bluuebunny/crossref_metadata_2025 huggingface dataset:
Valproic acid treatment attenuates cisplatin‐induced kidney injury by suppressing proximal tubular cell damage
Authors: Yoshioka Toshihiko , Goda Mitsuhiro , Kanda Masaya , Itobayashi Sayuri , Sugimoto Yugo , Izawa‐Ishizawa Yuki , Yagi Kenta , Aizawa Fuka , Miyata Koji , Niimura Takahiro , Hamano Hirofumi , Sakurada Takumi , Zamami Yoshito , Ishizawa Keisuke
Published: September 2023

Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin‐induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin‐induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin‐induced toxicity. In the mouse model of cisplatin‐induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin‐treated and valproic acid‐treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin‐induced decrease in cell viability was significantly suppressed by co‐treatment with valproic acid. Valproic acid may inhibit cisplatin‐induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.
Geographische Unterschiede zwischen städtischem und ländlichem Raum beim Risiko für atopische Dermatitis: Systematischer Review und Meta‐Analyse
Authors: Shin Jun‐Oh , Kim Kihun , Kim Hoon‐Soo , Ko Hyun‐Chang , Kim Byungsoo , Kim Moon‐Bum , Shin Kihyuk , Kim Yun Hak
Published: September 2023

Die atopische Dermatitis ist die häufigste chronisch‐entzündliche Hauterkrankung im Kindesalter. Einige Studien kamen zu dem Ergebnis, das Risiko für diese Erkrankung sei im städtischen Raum höher als im ländlichen. Wir haben die verfügbaren Studien systematisch untersucht und eine Meta‐Analyse durchgeführt, um Unterschiede im Risiko für atopische Dermatitis zwischen städtischem und ländlichem Raum zu erkennen. Die Suche in den Datenbanken Embase und MEDLINE wurde am 19. April 2021 durchgeführt. Einschlusskriterium war das Stichwort “Beobachtungsstudie”. Wir haben außerdem Subgruppenanalysen bezüglich Patientenalter, Publikationsjahr und Land durchgeführt. Insgesamt wurden bei der Datenbanksuche 2115 Studien aufgefunden, von denen letztlich 43 Studien mit insgesamt 1 728 855 Patienten in die Meta‐Analyse eingeschlossen wurden. Ein Wohnsitz im städtischen Raum war mit einem erhöhten Risiko für atopische Dermatitis assoziiert; die Odds Ratio war 1,56 (95 %‐Konfidenzintervall 1,43–1,71). Dieses signifikant erhöhte Risiko war nur bei Kindern zu beobachten (Odds Ratio 1,55, 95 %‐Konfidenzintervall 1,39–1,73), nicht jedoch bei Erwachsenen. Hier betrug die Odds Ratio 1,29 (95 %‐Konfidenzintervall 0,99–1,67). Das Risiko für atopische Dermatitis ist in den letzten Jahrzehnten angestiegen, wobei das Risiko in Entwicklungsländern mit einer Odds Ratio von 1,95 höher liegt als in Industrieländern (Odds Ratio 1,35). Unsere Studie bestätigt die Assoziation zwischen atopischer Dermatitis und dem Wohnsitz im städtischen gegenüber dem ländlichen Raum.
Die Wirkung von Mogamulizumab auf die aberrante T‐Zell‐Population im peripheren Blut – eine monozentrische retrospektive Analyse
Authors: Gosmann Janika , Bielefeld Annette , Schmitz Franz‐Josef , Schaper‐Gerhardt Katrin , Gutzmer Ralf , Stadler Rudolf
Published: September 2023

Hintergrund

Die Wirkung von Mogamulizumab bei kutanen T‐Zell‐Lymphomen (CTCL) auf die T‐Zellen (TZ) im peripheren Blut und deren potenzielle Rolle bei der Steuerung von Behandlungsintervallen wird noch erforscht.

Methodik

Wir untersuchten in einer retrospektiven monozentrischen Analyse die Wirkung von Mogamulizumab auf die CD3+ TZ und die aberrante T‐Zellpopulation (TZP), CD4+/CD7– und die CD4+/CD26– TZ, die mittels Durchflusszytometrie analysiert wurden.

