bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine
Authors: Liu Shuang , Zhang YuYing , Luo YunFei , Liu JianPing 
Published: April 2024

AbstractAlthough pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin‐dependent diabetes, a shortage of donors is a major obstacle to tissue and organ transplantation. Stem cell therapy is an effective treatment for diabetes and other pancreatic‐related diseases, which can be achieved by inducing their differentiation into insulin‐secreting cells. The liver is considered an ideal source of pancreatic cells due to its similar developmental origin and strong regenerative ability as the pancreas. This article reviews the traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine and evaluates their advantages and challenges. Gene reprogramming and chemical reprogramming technologies are traditional strategies with potential to improve the efficiency and specificity of cell reprogramming and promote the transformation of hepatocytes into islet cells. At the same time, organoid technology, as an emerging strategy, has received extensive attention. Biomaterials provide a three‐dimensional culture microenvironment for cells, which helps improve cell survival and differentiation efficiency. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology has brought new opportunities and challenges to the development of organoid technology.image
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

AbstractBackgroundFor 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.MethodsIn 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.ResultsIn 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.ConclusionsIn 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

AbstractWhat 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

AimsPrednisolone 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).MethodsChildren (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.ResultsFrom 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.ConclusionSaliva 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

AbstractThe 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

AbstractAmyotrophic 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 PurposeThe discovery of new bromo‐ and extra‐terminal inhibitors presents new drugs to treat osteoarthritis (OA).Experimental ApproachThe 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 ResultsTR‐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 ImplicationsThis 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 PurposeAn 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 ApproachWe 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 ResultsIP2015 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 ImplicationsOur 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

AbstractLocally 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

AbstractAimThis study aims to assess the general health status and factors affecting the general health status in the 0–14 age group in Turkey.MethodsThis cross‐sectional study was conducted using the Turkish Statistical Institute Turkey Health Survey 2022 micro data set.ResultsThis 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).ConclusionIn 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

AbstractBackgroundAllergic 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.ObjectivesTo 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.MethodsThe 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.ResultsCEDMC 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.ConclusionsCEDMC 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

AbstractBackgroundEcological 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.AimsMany 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 MethodsHere, 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.ResultsWe 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.DiscussionIntegrative 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.ConclusionThe 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

AbstractAimThis 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.LocationJapanese archipelago.MethodsWe 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.ResultsWe 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 ConclusionsThe 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.