bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iatrogenic copper deficiency: Risks and cautions with zinc prescribing
Authors: Duncan Andrew , Morrison Ian , Bryson Scott 
Published: April 2023

AimsCopper deficiency resulting from prescribing zinc in high doses is a rare but life‐changing diagnosis that is frequently overlooked. The aim of this study is to gauge how often zinc‐induced copper deficiency is missed, to raise awareness of the condition and to stress the need for guidelines for prescribing zinc.MethodsSuspected cases of zinc‐induced copper deficiency were retrospectively obtained by selecting those patients with hyperzincaemia and hypocupraemia from the database of the Scottish Trace Element Laboratory. Case records were reviewed to determine the validity of the suspected diagnosis.ResultsAfter exclusions, 23 instances of high serum zinc and low serum copper concentrations were found. A positive diagnosis of zinc‐induced copper deficiency was made in 14 patients, of which 7 (50%) were previously undiagnosed.ConclusionSerum zinc and copper concentrations are rarely measured in patients prescribed zinc and so the vast majority of cases of zinc‐induced copper deficiency are likely to be undiagnosed. We recommend the current official advice on the dose and frequency of zinc administration is revised in order to limit, and potentially eradicate, the condition.
Discovering interactions in augmentation strategies: Impact of duloxetine on the metabolism of aripiprazole
Authors: Margraff Teresa , Schoretsanitis Georgios , Neuner Irene , Haen Ekkehard , Gaebler Arnim Johannes , Paulzen Michael 
Published: April 2023

AbstractObjectiveWe aimed to unravel potential pharmacokinetic interactions between aripiprazole and duloxetine.MethodsPlasma concentrations of aripiprazole in two groups of 78 patients each, receiving aripiprazole as a monotherapy or combined with duloxetine, were compared. A potential impact of duloxetine on the metabolism of aripiprazole was expected in higher plasma concentrations of aripiprazole and higher dose‐adjusted plasma concentrations.ResultsPatients co‐medicated with duloxetine showed significantly higher plasma concentrations of aripiprazole by 54.2% (p = 0.019). Dose‐adjusted plasma concentrations were 45.6% higher (p = 0.001); 12.8% of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the control group this was only the case for 10.3% of the patients. A positive relationship was found between the daily dose of duloxetine and dose‐adjusted plasma concentrations of aripiprazole (p = 0.034). As dehydroaripiprazole concentrations were not available, conclusions for the active moiety (aripiprazole plus dehydroaripiprazole) could not be drawn.ConclusionsCombining duloxetine and aripiprazole leads to significantly higher drug concentrations of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with aripiprazole.
YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
Authors: Su Yinjie , Wang Bo , Huang Jian , Huang Ming , Lin Tianxin 
Published: April 2023

AbstractActivation of PI3K/AKT signalling by PTEN loss significantly enhances chemoresistance in bladder cancer. This study aims to evaluate PTEN regulation and identify targets that could be used to relieve chemoresistance. Expression of YTHDC1, γ‐H2AX and PTEN were detected by IHC assay. Cell Counting Kit‐8 assay, colony formation assay and tumour xenograft experiment evaluated cisplatin response. Flow cytometry and comet assay estimated cell apoptosis, cell cycle distribution and DNA repair capability. Quantitative real‐time polymerase chain reaction, Western blot and RIP assay assessed binding properties between PTEN mRNA and YTHDC1. Silencing YTHDC1 in bladder cancer cells reduced PTEN expression and activated PI3K/AKT signalling by destabilizing PTEN mRNA in an m6A‐dependent manner. Low YTHDC1 expression indicated poor cisplatin sensitivity in bladder cancer patients. Reducing YTHDC1 expression promoted drug resistance to cisplatin, while over‐expressing YTHDC1 promoted cisplatin sensitivity. Reducing YTHDC1 expression activated DNA damage response, which includes quicker cell cycle recovery, apoptosis evasion and an enhanced DNA repair capability, whereas these effects were attenuated when MK2206, a PI3K/AKT inhibitor was applied. We provide novel evidence that PTEN/PI3K/AKT signalling pathway could be regulated by YTHDC1 in an m6A‐dependent manner and highlight a critical role of YTHDC1 in cisplatin resistance of bladder cancer.
Predictors of severe submucosal fibrosis during endoscopic submucosal dissection in patients with ulcerative colitis: Retrospective cohort study
Authors: Nishio Masafumi , Hirasawa Kingo , Saigusa Yusuke , Atsusaka Reo , Azuma Daisuke , Ozeki Yuichiro , Sawada Atsushi , Ikeda Ryosuke , Fukuchi Takehide , Kobayashi Ryosuke , Sato Chiko , Ogashiwa Tsuyoshi , Inayama Yoshiaki , Kunisaki Reiko , Maeda Shin 
Published: April 2023

