bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis
Authors: Perez‐Sanchez Carlos , Escudero‐Contreras Alejandro , Cerdó Tomás , Sánchez‐Mendoza Luz Marina , Llamas‐Urbano Adrián , la Rosa Iván Arias‐de , Pérez‐Rodriguez Miguel , Muñoz‐Barrera Laura , del Carmen Abalos‐Aguilera María , Barbarroja Nuria , Calvo Jerusalem , Ortega‐Castro Rafaela , Ruiz‐Vilchez Desiree , Moreno Juan Antonio , Burón María Isabel , González‐Reyes José Antonio , Collantes‐Estevez Eduardo , Lopez‐Pedrera Chary , Villalba José Manuel 
Published: April 2023

ObjectiveWe analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting.MethodsOur study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+‐related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti–tumor necrosis factor (anti‐TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside.ResultsReduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP‐ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti‐TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status.ConclusionRA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti‐TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.
On robust state derivative feedback control for uncertain polytopic systems with uncertain sampling period and network‐induced delay
Authors: Leandro Marco A. C. , Pereira Renan L. 
Published: April 2023

AbstractThis paper addresses the state derivative feedback control problem for uncertain polytopic systems subject to an uncertain sampling period and network‐induced delay. The distinctive contribution relies on the direct design of a robust state derivative feedback controller employing an augmented discretized model derived in terms of the state derivative feedback such that network‐induced delay and uncertain sampling periods can be incorporated from the original continuous‐time state‐space representation into the discretized model. Two augmented models are provided to handle longer input time delays, as well as delays less or equal to the sampling period. In this work, all the uncertain parameters are modeled as a polytopic form whose resulting discrete‐time model has matrices with polynomial dependence on the uncertain parameters and an additive norm‐bounded term featuring the discretization residual error. Moreover, synthesis conditions are derived using a set of linear matrix inequalities (LMI) to solve the stabilization problem for this class of systems under different input time delays. Finally, numerical simulations are carried out to evaluate the effectiveness of the proposed method.
Achieving Enhanced Electrochemical Performance for Cobalt‐Free Layered Cathode Material by Aluminum Doping
Authors: Ma Mingyuan , Yang Dan , Ji Yongsheng , Qie Long , Liu Zhikang , Huang Yunhui 
Published: April 2023

AbstractWe introduce a facile strategy to greatly improve the electrochemical reversibility of cobalt‐free cathode material by doping trace quantity of aluminum (Al) in LiNi0.65Mn0.35O2. X‐ray diffraction and X‐ray photoelectron spectroscopy results reveal that Al doping reduces the cation disorder consequently and hence increases structural stability. Electrochemical measurements show that rate capability and cycling stability are remarkably enhanced by Al doping. Al‐doped LiNi0.65Mn0.35O2 exhibits the optimized electrochemical performance with a capacity retention of 94.2 % after 200 cycles at 2 C in voltage range of 2.75–4.2 V in cylindrical full cell, demonstrating that Al‐doped cathode exhibits enhanced cyclability, reduced polarization and high‐rate capability during charge/discharge process. Moreover, the full cell shows good low‐temperature performance with more than 70 % capacity retention at −20 °C. The improved performances can be ascribed to the enhanced stability in layered structure of the Co‐free material by the support of doped Al ions.
The endocannabinoidome in human placenta: Possible contribution to the pathogenesis of preeclampsia
Authors: Maia João , Iannotti Fabio Arturo , Piscitelli Fabiana , Fonseca Bruno Miguel , Braga António , Braga Jorge , Teixeira Natércia , Di Marzo Vincenzo , Correia‐da‐Silva Georgina 
Published: April 2023

