bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Regulation of Invasive Protrusion Formation at the Mammalian Fusogenic Synapse
Authors: Lu Yue , Walji Tezin , Ravaux Benjamin , Pandey Pratima , Li Bing , Lam Kevin H. , Zhang Ruihui , Goldhamer David J. , Li Rong , Schmidtke David W. , Pan Duojia , Chen Elizabeth H.
Published: November 2023

Invasive membrane protrusions play a central role in a variety of cellular processes. Unlike filopodia, invasive protrusions are mechanically stiff and propelled by branched actin polymerization. However, how branched actin filaments are organized to create finger-like invasive protrusions remains a longstanding question in cell biology. Here, by examining the mammalian fusogenic synapse, where invasive protrusions are generated to promote cell membrane juxtaposition and fusion, we have uncovered the mechanism underlying invasive protrusion formation. We show that two Arp2/3 nucleation promoting factors (NPFs), WAVE and N-WASP, exhibit distinct and complementary localization patterns in the protrusions. While WAVE is at the leading edge, N-WASP is recruited by its interacting protein, WIP, to the shaft of the protrusion. During protrusion growth, new branched actin filaments are polymerized at the periphery of the shaft and crosslinked to preexisting actin bundles by the “pioneer” actin-bundling protein dynamin. The thickened actin bundles are further stabilized by WIP, which functions as a WH2 domain-mediated actin-bundling protein. Disrupting any of these components results in defective protrusions and myoblast fusion in cultured cells and/or in mouse embryos. Thus, our study has revealed the intricate spatiotemporal coordination between two NPFs and two actin-bundling proteins in creating invasive protrusions and has general implications in understanding protrusion formation in many cellular processes beyond cell-cell fusion.
Frontal cortex norepinephrine, serotonin, and dopamine dynamics in an innate fear-reward behavioral model
Authors: Yang Jen-Hau , Basu Aakash , Liu Rong-Jian , Staszko Stephanie M. , Yu Abigail L. , Rondeau Jocelyne , Glaeser-Khan Samira , Feng Jiesi , Li Yulong , Che Alicia , Kaye Alfred P.
Published: November 2023

Animals must survive by foraging for food in an uncertain and dangerous world. Experimental tasks such as Pavlovian learning have yielded insights into how neural circuits balance these conflicting motivational drives. Neuromodulators play a fundamental role in this process, enabling flexible switching between motivational drives. The question of how neuromodulators synergistically encode motivational state is thus fundamental to systems neuroscience, yet the interplay between these neuromodulators during naturalistic decision making are not fully understood. Here, we developed a naturalistic approach/avoidance task in mice involving a tradeoff between seeking reward versus safety in the presence of looming predation risk. We utilized multi-fiber photometry, computational behavior tracking, and slice electrophysiology to understand the. Mice that experienced looming stimuli showed increased c-fos expression in regions including frontal cortex, locus coeruleus, and ventral tegmental area, but decreased expression in dorsal raphe nucleus. Moreover, by using multi-fiber photometry combined with GPCR-based sensors, we found that cortical norepinephrine (NE) plays a more prominent role in encoding looming threats while dopamine (DA) represents reward and threat. In contrast, serotonin (5HT) dynamic negatively correlates to both emotional valences. To begin to understand neuromodulatory interactions, we usedex vivoslice physiology to understand 5HT impact on spontaneous firing of locus coeruleus NE neurons. In conclusion, monoamines such as NE, DA, 5HT can converge in their encoding of naturalistic motivated behaviors as well as dissociate from one another. By utilizing this approach, interactions between innate fear and incentive for food may be delineated in terms of basis in neurochemical signaling events during natural behavior, and may contribute to the understanding of neural mechanisms underlying emotional disorders including anxiety and post-traumatic stress disorder.
Genotypes and associations with symptoms in primary ciliary dyskinesia
Authors: Pedersen Eva SL , Goutaki Myrofora , Schreck Leonie D , Rindlisbacher Bernhard , Dixon Lucy ,   COVID-PCD patient advisory group, Lucas Jane S , Kuehni Claudia E
Published: November 2023

Background

Knowledge about genotype-phenotype associations is crucial for understanding the clinical variability of primary ciliary dyskinesia (PCD). We studied how feasible it is to collect information about causative genes directly from people with PCD through questionnaires, and investigated associations between clinical characteristics, symptoms, and genotype.

Methods

We used data from the anonymous international participatory cohort COVID-PCD, set up in 2020 to follow people with PCD during the COVID-19 pandemic. A baseline questionnaire asked genetic test results, clinical characteristics, and current symptoms. We grouped reported causative genes into categories based on associated defects and studied differences between groups.

