bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge
Authors: Coates Matthew L. , Richoz Nathan , Tuong Zewen K. , Bowyer Georgie , Lee Colin Y.C. , Ferdinand John R. , Gillman Eleanor , McClure Mark , Di Marco Barros Rafael , Stewart Benjamin J , Clatworthy Menna R.
Published: September 2023

Adaptive immunity is generated in lymphoid organs, but how these structures defend themselves during infection in humans is unknown. The nasal epithelium is a major site of viral entry, with adenoid nasal-associated lymphoid tissue (NALT) generating early adaptive responses. Here, using a nasopharyngeal biopsy, we examined longitudinal immune responses in NALT following viral challenge, using SARS-CoV-2 infection as a natural experimental model. In acute infection, infiltrating monocytes formed a subepithelial and peri-follicular shield, recruiting NET-forming neutrophils, whilst tissue macrophages expressed pro-repair molecules during convalescence to promote the restoration of tissue integrity. Germinal centre B cells expressed anti-viral transcripts that inversely correlated with fate-defining transcription factors. Among T cells, tissue-resident memory CD8 T cells alone showed clonal expansion and maintained cytotoxic transcriptional programmes into convalescence. Together our study provides a unique insight into how human nasal adaptive immune responses are generated and sustained in the face of viral challenge.
Deep Learning for Heart Sound Analysis: A Literature Review
Authors: Zhao Qinghao , Geng Shijia , Wang Boya , Sun Yutong , Nie Wenchang , Bai Baochen , Yu Chao , Zhang Feng , Tang Gongzheng , Zhang Deyun , Zhou Yuxi , Liu Jian , Hong Shenda
Published: September 2023

Abstract

Heart sound auscultation is a physical examination routinely used in clinical practice to identify potential cardiac abnormalities. However, accurate interpretation of heart sounds requires specialized training and experience, thereby limiting its generalizability. Deep learning, a subset of machine learning, involves training artificial neural networks to learn from large datasets and perform complex tasks related to intricate patterns, such as disease diagnosis, event prediction, and clinical decision-making. Over the past decade, deep learning has been successfully applied to heart sound analysis with remarkable achievements. Meanwhile, as heart sound analysis is gaining attention, many public and private heart sound datasets have been established for model training. The massive accumulation of heart sound data improves the performance of deep learning-based heart sound models and extends their clinical application scenarios. In this review, we will compile the commonly used datasets in heart sound analysis, introduce the fundamentals and state-of-the-art techniques in heart sound analysis and deep learning, and summarize the current applications of deep learning for heart sound analysis and their limitations for future improvement.
Platelet dysfunction reversal with cold-stored vs. room temperature-stored platelet transfusions
Authors: Kogler Valery J. , Miles Jeffrey A. , Özpolat Tahsin , Bailey S. Lawrence , Byrne Daire A. , Bawcom-Randall Morgan , Wang Yi , Larsen Hannah J. , Reed Franklin , Fu Xiaoyun , Stolla Moritz
Published: September 2023

Background

Platelets are stored at room temperature for 5-7 days (RSP). Due to frequent and severe shortages, the FDA recently approved up to 14-day cold-stored platelets in plasma (CSP). However, the post-transfusion function of CSP is unknown and it is unclear which donors are best suited to provide either RSP and/or CSP.

Objective

To evaluate thepost-transfusionfunction and predictors ofpost-transfusionfunction for platelets stored for the maximum approved storage times (7-day RSP, 14-day CSP) in healthy volunteers on acetylsalicylic acid (ASA).

Methods

We conducted a randomized cross-over study in ten healthy humans. Subjects donated one platelet unit stored at either RT (RSP) or 4 °C (CSP) based on randomization. Before transfusion, subjects ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round with transfusion of the alternative product and an identical testing sequence followed.

Results

RSP reversed platelet inhibition significantly better in αIIbβ3 integrin activation-dependent assays. In contrast, CSP led to significantly more thrombin generation in recipients, which was not dependent on platelet microparticles, but CSP themselves. Lysophosphatidylcholine-O (Lyso-Platelet Activating Factor) species levels predicted the procoagulant capacity of CSP. In contrast, polyunsaturated fatty acid concentration predicted the aggregation response of RSP.

Conclusion

We provide the first efficacy data of extended-stored CSP in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible and pave the way for larger studies in the future.Graphical Abstract 1:

Overview of CSP function after 14 days of storage (Created with Biorender)
Intra-ocular Predation of Fluoroquinolone-ResistantPseudomonas aeruginosaandSerratia marcescensby Predatory Bacteria
Authors: Romanowski Eric G. , Brothers Kimberly M. , Calvario Rachel C. , Stella Nicholas A. , Kim Tami , Elsayed Mennat , Kadouri Daniel E. , Shanks Robert M. Q.
Published: September 2023

