bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐world evidence of efficacy of pembrolizumab plus chemotherapy and nivolumab plus ipilimumab plus chemotherapy as initial treatment for advanced non‐small cell lung cancer
Authors: Kaneko Ayami , Kobayashi Nobuaki , Miura Kenji , Matsumoto Hiromi , Somekawa Kohei , Hirose Tomofumi , Kajita Yukihito , Tanaka Anna , Teranishi Shuhei , Sairenji Yu , Kawashima Hidetoshi , Yumoto Kentaro , Tsukahara Toshinori , Fukuda Nobuhiko , Nishihira Ryuichi , Watanabe Keisuke , Horita Nobuyuki , Hara Yu , Kudo Makoto , Miyazawa Naoki , Kaneko Takeshi
Published: April 2024

Background

For advanced non‐small cell lung cancer (NSCLC), combination therapies including a PD‐1 inhibitor plus chemotherapy or a PD‐1 inhibitor, CTLA‐4 inhibitor, and chemotherapy are standard first‐line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real‐world setting.

Methods

In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first‐line therapies in 182 patients with stage IIIB–IV NSCLC. Primary outcomes were overall survival (OS) and progression‐free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan–Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD‐L1 expression.

Results

In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3–4 adverse events occurred comparably, but immune‐related adverse events were numerically more frequent in the CNI group.

Conclusions

In real‐world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.
Ultra‐Processed Food, Depletion, and Social Reproduction: A Conceptual Intervention
Authors: Stevano Sara
Published: April 2024

What we eat and how we think about food and nutrition are undergoing a momentous change, driven by the rise of ultra‐processed food. There is a growing body of evidence linking the consumption of ultra‐processed food to poor health outcomes. However, the health depleting effects of ultra‐processed food go beyond changes in discrete indicators of nutrition and health. Processes of depletion entail social, economic, and political relations. This paper aims to emphasise the importance of a social science research agenda on ultra‐processed food by establishing the conceptual connections between ultra‐processed food and depletion using a social reproduction approach. To do this, it draws on the notion of depletion through social reproduction elaborated by Shirin Rai, Catherine Hoskyns and Dania Thomas, which provided inspiration to unpack the totality of social reproduction and consider specific resources needed for social reproduction. Such an approach reveals that ultra‐processed food is both an input for social reproduction, through consumption, and a form of social reproduction work, when food work and the associated (health) care work are considered. On this basis, the paper identifies four conceptual dimensions to explore whether and to what extent the expansion of ultra‐processed food can cause depletion and the key methodological principles to use this conceptual approach in empirical research.
Saliva monitoring of prednisolone in children with first onset steroid‐sensitive nephrotic syndrome: Is it possible?
Authors: Veltkamp Floor , Pistorius Marcel C. M. , Mak‐Nienhuis Elske M. , Schreuder Michiel F. , Bouts Antonia H. M. , Mathôt Ron A. A. ,   LEARNS consortium
Published: April 2024

Aims

Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side‐effects. Therapeutic drug monitoring using saliva would be a patient‐friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid‐sensitive nephrotic syndrome (SSNS).

Methods

Children (age 2–16 years) with SSNS participating in a randomized, placebo‐controlled trial with levamisole were treated with an 18‐week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed‐effects model was used to estimate the PK parameters of unbound prednisolone and the saliva‐to‐plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring.

Results

From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h−1 70 kg−1 and 158 (7%) L 70 kg−1, respectively. Typical saliva‐to‐plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area‐under‐the‐concentration–time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples.

Conclusion

Saliva proved to be a reliable and patient‐friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.
The ratchet effect and the probability of proceeding to the next stage: An experiment
Authors: Morita Shigeo , Mori Tomoharu
Published: April 2024

The ratchet effect is an economic phenomenon where agents strategically restrict their efforts to conceal information on their characteristics under the dynamic setting. This study experimentally examines the effect of the probability of proceeding to the next stage on ratcheting behavior. We find evidence that if the probability is smaller than 1, the ratchet effect is mitigated.
Detection of pTDP‐43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis
Authors: Zhang Qi‐Jie , Lin Jie , Wang You‐Liang , Chen Long , Ding Ying , Zheng Fu‐Ze , Song Huan‐Huan , Lv Ao‐Wei , Li Yu‐Ying , Guo Qi‐Fu , Lin Min‐Ting , Hu Wei , Xu Liu‐Qing , Zhao Wen‐Long , Fang Ling , Cui Meng‐Chao , Fu Zhi‐Fei , Chen Wan‐Jin , Zhang Jing , Wang Zhi‐Qiang , Wang Ning , Fu Ying
Published: April 2024