ObjectivesSevere submucosal fibrosis is a crucial technical difficulty encountered during endoscopic submucosal dissection (ESD) in patients with ulcerative colitis (UC). We aimed to identify predictors of severe submucosal fibrosis in patients with UC.MethodsWe retrospectively included 55 tumors resected using ESD from 48 consecutive patients with UC. We analyzed the clinicopathological characteristics and treatment outcomes between the F0/1 (none to mild submucosal fibrosis) group (n = 28) and F2 (severe submucosal fibrosis) group (n = 27).ResultsNo significant difference was found between the F0/1 and F2 groups in en bloc resection rate (100% vs. 96%, P = 0.49), the R0 resection rate (100% vs. 93%, P = 0.24), and the dissection speed (0.18 vs. 0.13 cm2/min, P = 0.07). Intraoperative perforation was more common in the F2 group (30%) than in the F0/1 group (8%; P = 0.01). Multivariable analysis showed that a longer duration of UC (≥10 years; odds ratio [OR] 6.11; 95% confidence interval [CI] 1.20–31.03; P = 0.03) and scarring of background mucosa of the tumor (OR 39.61; 95% CI 3.91–400.78; P < 0.01) were independent predictors of severe submucosal fibrosis.ConclusionLong UC duration and scarring background mucosa were predictors of severe submucosal fibrosis associated with perforation during ESD.
Toward a universal measure of robustness across model organs and systems
Authors: Jernvall Jukka , Di‐Poï Nicolas , Mikkola Marja L. , Kratochwil Claudius F. 
Published: April 2023

AbstractThe development of an individual must be capable of resisting the harmful effects of internal and external perturbations. This capacity, called robustness, can make the difference between normal variation and disease. Some systems and organs are more resilient in their capacity to correct the effects of internal disturbances such as mutations. Similarly, organs and organisms differ in their capacity to be resilient against external disturbances, such as changes in temperature. Furthermore, all developmental systems must be somewhat flexible to permit evolutionary change, and understanding robustness requires a comparative framework. Over the last decades, most research on developmental robustness has been focusing on specific model systems and organs. Hence, we lack tools that would allow cross‐species and cross‐organ comparisons. Here, we emphasize the need for a uniform framework to experimentally test and quantify robustness across study systems and suggest that the analysis of fluctuating asymmetry might be a powerful proxy to do so. Such a comparative framework will ultimately help to resolve why and how organs of the same and different species differ in their sensitivity to internal (e.g., mutations) and external (e.g., temperature) perturbations and at what level of biological organization buffering capacities exist and therefore create robustness of the developmental system.
Pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α in major depressive disorder: Sex‐specific associations with psychological symptoms
Authors: Elgellaie Asmahan , Thomas Susan J. , Kaelle Jacqueline , Bartschi Jessica , Larkin Theresa 
Published: April 2023

AbstractThe pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α are associated with major depressive disorder, psychological distress, cardiovascular health and obesity. However, there is limited research that has examined multiple associations between these variables, particularly among individuals with major depressive disorder who are treatment free, in comparison with a control cohort, and including analyses of sex differences. In this study, data were analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL‐1α, IL‐6 and TNF‐α, adiposity measures (body mass index, waist circumference), cardiovascular health indices (blood pressure, heart rate) and psychological symptoms (depressive severity, anxiety, hostility, stress). The cytokines were compared by group and sex and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL‐1α and IL‐6 were higher in major depressive disorder group versus control, but with a sex interaction for IL‐6, with this group difference only among females. TNF‐α did not differ between groups. IL‐1α and IL‐6 correlated with depressive severity, anxiety, hostility and stress, whereas TNF‐α correlated only with anxiety and hostility. Psychopathology was associated with IL‐1α in males only and with IL‐6 and TNF‐α in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL‐6 and sex‐specific associations between pro‐inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.
Effect of mouthwashes on gingival healing after surgical procedures: A systematic review
Authors: Casarin Maísa , de Matos Raquele Soares , da Silva Nolasco Wagner , Pirih Flavia Q. , Muniz Francisco Wilker Mustafa Gomes 
Published: April 2023

