bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis in immunostimulation and immunosuppression
Authors: Tang Daolin , Kroemer Guido , Kang Rui 
Published: July 2023

SummaryFerroptosis is a form of iron‐dependent regulated cell death characterized by the accumulation of toxic lipid peroxides, particularly in the plasma membrane, leading to lytic cell death. While it plays a crucial role in maintaining the overall health and proper functioning of multicellular organisms, it can also contribute to tissue damage and pathological conditions. Although ferroptotic damage is generally recognized as an immunostimulatory process associated with the release of damage‐associated molecular patterns (DAMPs), the occurrence of ferroptosis in immune cells or the release of immunosuppressive molecules can result in immune tolerance. Consequently, there is ongoing exploration of targeting the upstream signals or the machinery of ferroptosis to therapeutically enhance or inhibit the immune response. In addition to introducing the core molecular mechanisms of ferroptosis, we will focus on the immune characteristics of ferroptosis in pathological conditions, particularly in the context of infection, sterile inflammation, and tumor immunity.
Saving Popular Sovereignty From a Slow Death in the European Union
Authors: Beetz Jan Pieter 
Published: July 2023

AbstractThe European Union (EU) faces a pressing challenge with democratic backsliding potentially resulting in an authoritarian member state. EU institutions have sought to safeguard member state democracy. Most normative studies submit that the EU can legitimately intervene based on either current treaties or the theory of militant democracy, but they leave unanswered the fundamental question of the EU's normative political authority. I argue that shared popular sovereignty, which entails Europe's peoples directly authorizing the EU, is the most appropriate principle to theorize the EU's political authority for the foreseeable future. This principle results in a duty for the EU to protect its democratic peoples from backsliding governments and an account of who can legitimately decide on whether backsliding is taking place. A comprehensive normative assessment follows on the democratic legitimacy of various democracy protection measures. My argument bolsters the normative case for EU democracy protection.
The Neglected Integration Crisis: France, Germany and Lacking European Co‐operation During the 1973/1974 Oil Shock
Authors: Schramm Lucas 
Published: July 2023

AbstractWhen does European co‐operation and (further) integration not happen in the face of a major integration crisis? When do France and Germany not emerge as regional stabilizers, forging and uploading bilateral compromises to the European level? By developing a combined theoretical framework based on liberal intergovernmentalism and leadership approaches, this article analyses the European Economic Community's (EEC) reaction to the 1973/1974 oil crisis. Despite some favourable conditions, differences in domestic energy markets and relations with Arab oil‐producing countries complicated member state co‐operation. In turn, divergent economic philosophies and foreign policy priorities prevented France and Germany from filling the European leadership vacuum. As a consequence, the EEC did not find a unified stance on the Arab oil embargo, subordinated itself to US‐American dominance and undermined its common market via export restrictions for oil. The findings suggest that without minimum convergent member state preferences or compensating regional leadership, European integration and today's European Union risk stalling or even disintegrating.
Histological assessment and gene expression analysis of intra‐oral soft tissue graft donor sites
Authors: Stuhr Sandra , Nör Felipe , Gayar Kareem , Couso‐Queiruga Emilio , Chambrone Leandro , Gamborena Iñaki , Kumar Purnima , Avila‐Ortiz Gustavo , Ganesan Sukirth M. 
Published: July 2023

AbstractAimTo determine the structural and gene expression features of different intra‐oral soft tissue donor sites (i.e., anterior palate, posterior palate, maxillary tuberosity and retromolar pad).Materials and MethodsStandardized mucosal tissue punch biopsies were collected from at least one donor site per subject. Histological processing was performed to determine tissue morphometry and quantify collagen composition. Site‐specific gene distribution was mapped using targeted gene expression analysis and validated using real time polymerase chain reaction (qPCR).ResultsA total of 50 samples from 37 subjects were harvested. Epithelial thickness did not differ between sites. However, lamina propria was thicker in the maxillary tuberosity (2.55 ± 0.92 mm) and retromolar pad (1.98 ± 0.71 mm) than in the lateral palate. Type I collagen was the predominant structural protein in the lamina propria (75.06%–80.21%). Genes involving collagen maturation and extracellular matrix regulation were highly expressed in the maxillary tuberosity and retromolar pad, while lipogenesis‐associated genes were markedly expressed in the lateral palate. The retromolar pad showed the most distinct gene expression profile, and the anterior and posterior palate displayed similar transcription profiles.ConclusionsTissue samples harvested from the anterior and posterior palate differed morphologically from those from the maxillary tuberosity and retromolar pad. Each intra‐oral site showed a unique gene expression profile, which might impact their biological behaviour and outcomes of soft tissue augmentation procedures.
Callings can take different shapes: Scope, proximity and duration as new complexifications of calling
Authors: Zhou Steven , Aitken John A. , Kuykendall Lauren 
Published: July 2023