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP‐43 aggregates. Recent evidence has been indicated that phosphorylated TDP‐43 (pTDP‐43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP‐43 detectable in routine biopsied muscles? (ii) Can detection of pTDP‐43 aggregation discriminate between ALS and non‐ALS patients? (iii) Can pTDP‐43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non‐ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP‐43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP‐43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non‐ALS controls (16/54; p < 0.001). The pTDP‐43 aggregates were mainly close to the sarcolemma. Using a semi‐quantified pTDP‐43 aggregates score, we applied a cut‐off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof‐of‐concept for the detection of pTDP‐43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.
BRD2‐specific inhibitor, BBC0403, inhibits the progression of osteoarthritis pathogenesis in osteoarthritis‐induced C57BL/6 male mice
Authors: Lee Hyemi , Nam Jiho , Jang Hahyeong , Park Young‐Sik , Son Min‐Hee , Lee In‐Hyun , Eyun Seong‐il , Yang Jae‐Hyun , Jeon Jimin , Yang Siyoung
Published: April 2024

Background and Purpose

The discovery of new bromo‐ and extra‐terminal inhibitors presents new drugs to treat osteoarthritis (OA).

Experimental Approach

The new drug, BBC0403, was identified in the DNA‐encoded library screening system by searching for compounds that target BRD (bromodomain‐containing) proteins. The binding force with BRD proteins was evaluated using time‐resolved fluorescence energy transfer (TR‐FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12‐week‐old male C57BL/6 mouse model, and intra‐articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA‐seq.

Key Results

TR‐FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti‐OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 μM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF‐κB and MAPK signalling pathways.

Conclusion and Implications

This study demonstrated that BBC0403 is a novel BRD2‐specific inhibitor and a potential i.a.‐injectable therapeutic agent to treat OA.
A novel reuptake inhibitor, IP2015, induces erection by increasing central dopamine and peripheral nitric oxide release
Authors: Comerma‐Steffensen Simon , Kun Attila , Prat‐Duran Judit , Mogensen Susie , Alan Albayrak Elif , Fais Rafael , Munro Gordon , Peters Dan , Simonsen Ulf
Published: April 2024

Background and Purpose

An estimated 40% of patients with erectile dysfunction have a poor prognosis for improvement with currently available treatments. The present study investigated whether a newly developed monoamine transport inhibitor, IP2015, improves erectile function.

Experimental Approach

We investigated the effects of IP2015 on monoamine uptake and binding, erectile function in rats and diabetic mice and the effect on corpus cavernosum contractility.

Key Results

IP2015 inhibited the uptake of 5‐HT, noradrenaline and dopamine by human monoamine transporters expressed in cells and in rat brain synaptosomes. Intracavernosal pressure measurement in anaesthetized rats revealed that IP2015 dose‐dependently increased the number and the duration of spontaneous erections. Whereas pretreatment with the dopamine D2‐like receptor antagonists, clozapine and (−)‐sulpiride, or cutting the cavernosal nerve inhibited IP2015‐induced erectile responses, the phosphodiesterase type 5 inhibitor sildenafil further enhanced the IP2015‐mediated increase in intracavernosal pressure. IP2015 also increased the number of erections in type 2 diabetic db/db mice. Direct intracavernosal injection of IP2015 increased penile pressure, and in corpus cavernosum strips, IP2015 induced concentration‐dependent relaxations. These relaxations were enhanced by sildenafil and blunted by endothelial cell removal, a nitric oxide synthase inhibitor, NG‐nitro‐l‐arginine and a D1‐like receptor antagonist, SCH23390. Quantitative polymerase chain reaction (qPCR) showed the expression of the dopamine transporter in the rat corpus cavernosum.