AbstractPreeclampsia (PE) was first reported thousands of years ago, yet there is still a shortage of biomarkers to determine the severity and type of PE. The importance of the expanded endocannabinoid system, or endocannabinoidome (eCBome), has emerged recently in placental physiology and pathology, though the potential alterations of the eCBome in PE have not been fully explored. Analysis by qRT‐PCR using placental samples of normotensive and PE women demonstrate for the first time the presence of ABHD4, GDE1, and DAGLβ in both normotensive and PE placental tissues. Interestingly, NAPE‐PLD, FAAH‐1, DAGLα, MAGL, and ABHD6 mRNA levels were increased in the placental tissues of PE patients. Quantification in plasma and placental tissues showed a decrease for anandamide (AEA), N‐oleoylethanolamine (OEA), and N‐docosahexaenoylethanolamine (DHEA) in the placenta, accompanied only by a decrease in plasma levels of AEA. In addition, a strong negative correlation was obtained between OEA and the biomarker of PE, soluble fms‐like tyrosine kinase‐1. Given the inflammatory nature of PE and the anti‐inflammatory role of OEA and DHEA, the decrease in the local levels of these mediators may underlie the inflammatory component of this pathology. Additionally, lower AEA levels in both placenta and plasma may contribute to the atypical alterations of the spiral arteries in PE due to the vasorelaxation effects of AEA. These results add new information to the role of the eCBome members in placental development, while also pointing to a potential role as biomarkers of PE.
Amount and spatial arrangement of muscle fibers in the human laryngeal Musculus ventricularis
Authors: Gocht Andreas , Lüers Georg , Schumacher Udo 
Published: April 2023

AbstractTextbooks and atlases of human macroscopic and microscopic anatomy of the larynx generally provide, if at all, only sparse information on the laryngeal Musculus ventricularis. However, several studies indicate that this muscle takes over the function of vestibular (ventricular) fold phonation after denervation of the Musculus vocalis. In the present study, 29 laryngeal specimens were coronally dissected at different levels, i.e. the anterior (L1), middle (L2), and posterior third of the vestibular fold (L3), and they underwent histological analysis. In all specimens the vestibular folds of both hemi‐larynxes contained striated muscle bundles in variable amounts, representing a ventricularis muscle. These muscle bundles obviously originated from the lateral (external) and thyroepiglottic part of the thyroarytenoid muscle and the aryepiglottic part of the oblique arytenoid muscle, as has been described by other authors. The areas of vestibular folds and their amounts of ventricularis muscle bundles were measured using image analysis software (imageJ) by manual tracing. The mean area of the vestibular folds of both hemi‐larynxes was 27.9 mm2 (SD [standard deviation] ± 9.17), and the area occupied by fibers of the ventricularis muscle was 1.5 mm2 (SD ± 1.78). Statistical analysis comparing the areas of both hemi‐larynxes and levels resulted in no significant differences, except for the levels 2 and 3. In level 2, significantly more muscle fibers (2.0 mm2; SD ± 2.21) were detectable within the vestibular fold than in level 3 (0.9 mm2; SD ± 1.43). Level 1 also contained more muscle fibers (1.1 mm2; SD ± 1.06) than level 3, however, without significance. In conclusion, the laryngeal ventricularis muscle is present in the majority of reported cases. Since the muscle is of clinical relevance, it should be included in anatomical textbooks by default.
A real‐world study of immune checkpoint inhibitors in advanced triple‐negative breast cancer
Authors: Zhang Zheng , Zhang Yadi , Liu Chuanling , Shao Jiakang , Chen Yimeng , Zhu Yimin , Zhang Li , Qin Boyu , Kong Ziqing , Wang Xixi , Wang Yutong , Huang Deqin , Liu Liqun , Zhou Yuxin , Tao Ran , Yang Zengjie , Liu Mei , Zhao Weihong 
Published: April 2023

AbstractBackgroundTriple‐negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real‐world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real‐world setting and to explore possible correlates.MethodsThe clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed.ResultsEighty‐one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression‐free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later‐line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable.ConclusionsICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.
A Clickable Photosystem I, Ferredoxin, and Ferredoxin NADP+ Reductase Fusion System for Light‐Driven NADPH Regeneration**
Authors: Medipally Hitesh , Mann Marvin , Kötting Carsten , van Berkel Willem J. H. , Nowaczyk Marc M. 
Published: April 2023