Endogenous endophthalmitis caused by Gram-negative bacteria is an intra-ocular infection that can rapidly progress to irreversible loss of vision. While most endophthalmitis isolates are susceptible to antibiotic therapy, the emergence of resistant bacteria necessitates alternative approaches to combat intraocular bacterial proliferation. In this study the ability of predatory bacteria to limit intraocular growth ofPseudomonas aeruginosa, Serratia marcescens, andStaphylococcus aureuswas evaluated in a New Zealand White rabbit endophthalmitis prevention model. Predatory bacteriaBdellovibrio bacteriovorusandMicavibrio aeruginosavoruswere able to reduce proliferation of keratitis isolates ofP. aeruginosaandS. marcescens. However, it was not able to significantly reduceS. aureus, which is not a productive prey for these predatory bacteria, suggesting that the inhibitory effect onP. aeruginosarequires active predation rather than an antimicrobial immune response. Similarly, UV-inactivatedB. bacteriovoruswere unable to prevent proliferation ofP. aeruginosa. Together, these data suggestin vivopredation of Gram-negative bacteria within the intra-ocular environment.
Identification of neuronal ensembles involved in remote fear memory extinction impairments
Authors: Tomaszewski Kamil F. , Łukasiewicz Kacper , Robacha Magdalena , Radwańska Kasia
Published: September 2023

Remote memory consolidation, extinction, and its impairments have been of interest to researchers for years, especially due to its clinical relevance in patients with emotional disorders, like PTSD (Post Traumatic Stress Disorder), anxiety, and phobias. Its neuronal substrates are key elements to understand the persistent nature of remote memory and open a new perspective to novel therapeutic approaches for human fear-related disorders. While the majority of reports investigate the mechanisms and ensembles of recent fear memory extinction (hours to days following conditioning), only a few refer to the remote time point (i.e. weeks after conditioning), usually describing successful memory extinction. The neuronal correlates of impaired remote fear memory extinction were yet beyond the scope. Here we present selective impairment of contextual remote fear memory extinction in alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) autophosphorylation-limited mice (T286A+/-). To map brain regions involved in this phenomenon, we applied screening of c-Fos expression, a neuroplasticity marker, across 23 brain areas following contextual fear conditioning and extinction of recent (1-day old) and remote (30-days old) fear memory in WT and T286A+/-mice. Following impaired remote fear memory extinction in T286A+/-mice, we found upregulated c-Fos expression in the entorhinal cortex (ENT), nucleus reuniens (RE), centromedial (CM), mediodorsal (MD), anterodorsal (AD) thalamic nuclei, and medial septum (MS), compared to WT animals performing normal remote fear memory extinction. Thus our data suggest that αCaMKII-autophosphorylation-dependent c-Fos expression in these areas controls distant contextual fear extinction and may shed light on these brain regions as potential targets for therapeutic strategies against emotional disorders such as PTSD.
Multiple Introductions of Mpox virus to Ireland during the 2022 International Outbreak
Authors: Gonzalez Gabriel , Carr Michael , Kelleher Tomás M. , O’Byrne Emer , Banka Weronika , Keogan Brian , Bennett Charlene , Franzoni Geraldine , Keane Patrice , Meredith Luke W. , Fletcher Nicola , Urtasun-Elizari Jose Maria , Dean Jonathan , Crowley Brendan , Igoe Derval , Robinson Eve , Martin Greg , Connell Jeff , De Gascun Cillian F. , Hare Daniel
Published: September 2023

Background

mpox (formerly Monkeypox) virus (MPXV) was considered a rare zoonotic disease prior to May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Previously, mpox infection was associated with symptoms similar to smallpox, although substantially less severe, including fever, an extensive characteristic rash and swollen lymph nodes.

Aim

Elucidating the origin and molecular characteristics of the virus circulating in the Republic of Ireland in the period between May and November 2022.

Methods

Whole-genome sequencing of all MPXV cases (80%; n=178/219) analysed against sequences from public databases (n=2695). Bayesian approaches were used to infer the divergence time between sequences from different subclades and transmission events involving different countries.

Results

The circulating virus belonged to the clade IIb B.1 lineage and, notably, the presence of twelve separable and highly-supported subclades consistent with multiple introductions into the country. Such a hypothesis of multiple importation events was supported further by the estimation of the time to the divergence of subclades. Additionally, inferred MPXV transmissions involving different countries and continents were indicative of an extended international spread. The analysis of the mutations in the Irish sequences revealed 93% of the mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across the subclades.

Conclusion

In the context of extremely high national sequencing coverage, we provide new insights into the international origin and transmission dynamics supporting multiple introductions into the Republic of Ireland.

