately targeted investigations, hindering the effective use of their medical history. Third, patients' limited understanding of their investigations and results may impede their ability to engage in patient safety by reporting potential care errors.Patient or Public ContributionPatient, public, clinical and policy representatives contributed to developing the research objectives through a series of meetings and individual conversations in preparation for the study. We have held several events in which patients and the public have had an opportunity to give feedback about our results, such as local interest groups in North London and academic conferences. A clinical contributor (J.‐A. M.) was involved in data analysis and writing the manuscript.
Gastric cancer molecular classification based on immunohistochemistry and in‐situ hybridisation and mortality
Authors: Eskuri Maarit , Birkman Eva‐Maria , Kauppila Joonas H 
Published: May 2024

Background and aimsGastric cancers (GC) are divided into subtypes based on molecular profile: Epstein–Barr virus (EBV)‐positive, microsatellite instability (MSI), chromosomal instability (CIN) and genomically stable (GS) tumours. The prognostic impact of this classification is unclear. The aim was to evaluate whether the molecular subtypes determined using in‐situ hybridisation (ISH) and immunohistochemistry (IHC) are associated with clinicopathological parameters and prognosis.Methods and resultsThe study included 503 GC patients. Based on ISH (EBV) and IHC (MSI and TP53), tumours were divided into EBV‐positive, MSI, CIN (EBVneg/MSS/TP53aberrant) and GS (EBVneg/MSS/TP53wild‐type) subgroups. Survival analyses with intestinal‐ and diffuse‐type tumours were examined separately. EBV‐positive tumours associated with male sex. Both EBV‐positive and MSI tumours associated with intestinal type. CIN tumours associated with intestinal‐type and positive lymph node status. GS tumours associated with diffuse‐type and negative lymph node status. In the total cohort, no significant differences in the 5‐year survival were observed. In intestinal tumours, the 5‐year survival was better in EBV‐positive tumours compared with GS tumours [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.99]. In diffuse tumours, the 5‐year survival was worse in CIN tumours compared with GS tumours (HR = 1.57, 95% CI = 1.14–2.18). In radically resected diffuse tumours, the 5‐year survival was worse in MSI tumours compared with GS tumours (HR = 3.26, 95% CI = 1.20–8.82).ConclusionsThe molecular classification is associated with histological type but not prognosis in GC. As the prognostic effects of molecular subtypes in intestinal‐ and diffuse‐type cancers may differ, combining histological and molecular information is recommended for future studies.
Ecology of multispecies biofilm formed in refrigerated raw milk in the presence of nisin and the quorum quenching furanone
Authors: Oliveira Gabriel Silva , Lima Helena Santiago , Silva Cynthia Canêdo , Vanetti Maria Cristina Dantas 
Published: May 2024

SummaryCharacterisation of bacterial communities in multispecies biofilm can aid the search for prevention and control strategies. This study evaluated the influence of nisin and quorum quenching compound furanone on the diversity of biofilm formed from raw milk. Stainless steel coupons were immersed in raw milk containing either nisin or furanone. Biofilm DNA was extracted, followed by metataxonomic analyses. Chao‐1 richness, Simpson, and Shannon diversity indexes fluctuated over the 10‐day period in the control biofilm. However, both nisin and furanone led to a decrease in the Chao‐1 index of the biofilm microbiota and small fluctuation in the Simpson and Shannon diversity indexes without altering the number of sessile cells. Gammaproteobacteria, recognised contaminants of significance in milk, was the dominant class in all biofilms. Addition of nisin or furanone to the raw milk altered the microbial community of the biofilm, resulting particularly in the abundance of the genera Acinetobacter, Lactococcus, and Serratia.
Exploring language assessment literacy: A case of perceived needs of two stakeholder groups in Egypt
Authors: Ali Amira Desouky 
Published: May 2024