Results

Among the 759 COVID-PCD study participants, 444 (58%) reported genetic testing, and of these, 289 (65%) reported that a gene was identified. We included 206 who knew and reported a causative gene. The most common genes wereDNAH5(n=71; 34%),DNAH11(n=27; 13%),CCDC40(n=21; 10%),DNAI1(n=18; 9%),CCDC39(n=13; 6%), and RSPH1 (n=8; 4%). The dynein structure (DS) group was the largest (n=127) followed by the nexin-dynein regulatory complex (ND-RC) group (n=38), dynein assembly (DA) group (n=21), and radial spoke and central complex (RS-CC, n=20) Current age and sex were similar across groups; but median age at diagnosis was markedly higher in the RS-CC group (11 years) compared to 4–7 years in the other groups (p=0.035). Laterality defects were reported by one person (5%) in RS-CC group, compared with 37%-60% in other groups (p=0.001). Overall, symptoms were frequently reported by participants in all 4 groups with little difference between groups.

Conclusion

Our results confirmed known differences in laterality defects and congenital heart disease between genotypes and showed frequent upper and lower respiratory symptoms in all groups regardless of reported gene.
Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue
Authors: Duerre Dylan J. , Hansen Julia K. , John Steven , Jen Annie , Carrillo Noah , Bui Hoang , Bao Yutong , Fabregat Matias , Overmeyer Katherine , Shishkova Evgenia , Keller Mark P. , Anderson Richard A. , Cryns Vincent L. , Attie Alan D. , Coon Joshua J. , Fan Jing , Galmozzi Andrea
Published: November 2023

With age, people tend to accumulate body fat and reduce energy expenditure1. Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles2,3. The activity of brown and beige depots inversely correlates with BMI and age4–11, suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease12–15. Heme is an enzyme cofactor and signaling molecule that we recently showed to regulate BAT function16. Here, we show that heme biosynthesis is the primary contributor to intracellular heme levels in brown adipocytes. Inhibition of heme biosynthesis leads to mitochondrial dysfunction and reduction in UCP1. Although supplementing heme can restore mitochondrial function in heme-synthesis-deficient cells, the downregulation of UCP1 persists due to the accumulation of the heme precursors, particularly propionyl-CoA, which is a product of branched-chain amino acids (BCAA) catabolism. Cold exposure promotes BCAA uptake in BAT, and defects in BCAA catabolism in this tissue hinder thermogenesis17. However, BCAAs’ contribution to the TCA cycle in BAT and WAT never exceeds 2% of total TCA flux18. Our work offers a way to integrate current literature by describing heme biosynthesis as an important metabolic sink for BCAAs.
Cortical ductility governs cell-cell adhesion mechanics
Authors: Arora Aditya , Rizvi Mohd Suhail , Grenci Gianluca , Dilasser Florian , Fu Chaoyu , Ganguly Modhura , Vaishnavi Sree , Paramsivam Kathirvel , Budnar Srikanth , Noordstra Ivar , Yap Alpha S. , Viasnoff Virgile
Published: November 2023

This paper challenges our understanding of cell-cell adhesion by emphasising the role of mechanical dissipation at the cellular level. We have developed new microdevices to measure the energy dissipated during the rupture of junctions between cell-cell doublets. Using a synthetic cadherin approach, we decoupled the role of cadherin binding energy, signalling and downstream regulation of cytoskeletal architecture. This yielded a phase diagram in which cell junctions transition from a ductile to a brittle fracture mode based on their ratio of cortical tension and shape relaxation time. We recapitulated our results using a descriptive mechanical simulation approach. Our results shift our understanding of cell-cell adhesion from the current focus on bond energy and tension to the key role played by energy dissipation in the cytoskeleton during junction deformation and its active mechanosensitive regulation.
Rescuing error control in crosslinking mass spectrometry
Authors: Fischer Lutz , Rappsilber Juri
Published: November 2023

Crosslinking mass spectrometry is a powerful tool for studying protein-protein interactions under native or near native conditions in complex mixtures. By help of novel search controls, we show that measures that aim to improve the number of identifications based on heuristic considerations can undermine error estimation in non-obvious ways. The relationship between decoys and false positives is very sensitive to the injection of information that favour likely correct matches. We identify a wider challenge in crosslinking data analysis tools with maintaining the decoy-false positive relationship, and exemplify this with the filtering of results based on the information of which proteins can be observed as having reacted with the crosslinker. Without correcting for this problem, we could identify an average of 260 interspecies protein-protein interactions in 16 analyses, “solidly” suggesting groundbreaking biological connections that don’t actually exist. We also show how data analysis procedures can be tested and modified to rescue the decoy-false positive relationship. The importance of this relationship for reliably identifying protein-protein interactions cannot be overstated.
Mutual stabilization of charge-density-wave and monoclinic distortion in sulfur at high pressures
Authors: Moulding Owen , Conway Lewis J. , Osmond Israel , Cross Sam , Hermann Andreas , Buhot Jonathan , Friedemann Sven
Published: November 2023

The charge-density-wave (CDW) amplitude mode of the high-pressure sulfur-IV phase is observed between 83 and 146 GPa using Raman spectroscopy. The energy of this excitation softens with pressure yet remains finite at νCDW>100cm−1 up to the critical pressure, which is indicative of a weakly first-order transition. Our calculations show that the finite energy of the excitation originates from the coupling and mutual stabilization of the CDW modulation and a monoclinic lattice distortion. At the critical pressure, both the CDW modulation and lattice distortion disappear simultaneously. Due to the prevalence of CDW phases, this coupling between the CDW modulation and lattice distortion is expected to be relevant for a wide variety of elements and compounds.