Conflict of Interests

None to declare.
A new route for the syntheses of coordination polymers using magnetic influence: syntheses, crystal structures and fluorescence properties
Authors: Guan Lei , Wang Ying , Jin Hongzhe , Yin Pengpeng
Published: September 2023

Five coordination polymers [TM1(absa)(H2O)4]
n
and [TM2(absa)(bipy)(H2O)]
n
[TM1 = Zn (1), Co (2); TM2 = Zn (3), Co (4), Cu (5); Na2absa = 5,5′-azobissalicylic acid disodium salt; bipy = 4,4′-bipyride] were synthesized by solvent evaporation under a magnetic field. It is evident that magnetic fields bring significant and noticeable changes to the absa2− ligand orientation and the component movement behaviors to construct coordination polymers. The absa2− ligands bind to the metal ions in bridging coordination mode through the carboxylate groups, in addition to the bipy molecules adopting bridging modes. Photoluminescence measurements indicate that the emissions of compounds 1–5 are at 626, 600, 632, 658 and 682 nm in the solid state, respectively.
Synthesis and crystal structure of silicon pernitride SiN2 at 140 GPa
Authors: Jurzick Pascal L. , Krach Georg , Brüning Lukas , Schnick Wolfgang , Bykov Maxim
Published: September 2023

Silicon pernitride, SiN2, was synthesized from the elements at 140 GPa in a laser-heated diamond anvil cell. Its crystal structure was solved and refined by means of synchrotron-based single-crystal X-ray diffraction data. The title compound crystallizes in the pyrite structure type (space group Pa\overline{3}, No. 205). The Si atom occupies a site with multiplicity 4 (Wyckoff letter b, site symmetry .\overline{3}.), while the N atom is located on a site with multiplicity 8 (Wyckoff letter c, site symmetry .3.). The crystal structure of SiN2 is comprised of slightly distorted [SiN6] octahedra interconnected with each other by sharing vertices. Crystal chemical analysis of bond lengths suggests that Si has a formal oxidation state of +IV, while nitrogen forms pernitride anions (N—N)4–.
Related party transactions, ownership structures and cost of debt: evidence from GCC listed firms
Authors: Eulaiwi Baban , Al-Hadi Al-Hadi Ahmed , Duong Lien , Perrin Brian , Taylor Grantley
Published: September 2023

Purpose

This study aims to investigate the relation between firms’ use of related party transactions (RPTs) and cost of debt (COD) in Gulf Cooperation Council (GCC) countries.

Design/methodology/approach

The authors obtain data from annual reports and the Standard and Poor’s Capital IQ database over the period 2005–2016 period of nonfinancial publicly listed firms on the UAE, KSA, Oman, Bahrain, Kuwait and Qatar stock exchanges. Using a final sample of 1,810 firm-year observations, the authors empirically assess the relation between strategic use of RPTs, the COD issuance and the moderating effects of governance mechanisms.

Findings

The authors find that high levels of total RPTs and purchase-based RPTs increase firms’ COD. Furthermore, propping of sales through increased sale-based RPTs is found not to have a significant effect on firms’ COD. The authors also find that ownership factors pertaining to family member founding and royal family ownership negatively moderate the association between the firm’s RPTs and COD. Additionally, the voluntary formation of executive committees has a positive and significant mediating effect on the relation between firms’ purchase-based RPTs and COD. The results are robust to several additional tests and alternative measurement specifications.

Research limitations/implications

The positive relationship between purchase-based RPTs and firm financing costs is magnified in countries with high quality of RPT disclosures. This has implications for funding of GCC entities by governments and financial institutions.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine how wealth transfer via RPTs in the GCC region is associated with higher COD. The authors also contribute to the outcome of emerging governance regimes in the GCC, which could impact the level of credit risk and/or default risk faced by a firm and, thus, the relation between RPTs and COD. In doing so, the authors provide a more nuanced study by investigating the potential channels that could account for such a relation in an emerging market setting.
ICICI Bank and SBI – too big to fail
Authors: Bhusan Soumik , Singh Amrinder
Published: September 2023

Learning outcomes

The learning outcomes of this study are to gain an understanding of the banking regulations and their impact on banking performance, to understand the intermediation role of banks by channelizing depositors’ savings and providing loans to borrowers, to explain an impact of a recent regulatory change in the Indian banking that directly impacts their financial performance, to critically evaluate the different financial ratios to analyze the performance of a bank and to build a DuPont analysis framework for banks.

Case overview/synopsis

The case serves as a primer on banking regulations in India and provides insights into banking performance. Banking regulations play an important role in maintaining financial stability, specifically in emerging economies like India. The protagonist of the case is Salil Kumar who presented his internship project to the review committee of Stock Investment Company on April 16, 2021. However, he had to rework and present his final project within seven days on the basis of the feedback received from the committee. Kumar faced the dilemma of bringing together a comparative study across two banks, namely, Industrial Credit and Investment Corporation of India (ICICI Bank) and State Bank of India (SBI) and building a DuPont framework covering the different aspects of banking performance. The case exemplifies the intricate regulatory landscape in India within which banks operate and highlights the recent alterations introduced by the Reserve Bank of India. For instance, the framework for dealing with domestic systemically important banks (D-SIBs) was introduced in 2014 and subsequently adopted in August 2015. The D-SIB framework provides inherent guarantee to large banks such as ICICI Bank and SBI. This ensures government backup in the event of any failure, thereby securing financial stability. The case study is suitable for banking and financial accounting courses taught in postgraduate management programs. Once the case is studied, the students are expected to understand the basics of banking, regulations, impact of regulations on banking performance and financial measures.

