bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child‐Pugh A and B cirrhosis: A real‐world study
Authors: D’Alessio Antonio , Fulgenzi Claudia Angela Maria , Nishida Naoshi , Schönlein Martin , von Felden Johann , Schulze Kornelius , Wege Henning , Gaillard Vincent E. , Saeed Anwaar , Wietharn Brooke , Hildebrand Hannah , Wu Linda , Ang Celina , Marron Thomas U. , Weinmann Arndt , Galle Peter R. , Bettinger Dominik , Bengsch Bertram , Vogel Arndt , Balcar Lorenz , Scheiner Bernhard , Lee Pei‐Chang , Huang Yi‐Hsiang , Amara Suneetha , Muzaffar Mahvish , Naqash Abdul Rafeh , Cammarota Antonella , Personeni Nicola , Pressiani Tiziana , Sharma Rohini , Pinter Matthias , Cortellini Alessio , Kudo Masatoshi , Rimassa Lorenza , Pinato David J. 
Published: March 2022

Abstract

Background and Aims
Atezolizumab plus bevacizumab (AtezoBev) is the standard of care for first‐line treatment of unresectable HCC. No evidence exists as to its use in routine clinical practice in patients with impaired liver function.

Approach and Results
In 216 patients with HCC who were consecutively treated with AtezoBev across 11 tertiary centers, we retrospectively evaluated treatment‐related adverse events (trAEs) graded (G) according to Common Terminology Criteria for Adverse Events v5.0, including in the analysis all patients treated according to label (n = 202, 94%). We also assessed overall survival (OS), progression‐free survival (PFS), overall response (ORR), and disease control rates (DCR) defined by Response Evaluation Criteria in Solid Tumors v1.1. Disease was mostly secondary to viral hepatitis, namely hepatitis C (n = 72; 36%) and hepatitis B infection (n = 35, 17%). Liver function was graded as Child‐Pugh (CP)‐A in 154 patients (76%) and CP‐B in 48 (24%). Any grade trAEs were reported by 143 patients (71%), of which 53 (26%) were G3 and 3 (2%) G4. Compared with CP‐A, patients with CP‐B showed comparable rates of trAEs. Presence and grade of varices at pretreatment esophagogastroduodenoscopy did not correlate with bleeding events. After a median follow‐up of 9.0 months (95% CI, 7.8–10.1), median OS was 14.9 months (95% CI, 13.6–16.3), whereas median PFS was 6.8 months (95% CI, 5.2–8.5). ORR and DCR were respectively 25% and 73%, with no difference across CP classes.

Conclusions
This study confirms reproducible safety and efficacy of AtezoBev in routine practice. Patients with CP‐B reported similar tolerability compared with CP‐A, warranting prospective evaluation of AtezoBev in this treatment‐deprived population.
Efficacy of tiapride in the treatment of psychiatric disorders: A systematic review
Authors: Zangani Caroline , Giordano Barbara , Stein Hans‐Christian , Bonora Stefano , Ostinelli Edoardo Giuseppe , D'Agostino Armando 
Published: March 2022

AbstractBackgroundTiapride is an atypical antipsychotic used to treat alcohol withdrawal, aggressiveness and agitation, headache, dyskinesias, tic and Tourette's disorder. More recently, it has been proposed for the treatment of delirium and agitation in hospitalised patients with COVID‐19. Although its safety profile makes it suitable for use in vulnerable populations, the use of tiapride for psychiatric disorders is limited. This work aims to systematically review the available evidence on the efficacy and tolerability of tiapride in individuals with a psychiatric disorder.MethodsWe searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for randomised controlled trials focussing on the use of tiapride in the treatment of individuals with a psychiatric disorder (e.g., mood disorder, schizophrenia spectrum, substance use disorder). The Risk of Bias 2 was performed for the quality assessment of the included studies.ResultsWe identified 579 records. Of them, six studies (published between 1982 and 2010) were included in the review. Four studies referred to alcohol withdrawal, and two to the management of agitation in elderly patients with dementia. None of the studies reported significant differences between tiapride and other active comparators in terms of efficacy and tolerability. The overall risk of bias was moderate to high.ConclusionTiapride may be considered as a relatively safe treatment option for selected patients with alcohol withdrawal or agitation in dementia. However, solid evidence of its efficacy in the scientific literature is lacking. High‐quality trials remain necessary to fully sustain its use in clinical practice.
Catalpol protects AC16 cells from hypoxia/reoxygenation injury by regulating the miR‐22‐3p/DPP4 axis
Authors: Li Ziyang , Zhao Jianrong , Li Hui , Li Yan , Lin Caixia 
Published: March 2022