Ergebnisse

Dreizehn Patienten mit CTCL wurden eingeschlossen. Nach vier Zyklen kam es zu einer durchschnittlichen Reduktion der CD3+ TZ um 57%, der CD4+/CD7− um 72% und der CD4+/CD26− TZ um 75% im Vergleich zum individuellen Ausgangswert eines jeden Patienten. Die Reduktionen der CD4+/CD7+ und CD4+/CD26+ TZ fielen mit durchschnittlich 54% und 41% geringer aus. Ein signifikanter Rückgang der aberranten TZP war bereits nach der ersten Infusion zu beobachten. Ein medianes Plateau der TZP trat bereits während der Induktionsphase ein. Bei 5/13 Patienten kam es zu einem Progress der Erkrankung, ohne dass eine eindeutige Korrelation mit der aberranten TZP bestand.

Schlussfolgerungen

Bereits nach einer Gabe Mogamulizumab reduzierte sich die aberrante TZP und – in geringerem Maße – die normale TZP. Wir konnten keine eindeutige Korrelation der TZP mit der Wirksamkeit von Mogamulizumab beobachten. Es werden weitere Untersuchungen mit einer größeren Anzahl von Patienten benötigt.
Safety and efficacy of endoscopic ultrasound‐guided radiofrequency ablation for pancreatic neuroendocrine neoplasms: Systematic review and meta‐analysis
Authors: Khoury Tawfik , Sbeit Wisam , Fusaroli Pietro , Campana Davide , Brighi Nicole , Napoleon Bertrand , Lisotti Andrea
Published: September 2023

Objective

Endoscopic ultrasound‐guided radiofrequency ablation (EUS‐RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS‐RFA for pNENs.

Methods

The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS‐RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% confidence interval (CI) were calculated using a random‐effect model.

Results

Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9–99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1–92.8%). The pooled partial response was 11.4% (95% CI 6.2–18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7–97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0–26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2–2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported.

Conclusion

Endoscopic ultrasound‐guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate.
Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT‐1 trial
Authors: Hankosky Emily R. , Wang Hui , Neff Lisa M. , Kan Hong , Wang Fangyu , Ahmad Nadia N. , Stefanski Adam , Garvey W. Timothy
Published: September 2023

Aim

We assessed the impact of tirzepatide on 10‐year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT‐1 trial.

Materials and Methods

In this post hoc analysis of SURMOUNT‐1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10‐year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline.

Results

Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%‐24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%‐20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%‐11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo.

Conclusion

Tirzepatide treatment significantly reduced the 10‐year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.
Effect of tirzepatide on blood pressure and lipids: A meta‐analysis of randomized controlled trials
Authors: Kanbay Mehmet , Copur Sidar , Siriopol Dimitrie , Yildiz Abdullah Burak , Gaipov Abduzhappar , van Raalte Daniel H. , Tuttle Katherine R.
Published: September 2023

Aim

To perform a meta‐analysis to quantify the effect of tirzepatide on blood pressure and lipids.

Methods

PubMed, Ovid/Medline, Web of Science, Scopus, Cochrane Library and CINAHL databases were screened and the randomized controlled trials evaluating the effects of tirzepatide on either blood pressure or lipid profiles were included.

Results

Seven randomized controlled trials have investigated the effects of tirzepatide on blood pressure and lipid profiles. Regardless of the dose administered, tirzepatide resulted in significant decreases in systolic blood pressure of median −4.20 (95% confidence interval [CI] −5.17 to −3.23) mmHg for 5 mg, −5.34 (−6.31 to −4.37) mmHg for 10 mg, and −5.77 (−6.73 to −4.81) mmHg for 15 mg. At all three once‐weekly doses, tirzepatide treatment resulted in significant decreases in total cholesterol levels: median −3.76% (95% CI −5.20% to −2.31%) for 5 mg; −4.63% (−6.07% to −3.19%) for 10 mg; and −5.93% (−7.36% to −4.49%) for 15 mg. Additionally, tirzepatide treatment led to increased high‐density lipoprotein (HDL) cholesterol levels and decreased low‐density lipoprotein (LDL) cholesterol and triglyceride levels.

Conclusions

Tirzepatide induced clinically meaningful reductions in the levels of systolic and diastolic blood pressure, total cholesterol, LDL cholesterol and triglycerides, along with increases in the level of HDL cholesterol.
Addressing uncertainty when projecting marine species' distributions under climate change
Authors: Davies Sarah C. , Thompson Patrick L. , Gomez Catalina , Nephin Jessica , Knudby Anders , Park Ashley E. , Friesen Sarah K. , Pollock Laura J. , Rubidge Emily M. , Anderson Sean C. , Iacarella Josephine C. , Lyons Devin A. , MacDonald Andrew , McMillan Andrew , Ward Eric J. , Holdsworth Amber M. , Swart Neil , Price Jeff , Hunter Karen L.
Published: September 2023