AbstractRecent research on calling has highlighted its nature as a ‘double‐edged sword’ that—while conferring benefits generally—may create vulnerabilities in some cases. We suggest an explanation that complexifies our conceptualization of what calling is. Traditional conceptualizations of calling focus on differences in degree, measuring calling on some numerical scale to answer the question, ‘To what degree do you perceive a calling?’ Our proposed conceptualization of calling argues for differences in the shape of calling, arguing that calling can take different shapes based on three facets: scope (callings can differ between narrow and broad), time proximity (callings can differ between immediate and distal) and duration (callings can differ between short‐term and lifelong). We present a new model depicting these shapes of calling, explain how each advances our understanding of calling above and beyond existing conceptualizations and taxonomies and offer propositions as to how this new conceptualization provides insight into individuals' experiences of pursuing their calling.
Early detection of squamous cell carcinoma of the oral tongue using multidimensional plasma protein analysis and interpretable machine learning
Authors: Gu Xiaolian , Salehi Amir , Wang Lixiao , Coates Philip J. , Sgaramella Nicola , Nylander Karin 
Published: July 2023

AbstractBackgroundInterpretable machine learning (ML) for early detection of cancer has the potential to improve risk assessment and early intervention.MethodsData from 261 proteins related to inflammation and/or tumor processes in 123 blood samples collected from healthy persons, but of whom a sub‐group later developed squamous cell carcinoma of the oral tongue (SCCOT), were analyzed. Samples from people who developed SCCOT within less than 5 years were classified as tumor‐to‐be and all other samples as tumor‐free. The optimal ML algorithm for feature selection was identified and feature importance computed by the SHapley Additive exPlanations (SHAP) method. Five popular ML algorithms (AdaBoost, Artificial neural networks [ANNs], Decision Tree [DT], eXtreme Gradient Boosting [XGBoost], and Support Vector Machine [SVM]) were applied to establish prediction models, and decisions of the optimal models were interpreted by SHAP.ResultsUsing the 22 selected features, the SVM prediction model showed the best performance (sensitivity = 0.867, specificity = 0.859, balanced accuracy = 0.863, area under the receiver operating characteristic curve [ROC‐AUC] = 0.924). SHAP analysis revealed that the 22 features rendered varying person‐specific impacts on model decision and the top three contributors to prediction were Interleukin 10 (IL10), TNF Receptor Associated Factor 2 (TRAF2), and Kallikrein Related Peptidase 12 (KLK12).ConclusionUsing multidimensional plasma protein analysis and interpretable ML, we outline a systematic approach for early detection of SCCOT before the appearance of clinical signs.
Parrotiaflower blooming in Miocene rainforest
Authors: Wu Xie‐Ting , Shu Jun‐Wu , Yin Su‐Xin , Sadowski Eva‐Maria , Shi Gong‐Le 
Published: July 2023

AbstractParrotiaC. A. Meyer (Hamamelidaceae) is a relictual genus with only two extant species disjunctly distributed in the subtropical forests of East China and temperate forests of North Iran. Fossil records suggest thatParrotiawas widespread in Europe and Asia during the Miocene, but its fossils are predominantly based on pollen and leaves. In this paper we describe the first fossil flower ofParrotiabased on an exceptionally well‐preserved amber inclusion from the middle Miocene of Zhangpu, Southeast China. The fossil flower was investigated with light microscope and microcomputed tomography techniques.Parrotia zhiyaniisp. nov. is a small apetalous staminate flower subtended by a pair of prominent bracts. The androecium consists of 12 stamens, and each stamen consists of a short, slender filament and a prominent, elongated anther. The anthers with short simple trichomes on the outer surface and a prominent apical connective extension are opened by longitudinal slits. Unlike its living relatives, the newParrotiafrom Zhangpu grew in a Miocene seasonal tropical rainforest.
Carving the meat at the joint: The role of defining how animals are viewed and treated in the governance of (re‐)emergent pandemic zoonoses in international law
Authors: Viens A. M. , Cassar Victoria , Atique Asma 
Published: July 2023