Conclusion and Implications

Our findings suggest that IP2015 stimulates erectile function by a central mechanism involving dopamine reuptake inhibition and direct NO‐mediated relaxation of the erectile tissue. This novel multi‐modal mechanism of action could offer a new treatment approach to erectile dysfunction.
Antiapoptotic PON2 expression and its clinical implications in locally advanced oral squamous cell carcinoma
Authors: Kamal Mehta Vedant , Damerla Rama Rao , Parida Preetiparna , Chakrabarty Sanjiban , Rao Mahadev , Kumar Naveena AN
Published: April 2024

Locally advanced oral squamous cell carcinoma poses a significant challenge in oncology due to its rising incidence and mortality rates. Despite therapeutic progress, understanding molecular intricacies is essential. This study explored the role of PON2, a multifunctional enzyme implicated in antiapoptotic mechanisms. Aberrant PON2 expression in oral cancers raises questions regarding its involvement in evading programmed cell death and treatment resistance. Patients with locally advanced disease were enrolled, and molecular analyses were undertaken on the collected tumor and normal tissues. Utilizing computational datasets, this study used in silico gene expression analysis, differential gene expression analysis in our patient cohort, survival analysis, and gene set enrichment analysis to unravel role of PON2 in disease prognosis. The results showed elevated PON2 levels in advanced tumor stages, correlating with factors such as tobacco exposure, higher tumor grade, and nodal metastasis. Survival analysis revealed prognostic relevance of PON2, with lower expression linked to extended survival rates. Gene set enrichment analysis identified pathways aiding in cancer metastasis influenced by PON2. This study underscores the significance of PON2 expression as a prognostic marker for oral malignancies, with increased expression associated with advanced disease stages. Understanding the molecular profile of the PON2 gene suggests its potential as a valuable biomarker for the management of cancer.
Assessment of the general health status of children in Turkey: A community‐based cross‐sectional study
Authors: Ikiisik Hatice , Ozkaptan Beyzanur , Cakir Mustafa , Maral Isil
Published: April 2024

Aim

This study aims to assess the general health status and factors affecting the general health status in the 0–14 age group in Turkey.

Methods

This cross‐sectional study was conducted using the Turkish Statistical Institute Turkey Health Survey 2022 micro data set.

Results

This study included 7019 participants. Household heads described the general health status of 91.3% of children and the dental and gum status of 82.4% of children as very good or good, and 9.2% of children had any chronic disease. Although the median breastfeeding duration was 15 months, there is statistical significant association between sex and general health status (p = 0.014) and sex and duration of breastfeeding (p = 0.006). A statistical difference was found between duration of breastfeeding and general health status (p = 0.009) and dental and gum status (p = 0.001).

Conclusion

In 2022, the majority of children in Turkey had very good or good general health and dental and gum status. More than a third of children were breastfed for less than 12 months. Considering the possibility of neglecting oral and dental health problems, it is recommended to prioritize oral and dental health literacy trainings and to continue breastfeeding promotion programmes.
2‐Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator‐free nitrile gloves
Authors: Ljungberg Silic Linda , Persson Christina , Pesonen Maria , Suuronen Katri , Svedman Cecilia , Bergendorff Ola
Published: April 2024

Background

Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator‐free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them.

Objectives

To identify and chemically characterize a new allergen, 2‐cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC.

Methods

The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High‐performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2.

Results

CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC.

Conclusions

CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.
The integration of whole‐genome resequencing and ecological niche modelling to conserve profiles of local adaptation
Authors: Jeon Jong Yoon , Shin Yucheol , Mularo Andrew J. , Feng Xiao , DeWoody J. Andrew
Published: April 2024

Background

Ecological and genomic attributes of populations can provide two orthologous perspectives on the biological profiles associated with local adaptation. The ability of organisms to track suitable habitats (ecological adaptability) and of populations to shift allele frequencies (adaptive potential) are prerequisite for population sustainability.

Aims

Many contemporary populations are threatened by habitat loss (ecological vulnerability) and a lack of adaptive potential (evolutionary vulnerability). Technical advances provide new opportunities to address these challenges in biological conservation: Future habitat shifts can be predicted by ecological niche modelling and adaptive genetic diversity can be discerned using genome sequence data. Together, these two approaches illuminate the local adaptation profile and help identify the environmental and genomic conditions that should maximize evolutionary fitness.

Materials and Methods

Here, we reviewed the primary literature to identify key studies that utilize both whole‐genome resequencing (WGR) and ecological niche modelling (ENM) in an effort to envisage future research directions that may benefit conservation efforts.

Results

We identified ways to integrate different approaches, such as ENM‐informed adaptive genomics and adaptive genomics‐informed ENMs, that can be used to delineate and conserve local adaptation profiles.