Species distribution models (SDMs) have been widely used to project terrestrial species' responses to climate change and are increasingly being used for similar objectives in the marine realm. These projections are critically needed to develop strategies for resource management and the conservation of marine ecosystems. SDMs are a powerful and necessary tool; however, they are subject to many sources of uncertainty, both quantifiable and unquantifiable. To ensure that SDM projections are informative for management and conservation decisions, sources of uncertainty must be considered and properly addressed. Here we provide ten overarching guidelines that will aid researchers to identify, minimize, and account for uncertainty through the entire model development process, from the formation of a study question to the presentation of results. These guidelines focus on correlative models and were developed at an international workshop attended by over 50 researchers and practitioners. Although our guidelines are broadly applicable across biological realms, we provide particular focus to the challenges and uncertainties associated with projecting the impacts of climate change on marine species and ecosystems.
Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE
Authors: Li Mingfang , Luo Li , Lin Chuanchuan , Ni Bing , Zou Liyun , Song Zhiqiang , Hao Fei , Wu Yi , Luo Na
Published: September 2023

Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA‐containing immune complex (DNA‐ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA‐ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA‐ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA‐ICs on RelB, IL‐10 and TNF‐α in mDCs. Further analysis indicated that DNA‐ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3‐mediated effects. Co‐culture of mDCs and CD4+ T cells showed that VitD3 inhibited multiple processes mediated by DNA‐ICs, including proliferation, downregulation of IL‐10, TGF‐β and upregulation of TNF‐α. Moreover, VitD3 could also reverse the effects of DNA‐IC‐induced imbalance of CD4+ CD127− Foxp3+ T cells and CD4+ IL17+ T cells. Taken together, our results indicated that autologous DNA‐ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA‐ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.
Using ultraviolet dermoscopy in diagnosing scabies
Authors: Yürekli Aslan , Muslu İlayda , Pektaş Suzan Demir , Alataş Emine Tuğba , Aydoğdu Ceyda Tetik , Daşgin Dilek
Published: September 2023

The latest generation ultraviolet (UV) dermatoscopes, which emit UV light at a wavelength of 365 nm and enlarge lesions, are practical devices that can facilitate the diagnosis and follow‐up of some dermatological diseases with fluorescence that can be observed in skin lesions. In 305 patients, 468 tunnels were evaluated: first in polarized mode and later in UV mode. The recorded samples were compared one‐to‐one by the same dermatologist. Due to the study's design, images were examined in three stages: tunnel borders, tunnel content and mite appearance. In UV mode, the entire body of mites gives a bright reflex along with an oval‐shaped diagnostic clue well beyond the delta sign. The borders of the tunnel reflect brightly in UV mode, with borders that are more sharply visible than in polarized mode. Although the tunnel content cannot be clearly distinguished in polarized mode, especially in people with hyperkeratotic palms, or ‘working hands’ (e.g. farmers, mechanics and construction workers), with the bright reflex, the tunnel borders in UV mode give a bright reflection and provide a clear view of tunnels. Tunnel content gives a bright reflection in UV mode. Our results show that UV dermatoscopes provide more effective and clearer images than polarized dermatoscopes in the diagnosis of scabies.
MapIntel: A visual analytics platform for competitive intelligence
Authors: Silva David , Bação Fernando
Published: September 2023

Competitive Intelligence allows an organization to keep up with market trends and foresee business opportunities. This practice is mainly performed by analysts scanning for any piece of valuable information in a myriad of dispersed and unstructured sources. Here we present MapIntel, a system for acquiring intelligence from vast collections of text data by representing each document as a multidimensional vector that captures its own semantics. The system is designed to handle complex Natural Language queries and visual exploration of the corpus, potentially aiding overburdened analysts in finding meaningful insights to help decision‐making. The system searching module uses a retriever and re‐ranker engine that first finds the closest neighbours to the query embedding and then sifts the results through a cross‐encoder model that identifies the most relevant documents. The browsing or visualization module also leverages the embeddings by projecting them onto two dimensions while preserving the multidimensional landscape, resulting in a map where semantically related documents form topical clusters which we capture using topic modelling. This map aims at promoting a fast overview of the corpus while allowing a more detailed exploration and interactive information encountering process. We evaluate the system and its components on the 20 newsgroups data set, using the semantic document labels provided, and demonstrate the superiority of Transformer‐based components. Finally, we present a prototype of the system in Python and show how some of its features can be used to acquire intelligence from a news article corpus we collected during a period of 8 months.
To recommend or not recommend: That is still the question
Authors: Braunstein Lawrence Jay , Wittmann Jeffrey P.
Published: September 2023