Complexity academic level

The case provides valuable insights into the intricate dynamics of the banking industry, offering a critical perspective for analysis. A well-structured teaching note would serve as a valuable tool for instructors, allowing them to facilitate engaging classroom discussions and effectively guide students toward achieving the desired teaching objectives.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
ODLC_SAM: a novel LiDAR SLAM system towards open-air environments with loop closure
Authors: Zhang Jiazhong , Wang Shuai , Tan Xiaojun
Published: September 2023

Purpose

The light detection and ranging sensor has been widely deployed in the area of simultaneous localization and mapping (SLAM) for its remarkable accuracy, but obvious drift phenomenon and large accumulated error are inevitable when using SLAM. The purpose of this study is to alleviate the accumulated error and drift phenomenon in the process of mapping.

Design/methodology/approach

A novel light detection and ranging SLAM system is introduced based on Normal Distributions Transform and dynamic Scan Context with switch. The pose-graph optimization is used as back-end optimization module. The loop closure detection is only operated in the scenario, while the path satisfies conditions of loop-closed.

Findings

The proposed algorithm exhibits competitiveness compared with current approaches in terms of the accumulated error and drift distance. Further, supplementary to the place recognition process that is usually performed for loop detection, the authors introduce a novel dynamic constraint that takes into account the change in the direction of the robot throughout the total path trajectory between corresponding frames, which contributes to avoiding potential misidentifications and improving the efficiency.

Originality/value

The proposed system is based on Normal Distributions Transform and dynamic Scan Context with switch. The pose-graph optimization is used as back-end optimization module. The loop closure detection is only operated in the scenario, while the path satisfies condition of loop-closed.
Interprofessional education for mental health professions and peer support workers – to facilitate learning in teamwork
Authors: Viking Tuija , Repper Julie
Published: September 2023

Purpose

In mental health care the peer support workers (PSWs) are, by their experience based expertise, supporting the recovery of people using services and have also been shown to stimulate interprofessional learning (IPL) but which, due to hierarchical teams, is challenged. Therefore, to prepare the teams for IPL that includes PSWs, this study aims to suggest an interprofessional education (IPE) for mental health professions and PSWs. What would such an education look like?

Design/methodology/approach

The base, in the development of the IPE, is two earlier studies of teams’ inclusion of PSWs and the IPL.

Findings

The present study suggests Knowledge base 1 with three categories: different roles, expertise and perspectives, and Knowledge base 2 with two categories: teamwork and IPL. The conclusion is that such online IPE offers a readiness for mental health professions and PSWs, in teamwork, to exchange their different expertise to facilitate IPL. This is important to improve the quality of mental health services.

Research limitations/implications

One limitation is that the empirical study, this paper is based on, is a small-scaled study. Nevertheless, the main results from this study and the other were considered useful as a ground for the development of the IPE.

Originality/value

By suggesting an IPE for mental health professions and PSWs, this paper adds to the literature on peer support as well as IPL.
When CEO compensation plan based on risk changes firm strategic variation and strategic deviation? The moderating role of shareholder return
Authors: Severgnini Elizandra , Vieira Valter Afonso , Abib Gustavo , Leonel Ronei
Published: September 2023

Purpose

The authors extend the recent research using the risk component of human resource’s (HR’s) compensation plans to examine the effects of risk components on two strategic outcomes: within-firm temporal change, or strategic variation, and firm strategic divergence from the industry, or strategic deviation. In addition, the authors examine the role of previous financial performance as a boundary moderator condition of the effects of risk components in the compensation plan and firm strategic outcomes.

Design/methodology/approach

To examine the effects of low- and high-risk components of executive compensation on strategic variation and deviation over time, the authors collected data from 2,510 companies listed in the Standard and Poor’s 500 index in a panel data format of a 12-year period. The authors gathered financial and other firm-level data from COMPUSTAT, and executive compensation and executive-level data from ExecuComp.

Findings

The findings support the main effects of risk components on strategic change, while both high- and low-risk components act on strategic deviation contingent on the moderating role of total shareholder return (TSR). In the theoretical framework, the authors test the moderating role of total shareholder return (TSR) as a boundary condition of the effects of risk components in the compensation plan. In doing so, the authors provide a fine-grained understanding of the influence of compensation plan risk components on outcomes proximal to executives, such as the maintenance of the status quo and the search for financial gains.

Research limitations/implications

New studies can explore a three-way moderating effect on performance indicators, such as TSR, Tobin’s Q and return on asset. The authors addressed this limitation and did a comparative analysis, but the authors did not include additional moderating mechanisms in these interactive effects.

Practical implications

By disaggregating the executive’s compensation based on the risk components, boards of directors can mitigate any possible unwanted biases in the relationship between principal and agent.