Discussion

Integrative approaches can identify adaptive characteristics, vulnerable populations subject to environmental changes, and the patterns of local adaptation from geographic and genomic analyses. We discuss future research directions, limitations and their potential solutions with suggestions for collaborative workflows.

Conclusion

The integration of WGR and ENM is promising with their continuous advancement. An integrative approach can be used to evaluate eco‐evolutionary attributes, at both organismal and molecular levels, that can be used to help conserve local adaptation profiles.
Native fish assemblages in natural lakes across Japan: Endemism deterioration lasting centuries
Authors: Dai Bingguo , Matsuzaki Shin‐ichiro S. , Negishi Junjiro N. , Xia Zhijun , Alam Md. Khorshed , Jiang Zhongguan
Published: April 2024

Aim

This study aimed to illustrate the changing diversity patterns of native freshwater fish in the past two centuries and to identify priority locations for native fish conservation to counter future degradation.

Location

Japanese archipelago.

Methods

We used the published native fish fauna data in 39 lakes across Japan, analysing historical and current diversity and projecting future distribution patterns based on the Japanese Red List. We assessed fish assemblages' taxonomic, phylogenetic, and functional alpha and beta diversity across different periods. Additionally, we proposed a cumulative diversity index that incorporated taxonomic, phylogenetic and functional facets, and then examined its relationship with the latitudinal positioning of the lakes across periods.

Results

We observed a significant decrease in the richness of native freshwater fish since historical periods. Accompanying this decline were significant reductions in both phylogenetic relatedness and functional redundancy. Fish beta diversity increased from the past to the present and is predicted to decline drastically, indicating an ongoing homogenization process. Using the cumulative diversity index, we identified Hokkaido and Kyushu as crucial habitats for endemic fishes. These islands, with unique biogeographical backgrounds, contributed substantially to the national dissimilarity patterns of native fish assemblages in the historical period. However, the contribution is diminishing due to the ongoing decline in fish endemism.

Main Conclusions

The conservation priority of native freshwater fish in Japan should be assigned to Hokkaido and Kyushu due to the inhabited endemic species. The proposed framework for assessing the cumulative diversity of biotic communities presented the potential to aid macroecological explorations that underpin biodiversity conservation.
Artificial intelligence‐enhanced electrocardiogram analysis for identifying cardiac autonomic neuropathy in patients with diabetes
Authors: Irlik Krzysztof , Aldosari Hanadi , Hendel Mirela , Kwiendacz Hanna , Piaśnik Julia , Kulpa Justyna , Ignacy Paweł , Boczek Sylwia , Herba Mikołaj , Kegler Kamil , Coenen Frans , Gumprecht Janusz , Zheng Yalin , Lip Gregory Y. H. , Alam Uazman , Nabrdalik Katarzyna
Published: April 2024

Aim

To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN).

Materials and Methods

We used motif and discord extraction techniques, alongside long short‐term memory networks, to analyse 12‐lead, 10‐s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10‐fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver‐operating characteristic curve (AUC).

Results

Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91–0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54–0.81).

Conclusion

Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large‐scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.
Teaching information flow in supply chains: A role‐playing game using TagScan
Authors: Wang Xiaojia , Enstroem Rickard
Published: April 2024

Information flow is one of the three main flows of supply chains. It is an abstract concept that can be challenging for students to grasp in its entirety. This article describes a role‐playing game for teaching the topic of information flow in an undergraduate supply chain management course. The game allows students to simulate receiving and fulfilling customer orders by playing five roles within a manufacturing company. Students use TagScan, an augmented reality barcoding and logistics system launched by a technology company in western Canada, to track information throughout the game. Pre‐ and postsurvey results demonstrate the effectiveness of the proposed game in helping students visualize abstract course concepts and understand the types of information being tracked, the available information transmission technology, and the dynamics of information flow in a supply chain. Students were actively engaged in this in‐class activity and responded positively to the learning‐by‐gaming experience.
Application of cefuroxime in the eradication therapy of Helicobacter pylori infection: A review article
Authors: Mi Changmin , Suo Baojun , Tian Xueli , Wang Yuxin , Ma Lingling , Song Zhiqiang
Published: April 2024

Background

Helicobacter pylori infection and its associated diseases represent a significant global health concern. Patients who cannot use amoxicillin pose a therapeutic challenge and necessitate alternative medications. Preliminary research indicates that cefuroxime demonstrates promising potential for eradicating H. pylori infection, and there is a lack of comprehensive review articles on the use of cefuroxime.