The boundaries around what parenting plan evaluators should and should not say in their reports to Courts has been debated in both mental health and legal circles for decades. The controversy about whether parenting plan evaluators should make specific recommendations to Courts regarding access plans and decision‐making rights revolves around varied views of the limits of mental health professionals' knowledge about such matters, whether they are socio‐moral or psychological in nature, and the benefits to children and society of facilitating case‐resolution. In the conversation presented below a seasoned family law attorney and a psychologist who is a frequent critic of the practice of making specific recommendations debate this area of controversy.
GR‐KLF15 pathway controls hepatic lipogenesis during fasting
Authors: Takeuchi Yoshinori , Murayama Yuki , Aita Yuichi , Mehrazad Saber Zahra , Karkoutly Samia , Tao Duhan , Katabami Kyoka , Ye Chen , Shikama Akito , Masuda Yukari , Izumida Yoshihiko , Miyamoto Takafumi , Matsuzaka Takashi , Kawakami Yasushi , Shimano Hitoshi , Yahagi Naoya
Published: September 2023

During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element‐binding protein‐1 (SREBP‐1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting‐induced Kruppel‐like factor 15 (KLF15) with liver X receptor serves as the essential mechanism for the nutritional regulation of SREBP‐1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15‐SREBP‐1 pathway during fasting. KLF15 is necessary for the suppression of SREBP‐1 by GR, as demonstrated through experiments using KLF15 knockout mice. Additionally, we show that GR is involved in the fasting response, with heightened binding to the KLF15 enhancer. It has been widely known that the hypothalamic–pituitary–adrenal (HPA) axis regulates the secretion of glucocorticoids and plays a significant role in the metabolic response to undernutrition. These findings demonstrate the importance of the HPA‐axis‐regulated GR‐KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
The historical shifts of in/formality of learning within craft skills ecosystems in the United Kingdom
Authors: Li Mixue , Holstein Jeannie , Wedekind Volker
Published: September 2023

In this paper, we address the debate on local skills ecosystems and informal learning. We use the social ecosystem model as a tool to help us analyse the role played by various actors in learning and skills ecosystems and highlight the role of informal learning in vocational education and training. We draw on the case of craft pottery to discuss the historical shifts and transformations of ecosystems, including the centrality of informal learning occurring in different spaces and times, and subsequent transformation of the learning ecosystem. Our paper contributes in two ways. First, we add the lens of temporality to understanding of how learning and skills ecosystems are maintained and developed, in the absence of supportive government policy. Second, we show how multiple horizontal sectors contribute to reconstruct a learning and skills ecosystem, as an informal one, over time.
Macrophage memory: Types, mechanisms, and its role in health and disease
Authors: Fang Xu‐Hui , Li Zhi‐Jing , Liu Chun‐Yan , Mor Gil , Liao Ai‐Hua
Published: September 2023

On the basis of the mechanisms of action and characteristics of immune effects, immunity is commonly categorized into innate and adaptive immunity. Adaptive immunity is associated with the response to non‐self‐entities and is characterized by high specificity and memory properties. In contrast, innate immunity has traditionally been considered devoid of memory characteristics. However, an increasing number of studies have sought to challenge this conventional immunological dogma and shown that innate immune cells exhibit a more robust and rapid response to secondary stimulation, thus providing evidence of the immunological memory in innate immunity. Macrophages, which are among the most important innate immune cells, can also acquire memory phenotype that facilitates the mediation of recall responses. Macrophage memory is a relatively new concept that is revolutionizing our understanding of macrophage biology and immunological memory and could lead to a new class of vaccines and immunotherapies. In this review, we describe the characteristics and mechanisms of macrophage memory, as well as its essential roles in various diseases.
Management's Key Responsibility
Authors: Madden Bartley J.
Published: September 2023

Bartley Madden, a leading management consultant and author, follows up after Edmund Phelps' leading article on innovation and mass flourishing with specific recommendations for business managers.

Madden identifies a firm's knowledgebuilding proficiency as its most important capability in order to survive and prosper over the long term. Even a firm's competitive advantage and intangible assets are best understood as the result of its ability to build knowledge. Along with a firm's organizational structure, knowledge‐building proficiency coordinates and improves work, innovation, and resource allocation.

Madden is very critical of much of the current academic finance research that, while ostensibly focused what creates “excess shareholder returns” (i.e., economic profit or economic value‐added), is actually irrelevant to a fundamental understanding of what creates long‐term value.