Published by the American Physical Society
2023
Transformation in Indian health care: the Tata 1mg merger story
Authors: Aqeel Ubada , Gera Shikha
Published: November 2023

Learning outcomes

This case study would enable students to understand the concept, process and advantages of mergers and acquisitions as a growth strategy with respect to 1mg. Also, the students would be able to use the threats, opportunities, weaknesses and strengths matrix to map 1mg’s strengths, weaknesses, opportunities and threats.

Case overview/synopsis

This case study analyses the transformation journey of 1mg to Tata 1mg, one of the most trusted internet pharmacies in India. This case describes a small start-up that was launched in 2013 and had made many acquisitions since then. This case revolves around Tata Digital’s purchase of 1mg. The case starts out by explaining 1mg’s financial situation and why the company was acquired. This case study focuses on how the integration helped Tata Digital and 1mg realize their respective missions. Furthermore, the case study illustrates the benefits and difficulties of this integration.

Complexity academic level

This case study is basically aimed at postgraduate management students; it can be used in strategic management and health-care courses. Students can understand the concept of diversification and acquisition with the help of this case study. Students can also gain an insight into the organic and inorganic diversification as a growth strategy.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy.
Digital transformation or not? Manufacturer's selection strategy under carbon cap-and-trade mechanism
Authors: Chen Anhang , Zhang Huiqin , Zhang Yuxiang , Zhao Junwei
Published: November 2023

Purpose

The digital economy is profoundly transforming the manufacturing industry's fundamental concepts and value creation logic, making digital transformation (DT) strategy a crucial decision for manufacturers. And faced with increasingly severe environmental issues, DT may become an important means to achieve sustainable development. This paper mainly discusses the strategic choice of the manufacturer's DT and analyzes the impact of DT on carbon emissions.

Design/methodology/approach

Based on the carbon cap-and-trade mechanism, the authors have constructed two decision models to study the DT strategy of the manufacturer, further exploring the impact of the mechanism on the DT strategy and production strategy of the manufacturer. Finally, the authors discussed the effect of manufacturers' DT on their carbon emissions.

Findings

The authors found that the manufacturer should initiate DT to enhance their competitiveness, regardless of whether they are in a low digital technology scenario or a high digital technology scenario. Notably, DT can enhance the ability of the manufacturer to respond to external emergencies. In a low digital technology market scenario, both carbon emissions per unit of product and carbon price are positively affecting the digitization level of the manufacturer. In a high digital technology market scenario, the manufacturer will initiate a full degree of DT. Moreover, the impact of DT on total carbon emissions varies in markets with different levels of digital technology.

Originality/value

Innovatively, the authors divided the DT of the manufacturer into market scenarios with low digital technology and high digital technology. Provide the manufacturer with DT decisions according to different scenarios. At the same time, it verifies the uncertainty of DT on carbon emission and enriches the related research.
Effectiveness criteria of suspicious transaction reporting for early detection of terrorist financing activities
Authors: Gowhor Hussain Syed
Published: November 2023

Purpose

This study aims to evaluate the suspicious transaction reporting (STR) as a financial intelligence tool to identify the potential strengths and limitations of STR and to come up with the criteria, which will make this tool an effective one in early detection of terrorist financing activities.

Design/methodology/approach

Considering the research aim, this research uses the funnelling method for identifying effectiveness criteria. Funnelling is a method of literature review that helps find pertinent literature by refining the search through filtering the available research (Ridley, 2008). Using this method, the researcher first applied the criteria of actionable intelligence to filter the financial intelligence tools to select the most promising and important tool (suspicious transaction reporting) for early detection of terrorist financing activities. The funnelling method was also applied to derive the effectiveness criteria from the operational features, and corresponding limitations, of the suspicious transaction reporting system. The funnelling method was also used to identify those operational features and limitations of suspicious transaction reporting that have the most direct relevance to the early detection problem of suspicious transaction reporting.

Findings

There are some operational features of STR that give rise to certain limitations that undermine its effectiveness in terms of early detection of terrorist financing activities. The limitations of STR necessitate a search for criteria that will make STR effective in early detection of terrorist financing activities. Based on the operational features and their corresponding limitations, effectiveness criteria for STR have been derived in this study. It is shown how these effectiveness criteria can remove the limitations of STR.

Research limitations/implications

The list of operational features and the corresponding limitations based on which the effectiveness criteria have been derived may not be exhaustive. There may have other operational features, and corresponding limitations that also make STR largely ineffective in the early detection of terrorist financing activities, and for which more effectiveness criteria should also be derived.

Practical implications

The limitations and the effectiveness criteria will pave the way for redesigning STR in such a way that will make it highly useful for detecting financing activities relating to imminent terrorist attacks.

Social implications

The society will experience fewer terrorist attacks that will make the society peaceful, happy and vibrant.