Originality/value

By considering the influence of both low- and high-risk components of compensation plans on strategic outcomes –instead of firm performance – this study expands strategy literature supporting the influence of compensation schema on a firm’s outcomes. This path is new because it offers a moderating perspective to understand the strategic deviations and changes that chief executive officers imprint in their firms.
Interfacial reactions in the Sn-9.0 wt.% Zn/Cu-Ti alloy (C1990 HP) couple
Authors: Laksono Andromeda Dwi , Chen Chih-Ming , Yen Yee-Wen
Published: September 2023

Purpose

The purpose of this study was to examine the influence of adding a small amount of Ti to a Cu-based alloy, specifically the commercial Hyper Titanium Copper alloy (C1990 HP), which contains Cu-3.28 wt.% Ti, on its interfacial reaction with Sn-9.0 wt.% Zn (SnZn) solder, using the liquid/solid reaction couple technique.

Design/methodology/approach

The SnZn/C1990 HP couples were subjected to a reaction temperature of 240–270°C for a duration of 0.5–5 h. The resulting reaction couple was characterized using a scanning electron microscope, energy dispersive spectrometer, electron probe microanalyzer and X-ray diffractometer.

Findings

It was observed that the scallop-shaped CuZn5 and planar Cu5Zn8 phases were formed in almost all SnZn/C1990 HP couples. With increased reaction duration and temperature, the Cu-rich intermetallic compound (IMC)-Cu5Zn8 phase became a dominant IMC formed at the interface. The total thickness of the IMCs was increased with the increase in the reaction duration and temperature. The IMC growth obeyed the parabolic law, and the IMC growth mechanism was diffusion controlled. The activation energy of the SnZn/C1990 HP couple was 64.71 kJ/mol.

Originality/value

This article presents an analysis of the IMC thickness in each sample using ImageJ software, followed by kinetic analysis using Origin software at various reaction temperatures of SnZn/C1990 HP in liquid/solid couples. The study also includes detailed reports on the morphology, interface composition and X-ray diffraction analysis, as well as the activation energy. The findings can serve as a valuable reference for electronic packaging companies that utilize C1990 HP substrates.
Trans misogyny in the colonial archive: Re‐membering trans feminine life and death in New Spain, 1604–1821
Authors: Jesperson Jamey
Published: September 2023

Traces of trans feminine pasts are scattered all across the colonial archive. In New Spain, glimpses of Indigenous trans women's lives can be found in the records of conquistadors as early as the sixteenth century. While such early colonial representations of trans femininity span myriad religious, imperial and literary contexts, they are all underpinned by one harrowing reality: the widespread, colonial pursuit of trans feminine death. To ‘re‐member’ – á la Saylesh Wesley – trans feminine pasts in the colonial archive, this article traces structures of, and resistance to, colonial trans misogyny in the sodomy criminal trials of Mexico (1604–1771) and the Catholic missions of California (1769–1821). Pushing against an extant ‘cistoriography’ that has simply archived these stories within the history of sexuality, I ask: What may be gleaned by centring trans femininity and womanhood as core to not only the lives of historical subjects, but the reason many of their lives were so violently taken? By re‐membering trans misogyny in this way, we may finally name and centre the long‐erased trans feminine historical subject, illuminate the complex, changing structures of her past worlds and trace the oft‐forgotten lineages of not just trans feminine death, but trans feminine survivance in its face.
Potential water‐related risks to the electric power industry associated with changing surface water conditions
Authors: Hersh Eric , Jackson Morgan , Menninger John , Shippee Norman , Thomas Jeff , Rao Nalini
Published: September 2023

This study identifies and summarizes potential risks to operations, regulatory compliance, supply chains, and infrastructure of the electric power industry from changing surface water conditions resulting from global climate change. The results help inform companies/utilities seeking to incorporate climate change risk in their planning and decision‐making processes by ranking risk severity and likelihood of occurrence on both a regional basis and by risk receptor. The assessment includes identification of potential risks to: (1) thermal generating, (2) hydroelectric, (3) land‐based renewable generating, and (4) transmission and distribution assets. These risks may result from such projected changes as reduced water availability (e.g., for hydroelectric or once‐through cooling), increased water temperatures (e.g., decrease in cooling efficiency, inability to meet discharge permit conditions), increased flood severity (e.g., increased streambank erosion and/or damage to river‐adjacent infrastructure), and decreased water quality (e.g., from increased transport of sediment and dissolved solids). The potential risks identified from this qualitative risk‐assessment are documented in a graphical format depicting both severity and likelihood. This approach allows for comparison of risks across a portfolio and for future prioritization of adaptation strategies. A total of 32 risks were identified in the study, including nine risks to infrastructure, six risks to operations, four risks to supply chain, and 13 environmental/regulatory risks.
Exercise ameliorating myocardial injury in type 2 diabetic rats by inhibiting excessive mitochondrial fission involving increased irisin expression and AMP‐activated protein kinase phosphorylation
Authors: Wang Bin , Zhao Chen , Wang Yuanxin , Tian Xin , Lin Junjie , Zhu Baishu , Zhou Yalan , Zhang Xin , Li Nan , Sun Yu , Xu Haocheng , Zhao Renqing
Published: September 2023

Purpose

Though exercise generates beneficial effects on diabetes‐associated cardiac damage, the underlying mechanism is largely unclear. Therefore, we prescribed a program of 8‐week treadmill training for type 2 diabetes mellitus (T2DM) rats and determined the role of irisin signaling, via interacting with AMP‐activated protein kinase (AMPK), in mediating the effects of exercise on myocardial injuries and mitochondrial fission.