AbstractThe aim of the present study was to perform a systematic review of the literature regarding the effect of different mouthwashes on gingival healing after oral surgery in adults. Searches were conducted in seven databases (PubMed/MEDLINE, Cochrane Library, Clinical Trials Registry, Embase, LILACS, Web of Science, and Google Scholar) for relevant randomized controlled trials (RCTs) published up to April 2022. The selection of studies, data extraction, and risk of bias appraisal were performed independently by two reviewers, and a third researcher was consulted to resolve disagreements. Data syntheses were presented narratively for the different criteria of gingival wound healing. Among 4502 articles retrieved from the databases, 13 studies met the eligibility criteria and were included in the present review. Chlorhexidine was the most frequent mouthwash studied (eight studies) and was used in different concentrations and combinations. Cetylpyridinium chloride, H2Ocean Sea Salt, Commiphora molmol 0.5%, chlorhexidine 0.12%, and essential oils reported better healing than a negative control. However, the uncertain risk of bias in most RCTs included in this review precludes definitive conclusions. Well‐designed RCTs are therefore still needed in this area.
Carryover effects from environmental change in early life: An overlooked driver of the amphibian extinction crisis?
Authors: Lundsgaard Niclas U. , Hird Coen , Doody Kathleen A. , Franklin Craig E. , Cramp Rebecca L. 
Published: April 2023

AbstractEcological carryover effects, or delayed effects of the environment on an organism's phenotype, are central predictors of individual fitness and a key issue in conservation biology. Climate change imposes increasingly variable environmental conditions that may be challenging to early life‐history stages in animals with complex life histories, leading to detrimental physiological and fitness effects in later life. Yet, the latent nature of carryover effects, combined with the long temporal scales over which they can manifest, means that this phenomenon remains understudied and is often overlooked in short‐term studies limited to single life‐history stages. Herein, we review evidence for the physiological carryover effects induced by elevated ultraviolet radiation (UVR; 280–400 nm) as a potential contributor to recent amphibian population declines. UVR exposure causes a suite of molecular, cellular and physiological consequences known to underpin carryover effects in other taxa, but there is a lack of research linking embryonic and larval UVR exposures to fitness consequences post‐metamorphosis in amphibians. We propose that the key impacts of UVR on disease‐related amphibian declines are facilitated through carryover effects that bridge embryonic and larval UVR exposure with potential increased disease susceptibility post‐metamorphosis. We conclude by identifying a practical direction for the study of ecological carryover effects in amphibians that could guide future ecological research in the broader field of conservation physiology. Only by addressing carryover effects can many of the mechanistic links between environmental change and population declines be elucidated.
Positive aspects of caregiving attenuate the relationship between behavioral bother and anxiety and depressive symptoms in dementia family caregivers
Authors: Cheng Sheung‐Tak 
Published: April 2023

AimTo examine the protective role of positive aspects of caregiving (PAC) in terms of whether it dampens the relationship between behavioral bother and anxiety/depressive symptoms.MethodsThe baseline data of the Resources for Enhancing Alzheimer's Caregiver Health I trial were used. US dementia family caregivers (N = 1222) responded to standard self‐report measures of PAC, behavioral bother, depression, anxiety, challenging behaviors, and functional impairment. The buffering effect of PAC was tested using moderational regression.ResultsControlling for caregivers' age, sex and behavioral bother, and care‐recipients' challenging behaviors and functional impairment, PAC was mildly inversely related to depressive and anxiety symptoms. Moreover, a significant PAC × behavioral bother interaction effect was found such that the relationship between behavioral bother, on the one hand, and depression and anxiety, on the other, became weaker with higher PAC. In particular, when behavioral bother was low, depressive and anxiety symptoms were similar regardless of levels of PAC. But when behavioral bother was high, caregivers who reported higher levels of PAC were less depressed and anxious than those with lower levels, with their standardized mean differences being small to moderate.ConclusionsPAC was found to be associated with less mood symptoms partly directly and partly through modifying the effect of behavioral bother on depression and anxiety. Caregivers who were highly troubled by the relative's challenging behaviors, but who found higher levels of PAC at the same time, experienced better emotional well‐being. Having PAC may make the burden of caregiving more tolerable, thereby alleviating caregiver distress down the road. Geriatr Gerontol Int 2023; 23: 366–370.
Multiple pathways and independent functional pools in insulin granule exocytosis
Authors: Izumi Tetsuro 
Published: April 2023

AbstractIn contrast to synaptic vesicle exocytosis, secretory granule exocytosis follows a much longer time course, and thus allows for different prefusion states prior to stimulation. Indeed, total internal reflection fluorescence microscopy in living pancreatic β cells reveals that, prior to stimulation, either visible or invisible granules fuse in parallel during both early (first) and late (second) phases after glucose stimulation. Therefore, fusion occurs not only from granules predocked to the plasma membrane but also from those translocated from the cell interior during ongoing stimulation. Recent findings suggest that such heterogeneous exocytosis is conducted by a specific set of multiple Rab27 effectors that appear to operate on the same granule; namely, exophilin‐8, granuphilin, and melanophilin play differential roles in distinct secretory pathways to final fusion. Furthermore, the exocyst, which is known to tether secretory vesicles to the plasma membrane in constitutive exocytosis, cooperatively functions with these Rab27 effectors in regulated exocytosis. In this review, the basic nature of insulin granule exocytosis will be described as a representative example of secretory granule exocytosis, followed by a discussion of the means by which different Rab27 effectors and the exocyst coordinate to regulate the entire exocytic processes in β cells.
Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment
Authors: Vocino Trucco Giulia , Benazzo Giacomo Maria , Ricci Alessia Andrea , Mangherini Luca , Falco Enrico , Gambella Alessandro , Bertero Luca , Cassoni Paola 
Published: April 2023