Originality/value

In this study, the effectiveness criteria of STR for early detection of terrorist financing activities have been derived in an innovative way by deducing them from the operational features of STR and the corresponding limitations.
Empathic accuracy in artificial intelligence service recovery
Authors: Xu Xing’an , Wen Najuan , Liu Juan
Published: November 2023

Purpose

Artificial intelligence (AI) agents have been increasingly applied in the tourism and hospitality industry. However, AI service failure is inevitable. Thus, AI service recovery merits empirical investigation. This study aims to explore how AI empathic accuracy affects customers’ satisfaction in the context of AI service recovery.

Design/methodology/approach

A moderated mediation model was presented to describe the effect of empathic accuracy on customer satisfaction via four scenario-based experiments.

Findings

The results reveal the positive impact of AI empathic accuracy on customer satisfaction and the mediating effects of perceived agency and perceived experience. Moreover, anthropomorphism moderates the empathic accuracy effect.

Originality/value

This paper expanded AI service studies by exploring the significance of empathic accuracy in customer recovery satisfaction. The results provide a novel theoretical viewpoint on retaining customers following AI service failure.
Connectivity and short‐term flood interactively affect fish community composition in drainage ditches of paddy fields in an agricultural landscape
Authors: Iwamoto Hideyuki , Tahara Daisuke , Yoshida Takehito
Published: November 2023

Community assembly can change over time following variations in connectivity among habitats. Previous studies have demonstrated the influence of seasonal pulse floods on community structures by facilitating species dispersal, but the effects of short‐term flash floods have been poorly investigated. We investigated fish community structures before and after a short‐term flood in drainage ditches of paddy fields in the Kita River basin, Japan. The study sites were classified into three connectivity types, “Transient” (connected only during the flood, with a temporally disappearing vertical gap between drainage ditches and downstream rivers), “Connected” (always connected, without the vertical gap), and “Disconnected” (always not connected, with the vertical gap). The abundance of Misgurnus anguillicaudatus, the only species that dispersed from paddy fields to drainage ditches, increased after the flood irrespective of the connectivity types, although the total abundance of the other species significantly increased after the flood only in the “Transient” sites. The dissimilarity of species composition between the (n − 1)‐th and n‐th surveys at each site was consistently low in the “Connected” and “Disconnected” sites, whereas it rose just after the flood and gradually declined in the “Transient” sites. Species composition was significantly different among the connectivity types, indicating that some fish species need stable connectivity even during the non‐flood period. The results showed that the short‐term flood facilitated fish dispersal from paddy fields by the increased water discharge and that from downstream rivers by the temporary removal of vertical gap, emphasizing the importance of hydrological connectivity for biodiversity conservation in an agricultural landscape.
Impact of fiscal decentralisation on economic growth in Vietnam—A spatial regression approach
Authors: Oanh Tran Thi Kim
Published: November 2023

Approaching by spatial regression method, this study examines the impact of fiscal decentralisation on economic growth in 63 provinces/cities of Vietnam in the period 2010–2020. Findings suggest that, in general, revenue decentralisation and expenditure decentralisation not only have a positive impact on the economic growth of provinces/cities but also have spillover effects on other locations in improving GRDP per capita. The above findings provide some important policy implications for improving fiscal decentralisation to promote economic growth in Vietnam.
Eliminating health care inequities through strengthening access to care
Authors: Jindal Monique , Chaiyachati Krisda H. , Fung Vicki , Manson Spero M. , Mortensen Karoline
Published: November 2023

Objective

To provide a research agenda and recommendations to address inequities in access to health care.

Data Sources and Study Setting

The Agency for Healthcare Research and Quality (AHRQ) organized a Health Equity Summit in July 2022 to evaluate what equity in access to health care means in the context of AHRQ's mission and health care delivery implementation portfolio. The findings are a result of this Summit, and subsequent convenings of experts on access and equity from academia, industry, and the government.

Study Design

Multi‐stakeholder input from AHRQ's Health Equity Summit, author consensus on a framework and key knowledge gaps, and summary of evidence from the supporting literature in the context of the framework ensure comprehensive recommendations.

Data Collection/Extraction Methods

Through a stakeholder‐engaged process, themes were developed to conceptualize access with a lens toward health equity. A working group researched the most appropriate framework for access to care to classify limitations identified during the Summit and develop recommendations supported by research in the context of the framework. This strategy was intentional, as the literature on inequities in access to care may itself be biased.

Principal Findings

The Levesque et al. framework, which incorporates multiple dimensions of access (approachability, acceptability, availability, accommodation, affordability, and appropriateness), is the backdrop for framing research priorities for AHRQ. However, addressing inequities in access cannot be done without considering the roles of racism and intersectionality. Recommendations include funding research that not only measures racism within health care but also tests burgeoning anti‐racist practices (e.g., co‐production, provider training, holistic review, discrimination reporting, etc.), acting as a convener and thought leader in synthesizing best practices to mitigate racism, and forging the path forward for research on equity and access.