Academic studies are usually just statistical factor analyses. Even when economists study individual firms, they usually do so by modeling them simply as production functions: management is assumed to coordinate factors of production to make and sell products until marginal costs equal marginal revenue and profits are maximized. Such a firm is assumed to have clear boundaries and its management tightly controls the work of employees and the accumulation and allocation of its physical assets.

Instead, Madden proposes a new and more sophisticated concept of the firm to position human capital, in general, and knowledge‐building proficiency, in particular, at the center of value creation. In this connection he offers two business exemplars: the American retailer Walmart and the Chinese Haier Group that makes consumer electronics and home appliances.
Prospective validation of a risk score to predict pacemaker implantation after transcatheter aortic valve replacement
Authors: Black George B. , Kim Joshua H. , Vitter Sophie , Ibrahim Rand , Lisko John C. , Perdoncin Emily , Shekiladze Nikoloz , Gleason Patrick T. , Grubb Kendra J. , Greenbaum Adam B. , Devireddy Chandan M. , Guyton Robert A. , Leshnower Bradley , Merchant Faisal M. , El‐Chami Mikhael , Westerman Stacy B. , Shah Anand D. , Leon Angel R. , Lloyd Michael S. , Babaliaros Vasilis C. , Kiani Soroosh
Published: September 2023

Introduction

The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre‐existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score.

Methods

We prospectively evaluated all patients without pre‐existing pacemakers, ICD, or pre‐existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision‐making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis.

Results

A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05–3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74–0.88], p < 0.001).

Conclusions

The ERS prospectively predicted the need for PPM in a serial, real‐world cohort of patients undergoing TAVR with a balloon‐expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.
Prolonged haematologic toxicity in CAR‐T‐cell therapy: A review
Authors: Liu Qi , Hu Tonglin , Li Hangchao , Shen Yingying , Wu Dijiong , Ye Baodong
Published: September 2023

Chimeric antigen receptor‐T‐cell (CAR‐T‐cell) therapy is a novel immunotherapy with encouraging results for treatment of relapsed/refractory haematologic malignancies. With increasing use, our understanding of immune‐mediated side effects such as cytokine release syndrome and neurotoxicity has improved; nevertheless, prolonged haematologic toxicity (PHT), with a high incidence rate, remains underrecognized. Owing to heterogeneity in populations, the CAR‐T cells used and diseases treated as well as differences in the definition of PHT, its rate, risk factors and management vary across studies. In this review, we provide a narrative of PHT occurring in patients following CAR‐T‐cell therapy; evidence of PHT treatment strategies is also presented, with the aim of contributing to systematic understanding of PHT.
Activation of vascular endothelial cells by synovial fibrosis promotes Netrin‐1‐induced sensory nerve sprouting and exacerbates pain sensitivity
Authors: Ma Zhenyuan , Wei Yibao , Liao Taiyang , Jie Lishi , Yang Nan , Yu Likai , Wang Peimin
Published: September 2023

Synovial fibrosis is one of the most dominant histopathological changes in osteoarthritis of the knee (KOA), and activation of vascular endothelial cells in synovial fibrosis is both an important factor in mediating pain in KOA and a major contributor to the generation of pain signals. At the same time, angiogenesis and nerve fibres are more likely to underlie the pathology of pain induced by synovial fibrosis. In the present study, we established a co‐culture model of human umbilical vein endothelial cells (HUVECs) with dorsal root ganglion (DRG) and detected tissue and cellular Netrin‐1, vascular cell adhesion molecule‐1 (VCAM‐1), intercellular cell adhesion molecule‐1 (ICAM‐1), growth‐associated protein‐43 (GAP43), colorectal cancer deleted (DCC), uncoordinated 5 (UNC5), and the related expression of calcitonin gene‐related peptide (CGRP), substance P (SP) and nerve growth factor (NGF) in supernatant by ELISA to investigate the intervention of vascular endothelial cell activation on sensory nerve sprouting exacerbating peripheral pain sensitivity and to investigate the effect of Netrin‐1 from the perspective of Netrin‐1 secretion to illustrate its effector mechanism.
Efficacy and safety of a 14‐day modified concomitant therapy for refractory Helicobacter pylori infection: a pilot study
Authors: Zeng Shu‐yan , Wang Juan , Liu Jing , Lin Min‐Juan , Lin Bo‐Shen , Ding Yu‐Ming , Kong Qing‐Zhou , Zhang Wen‐Lin , Duan Miao , Han Zhong‐Xue , Li Yue‐yue , Zuo Xiu‐Li , Li Yan‐Qing
Published: September 2023

Background and Aim

After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14‐day modified concomitant therapy for managing refractory H. pylori infection.