Materials and Methods

This study conducts a thorough systematic literature review and synthesis. A comprehensive systematic search was conducted in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data up to January 13, 2024. The search strategy utilized the following keywords: (Cefuroxime) AND (Helicobacter pylori OR Helicobacter nemestrinae OR Campylobacter pylori OR Campylobacter pylori subsp. pylori OR Campylobacter pyloridis OR H. pylori OR Hp) for both English and Chinese language publications. Sixteen studies from five different countries or regions were included in final literature review.

Results

Analysis results indicate that H. pylori is sensitive to cefuroxime, with resistance rates similar to amoxicillin being relatively low. Regimens containing cefuroxime have shown favorable eradication rates, which were comparable to those of the regimens containing amoxicillin. Regarding safety, the incidence of adverse reactions in cefuroxime‐containing eradication regimens was comparable to that of amoxicillin‐containing regimens or other bismuth quadruple regimens, with no significant increase in allergic reactions in penicillin‐allergic patients. Regarding compliance, studies consistently report high compliance rates for regimens containing cefuroxime.

Conclusion

Cefuroxime can serve as an alternative to amoxicillin for the patients allergic to penicillin with satisfactory efficacies, safety, and compliance.
Microstructure change and functional characteristic promotion: the structural manipulation of soy protein microparticles through pH
Authors: Lin Yufeng , Luo Weiqian , Xiong Beibei , Guo Jian , Wang Jinmei , Tan Wenhao , Yang Xiaoquan
Published: April 2024

In this work, soy protein isolates (SPIs) were subjected to microparticulation, turning soy protein ingredients into microparticles with improved thermal stability which could be used in high‐protein foods. The pH is a critical determinant in microparticulation. Our work is mainly to investigate the effect of pH on the formation and properties of protein microparticles. To clarify the effects of pH conditions on the properties of the resulting particles, microparticulation was performed at different pH conditions (7.0, 6.0 and 5.0). Aggregation behaviours described by the parameters calculated from the protein dispersion viscosity combined with the observation of the morphology change were used to analyse the particle formation process. For the microparticles prepared at pH 5.0, soy proteins were more inclined to aggregate into clusters on a micro‐scale which had a flexible conformation. After spray drying, This powder could be easily dispersed in water, creating a dispersion with a protein concentration of 10 wt%. At this concentration, the thermal gelation capacity of the proteins was observed to decrease. Conversely, the tendency of protein aggregation was largely restricted when soy protein microparticulation was carried out at pH 7.0. As these soy protein particles in nano‐scale were dispersed in water, a decrease rather than an increase was recorded in the viscosity of this dispersion after it was heated, suggesting that these particles had improved thermal stability. This work has demonstrated that implementing appropriate pH conditions during microparticulation can prepare soy protein particles with different sizes and rheological properties, which might meet the demands of various food processing.
Effects of in situ formed nanostructures on the structure and properties of C/SiOC composites
Authors: Zhao Yuhang , Guo Lei , Ma Qingsong
Published: April 2024

In this paper, Ni was introduced into the matrix of carbon fiber reinforced SiOC (C/SiOC) composites by the precursor infiltration and pyrolysis method to catalyze the generation of in situ formed nanostructures including carbon nanotubes (CNTs), turbostratic carbon, and SiC. The effect of in situ formed nanostructures catalyzed by Ni on the properties of the C/SiOC composites was investigated. The results demonstrated that the presence of in situ formed nanostructures in the matrix improved the densification and mechanical properties of C/SiOC composites. In addition, the incorporation of in situ formed nanostructures facilitated the formation of thermal conductivity pathways within the composites, thereby enhancing the thermal conductivity of C/SiOC composites. Furthermore, in situ formed nanostructures‐containing C/SiOC composites developed a carbon friction layer comprising CNTs and turbostratic carbon, which significantly enhanced the abrasion resistance, endowing C/SiOC composites stable friction coefficients, and lower levels of wear.
A Turn to Export‐Led Growth? Rethinking the Growth Models in Greece and Portugal
Authors: Myrodias Konstantinos
Published: April 2024