Conclusions

AHRQ is well‐positioned to develop an action plan, strategically fund it, and convene stakeholders across the health care spectrum to employ these recommendations.
Association of antibiotic exposure with survival in patients with extensive‐stage small cell lung cancer receiving immune checkpoint inhibitor therapy
Authors: Zhong Jiaqi , Xiong Dali , Liu Yu , Yuan Shuanghu
Published: November 2023

Background

Immune checkpoint inhibitors (ICIs) have dramatically shifted the therapeutic paradigm of extensive‐stage small cell lung cancer (ES‐SCLC). Antibiotic (ATB) exposure before or during ICI therapy can harm the integrity of the gut microbiome and lead to intestinal dysbiosis, which has a profoundly negative impact on the treatment response for various malignancies. Whether this is applicable to ES‐SCLC remains unclear.

Methods

We retrospectively reviewed the electronic medical records of all patients diagnosed with ES‐SCLC who were treated with ICI‐based immunotherapies from July 2019 to December 2020 at Shandong Cancer Hospital and Institute, China. Outcomes with the use of ATBs before or after the first infusion of ICI, including progression‐free survival (PFS) and overall survival (OS), were investigated using the Kaplan–Meier method. Multivariate analyses were also conducted using a Cox proportional hazards model.

Results

A total of 214 patients were included, among whom 41 (19.2%) received ATBs within 2 months before or after the first initiation of ICI therapy and were assigned to the ATB group. The ATB group showed a shorter median PFS (4.3 vs. 6.3 months; HR = 1.43, 95% CI: 0.97–2.11; p = 0.043) and a significantly shorter median OS (6.9 vs. 13 months; HR = 1.47, 95% CI: 0.98–2.20; p = 0.033) than the non‐ATB group. In the multivariate analysis, ATB exposure was markedly associated with worse PFS (HR = 1.47, 95% CI: 1.03–2.09, p = 0.035) and OS (HR = 1.46, 95% CI: 1.01–2.11, p = 0.043).

Conclusions

Our results demonstrate that ATB exposure was significantly associated with worse survival in ES‐SCLC patients who received ICI therapy.
Middle range theory for the nursing phenomenon Ineffective social support network
Authors: de França Michelline Santos , Linhares Francisca Márcia Pereira , Marques Gomes Mendes Ryanne Carolynne , Lopes Marcos Venícios de Oliveira , de Queiroz Frazão Cecília Maria Farias , de Maria Alves de Sousa Santana , Pontes Cleide Maria
Published: November 2023

Purpose

To describe a middle range theory (MRT) with conceptual and explicative capacity of cause and effect situations of Ineffective social support network in nursing.

Data sources

Descriptive study developed through the Lopes, Silva, and Herdman theoretical‐causal validity method, using five steps for theory construction: definition of the approach for constructing the MRT, definition of the main concepts, development of the pictorial diagram, construction of propositions, and establishment of causal relationships and evidence for practice. The foundation of these steps and the development of a predictive nursing theory occurred through Sanicola's Social Network Theory combined with studies from an integrative literature review using the six steps proposed by Whittemore and Knafl.

Data synthesis—findings

The theory presents etiological factors and clinical indicators for Ineffective social support network, connecting situations related to the person, the members and the configuration of this network, and external situations. The pictogram, symbolically created, represents the hierarchical classification of proximal, intermediate, and distal etiological factors, and their relationship with clinical indicators.

Conclusions

The MRT, predictive for the nursing phenomenon Ineffective social support network, provides understanding of the person from an interpersonal perspective, which interferes with and is affected by a network of virtues and vicissitudes, and has negative influences on health outcomes. Due to its practical vocation, this theory represents an advance in the science and praxis of nursing.

Implications for clinical practice

The findings of this study will contribute to the understanding of the nursing phenomenon Ineffective social support network and consequently support the identification of the nursing diagnosis Ineffective social support network, proposed for inclusion in the NANDA‐I classification.
Immune checkpoint inhibitor‐induced lichenoid drug eruption‐sparing scar burns
Authors: Truong Kelvin , Chamberlin Charmaine Vanessa , Kim Jennifer , Carlino Matteo S. , Araujo Raquel Ruiz
Published: November 2023

The authors present a striking case of a patient experiencing a lichenoid drug eruption secondary to immunotherapy, curiously sparing scarred skin from past burns. We observed vastly higher amounts of inflammatory lymphoid cells staining for PD‐1; 70% in skin with a lichenoid drug reaction and 50% in scarred skin. The lack of a lichenoid reaction at sites of scarred skin may indicate that a basement membrane component may be causative for a lichenoid drug eruption.
DistSNE: Distributed computing and online visualization of DNA methylation‐based central nervous system tumor classification
Authors: Schmid Kai , Sehring Jannik , Németh Attila , Harter Patrick N. , Weber Katharina J. , Vengadeswaran Abishaa , Storf Holger , Seidemann Christian , Karki Kapil , Fischer Patrick , Dohmen Hildegard , Selignow Carmen , von Deimling Andreas , Grau Stefan , Schröder Uwe , Plate Karl H. , Stein Marco , Uhl Eberhard , Acker Till , Amsel Daniel
Published: November 2023