Methods

Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14‐day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome.

Results

Overall, 59 participants received the 14‐day modified concomitant therapy. In the intention‐to‐treat and per‐protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported.

Conclusion

The 14‐day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.
Stable licensing schemes in technology transfer
Authors: Kishimoto Shin
Published: September 2023

By considering combinations of a lump‐sum fee and a per‐unit royalty as licensing schemes in the transfer of new technology through licensing from a technology holder to oligopolistic firms, we investigate stable licensing schemes that are realized as bargaining outcomes. The licensing schemes agreeable to both the technology holder and licensees are necessarily rejection‐proof; that is, no subgroup of licensees has an incentive to reject the licensing schemes. We newly define the rejection‐proof core for each group of licensees as the set of rejection‐proof licensing schemes for its group that are not dominated by any other rejection‐proof licensing schemes for any licensees' group. Our principal findings are as follows: For the group of licensees that maximizes the sum of the technology holder's (gross) profit and licensees' total surplus, the rejection‐proof core is always nonempty. Furthermore, from the perspective of profit maximization, the nonempty rejection‐proof cores suggest that the technology holder should license the new technology to such a group.
Transforming food supply chains for sustainability
Authors: Gómez Miguel I. , Lee Deishin
Published: September 2023

Modern food supply chains—infused with scientific and engineering innovations—have made food increasingly more affordable and accessible. Yet there is growing concern about the long‐term sustainability of our food system. Over time, the inputs (e.g., water, fertile soil, fossil fuels, and chemicals) and working resources (e.g., land and labor) required for industrial food production and its associated supply chain structure have become more scarce and hence more expensive. At the same time, the by‐products of these farming and supply chain activities (e.g., farm runoff and greenhouse gas emissions) have often created negative externalities on the environment and human health. To improve the sustainability of food production, research from the life sciences recommends adoption of transformative farming methods that incorporate ecological principles in a sustainable approach to farming. Operationally, this approach leverages economies of scope. In order to maintain strategic alignment, changing food production methods should be complemented with appropriate changes in the rest of the supply chain, including consumption habits. We propose a research agenda informed by findings from the life sciences, which integrates approaches from supply chain management as well as food and agricultural economics, to align all food supply chain partners with sustainable food production.
Long‐term remission and survival in dogs with high‐grade, B cell lymphoma treated with chemotherapy with or without sequential low‐dose rate half‐body irradiation
Authors: Best Matthew P. , Straw Rod C. , Gumpel Elias , Fry Darren R.
Published: September 2023

Background

Standard of care for dogs with high‐grade lymphoma, multiagent chemotherapy, achieves good initial responses but long‐term remissions are infrequent; previous studies using half‐body irradiation suggest improved long‐term outcomes.

Hypothesis

The addition of low‐dose rate half‐body irradiation would improve outcomes in dogs with B‐cell lymphoma.

Animals

Client‐owned dogs with stage III or higher, substage a, B‐cell lymphoma that achieved complete remission after 4 doses of multiagent chemotherapy.

Methods

A case‐controlled design comparing 2‐year remission and survival rates between dogs treated with CHOP‐based chemotherapy and those treated with chemotherapy and sequential low‐dose rate half‐body irradiation.

Results

Thirty‐eight dogs were enrolled with 18 included in final analysis, 9 prospectively‐enrolled dogs and 9 case‐matched historical controls. The irradiation cohort's 2‐year disease‐free rate was 56% whereas median duration exceeded the 730‐day study period compared with 0% and 261 days in the chemotherapy only group. Remission duration significantly differed between cohorts (P < .01), hazard ratio 0.218 (95% CI: 0.06‐0.77). The irradiation cohort's 2‐year survival rate was 78% with median overall survival duration exceeding the 730 day study period compared with 11% and 286 days in the chemotherapy only group. Overall survival time significantly differed between cohorts (P < .02), hazard ratio 0.173 (95% CI: 0.03‐0.839).

Conclusions and Clinical Importance

The improved long‐term outcome achieved by dogs administered sequential low‐dose rate half‐body irradiation in this study is similar to previous observational studies. Where long‐term remission is sought in dogs with B‐cell lymphoma low‐dose rate half‐body irradiation could be considered in addition to standard chemotherapy.
Microbiome analysis of bile from apparently healthy cats and cats with suspected hepatobiliary disease
Authors: Slead Tanner S. , Callahan Benjamin J. , Schreeg Megan E. , Seiler Gabriela S. , Stowe Devorah M. , Azcarate‐Peril Maria Andrea , Jacob Megan E. , Gookin Jody L.
Published: September 2023

Background

Bacterial infection of bile is a common cause of hepatobiliary disease in cats. Whether bile harbors a core microbiota in health or in cases of suspected hepatobiliary disease in cats is unknown.