AbstractPhotosynthetic organisms like plants, algae, and cyanobacteria use light for the regeneration of dihydronicotinamide dinucleotide phosphate (NADPH). The process starts with the light‐driven oxidation of water by photosystem II (PSII) and the released electrons are transferred via the cytochrome b6f complex towards photosystem I (PSI). This membrane protein complex is responsible for the light‐driven reduction of the soluble electron mediator ferredoxin (Fd), which passes the electrons to ferredoxin NADP+ reductase (FNR). Finally, NADPH is regenerated by FNR at the end of the electron transfer chain. In this study, we established a clickable fusion system for in vitro NADPH regeneration with PSI−Fd and PSI−Fd−FNR, respectively. For this, we fused immunity protein 7 (Im7) to the C‐terminus of the PSI−PsaE subunit in the cyanobacterium Synechocystis sp. PCC 6803. Furthermore, colicin DNase E7 (E7) fusion chimeras of Fd and FNR with varying linker domains were expressed in Escherichia coli. Isolated Im7−PSI was coupled with the E7−Fd or E7−Fd−FNR fusion proteins through high‐affinity binding of the E7/Im7 protein pair. The corresponding complexes were tested for NADPH regeneration capacity in comparison to the free protein systems demonstrating the general applicability of the strategy.
Racemic Benzenesulfonohydrazide Enantioconvergent Tertiary C(sp3)−H Amination Catalyzed by Copper and Chiral Phosphoric Acid: Mechanistic Insights and Computational Prediction
Authors: Li Rongrong , Yang Xinzheng 
Published: April 2023

AbstractDensity functional theory computations reveal mechanistic insights into Cu and chiral phosphoric acid (CPA) catalyzed enantioconvergent amination of racemic benzenesulfonohydrazide. The O−O bond homolysis of tert‐butyl 4‐phenylbutaneperoxoate was found to be the turnover‐limiting step with a total free energy barrier of 19.1 kcal/mol. The enantioconvergent amination is realized to obtain the same intermediate through prochiral carbon atom. The order and mode of hydrogen atom transferred by CPA and tert‐butyloxy have a significant influence on the enantioselectivity and energy barriers. The olefinic side product generated by β‐hydride elimination is 9.9 kcal/mol thermodynamically less favourable. A series of phosphoric acids are predicted as promising co‐catalysts with lower barriers for O−O bond homolysis.
Perceived difference in expertize and individual performance in cross‐functional teams
Authors: Chiang Yun‐Haw , Hsu Chu‐Chun , Hsieh Chang‐Lung 
Published: April 2023

AbstractPrevious studies examining diverse team knowledge resources and individual members' performance largely follow the information perspective and propose that team informational diversity may help individuals perform better. Unlike previous authors, we integrate arguments from subgroup theory and the social categorization perspective to argue that when a person works in a cross‐functional team, perceiving differences in expertize with other teammates may decrease the person's social exchange relationship with colleagues, that is, team‐member exchange/TMX. Thus, perceived differences in expertize with other teammates may reduce TMX and, in turn, weaken individual task performance. Moreover, team members' social exchange relationship with the leader/LMX may offset the individual's deficiency in TMX to complement the person's task performance. We examine dyadic data collected from Taiwanese worker‐supervisor pairs and find support for our hypotheses.
Amino acid profile changes during enrichment of spheroid cells with cancer stem cell properties in MCF‐7 and MDA‐MB‐231 cell lines
Authors: Ghanbari Movahed Zahra , Matin Maryam M. , Mansouri Kamran , Sisakhtnezhad Sajjad 
Published: April 2023