The global financial crisis in 2007 and, more recently, the Covid‐19 pandemic renewed interest in capitalist divergence and the evolution of growth models in the Eurozone. The varieties of capitalism (VoC) approach and more recently post‐Keynesian research, especially the growth model (GM) perspective, have made important contributions to comparative political economy. However, the focus on either the ‘supply‐side’ or ‘demand‐side’ aspects of modern models of capitalism has offered a limited framework to explain capitalist diversity in the global economy. This article brings insights from both the VoC and GM perspectives and provides a more comprehensive understanding of the evolution of the growth models in Greece and Portugal. The argument is that although both countries implemented internal devaluation and contractionary policies to curtail domestic demand and transform their economies into export‐led ones, they have been stuck in a suppressed demand‐led growth model since the global financial crisis.
Effectiveness, safety and impact of guselkumab on sexuality and perceived stigmatization in patients with psoriasis in routine clinical practice: Week 28 results from the prospective German multicentre G‐EPOSS study
Authors: Gerdes S. , Ostendorf R. , Süß A. , Schadeck T. , Taut F. , Makuc J. , Scharfenberger L. , Jacobsen S. , Trenkler N. , Behrens J. , Joks G. , Tabori S. , Mortazawi D.
Published: April 2024

Background

G‐EPOSS is a prospective, non‐interventional, German multicentre study of patients with moderate‐to‐severe plaque psoriasis receiving guselkumab, a therapeutic monoclonal antibody targeting interleukin‐23, in a real‐world setting.

Objectives

The objective of the study was to evaluate the effectiveness and safety of guselkumab, including its impact on skin, health‐related quality of life (HRQoL), sexuality, and perceived stigmatization.

Methods

Patients (≥18 years old) received guselkumab per routine clinical practice. The primary endpoint was the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 at Week (W)28. Secondary endpoint assessments over 28 weeks included the Nail Psoriasis Severity Index (NAPSI), anogenital Physician's Global Assessment (aPGA), and Dermatology Life Quality Index (DLQI). Sexuality and perceived stigmatization were assessed by patients using the Relationship and Sexuality Scale (RSS) and Perceived Stigmatization Questionnaire (PSQ), respectively.

Results

Overall, 293 patients were included in the evaluable set population. Mean age and disease duration were 45.6 and 17.6 years, respectively. At baseline, mean PASI, aPGA and DLQI scores were 15.3, 2.7 and 11.3, respectively. In total, 25.9% of patients had received a prior biologic. Overall, 83.0% of patients achieved PASI ≤ 3, and 56.2%/35.1% achieved PASI ≤ 1/PASI = 0, respectively, at W28. Among those with NAPSI ≥ 1 and aPGA ≥ 1 at baseline, NAPSI = 0 and aPGA = 0 were achieved by 39.2% and 61.1% of patients, respectively, and 61.4% of patients achieved DLQI 0–1 at W28. Improvements were observed over 28 weeks across individual items of the DLQI, RSS and PSQ, indicating improved HRQoL and sex life, and decreased perceived stigmatization. Based on DLQI Question (Q)9, 53.6% of patients experienced sexual difficulties at baseline, which decreased to 12.1% at W28. DLQI Q9 responses were consistent with RSS item responses, highlighting DLQI Q9 as a sentinel for sexual impairment.

Conclusions

Guselkumab improved overall skin symptoms and HRQoL in patients with psoriasis and decreased sexual impairment and perceived stigmatization. No new safety signals were observed.

Study code

CNTO1959PSO4008.
The detection of circulating tumor cells indicates poor therapeutic efficacy and prognosis in patients with nonsmall cell lung cancer: A systematic review and meta‐analysis
Authors: Wang Shan , Liu Xiaolin , Lv Hongwei , Yu Jing , Li Huihui
Published: April 2024

Objective

The efficacy and prognostic value of circulating tumor cells (CTCs) in nonsmall cell lung cancer (NSCLC) are controversial based on the existing research. This systematic review and meta‐analysis evaluated the significance of CTCs in NSCLC therapy monitoring and prognosis prediction, supporting their potential as clinical biomarkers.

Methods

We conducted a comprehensive search of PubMed, Embase, Web of Science, The Cochrane Library, WanFang Data, CNKI, and VIP through September 20, 2023. Inclusion criteria were cohort studies involving NSCLC patients, focusing on peripheral blood CTCs, and assessing outcomes such as pre‐ and posttreatment CTC rates or levels, progression‐free survival (PFS), and overall survival (OS). Two reviewers independently extracted the data and assessed risk of bias using the Newcastle‐Ottawa Scale. We utilized Review Manager 5.4.1 for meta‐analysis, calculating pooled odds ratios (ORs) for dichotomous outcomes, mean differences for continuous variables and hazard ratios (HRs) for survival data, applying fixed‐ or random‐effects models based on heterogeneity assessed by the I2 statistic. This study was registered in PROSPERO (No. CRD42023450035).