AbstractCatalpol (CA) is widely used in the protection of cardiomyocytes. Nevertheless, the mechanism of CA in alleviating ischemia‐reperfusion‐induced injury of cardiomyocytes remains unclear. Human cardiomyocyte AC16 cells were subjected to hypoxia/reoxygenation (H/R) injury. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis were applied to detect tumor necrosis factor‐alpha (TNF‐α) mRNA, interleukin‐6 (IL‐6) mRNA, interleukin‐1beta (IL‐1β) mRNA, microRNA‐22‐3p (miR‐22‐3p), dipeptidyl peptidase 4 (DPP4) mRNA, and DPP4 protein expressions. The cell viability and apoptosis were measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) and creatine kinase (CK‐MB) were examined by enzyme‐linked immunosorbent assay (ELISA) kits. A dual‐luciferase reporter gene assay was performed to confirm the binding sequence between miR‐22‐3p and DPP4 mRNA 3ʹ‐untranslated region (3ʹUTR). CA promoted the viability and reduced cell apoptosis of AC16 cells and repressed the release of inflammatory cytokines TNF‐α, IL‐6, and IL‐1β, and inhibited the leakage of myocardial injury markers LDH and CK‐MB. Furthermore, CA enhanced the expression of miR‐22‐3p in cardiomyocytes, and DPP4 was validated to be the target gene of miR‐22‐3p. The inhibition of miR‐22‐3p and augmentation of DPP4 reversed the above effects of CA. CA protects A16 cells from H/R injury by regulating the miR‐22‐3p/DPP4 axis.
Sumac and gallic acid‐loaded nanophytosomes ameliorate hippocampal oxidative stress via regulation of Nrf2/Keap1 pathway in autistic rats
Authors: Abbasalipour Haniyeh , Hajizadeh Moghaddam Akbar , Ranjbar Mojtaba 
Published: March 2022

AbstractAutism spectrum disorders cover a range of neurodevelopmental disorders characterized by impairments in social interaction and cognitive deficits. Phenolic compound applications have been restricted due to their poor solubility, bioavailability, and low stability. This paper aimed to explore the neuroprotective effects of sumac and gallic acid‐loaded nanophytosomes (GNP) on oxidative stress‐induced cognitive impairment and Nrf2/Keap1 gene expression in the autism model. Valproic acid (VPA) was administered intraperitoneally at doses of 500 mg/kg to female rats during gestational 12.5 days (E12.5). The prenatal VPA‐exposed rats were divided into five groups, including VPA, VPA treated with sumac, gallic acid (GA), sumac‐loaded nanophytosome (SNP), and GNP at doses of 20 mg/kg for 4 weeks (n = 6). A novel object test was conducted and antioxidant parameters and Nrf2/Keap1gene expression were evaluated in the hippocampus. According to the obtained results, the rat model of autism exhibited recognition memory impairment. We observed an increase in glutathione peroxidase (GPx), glutathione reductase (GRx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, total antioxidant capacity (TAC), and glutathione (GSH) levels. Furthermore, sumac and GNP improved recognition memory deficits and increased GPx, GRx, SOD, and CAT activities, GSH and TAC levels, and Nrf2/Keap1gene expression in the hippocampal area. Our results also suggested that SNP and GNP ameliorate VPA‐induced learning and memory deficits more efficiently than sumac extract and pure GA by reducing oxidative stress, enhancing antioxidant enzyme activity, and Keap1/Nrf2 gene expression. The present study demonstrated that the utilization of SNP and GNP significantly improved recognition memory deficits.
Terminal end‐on coordination of dinitrogen versus isoelectronic CO: A comparison using the charge displacement analysis
Authors: Schmitt Manuel , Krossing Ingo 
Published: March 2022