Methods

Forty 8‐week‐old male Wistar rats were randomly divided into groups of control (Con), diabetes mellitus (DM), diabetes plus exercise (Ex), and diabetes plus exercise and Cyclo RGDyk (ExRg). Ex and ExRg rats received 8 weeks of treadmill running, and the rats in the ExRg group additionally were treated with a twice weekly injection of Cyclo RGDyk, an irisin receptor‐αV/β5 antagonist. At the end of the experiment, murine blood samples and heart tissues were collected and analyzed with methods of ELISA, Western blot, real‐time quantitative polymerase chain reaction, as well as immunofluorescence staining.

Results

Exercise effectively mitigated T2DM‐related hyperglycemia, hyperinsulinemia, lipid dysmetabolism, and inflammation, which could be diminished by Cyclo RGDyk treatment. Additionally, exercise alleviated T2DM‐induced myocardial injury and excessive mitochondrial fission, whereas the beneficial effects were blocked by the administration of Cyclo RGDyk. T2DM significantly decreased serum irisin concentrations and fibronectin type III domain‐containing protein 5 (FNDC5)/irisin gene and protein expression levels in the rat heart, whereas exercise could rescue T2DM‐reduced FNDC5/irisin expression. Blocking irisin receptor signaling diminished the exercise‐alleviated mitochondrial fission protein expression and elevated AMPK phosphorylation.

Conclusion

Exercise is effective in mitigating diabetes‐related insulin resistance, metabolic dysfunction, and inflammation. Irisin signaling engages in exercise‐associated beneficial effects on myocardial injury and excessive mitochondrial fission in diabetes rats involving elevated AMPK phosphorylation.
Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China
Authors: Pu Xingxiang , Xu Chunwei , Wang Qian , Wang Wenxian , Wu Fang , Cai Xiuyu , Song Zhengbo , Yu Jinpu , Zhong Wenzhao , Wang Zhijie , Zhang Yongchang , Liu Jingjing , Zhang Shirong , Liu Anwen , Li Wen , Zhan Ping , Liu Hongbing , Lv Tangfeng , Miao Liyun , Min Lingfeng , Lin Gen , Huang Long , Yuan Jingping , Jiang Zhansheng , Rao Chuangzhou , Lv Dongqing , Yu Zongyang , Li Xiaoyan , Tang Chuanhao , Zhou Chengzhi , Zhang Junping , Guo Hui , Chu Qian , Meng Rui , Liu Xuewen , Wu Jingxun , Zhou Jin , Zhu Zhengfei , Pan Weiwei , Pang Fei , Huang Jintao , Wang Kai , Wu Fan , Shen Tingting , Zou Shirui , Xu Bingwei , Wang Liping , Zhu Youcai , Lin Xinqing , Cai Jing , Xu Ling , Li Jisheng , Jiao Xiaodong , Li Kainan , Feng Huijing , Wang Lin , Du Yingying , Yao Wang , Shi Xuefei , Niu Xiaomin , Yuan Dongmei , Yao Yanwen , Kang Jing , Zhang Jiatao , Zhang Chao , Fu Jianfei , Huang Jianhui , Zhang Yinbin , Sun Pingli , Wang Hong , Ye Mingxiang , Wang Dong , Wang Zhaofeng , Hao Yue , Wang Zhen , Wan Bing , Lv Donglai , Lan Gang , Yang Shengjie , Shi Lin , Wang Yina , Li Bihui , Zhang Zhang , Li Zhongwu , Li Yuan , Liu Zhefeng , Yang Nong , Wang Huijuan , Huang Wenbin , Hong Zhuan , Wang Guansong , Wang Jiandong , Fang Meiyu , Fang Yong , Zhu Xixu , Shen Yi , Zhang Yiping , Ma Shenglin , Song Yong , Lu Yuanzhi , Fang Wenfeng , Li Ziming , Wu Lin
Published: September 2023

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.
What is work engagement? A text mining approach using employees' self‐narratives
Authors: van Roekel Henrico , Wigger Enno F. J. , Veldkamp Bernard P. , Bakker Arnold B.
Published: September 2023

We introduce text mining to study work engagement by using this method to classify employees' survey‐based self‐narratives into high or low work engagement and analyzing the text features that contribute to the classification. We used two samples, representing the 2020 and 2021 waves of an annual survey among healthcare employees. In the first study, we used exploratory sample 1 (N = 5591) to explore which text features explain work engagement (unigrams, bigrams, psychological, or linguistic). In the second study, we confirmed whether features persisted over time between exploratory sample 1 and confirmatory sample 2 (N = 4470). We find that psychological features classify employees across two samples with 60% accuracy. These features partly validate the literature: High‐engaged employees refer more to affiliation and positive emotions, and low‐engaged employees refer more to negative emotions and power. We extend the literature by studying linguistics: High‐engaged employees use more first‐person plural (“we”) than low‐engaged employees. Finally, some results question the literature, like the finding that low‐engaged employees refer more to their managers. This study shows text mining can contribute by confirming, extending, or questioning the literature on work engagement and explores how future research could build on our findings with survey‐based or in vivo applications.
Compared to antibiotic, feeding peony byproducts can improve growth performance, rumen fermentation, slaughter parameters, and meat quality of lambs
Authors: Zhou Xiaoyang , Xiang Hai , Han Yujie , Chang Xiao , Gu Yue , Liu Zheng'an , Jiao Jinzhen , Fang Yi , Zhong Rongzhen
Published: September 2023