AimsThe current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD‐L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal.Methods and resultsHistopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non‐metastatic cases were assessed. PD‐L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD‐L1 expression and nodal metastasis, the optimal cut‐off values, interobserver agreement and impact upon patients' surgical management were determined. PD‐L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD‐L1CPS: OR = –2.5, 95% CI = −4.11 to −0.97, P = 0.008 and PD‐L1ICS: OR = −1.85, 95% CI = −2.90 to −0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut‐off values to discriminate between metastatic and non‐metastatic patients. In our cohort, the implementation of these cut‐off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD‐L1CPS = 43.2; PD‐L1ICS = 51.9%). Ultimately, PD‐L1 evaluation showed good interpathologist concordance in absolute terms [PD‐L1CPS interclass correlation coefficient (ICC) = 0.91; PD‐L1ICS ICC = 0.793] and using the identified cut‐off values (PD‐L1CPS ICC = 0.848; PD‐L1ICS ICC = 0.756).ConclusionsOur study shows that PD‐L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.
A nodal EBV‐positive T cell lymphoma with a T follicular helper cell phenotype
Authors: Zhang Zhaoxuan , Wang Wei , Li Yuan , Xu Zhouyi , Wu Haibo , Wang Zhe 
Published: April 2023

AimsNodal T follicular helper (TFH) cell lymphoma (nTFHL) is a rare type of clinically aggressive T cell lymphoma. With this lymphoma type, Epstein–Barr virus (EBV) infection is frequently detected in non‐neoplastic B lymphocytes, but not yet identified in neoplastic T cells. We report two cases of nTFHL showing a classic morphology and immunoprofile, with EBV‐encoded small RNAs (EBER) in‐situ hybridisation positivity in neoplastic TFH cells.Methods and resultsClonal T cell receptor (TR) gene rearrangement was detected in both cases. Whole exome sequencing identified TET2, RHOA p. G17V, as well as gene mutations unique to each case. Microdissection analysis showed EBER positivity in tumour cells and in background non‐neoplastic T lymphocytes.ConclusionThese two immunocompetent cases of nTFHL with EBV‐positive tumour cells exhibit the featured gene mutation profile and poor prognosis of this disease. This novel finding of EBV positivity in our cases expands the currently recognised spectrum of EBV‐positive nodal T cell lymphomas to include rare cases of nTFHL.
Relational Justice: Egalitarian and Sufficientarian
Authors: Bengtson Andreas , Nielsen Lasse 
Published: April 2023

ABSTRACTRelational egalitarianism is a theory of justice according to which people must relate as equals. In this article, we develop relational sufficientarianism – a view of justice according to which people must relate as sufficients. We distinguish between three versions of this ideal, one that is incompatible with relational egalitarianism and two that are not. Building on this, we argue that relational theorists have good reason to support a pluralist view that is both egalitarian and sufficientarian.
Changing the Scholarly Conversation: What it Means, Why it Matters, and How to Approach it in Micro Research
Authors: Healey Mark P. , Leroy Hannes , Post Corinne , Potočnik Kristina 
Published: April 2023

AbstractAcademics often assess contributions to management research in terms of their influence on the scholarly conversation. At JMS, we aspire to publish papers that significantly change scholarly conversations in productive ways. However, precisely what it means and what it takes to change a scholarly conversation is not entirely clear, especially in micro research in the management field where contributions are often framed in incremental terms. Accordingly, in this editorial we examine what distinguishes papers that significantly change the scholarly conversation on a topic and analyse the functions of such conversation‐changing papers, focussing on research in the micro domain. Based on an inductive analysis of exemplar conversation‐changing micro papers, we propose a typology that identifies how scholars substantially alter an existing conversation or stimulate a new conversation. For each type of conversation‐changing contribution, we identify its attributes and functions and discuss exemplars. We conclude with guidance and tips for authors, reviewers, and editors seeking to develop papers that reshape scholarly conversations. With this editorial, we hope to inspire more conversation changing papers, especially among micro scholars, and position JMS as a natural home for such papers.