The current state‐of‐the‐art analysis of central nervous system (CNS) tumors through DNA methylation profiling relies on the tumor classifier developed by Capper and colleagues, which centrally harnesses DNA methylation data provided by users. Here, we present a distributed‐computing‐based approach for CNS tumor classification that achieves a comparable performance to centralized systems while safeguarding privacy. We utilize the t‐distributed neighborhood embedding (t‐SNE) model for dimensionality reduction and visualization of tumor classification results in two‐dimensional graphs in a distributed approach across multiple sites (DistSNE). DistSNE provides an intuitive web interface (https://gin-tsne.med.uni-giessen.de) for user‐friendly local data management and federated methylome‐based tumor classification calculations for multiple collaborators in a DataSHIELD environment. The freely accessible web interface supports convenient data upload, result review, and summary report generation. Importantly, increasing sample size as achieved through distributed access to additional datasets allows DistSNE to improve cluster analysis and enhance predictive power. Collectively, DistSNE enables a simple and fast classification of CNS tumors using large‐scale methylation data from distributed sources, while maintaining the privacy and allowing easy and flexible network expansion to other institutes. This approach holds great potential for advancing human brain tumor classification and fostering collaborative precision medicine in neuro‐oncology.
Clinical outcomes of implant‐ versus abutment‐level connection in screw‐retained fixed dental prostheses: A 5‐year randomized controlled trial
Authors: Toia Marco , Parpaiola Andrea , Stevanello Nicole , Tattan Mustafa , Saleh Muhammad H. A. , Ravidà Andrea
Published: November 2023

Aim

The aim of the study was to evaluate the 5 years clinical outcomes associated with implant‐level connection (IL) versus abutment‐level connection (AL) for implants with an internal conical connection (ICC) supporting a screw‐retained fixed partial denture.

Materials and Methods

Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic (Marginal bone loss) and clinical outcomes (Bleeding on Probing, probing pocket depth, plaque accumulation, incidence of peri‐implantitis and peri‐implant mucositis as well as prosthetic complications) were collected and compared at 1, 2, 3, and 5 years. A linear mixed model was used to evaluate the differences between groups.

Results

Five years after treatment, the MBL change was not significantly different between the groups at any point. The MBL was 0.23 ± 0.64 mm (AL) and 0.23 ± 0.29 mm (IL). The bleeding on Probing was 44% (AL) and 45% (IL) (p = .89). The mean probing depth was 2.91 ± 1.01 mm (AL) and 3.51 ± 0.67 mm (IL). This difference between the groups was statistically significant but clinical insignificant. Presence of plaque was slightly higher (p = .06) in the IL group (34.4%) compared with the AL group (26.3%). The overall technical, biological, and prosthetic complication rates were similar between groups. None of the implants developed peri‐implantitis during the entire follow‐up period.

Conclusion

The results of this clinical trial indicated that all clinical and radiographical parameters were clinically comparable between the study groups.
Menthol induces apoptosis and inhibits proliferation and migration of nonsmall cell lung carcinoma in vitro and in vivo through Akt pathway
Authors: Liu Zhiyu , Li Chunlin , Mu Ling , Hu Haiyang , Qin Xiong
Published: November 2023

Background

About 40% of nonsmall cell lung cancers (NSCLCs) have already progressed in an advanced stage at the time of diagnosis. Development of effective prevention and therapy approaches against NSCLC is critical for reducing mortality. As a fundamental ingredient of peppermint oil, menthol has been demonstrated to possess an antitumor activity in several types of carcinomas. However, the potential role of menthol on NSCLC has not been reported. The present study aims to investigate the effect and underlying mechanism of menthol on proliferation, apoptosis, and mobility of human lung adenocarcinoma.

Methods

Cell apoptosis was examined by MTT and flow cytometry. The motility of cells was determined by Transwell assay. Western blot analysis was performed to determine expression level of proteins. In vivo model of nude mice was established for evaluating the influence of menthol on tumorigenicity of A549 cells. The expression lentiviral vector of Akt was established in NSCLC cells for further verifying the inhibiting effect of menthol on survival and mobility of NSCLC cells via Akt pathway.

Results

The results showed that menthol promoted A549 cell apoptosis, suppressed cell proliferation, and motility by altering the phosphorylated protein level of Akt. Menthol enhanced the expression level of Bax while decreasing expression of Bcl‐2, Caspase‐3, and MMPs proteins. In vivo experiments suggested that menthol exhibited an inhibitory effect in tumor growth on xenografts. These results were further validated in Akt over‐expressed A549 and H1299 cells.

Conclusions

Menthol could display an inhibitory effect on NSCLC cells through Akt signaling pathway, making it a potential target for NSCLC treatment.
Long‐term prognosis of fatty‐acid oxidation disorders in adults: Optimism despite the limited effective therapies available
Authors: Rouyer Alice , Tard Céline , Dessein Anne‐Frédérique , Spinazzi Marco , Bédat‐Millet Anne‐Laure , Dimitri‐Boulos Dalia , Nadaj‐Pakleza Aleksandra , Chanson Jean‐Baptiste , Nicolas Guillaume , Douillard Claire , Laforêt Pascal
Published: November 2023

Introduction

Fatty‐acid oxidation disorders (FAODs) are recessive genetic diseases.