Our objective was to determine effects of feeding lamb's peony byproducts, including stem and leaves (PSL), root (PR), and seeds meal (PSM), on growth, rumen fermentation, slaughter parameters, and meat quality. Sixty‐four lambs (14.0 ± 2.1 kg) were allocated into eight treatments based on BW: no additives (CON), 0.15% aureomycin (CONA), low/high levels of PSL (5%/10% PSL replaced 5%/10% Chinese hay), PR (basal diet with 0.5%/1.0% PR), PSM (5%/10% PSM replaced 5%/10% soybean meal). Growth, digestibility, and rumen fermentation had dose responses whereas slaughter parameters, meat quality, or amino acids indexes were not. Peony byproducts increased DMI (p < 0.001) compared to CON, but higher levels were more advantageous (p = 0.003). However, low levels of peony byproducts decreased the NH3‐N concentration, but increased total volatile fatty acids mole percent more than high levels of that (p < 0.001). All peony byproducts increased dressing percentage (p < 0.05), increased pH and tenderness than CON (p < 0.05). In addition, PSL and PSM improved amino acid profiles of meat compared to CON, and were even better than CONA (p < 0.05). Therefore, peony byproducts not only improved animal growth but also reduced the frequency of antibiotic use in animal feeding.
Oral famotidine reduces the plasma level of soluble P‐selectin in children with sickle cell disease
Authors: Allali Slimane , Marquant Fabienne , Rignault‐Bricard Rachel , Taylor Melissa , Brice Joséphine , de Montalembert Mariane , Maciel Thiago Trovati , Elie Caroline , Hermine Olivier
Published: September 2023

Plasma histamine levels are increased in patients with sickle cell disease (SCD), potentially promoting endothelial P‐selectin expression and vaso‐occlusion via histamine type 2 (H2) receptors. We conducted a prospective, non‐comparative, single‐centre study to determine whether famotidine, a H2 receptor antagonist, reduces P‐selectin expression in SCD children. The median plasma P‐selectin level was significantly reduced after 29 days of oral famotidine (53.2 ng/mL [IQR: 46.7–63.4] vs. 69.9 ng/mL [IQR: 53.6–84.2], median difference −10.2 ng/mL [IQR: −21.8 to −2.7], p = 0.005) in 28 patients. No effect was observed on other adhesion molecules, inflammation or haemolysis markers, except decreased reticulocyte count. No adverse events deemed related to famotidine were observed. Randomized controlled trials are now needed to assess the efficacy of famotidine in preventing vaso‐occlusion in SCD.
Tumor‐associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin‐2
Authors: Li Haishuang , Liu Yuqing , Liu Yantao , Xu Luzheng , Sun Ziwen , Zheng Danfeng , Liu Xiaodan , Song Chen , Zhang Yu , Liang Hui , Yang Bao , Tian Xinxia , Luo Jianyuan , Chang Qing
Published: September 2023

Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) accounts for about 25% of all subgroups of MB. Tumor microenvironment (TME) may play a key role in the tumor progression and therapeutic resistance. Tumor‐associated astrocytes (TAAs) are reshaped to drive tumor progression through multiple paracrine signals. However, the mechanism by which TAAs modulate MB cells remains elusive. Here, we illuminated that TAAs showed a specific and dynamic pattern during SHH‐MB development. Most TAAs gathered to the tumor margin during the tumor progression, rather than evenly distributed in the early‐stage tumors. We further demonstrated that lipocalin‐2 (LCN2) secreted by TAAs could promote the tumor growth and was correlated with the poor prognosis of MB patients. Knocking down LCN2 in TAAs in vitro impeded the proliferation and migration abilities of MB cells. In addition, we identified that TAAs accelerated the tumor growth by secreting LCN2 via STAT3 signaling pathway. Accordingly, blockade of STAT3 signaling by its inhibitor WP1066 and AAV‐Lcn2 shRNA, respectively, in TAAs abrogated the effects of LCN2 on tumor progression in vitro and in vivo. In summary, we for the first time clarified that LCN2, secreted by TAAs, could promote MB tumor progression via STAT3 pathway and has potential prognostic value. Our findings unveiled a new sight in reprogramming the TME of SHH‐MB and provided a potential therapeutic strategy targeting TAAs.
A partial agonist of PPARγ prevents paclitaxel‐induced peripheral neuropathy in mice, by inhibiting neuroinflammation
Authors: Benvenutti Larissa , Wolff Fellippe Ramos , Corrêa Thiago Patrício , Melato Jessica , Goldoni Fernanda Capitanio , De Faveri Renata , Patel Yasmin Beatrisse Klein , de Souza Jade André , Grockoski Heloise Adeli , Nilz Paulo Mateus , Bombardelli Cleber Luiz , Remor Aline Pertile , Varela Karina Giacomini , Costa Natáli Tereza Capistrano , Hernandes Marcelo Zaldini , Lacerda Mariella Guimarães , Rodrigues Kathlen Deruci , Milton Flora Aparecida , Neves Francisco de Assis Rocha , Pereira Maria Eduarda Signorini , Kormann Imianowsky Elaine Cristina , de Campos Buzzi Fátima , Brunaldi Marutani Victor Hugo , Stoeberl Luis Carlos , Correa Rogério , Eller Sarah , de Oliveira Tiago Franco , Gonçalves Thamires Bragança Paduam , da Silva Raquel Costa , Passos Giselle Fazzioni , da Costa Robson , Santin José Roberto , Quintão Nara Lins Meira
Published: September 2023