AbstractBackgroundCancer stem cells (CSCs), subpopulations of cancer cells, are responsible for tumor progression, metastasis, and relapse. Changes in amino acid metabolism are linked to breast cancer recurrence and metastasis.AimsThis study aimed to evaluate the changes in the amino acid profile in MCF‐7 and MDA‐MB‐231 cells during spheroid formation to discover the specific metabolic properties in CSCs.MethodsMCF‐7 and MDA‐MB‐231 breast cancer cells were cultured as spheroids and evaluated to characterize their CSC properties. The characteristics of CSC were evaluated by examining the expression of CSC markers and conducting drug resistance assays. In addition, amino acid profile change during the enrichment of breast cancer stem cells in the spheroids was investigated by high‐performance liquid chromatography (HPLC).ResultsThe results indicated that out of 20 different amino acids analyzed, 19 of them decreased during the spheroid formation process. Alanine, lysine, phenylalanine, threonine, and glycine showed significant reductions in the conditioned media of both cell lines in the spheroid form compared to the monolayer cells. Only one of the amino acids increased in MCF‐7 and MDA‐MB‐231 spheroids (histidine and serine, respectively).ConclusionOur results suggest that certain amino acids identified in this study can be used for a better understanding of the molecular mechanisms associated with breast cancer stem cell formation.
Pathologically confirmed women's breast cancer: A descriptive study of Tunisian and Algerian series
Authors: Sassi Farah , Rekaya Meriem Ben , Belarbi Ayed , Chilla Dalia , Mansouri Nada , Achouri Leila , Saied Essia , Kassa Reda , Kacem Linda Belhaj , Ouezani Manel , Debabeche Nadjiba , Rebhi Fatima , Rammeh Soumaya 
Published: April 2023

AbstractBackgroundBreast cancer (BC) is the most frequent malignancy among women in Tunisia and Algeria. Clinical and pathological characteristics of this cancer among these populations are not widely reported. The aim of the study was to report clinical and pathological characteristics of women's BC in a Tunisian and Algerian series.MethodsPathologically confirmed 1089 BCs were gathered in the pathology departments of three Northern Tunisian hospitals: Tunis military, Charles Nicolle and Jendouba and in the pathology department of Alger Douera hospital between January 2015 and December 2020. Clinical and pathological findings of the two series: age, tumor size, histological type, grading according to Scarff‐Bloom Richardson grading system, lymph node status at the time of diagnosis in axillary lymphadenectomy specimens and the immunohistochemical expression of estrogen and progesterone receptors (ER/PR), HER2 and Ki‐67, were collected from the pathological reports.ResultsThe median age at diagnosis was 50 and 48 years in Tunisian and Algerian series, respectively (p = 0.016). The diagnosis of BC was made on surgical specimens (lumpectomy or mastectomy) in 373/491 (76%) cases of the Tunisian series and in 225/598 (37.6%) cases of the Algerian one. Median tumor size was 2.8 cm and 2.5 cm in Algerian and Tunisian series, respectively (p = 0.252). Invasive BCs not otherwise specified was observed in 440/481 (91.5%) BCs in Tunisian series and in 519/586 (88.6%) BCs in Algerian series. Axillary lymph node positive tumors were observed in 64.6% and 58.8% of Tunisian and Algerian women, respectively (p = 0.926). BCs were ER positive in 311/385 (80.8%) and 486/571 (85.1%) cases and HER2 positive in 86/283 (30.4%) and 60/385 (15.6%) cases of Tunisian and Algerian series, respectively.ConclusionsIn Tunisia and Algeria, BC has poor prognostic factors with large tumor sizes and high rates of lymph nodes involvement at diagnosis.
New attribute‐based encryption schemes with anonymous authentication and time limitation in fog computing
Authors: Hafizpour Hadis , Shiri Mohammad Ebrahim , Rahmani Amir Masoud 
Published: April 2023