AbstractStakeholders in exam‐driven countries are responsible for developing test‐related tasks to assess the quality of English as a Foreign Language (EFL) teaching and learning. Hence, the language assessment literacy (LAL) of different stakeholders has to be investigated. This mixed‐methods study explored the required LAL competencies among two groups of Egyptian EFL supervisors and teachers and examined the impact of participants' demographic profiles on choosing LAL competencies. The groups prioritized their needs for assessment in language pedagogy. While supervisors were highly demanded to develop and administer language assessments, teachers were highly interested in developing their skills at assessment scoring and rating. Teachers' selection of LAL competencies was influenced by age, educational degree and professional training; whereas supervisors' LAL was impacted by experience and educational degree. The findings of interviews shed light on participants' perceived needs for LAL knowledge and skills, the challenges of achieving LAL, and ways for improvement.
Processing strategy and composite regulation on dielectric performance in Li2O–Al2O3–B2O3 dielectric systems using SrTiO3
Authors: Xiong Siyu , Chen Deqin , Zhu Xiaowei , Zhu Guobin , Xiao Hongxiang , Gong Weiping , Liu Laijun , Khaliq Jibran , Li Chunchun 
Published: May 2024

AbstractIn this paper, we investigated the effect of processing parameters and composite regulation on the structure and property relationship of lightweight low‐permittivity Li2O–Al2O3–B2O3 dielectric system. Li2BAlO4 ceramic and (1 − x)Li2BAlO4–xSrTiO3 ceramics were synthesized using a conventional solid‐state reaction method. Thermodynamic analysis, sintering temperature, phase formation, crystal structure, and microwave dielectric properties were investigated. Thermal analysis revealed a melting temperature of 847°C, suggesting a comparatively low temperature for the sintering of Li2BAlO4 ceramics. Li2BAlO4 crystalized into a monoclinic structure with P21/c space group, with [Al2B2O8] rings connected by [BO3] triangles and [AlO4] tetrahedra through Al–O–Al bridges. Dense Li2BAlO4 ceramics with a relative density of ∼97.7% were sintered at 750°C and had optimal microwave dielectric properties with relative permittivity (εr) of 5.13, quality factor (Q × f) of 22 610 GHz, and the temperature coefficient of resonance frequency (τf) of −112.5 ppm/°C. The 0.88Li2BAlO4–0.12SrTiO3 composite ceramic has excellent microwave dielectric properties with εr = 8.83, Q × f = 14 000 GHz, τf = 4.6 ppm/°C. The ceramics also demonstrated an inert behavior with silver electrodes proving its application in low‐temperature cofired ceramic (LTCC) technology.
Target organ damage in untreated hypertensive patients with primary aldosteronism
Authors: Li Shi‐Min , Huang Jia‐Yi , Zhu Ching‐Yan , Ng Ming‐Yen , Lin Qing‐Shan , Wu Min , Liu Ming‐Ya , Wang Run , Cao Gao‐Zhen , Chen Cong , Wu Mei‐Zhen , Ren Qing‐Wen , Tse Hung‐Fat , Yiu Kai‐Hang 
Published: May 2024

AbstractAn increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong‐Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima‐media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.
Intra‐operative dermoscopy (onychoscopy) of the nail unit—A systematic review
Authors: Sławińska M. , Żółkiewicz J. , Ribereau‐Gayon E. , Maińska U. , Sobjanek M. , Thomas L. 
Published: May 2024

AbstractDermoscopy of the nail unit (onychoscopy) is a method which allows for non‐invasive observation of the nail structures, increasing the accuracy of clinical diagnosis. Currently, it is used in evaluation of both inflammatory and neoplastic conditions of the nail unit. However, in contrast to the skin, the anatomy of the nail unit prevents direct observation of nail bed or nail matrix structure during classic onychoscopy. Intra‐operative onychoscopy is a variant of the technique which uses direct visualization of the nail unit structures after nail plate avulsion. The aim of this systematic review was to summarize the current state of knowledge on intra‐operative onychoscopy. The MEDLINE, EMBASE and Cochrane databases were systematically searched in January 2024. All types of study designs assessing intra‐operative dermoscopy of the nail unit were included in this study. The risk of bias in included studies was assessed using the Joanna Briggs Institute critical appraisal tools. The qualitative synthesis of 19 studies totalling a number of 218 cases in 217 patients included the following entities: melanoma, nevus, hypermelanosis (melanocytic activation), melanocytic hyperplasia, melanophages accumulation, squamous cell carcinoma, glomus tumour, lichen planus, onychomatricoma, onychomycosis and subungual exostosis. The main limitation of the study was a relatively low number of identified studies, most with low levels of evidence. Intra‐operative onychoscopy does not replace histologic examination, though it may be useful in determining the modality of surgical diagnostic procedures.