Background and Purpose

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common side effect of paclitaxel, affecting 30‐50% of patients. Increased survival and concern with patients' quality of life have encouraged the search for new tools to prevent paclitaxel‐induced neuropathy. This study presents the glitazone 4‐[(Z)‐(2,4‐dioxo‐1,3‐thiazolidin‐5‐ylidene)methyl]‐N‐phenylbenzene‐sulfonamide (TZD‐A1) as a partial agonist of peroxisome proliferator‐activated receptor γ (PPARγ), its toxicological profile and effects on paclitaxel‐induced CIPN in mice.

Experimental Approach

Interactions of TZD‐A1 with PPARγ were analysed using in silico docking and in vitro reporter gene assays. Pharmacokinetics and toxicity were evaluated using in silico, in vitro and in vivo (C57Bl/6 mice) analyses. Effects of TZD‐A1 on CIPN were investigated in paclitaxel‐injected mice. Axonal and dorsal root ganglion damage, mitochondrial complex activity and cytokine levels, brain‐derived neurotrophic factor (BDNF), nuclear factor erythroid 2‐related factor 2 (Nrf2) and PPARγ, were also measured.

Key Results

Docking analysis predicted TZD‐A1 interactions with PPARγ compatible with partial agonism, which were corroborated by in vitro reporter gene assays. Good oral bioavailability and safety profile of TZD‐A1 were shown in silico, in vitro and in vivo. Paclitaxel‐injected mice, concomitantly treated with TZD‐A1 by i.p. or oral administration, exhibited decreased mechanical and thermal hypersensitivity, effects apparently mediated by inhibition of neuroinflammation and mitochondrial damage, through increasing Nrf2 and PPARγ levels, and up‐regulating BDNF.

Conclusion and Implications

TZD‐A1, a partial agonist of PPARγ, provided neuroprotection and reduced hypersensitivity induced by paclitaxel. Allied to its safety profile and good bioavailability, TZD‐A1 is a promising drug candidate to prevent and treat CIPN in cancer patients.
Considering the role of integration experiences in shaping immigrants’ post‐migration food choices and eating practices
Authors: Kwon Eugena
Published: September 2023

This article draws on data collected from qualitative interviews with 38 recent immigrants in two Ontario cities to provide an overview of recent immigrants’ general dietary acculturation experiences. With insights from both Cockerham's health lifestyle theory and Berry's acculturation model, this article explores how structural inequalities related to integration and settlement may shape recent immigrants’ post‐migration food choices and eating practices. The results of this study revealed that immigrants from non‐Western countries experienced greater challenges in healthy eating. Findings are in line with Cockerham's health lifestyle theory: immigrants’ post‐migration food choices and dietary acculturation strategies were not only bounded by socioeconomic status and cultural differences but were also shaped by various structural inequalities, especially those related to systematic barriers during the integration and settlement process. Overall, this paper provides a more holistic understanding of the multifaceted nature of immigrants’ dietary acculturation experiences.
Number of CAG repeats and mortality in middle aged and older men
Authors: Heald Adrian , Cook Michael J. , Antonio Leen , Tournoy Jos , Ghaffari Parisa , Mannan Fahmida , Fachim Helene , Vanderschueren Dirk , Laing Ian , Hackett Geoff , Casanueva Felipe F. , Huhtaniemi Ilpo T. , Maggi Mario , Rastrelli Giulia , Slowikowska‐Hilczer Jolanta , Wu Fred , O'Neill Terence W.
Published: September 2023

Design

The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon‐1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all‐cause mortality in men and the influence of testosterone level on the association.

Patients and Measurements

Follow‐up data to 27 January 2018 were available for men aged 40–79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI).

Results

One thousand nine hundred and seventy‐seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow‐up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22–23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93–1.49) and >23 CAG repeats 1.14 (0.88–1.47). In a post‐hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97–2.27) and 1.68 (1.06–2.67) versus 22–23 repeats.

Conclusions

Our European‐wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.