SummaryFog computing is a suitable platform for the Internet of Things (IoT). However, it faces threats that pose security and privacy challenges. This article proposes two new, faster, and more secure schemes based on attribute‐based encryption (ABE) address some security concerns. The new schemes are Cipher text‐policy‐ABE‐anonymous authentication (CP‐ABE‐AA) and key‐policy‐ABE‐anonymous authentication (KP‐ABE‐AA), providing more secure communications and anonymous recognition between servers and users employing registration center (RC). Users and servers register with RC and receive time parameter t and aliases to build an access tree. During the valid time, t a more secure transfer is established. After each t has expired, the servers and users obtain new aliases. RC provides anonymous authentication, and t determines the key's validity period. For simulation, a multi‐paradigm programming language, Rust, was installed on Ubuntu 20. Compared to five existing schemes, the simulation results indicated that, on average, CP‐ABE‐AA has a 5.48% reduction time for key generation but an increased time of 11.28% in encryption and a reduction time of 11.33% in decryption. Also, compared to two other schemes, KP‐ABE‐AA produced an average time increase of 17.31% for key generation, but encryption and decryption times were reduced by 17.31% and 9.57%.
Role of heterogeneity in dictating tumorigenesis in epithelial tissues
Authors: Muthukrishnan Sindhu , Vishwakarma Medhavi 
Published: April 2023

AbstractBiological systems across various length and time scales are noisy, including tissues. Why are biological tissues inherently chaotic? Does heterogeneity play a role in determining the physiology and pathology of tissues? How do physical and biochemical heterogeneity crosstalk to dictate tissue function? In this review, we begin with a brief primer on heterogeneity in biological tissues. Then, we take examples from recent literature indicating functional relevance of biochemical and physical heterogeneity and discuss the impact of heterogeneity on tissue function and pathology. We take specific examples from studies on epithelial tissues to discuss the potential role of inherent tissue heterogeneity in tumorigenesis.
Risk of non‐fatal self‐harm and premature mortality in the three years following hospitalization in adolescents and young adults with an eating disorder: A nationwide population‐based study
Authors: Duriez Philibert , Goueslard Karine , Treasure Janet , Quantin Catherine , Jollant Fabrice 
Published: April 2023

AbstractIntroductionEating disorders (ED) are associated with high rates of suicide attempts and premature mortality. However, data in large samples of adolescents and young adults are limited. This study aims to assess the risk of self‐harm and premature mortality in young people hospitalized with an ED.MethodsIndividuals aged 12 to 25 years old hospitalized in 2013–2014 in France with anorexia nervosa and/or bulimia nervosa as a primary or associated diagnosis were identified from French national health records. They were compared to two control groups with no mental disorders, and with any other mental disorder than ED. The main outcomes were any hospitalization for deliberate self‐harm and mortality in the 3 years following hospitalization. Logistic regression models were used.ResultsThis study included 5, 452 patients hospitalized with an ED, 14,967 controls with no mental disorder, and 14,242 controls with a mental disorder other than an ED. During the three‐year follow‐up, 13.0% were hospitalized for deliberate self‐harm (vs. 0.2 and 22.0%, respectively) and 0.8% died (vs. 0.03 and 0.4%). After adjustment, hospitalization with an ED was associated with more self‐harm hospitalizations (hazard ratio [HR] = 46.0, 95% confidence interval [32.3–65.3]) and higher all‐cause mortality (HR = 12.6 [4.3–37.3]) relative to youths without any mental disorder; less self‐harm hospitalizations (HR = 0.5 [0.5–0.6]) but higher mortality (HR = 1.6 [1.0–2.4]) when compared to youths with any other mental disorder.ConclusionYoung patients hospitalized with an ED are at high risk of self‐harm and premature mortality. It is urgent to evaluate and implement the best strategies for post‐discharge care and follow‐up.Public significanceWe found that the risk of being hospitalized for a suicide attempt is 46 times higher and mortality 13 times higher than the general population in adolescents and young adults during the 3 years following hospitalization with an eating disorder. Eating disorders are also associated with a 1.5 higher risk of premature mortality relative to other mental disorders. This risk is particularly high in the 6 months following hospitalization. It is therefore crucial to implement careful post‐discharge follow‐up in patients hospitalized for eating disorders.