Objectives

Establish if gallbladder bile in apparently healthy cats harbors a core microbiota composed of bacterial taxa common to many individuals. Compare results of bile cytology, bile culture, and 16S rRNA gene amplicon sequencing in apparently healthy cats and cats with suspected hepatobiliary disease.

Animals

Forty‐three client‐owned cats with suspected hepatobiliary disease and 17 control cats.

Methods

Bile was collected by ultrasound guided cholecystocentesis (cats with suspected hepatobiliary disease) or laparotomy after euthanasia (controls). Bile samples underwent cytologic examination, aerobic and anaerobic culture, and DNA was extracted for 16S rRNA gene amplification and sequencing.

Results

Microbiome sequencing did not identify a core microbiota in control cats or cats having bile sampled because of clinical suspicion for hepatobiliary disease. Microbiome profiles from control cats were indistinguishable from profiles obtained from sampling instruments and reagents that were not exposed to bile (technical controls). Bacterial taxa that could not be explained by contamination or off‐target amplification were identified only in samples from cats with bactibilia and positive bile culture results forEscherichia coli. In severalE. colipositive samples, microbiome sequencing also identified a small number of potentially co‐infecting bacterial genera not identified by culture.

Conclusions and Clinical Importance

Cat bile does not harbor a core microbiota. Uncultured bacteria may contribute to pathogenesis of hepatobiliary disease in cats with bileE. coliinfection.
Curriculum renewal towards critically conscious graduates: Implications for faculty development
Authors: van Schalkwyk Susan , Blitz Julia
Published: September 2023

Introduction

Globally, faculty development initiatives in support of health professions (HP) educators continue to extend their remit. This work becomes more critical as HP curriculum renewal activities are influenced by needing to move beyond a biomedical focus attending to issues such as social accountability, social justice and health equity. This raises questions about how best to support our HP educators who may need to change their teaching practice as they embrace these more complex, social constructs.

Methods

The research question for this qualitative study was: What implications are there for faculty development that can support HP educators as they are expected to incorporate the principles of critical consciousness and social accountability into their teaching as part of a curriculum renewal process? Data from 11 focus group discussions and 11 subsequent individual interviews with HP educators from two undergraduate programmes were thematically analysed after which further analysis focussed on the implications of these findings for faculty development. Transformative learning theory and models about change provided a sensitising framework.

Results

Our findings pointed to an expanded role for HP educators and consequently also for those responsible for faculty development. Three main ideas were highlighted: Curriculum renewal catalyses a renewed need for faculty development, the nature of faculty development that can enable change and new foci for faculty development.

Conclusions

Faculty development can make a significant contribution to enabling change, including in the context of curriculum renewal that often extends the roles and responsibilities of HP educators. When renewal seeks to shift fundamental curriculum principles, providing support to embrace this expanded remit results in an equally expanded remit for faculty developers—one that calls for initiatives that enable critical, dialogic encounters that might foster critical consciousness, leading to change in HP education. This challenges us, as faculty developers, to turn the mirror on ourselves to consider the nature of such expanded support.
Ecology and diversity of mosquito larvae in ponds and lagoons of Northwestern Spain
Authors: Martínez‐Barciela Yasmina , Polina Alejandro , Garrido Josefina
Published: September 2023

Galicia, located in the northwestern part of Spain, has a great number and variety of aquatic ecosystems where mosquitoes can breed. Despite the sanitary relevance of these insects, studies on mosquito populations in the region are still scarce. The field research was carried out in 48 sampling points (27 continental lagoons, 12 coastal lagoons and 9 temporary ponds) throughout the entire Galician territory. The samples were collected intermittently and seasonally through different water quality monitoring projects between 2001 and 2017. More than 1500 mosquito larvae belonging to 10 species of five genera (Aedes, Anopheles, Coquillettidia, Culex and Culiseta) were identified. Anopheles (Anopheles) maculipennis s.l. Meigen was the most widely distributed species in the study, being especially dominant in rural areas. In contrast, Culex (Culex) pipiens Linnaeus and Culex (Culex) theileri Theobald showed a preference for breeding in urban areas. New contributions to the knowledge about the larval ecology and distribution of these mosquito species are made throughout this study, including information about the tolerance of each species to water parameters (temperature, pH, dissolved oxygen and conductivity). Likewise, the relationship between culicid diversity and the habitat characteristics of the breeding sites (water body type, climate and level of anthropization) is discussed.
Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19
Authors: Bertram Ralph , Naumann Hans‐Theodor , Bartsch Vanessa , Hitzl Wolfgang , Kinzig Martina , Haarmeyer Golo‐Sung , Baumgärtel Matthias , Geise Arnim , Muschner Dorothea , Nentwich Jens , John Stefan , Sörgel Fritz , Steinmann Joerg , Höhl Rainer
Published: September 2023

Background

The broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.