Results

Twenty‐two eligible studies with a total of 1674 NSCLC patients were included. Meta‐analysis results showed that the CTCs‐positive rate (OR = 0.59, 95% CI 0.45 to 0.77, p = 0.0001) and CTCs count (mean difference = –3.10, 95% CI –5.52 to –0.69, p = 0.01) were significantly decreased after antitumor treatment. Compared with the CTCs nonreduced group, the CTC‐reduced group showed better PFS (HR = 1.71, 95% CI 1.35 to 2.17, p < 0.00001) and OS (HR = 1.50, 95% CI 1.21 to 1.86, p = 0.0003) after treatment. PFS and OS in CTC‐positive groups were lower than those in the CTCs‐negative group pretreatment (HR = 2.49, 95% CI 1.78 to 3.47, p < 0.00001; HR = 1.80, 95% CI 1.29 to 2.52, p = 0.0006) and posttreatment (HR = 3.36, 95% CI 2.12 to 5.33, p < 0.00001; HR = 3.31, 95% CI 1.75 to 6.27, p = 0.0002).

Conclusions

CTCs can be used as a biomarker to monitor NSCLC efficacy, predict prognosis and guide follow‐up treatment.
Gauged and historical abrupt wave front floods (‘walls of water’) in Pennine rivers, northern England
Authors: Archer David , Watkiss Samuel , Warren Sarah , Lamb Rob , Fowler Hayley J.
Published: April 2024

Extremely rapid rates of rise in level and discharge in a subset of flash floods (‘abrupt wave front floods’, AWF) are separate hazards from peak level. Such flood events are investigated for Pennine catchments in northern England using both gauged and historical information. Gauged level and flow digital records at 15‐min intervals provide recent data. Historical information for 122 AWF events is extracted from a chronology of flash floods for Britain. Historical AWF events are mapped and found to occur on every major Pennine catchment; catchment descriptors are derived as a basis for assessing catchment vulnerability. We discuss the disputed origin of AWF. Using gauged data, we contrast the rising limb of AWF and ‘normal’ floods. We investigate time series of historical AWF, noting a puzzling peak in the late 19th century. Current rainfall and river monitoring does not provide a reliable basis for understanding AWF processes or for operational response and we suggest improvements. Similarly, current models for design flood estimation and forecasting do not generate the observed rapid increase in level in AWF floods.
Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome: a systematic review
Authors: Hilgenkamp T. I. M. , Beck V. D. Y. , Azar F. , Maloy‐Robertson M. , Matthews A. , Shahani M. , Goodman X. , Oppewal A.
Published: April 2024

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer‐reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta‐analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty‐three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4–226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.
Strengthening couple relationships through a digital connection
Authors: Johnson David J. , Pickens Jaclyn C. , Holyoak Derek , Denzer‐King Amanda
Published: April 2024

The proliferation of technology has accelerated exponentially over the past 50 years. Contemporarily, researchers have explored the influences technology use is having on individuals and relationships. Theoretical frameworks such as the couple, family, and technology (CFT) Framework have been applied to individuals and couples in committed relationships to better understand the implications of technology adoption and use within this relational subsystem. Research examining technology's impact on couple relationships recognizes the potential for technology use to be either helpful or unhelpful to the relationship but fails to fully examine the helpful aspects of technology use. This study addresses this gap with the creation of a theory grounded in data from N = 45 couples (n = 90 individuals) in committed relationships. Results indicate couples' technology use can augment emotional connection and unity within the relationship as couples manage the influence of technology in a way that is relationally helpful.
Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review
Authors: Cutellè Claudia , De Lorenzo Alberto , Doneddu Pietro Emiliano , Creta Maria Francesca , Selmi Carlo , Liberatore Giuseppe , Giordano Andrea , Gentile Francesco , Erre Gian Luca , Nobile‐Orazio Eduardo
Published: April 2024