AbstractPandemic zoonoses, such as COVID‐19, are one of the greatest challenges of the 21st century. International governance tasked with attempting to prevent the (re‐)emergence of zoonotic disease in the first place, or preparation and actual response once (re‐)emergence or spread has occurred, has largely been fragmented among different governance systems, such as health, food, environment, and trade. The international legal instruments that these governance systems use reflect different ways of viewing and treating animals, which has led to a similarly fragmented approach to the regulation of human–animal interactions related to zoonoses. To illustrate this state of affairs, we develop a descriptive conceptual taxonomy to elucidate and map out how the status and evaluative stance taken toward animals can lead to shaping human‐animal relationships by structuring the nature of their interactions and disposes us to adopt governance approaches that seek to regulate human–animal relationships in particular ways. This paper concludes by highlighting some implications surrounding the fragmented conceptualization and practice around how animals are viewed and treated for the future of international legal governance of pandemic zoonoses.
Definition, diagnosis and epidemiology of acute‐on‐chronic liver failure
Authors: Hernaez Ruben , Li Hai , Moreau Richard , Coenraad Minneke J. 
Published: July 2023

AbstractThis narrative review addresses the definition of acute‐on‐chronic liver failure, a condition associated with high short‐term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition. Nevertheless, all the definitions have their clinical utility: from the core concept of having the “liver” as a conditio sine qua non, the syndrome cannot exist (Asian Pacific Association for the Study of the Liver); a data‐driven, robust definition (European Association for the Study of the Liver); a bedside tool that can quickly identify patients at high risk of dying (North American Consortium for the Study of End‐stage Liver Disease [NACSELD]). In each section, we provide the overall definitions, the criteria of organ failure(s), and some epidemiological data illustrating how these apply in each area of the world.
Worldwide comparison between the potential distribution of Rhipicephalus microplus (Acari: Ixodidae) under climate change scenarios
Authors: Perez‐Martinez M. B. , Moo‐Llanes D. A. , Ibarra‐Cerdeña C. N. , Romero‐Salas D. , Cruz‐Romero A. , López‐Hernández K. M. , Aguilar‐Dominguez M. 
Published: July 2023

AbstractThe cattle tick Rhipicephalus microplus (Acari: Ixodidae) has demonstrated its ability to increase its distribution raising spatially its importance as a vector for zoonotic hemotropic pathogens. In this study, a global ecological niche model of R. microplus was built in different scenarios using Representative Concentration Pathway (RCP), Socio‐Economic Pathway (SSP), and a climatic dataset to determine where the species could establish itself and thus affect the variability in the presentation of the hemotropic diseases they transmit. America, Africa and Oceania showed a higher probability for the presence of R. microplus in contrast to some countries in Europe and Asia in the ecological niche for the current period (1970–2000), but with the climate change, there was an increase in the ratio between the geographic range preserved between the RCP and SSP scenarios obtaining the greatest gain in the interplay of RCP4.5‐SSP245. Our results allow to determine future changes in the distribution of the cattle tick according to the increase in environmental temperature and socio‐economic development influenced by human development activities and trends; this work explores the possibility of designing integral maps between the vector and specific diseases.
Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome
Authors: El‐Salhy Magdy , Gilja Odd Helge , Hatlebakk Jan Gunnar 
Published: July 2023