Materials and methods

We report here clinical and paraclinical data from a retrospective study of 44 adults with muscular FAODs from six French reference centers for neuromuscular or metabolic diseases.

Results

The study cohort consisted of 44 adult patients: 14 with carnitine palmitoyl transferase 2 deficiency (32%), nine with multiple acyl‐CoA deficiency (20%), 13 with very long‐chain acyl‐CoA dehydrogenase deficiency (30%), three with long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency (7%), and five with short‐chain acyl‐CoA dehydrogenase deficiency (11%). Disease onset occurred during childhood in the majority of patients (59%), with a mean age at onset of 15 years (range = 0.5–35) and a mean of 12.6 years (range = 0–58) from disease onset to diagnosis. The principal symptoms were acute muscle manifestations (rhabdomyolysis, exercise intolerance, myalgia), sometimes associated with permanent muscle weakness. Episodes of rhabdomyolysis were frequent (84%), with a mean creatinine kinase level of 68,958 U/L (range = 660–300,000). General metabolic complications were observed in 58% of patients, respiratory manifestations in 18% of cases, and cardiological manifestations in 9% of cases. Fasting acylcarnitine profile was used to orient genetic explorations in 65% of cases. After a mean follow‐up of 10 years, 33% of patients were asymptomatic and 56% continued to display symptoms after exercise. The frequency of rhabdomyolysis decreased after diagnosis in 64% of cases.

Conclusion

A standardized register would complete this cohort description of muscular forms of FAODs with exhaustive data, making it possible to assess the efficacy of therapeutic protocols in real‐life conditions and during the long‐term follow‐up of patients.
Twenty years on from the introduction of the high risk strategy for stroke and cardiovascular disease prevention: a systematic scoping review
Authors: Feigin Valery L. , Martins Sheila C. , Brainin Michael , Norrving Bo , Kamenova Saltanat , Giniyat Azhar , Kondybayeva Aida , Aldyngurov Daulet K. , Bapayeva Magripa , Zhanuzakov Murat , Hankey Graeme J.
Published: November 2023

Background and purpose

Early this century, the high risk strategy of primary stroke and cardiovascular disease (CVD) prevention for individuals shifted away from identifying (and treating, as appropriate) all at‐risk individuals towards identifying and treating individuals who exceed arbitrary thresholds of absolute CVD risk. The public health impact of this strategy is uncertain.

Methods

In our systematic scoping review, the electronic databases (Scopus, MEDLINE, Embase, Google Scholar, Cochrane Library) were searched to identify and appraise publications related to primary CVD/stroke prevention strategies and their effectiveness published in any language from January 1990 to August 2023.

Results

No published randomized controlled trial was found on the effectiveness of the high CVD risk strategy for primary stroke/CVD prevention. Targeting high CVD risk individuals excludes a large proportion of the population from effective blood‐pressure‐lowering and lipid‐lowering treatment and effective CVD prevention. There is also evidence that blood pressure lowering and lipid lowering are beneficial irrespective of blood pressure and cholesterol levels and irrespective of absolute CVD risk and that risk‐stratified pharmacological management of blood pressure and lipids to only high CVD risk individuals leads to significant underuse of blood‐pressure‐lowering and lipid‐lowering medications in individuals otherwise eligible for such treatment.

Conclusions

Primary stroke and CVD prevention needs to be done in all individuals with increased risk of CVD/stroke. Pharmacological management of blood pressure and blood cholesterol should not be solely based on the high CVD risk treatment thresholds. International guidelines and global strategies for primary CVD/stroke prevention need to be revised.
Metabolic dysfunction‐associated steatotic liver disease criteria may underestimate the number of lean female nonalcoholic fatty liver disease patients with significant liver fibrosis
Authors: Kobayashi Natsuko , Tada Toshifumi , Nishimura Takashi , Matono Tomomitsu , Yuri Yukihisa , Takashima Tomoyuki , Aizawa Nobuhiro , Ikeda Naoto , Fukunishi Shinya , Hashimoto Mariko , Ohyanagi Mitsumasa , Enomoto Hirayuki , Iijima Hiroko
Published: November 2023

Aim

It remains unclear whether the newly defined concept of metabolic dysfunction‐associated steatotic liver disease (MASLD) appropriately includes patients with nonalcoholic fatty liver disease with significant liver fibrosis.

Methods

A total of 4112 patients in whom nonalcoholic fatty liver disease was diagnosed by ultrasonography during medical checkups were enrolled. We defined a fibrosis‐4 index ≥1.3 in patients aged <65 years and ≥2.0 in patients aged ≥65 years as significant liver fibrosis.