Objectives

Isavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic drug levels (<1 μg/mL) were evaluated.

Patients and Methods

Isavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20–28 h after previous dosing were defined as trough (Cmin) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID‐19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID‐19 status, body mass index (BMI), sepsis‐related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement.

Results

The mean Cmin of isavuconazole in all patients was 1.64 μg/mL (interquartile range 0.83–2.24 μg/mL, total range 0.24–5.67 μg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 μg/mL. Drug concentrations between patients with or without COVID‐19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).

Conclusions

Isavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.
The perils of political advice
Authors: Kidd Colin , Rose Jacqueline
Published: September 2023

The vexed topic of political advice is as old as politics itself. But what form can it take, and who should give it, in a world that seems to have ‘had enough of experts’?
MALAT1 as a potential salivary biomarker in oral squamous cell carcinoma through targeting miRNA‐124
Authors: Shalaby Rania , Ibrahim Sally , Kotb Ali A. W. , Baz Safaa , Hafed Layla , Shaker Olfat , Afifi Salsabeel
Published: September 2023

Objectives

To determine the diagnostic accuracy of the long non‐coding RNA “MALAT1” measured in the saliva of patients with oral squamous cell carcinoma (OSCC) and assess the salivary expression of microRNA‐124, which MALAT1 targets.

Subjects and Methods

Forty subjects were collected in a consecutive pattern and allocated into two groups. Group A included 20 patients with OSCC, while Group B included 20 healthy subjects. Salivary expression of MALAT1 and microRNA (miRNA)‐124 was evaluated in the two study groups using quantitative real‐time polymerase chain reaction and correlated with histopathological examination of OSCC subjects.

Results

OSCC yielded a statistically significant higher expression of MALAT1 than healthy controls and a lower expression of miRNA‐124 in OSCC than controls. There is a statistically significant inverse relationship between salivary MALAT1 and miRNA‐124. Moreover, there is a statistically significant difference in the MALAT1 expression in saliva samples from metastatic cases compared with non‐metastatic cases, as well as in patients with lymph node involvement compared with those without involvement. At a cut‐off value of 2.24, salivary MALAT1 exhibited 95% sensitivity and 90% specificity in differentiating OSCC from healthy subjects.

Conclusion

Salivary MALAT1 acts as a sponge for miRNA‐124 and could be a potential salivary biomarker for OSCC.
Risk‐sensitive Markov decision processes with long‐run CVaR criterion
Authors: Xia Li , Zhang Luyao , Glynn Peter W.
Published: September 2023

CVaR (Conditional value at risk) is a risk metric widely used in finance. However, dynamically optimizing CVaR is difficult, because it is not a standard Markov decision process (MDP) and the principle of dynamic programming fails. In this paper, we study the infinite‐horizon discrete‐time MDP with a long‐run CVaR criterion, from the view of sensitivity‐based optimization. By introducing a pseudo‐CVaR metric, we reformulate the problem as a bilevel MDP model and derive a CVaR difference formula that quantifies the difference of long‐run CVaR under any two policies. The optimality of deterministic policies is derived. We obtain a so‐called Bellman local optimality equation for CVaR, which is a necessary and sufficient condition for locally optimal policies and only necessary for globally optimal policies. A CVaR derivative formula is also derived for providing more sensitivity information. Then we develop a policy iteration type algorithm to efficiently optimize CVaR, which is shown to converge to a local optimum in mixed policy space. Furthermore, based on the sensitivity analysis of our bilevel MDP formulation and critical points, we develop a globally optimal algorithm. The piecewise linearity and segment convexity of the optimal pseudo‐CVaR function are also established. Our main results and algorithms are further extended to optimize the mean and CVaR simultaneously. Finally, we conduct numerical experiments relating to portfolio management to demonstrate the main results. Our work sheds light on dynamically optimizing CVaR from a sensitivity viewpoint.