AbstractBackgroundA previous study that introduced a Fecal microbiota transplantation (FMT) protocol with a high efficacy applied a combination of favorable factors.AimsThe present study aimed to evaluate some of these factors.MethodsThis study included 186 patients with IBS randomized 1:1:1 into transplant administered to the colon (single LI), to the duodenum (single SI), or to the duodenum twice with a 1‐week interval (repeated SI). The patients provided a fecal sample and were asked to complete five questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3–V9.ResultsThe response rate was significantly higher in single SI than in single LI at 12 months after FMT. Symptoms and quality of life improved in all the treated groups at all time intervals after FMT. The abdominal symptoms were significantly reduced and the quality of life improved for repeated SI compared with for single SI. DI significantly decreased in all the treated groups at all observation times after FMT. The bacterial profiles changed in all groups at all observation intervals. However, these changes differed between single LI and single SI/repeated SI.ConclusionAdministrating transplant to the small intestine had a long‐term higher response rate than that administrated to the large intestine, and led to long‐term colonization of beneficial bacteria. Repeating FMT had more effect on symptoms and quality of life than a single FMT. (www.clinicaltrials.gov: NCT04236843).
ASPNSynergizes withHAPLN1to Inhibit the Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells and Extracellular Matrix Mineralization of Osteoblasts
Authors: Zhou Guohui , Yan Xinmin , Chen Zhenfei , Zeng Xing , Wu Fangqian 
Published: July 2023

ObjectiveBone marrow mesenchymal stromal cells (BMSCs) are major sources of osteogenic precursor cells in bone remodeling, which directly participate in osteoporosis (OP) progression. However, the involved specific mechanisms of BMSCs in OP warrant mass investigations. Initially, our bioinformatics analysis uncovered the prominent up‐regulation of Asporin (ASPN) and proteoglycan link protein 1 (HAPLN1) in osteoblasts (OBs) of OP patients and their possible protein interaction. Hence, this study aimed to explore the effects of ASPN and HAPLN1 on osteogenic differentiation of BMSCs, extracellular matrix (ECM) mineralization of OBs, and osteoclastogenesis, hoping to offer research basis for OP treatment.MethodsGSE156508 dataset was used for analysis and screening to acquire the differentially expressed genes in OBs of OP patients, followed by the predicative analysisviaSTRING. OP mouse models were induced by ovariectomy (OVX), and ASPN and HAPLN1 expression was determined. BMSCs and bone marrow macrophages (BMMs) were isolated from OVX mice and induced for osteogenic differentiation and osteoclastogenesis, respectively. After knockdown experiments, we assessed adipogenic differentiation and osteogenic differentiation in BMSCs. Osteogenic (OPN, OCN, and COL1A1) and osteoclast (Nfatc1 and c‐Fos) marker protein expression was determined. The binding of ASPN to HAPLN1 was analyzed.ResultsHigh expression of ASPN and HAPLN1 and their protein interaction were observed in OBs of OP patientsviabioinformatics and in bone tissues of OVX mice. ASPN interacted with HAPLN1 in BMSCs of OVX mice. ASPN/HAPLN1 knockdown increased ALP, OPN, OCN, and COL1A1 protein expression and ECM mineralization in BMSCs while decreasing Nfatc1 and c‐Fos expression in BMMs. These effects were aggravated by the simultaneous knockdown of ASPN and HAPLN1.ConclusionOur results indicate that ASPN synergises with HAPLN1 to suppress the osteogenic differentiation of BMSCs and ECM mineralization of OBs and promote the osteoclastogenesis in OP.
Sterilization efficacy of a new water‐free breast milk pasteurizer
Authors: Chishiki Mina , Nishiyama Kyoko , Suzutani Tatsuo , Hiruta Shun , Ichikawa Hirotaka , Haneda Kentaro , Maeda Hajime , Shimizu Hiromi , Kanai Yuji , Ogasawara Kei , Go Hayato , Sato Maki , Momoi Nobuo , Nollet Kenneth E. , Ohto Hitoshi , Hosoya Mitsuaki 
Published: July 2023