Results

The numbers of patients with a low, intermediate, and high probability of advanced ﬁbrosis based on the fibrosis‐4 index were 3360 (81.7%), 668 (16.2%), and 84 (2.0%). There were 3828 (93.1%) and 284 (6.9%) patients diagnosed with MASLD and non‐MASLD. The non‐MASLD group, compared with the MASLD group, was significantly younger (44 vs. 55 years) and had a higher percentage of women (62.3% vs. 27.7%). Significant fibrosis, defined based on the fibrosis‐4 index, was present in 18.5% of the MASLD group and 15.5% of the non‐MASLD group. In a multivariable analysis, female sex (OR 6.170, 95% CI 3.180–12.000; p < 0.001) was independently associated with non‐MASLD in patients with a significant fibrosis. Among non‐MASLD patients with a significant fibrosis (n = 44), body mass index was significantly lower in females than in males (p < 0.001). In a multivariable analysis of patients aged <65 years, female sex (OR, 7.700; 95% CI, 3.750–15.800; p < 0.001) remained independently associated with non‐MASLD in patients with a significant fibrosis.

Conclusions

MASLD may inappropriately exclude patients with significant fibrosis, especially lean females with nonalcoholic fatty liver disease.
Metabolomics of chemical constituents as a tool for understanding the quality of fruits during development and processing operations
Authors: Singh Narpinder , Kathuria Deepika , Barthwal Riya , Joshi Robin
Published: November 2023

Fruit is a crucial component of our diet, and breeding to produce nutrient‐rich cultivars necessitates a thorough examination of their metabolite composition. Fruit contains hundreds of different chemicals, including both primary and secondary (or specialised) metabolites. The structural diversity of health promoting and sensory attributes imparting metabolites and their complex interactions during fruit growth and developments were uncovered by high‐throughput metabolomics. Both targeted and non‐targeted metabolomics approach are used for the comprehensive analysis of small molecules from various complex matrices, addressing genetic, environment effect, metabolic programming, etc. With advances of mass spectrometer (MS), targeted metabolomics with non‐targeted metabolomics, MS‐based fingerprinting, profiling or imaging strategies and pseudo‐targeted are being employed to elucidate novel bioactive compounds. The exemplary reports cover a wide range of fruit metabolic implications, addressing the impact of processing on fruit flavour quality, the identification of sensory and nutraceutical biomarkers in fruits, metabolic alterations in fruits during post‐harvesting and future prospects. The examination of metabolomics profiles of multiple fruit species is anticipated to be benefitted for the expansion of fruits in terms of nutritional and health benefits aspects in the upcoming years.
Characterization of children's verbal input in a forager‐farmer population using long‐form audio recordings and diverse input definitions
Authors: Scaff Camila , Casillas Marisa , Stieglitz Jonathan , Cristia Alejandrina
Published: November 2023

There is little systematically collected quantitative empirical data on how much linguistic input children in small‐scale societies encounter, with some estimates suggesting low levels of directed speech. We report on an ecologically‐valid analysis of speech experienced over the course of a day by young children (N = 24, 6–58 months old, 33% female) in a forager‐horticulturalist population of lowland Bolivia. A permissive definition of input (i.e., including overlapping, background, and non‐linguistic vocalizations) leads to massive changes in terms of input quantity, including a quadrupling of the estimate for overall input compared to a restrictive definition (only near and clear speech), while who talked to and around a focal child is relatively stable across input definitions. We discuss implications of these results for theoretical and empirical research into language acquisition.
Risk factors for surgical site infection after closed proximal humerus fractures
Authors: Li Ming , Sun Guang‐chen , Cui Jun , Lou Qi‐liang
Published: November 2023

Proximal humerus fractures are common in clinical practice, and there are relatively a few studies on postoperative incision infections of such fractures. The purpose of this study was to explore the risk factors for surgical site infection (SSI) after internal fixation in patients with closed proximal humerus fractures. Patients with closed proximal humerus fractures who underwent surgery from January 2016 to January 2022 were retrospectively analysed. Cases with superficial or deep infections within 3 months after surgery were in the infection group and the remaining cases were in the non‐infection group. The types of pathogenic bacteria in the infection group were analysed. The potential risk factors for SSI in all patients were recorded: (1) patient‐related factors: gender, age, body mass index (BMI), smoking, comorbidities; (2) trauma‐related factors: mechanism of injury, Injury Severity Score, visual analogue scale, fracture type, soft tissue condition and combined dislocation; (3) laboratory‐related indexes: haemoglobin, albumin; (4) surgery‐related factors: time from injury to surgery, American Society of Anesthesiologists anaesthesia classification, surgical time, fixation mode, intraoperative blood loss, suture method, bone graft and postoperative drainage. The risk factors for the occurrence of SSI were analysed using univariate analysis and multivariate logistic regression. The incidence of SSI was 15.7%. The most common bacterium in the infection group was Staphylococcus aureus. High BMI (p = 0.033), smoking (p = 0.030), an increase in mean time from injury to definitive surgery (p = 0.013), and prolonged surgical time (p = 0.044) were independent risk factors for the development of SSI after closed proximal humeral fractures. In patients with closed proximal humerus fractures, weight loss, perioperative smoking cessation, avoidance of delayed surgery, and shorter surgical time may be beneficial in reducing the incidence of SSI.