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty‐five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3–71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)‐6, IL‐17, CXCL10, and tumor necrosis factor alpha (TNF‐α), were elevated in CIDP compared to controls in most of the studies. IL‐6 and TNF‐α levels are also correlated with disability. In MMN patients, IL‐1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL‐6, IL‐17, CXCL10, and TNF‐α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.
Who can see it coming? Demand‐side selection in long‐term care insurance related to decision‐making abilities
Authors: Lambregts Timo R. , Schut Frederik T.
Published: April 2024

Despite the growing demand for long‐term care (LTC), the uptake of private LTC insurance (LTCI) is low and even declining in the United States. One reason is the complexity of LTCI decisions. Researchers have therefore suggested to support decision‐making abilities. This paper shows, however, that such support would not unambiguously enhance functioning of the LTCI market. We analyze whether selection arises from two correlated but different decision‐making abilities at old age, education and numeracy, and interactions thereof with private information. Using historical data from the Health and Retirement Survey we find that education generates adverse selection, which is only partially offset by advantageous selection due to numeracy. In addition, individuals with greater decision‐making abilities make better LTCI choices, amplifying selection by education and numeracy. This points at a trade‐off between decision simplicity and selection in insurance markets and suggests other steps are needed to enhance the performance of private LTCI markets.
Effect of dietary chitosan on the growth performance, intestinal histology and growth‐related gene expression in stellate sturgeon (Acipenser stellatus) juveniles
Authors: Zakeri Donya , Pazooki Jamileh , Mohseni Mahmoud , Jamshidi Shirin
Published: April 2024

As sturgeon breeding has proliferated, there has been a heightened demand for growth stimulators in their diets. This study aimed to determine the impact of dietary chitosan on growth performance, whole‐body proximate composition, growth‐related gene expression, and intestinal histology in juvenile Acipenser stellatus. A total of 180 A. stellatus juveniles with an average weight of 31.90 ± 0.73 g were fed with diets containing 0 (control), 1.5, 3.0, 4.5, and 6.0 g chitosan.kg−1 basic diet for eight weeks. The findings revealed a significant enhancement in growth performance with rising chitosan concentrations. Furthermore, chitosan supplementation upregulated the expression of the growth hormone gene in both brain and liver tissues. In liver samples, the most pronounced expression of the insulin‐like growth factor‐1 gene was noted at 6.0 g chitosan.kg−1, while in brain samples, peak expressions were observed in both the 4.5 and 6.0 g chitosan.kg−1 treatments. While the whole‐body proximate composition remained relatively stable, there was a notable decrease in whole‐body lipids with the escalation of chitosan dosage. Intestinal villi dimensions, both height and width, were amplified in the chitosan‐supplemented groups compared to controls. In summation, chitosan supplementation showed promise in bolstering growth performance, refining intestinal morphology, and enhancing growth‐related gene expression. Analysis of the polynomial regression of weight gain and specific growth rate revealed that the optimum dietary chitosan requirements in A. stellatus were 5.32 and 5.21 g chitosan.kg−1, respectively.
Tobacco use disparities in rural communities
Authors: Hahn Ellen J. , Bucher Amanda , Rademacher Kathy , Beckett Whitney , Taylor LeeAnn , Darville Audrey , Ickes Melinda J.
Published: April 2024

Purpose

This exploratory study described facilitators and barriers to reducing tobacco disparities in 2 small rural communities and identified ways to reduce tobacco use.

Methods

This was a descriptive design using qualitative methods. We created a resource database for 2 rural Kentucky counties, using a Culture of Health Framework. We recruited 16 organizational stakeholders serving low‐socioeconomic populations and conducted focus groups and key informant interviews. We also completed key informant interviews with 7 tobacco users. Lastly, we tailored Community Action Plans for each county based on the data and then solicited feedback from the key stakeholders.

Findings

The 2 counties were similar in population size, but County A had fewer resources than County B, and the stakeholders expressed differences toward tobacco use and quitting. County A stakeholders talked most about the protobacco culture and that tobacco users accept the risks of smoking outweighing the benefits of quitting; they also expressed concerns about youth use and the influences of family, society, and industry. County B stakeholders described ambivalence about the health effects of use and quitting. County A's Action Plan identified an opportunity to build Community Health Worker‐delivered tobacco treatment into a new school‐based health center. County B's Action Plan focused on reaching tobacco users by providing incentives for participation and tailoring messages to different audiences.

Conclusions

Tobacco control resources and stakeholder perspectives vary in small rural communities, implying a need for tailored approaches. Tobacco users in rural areas are a critical population to target with cessation resources.