AbstractBackgroundBreast milk, nature's optimum source of nutrition for infants, can contain undesirable microorganisms that cause severe morbidity. After an outbreak of multidrug‐resistant Escherichia coli among neonates receiving breast milk donated by another mother in our neonatal intensive care unit (NICU), we were motivated to develop a high‐grade breast milk pasteurizer (BMP) designed to thaw and pasteurize breast milk at 63°C for 30 min in a sealed bag without having to open the bag or immerse it in water.MethodsPre‐existing bacteria and spiked cytomegalovirus (CMV) were measured pre‐ and post‐pasteurization in frozen breast milk donated by mothers of children admitted to the NICU.ResultsAmong 48 breast milk samples (mean ± standard deviation [SD]), pre‐existing bacterial counts of 5.1±1.1 × 104 colony forming units (cfu)/mL decreased to less than 10 cfu/mL (below detection level) in 45 samples after pasteurization for 30 min. In three samples, 10–110 cfu/mL persisted. As no CMV was detected in any of the 48 samples, CMV at ≥5 × 104 pfu/mL was spiked into 11 breast milk samples. After just 10 min of pasteurization, infectious CMV was not detected (threshold <50 pfu/mL) in any sample.ConclusionA new BMP was shown to pasteurize milk effectively with more than a 3‐log reduction of microorganisms. Compared to conventional pasteurizers, this device reduces the effort involved in pasteurizing breast milk, avoids various contamination risks, and may reduce the risk of infectious disease transmission via breast milk.
Effectiveness and safety of Tolvaptan in infants with congenital heart disease
Authors: Sakaguchi Haruhide , Hirano Daishi , Saito Aya , Takemasa Yoichi , Umeda Chisato , Miwa Saori , Ito Akira , Oishi Kimihiko 
Published: July 2023

AbstractBackgroundTolvaptan (TLV) is a selective vasopressin receptor 2 antagonist administered for congestive heart failure (CHF) after inadequate response to other diuretics. The effectiveness and safety of TLV have been evaluated well in adult patients. However, reports on its use in pediatric patients, especially infants, are scarce.MethodsWe retrospectively evaluated 41 children younger than 1 year of age who received TLV for CHF for congenital heart disease (CHD) between January 2010 and August 2021. We monitored the occurrence of adverse events, including acute kidney injury and hypernatremia, as well as laboratory data trends.ResultsOf the 41 infants included, 51.2% were male. The median age when TLV was initiated was 2 months, interquartile range (IQR) 1–4 months, and all infants had been administered other diuretics previously. The median dose of TLV was 0.1 mg/kg/day (IQR, 0.1–0.1). Urine output increased significantly after 48 h of treatment: baseline, 315 mL/day (IQR, 243–394); 48 h, 381 mL/day (IQR, 262–518) , p = 0.0004; 72 h, 385 mL/day (IQR, 301–569), p = 0.0013; 96 h, 425 mL/day (IQR, 272–524), p = 0.0006; and 144 h, 396 mL/day (IQR, 305–477), p = 0.0036. No adverse events were observed.ConclusionsTolvaptan can be used safely and efficiently in infants with CHD. From the perspective of adverse effects, initiating administration at a lower dosage is preferable because this was found to be sufficiently effective.
Comparative analysis of whole vs. split liver transplantation in infants
Authors: Rokop Zachary P. , Mangus Richard S. , Tolliver Kyla , Jarasvaraparn Chaowapong , Molleston Jean , Mihaylov Plamen , Kubal Chandrashekhar 
Published: July 2023

AbstractBackgroundLiver transplantation (LT) in infants can be challenging due to their small size and small vasculature. Although both whole LT (WLT) and split LT (SLT) have been described in infants, the head‐to‐head comparison of these techniques in this population is sparse.MethodsWe retrospectively analyzed the records of all patients with age ≤1 year at Indiana University between 2016 and 2022. All SLT were left lateral segment grafts split in situ.ResultsA total of 24 infants were transplanted, with 11 SLT and 13 WLT. The median follow‐up time was 52.1 months. Donor and recipient characteristics were comparable except for donor age (19 years vs. 2 years; p < .01) and weight (64 kg vs. 14.2 kg; p < .01). Early allograft dysfunction, primary nonfunction, and hepatic artery thrombosis developed more frequently in the WLT group. There were no biliary complications. There were two early deaths (2 and 4 days) in the WLT group. One‐year graft survival (100% vs. 77%; p = .10) and patient survival (100% vs. 85%; p = .18) were numerically higher in the SLT group.ConclusionsSLT with LLS offers a safe and viable option for liver transplantation in infants and is associated with a trend toward superior outcomes. SLT should be considered as a strategy to reduce waitlist times for infants in the absence of small, deceased donors for WLT.