AbstractThe metal dinitrogen bonding in a wide series of terminal end‐on dinitrogen complexes is investigated with the charge displacement analysis based on natural orbitals of chemical valence (CD‐NOCV). The effect of the σ donation and π backdonation on the NN bond are discussed and compared with the observations for a series of carbonyl complexes, published in 2016 by Tarantelli et al. The σ donation is relative invariant over the series of dinitrogen complexes and has no significant effect on the NN bond strength, whereas the π backdonation causes a considerable elongation of the NN bond. Some uncommon examples of weakly bound dinitrogen with blue‐shifted stretching frequency compared to free N2 (ν = 2330 cm−1) are known. The dinitrogen bonding in these complexes is simulated with a point charge. Apparently, electrostatics account for the shortened N─N bond in these systems.
Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan
Authors: Kaneshige Risa , Motoki Yukari , Yoshida Mika , Oku Kenji , Morishita Eriko , Ieko Masahiro , Ichihara Kiyoshi , Nojima Junzo 
Published: March 2022

AbstractBackgroundAnticardiolipin antibodies (aCL) and anti‐β2‐glycoprotein I antibodies (aβ2GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ2GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays.MethodsWe evaluated two manual and three automated assays for aCL and aβ2GPI of IgG‐ and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well‐defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve.ResultsA variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between‐year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aβ2GPI‐IgG and aCL‐IgG were generally high (AUC: 0.84−0.93); whereas those for IgM‐class assays were low (AUC: 0.57−0.67), implicating its utility is limited to rare IgG negative APS cases.ConclusionTo ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.
Establishment of an in‐house real‐time RT‐PCR assay for the detection of severe acute respiratory syndrome coronavirus 2 using the first World Health Organization international standard in a resource‐limited country
Authors: Nguyen Linh Tung , Nguyen Phuong Minh , Dinh Duc Viet , Pham Hung Ngoc , Bui Lan Anh Thi , Vo Cuong Viet , Nguyen Ben Huu , Bui Hoan Duy , Hoang Cuong Xuan , Ngo Nhat Minh Van , Dang Truong Tien , Do Anh Ngoc , Vu Dung Dinh , Nguyen Linh Thuy , Nguyen Mai Ngoc , Dinh Thu Hang Thi , Ho Son Anh , Hoang Luong Van , Hoang Su Xuan , Do Quyet 
Published: March 2022

AbstractBackgroundThe COVID‐19 pandemic caused by SARS‐CoV‐2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real‐time RT‐PCR are critical for the detection of SARS‐CoV‐2 in clinical specimens from patients suspected of COVID‐19.ObjectiveWe aimed to establish and validate an in‐house real‐time RT‐PCR for the detection of SARS‐CoV‐2.MethodologyPrimers and probes sets in our in‐house real‐time RT‐PCR assay were designed in conserved regions of the N and E target genes. Optimized multiplex real‐time RT‐PCR assay was validated using the first WHO International Standard (NIBSC code: 20/146) and evaluated clinical performance.ResultsThe limit of detection validated using the first WHO International Standard was 159 IU/ml for both E and N target genes. The evaluation of clinical performance on 170 clinical samples showed a positive percent agreement of 100% and the negative percent agreement of 99.08% for both target genes. The Kappa value of 0.99 was an excellent agreement, the strong correlation of Ct values observed between two tests with r2 = 0.84 for the E gene and 0.87 for the N gene. Notably, we assessed on 60 paired saliva and nasopharyngeal samples. The overall agreement was 91.66%, and Kappa value of 0.74 showed a high agreement between two types of samples. When using nasopharyngeal swabs as the reference standard, positive percent agreement, and negative percent agreement were 91.83% and 90.90%, respectively.ConclusionIn the present study, we established and validated an in‐house real‐time RT‐PCR for molecular detection of SARS‐CoV‐2 in a resource‐limited country.
Yes‐associated protein activation potentiates glycogen synthase kinase‐3 inhibitor‐induced proliferation of neonatal cardiomyocytes and iPS cell‐derived cardiomyocytes
Authors: Kametani Yusuke , Tanaka Shota , Wada Yuriko , Suzuki Shota , Umeda Ayaka , Nishinaka Kosuke , Okada Yoshiaki , Maeda Makiko , Miyagawa Shigeru , Sawa Yoshiki , Obana Masanori , Fujio Yasushi 
Published: March 2022

AbstractBecause mammalian cardiomyocytes largely cease to proliferate immediately after birth, the regenerative activity of the heart is limited. To date, much effort has been made to clarify the regulatory mechanism of cardiomyocyte proliferation because the amplification of cardiomyocytes could be a promising strategy for heart regenerative therapy. Recently, it was reported that the inhibition of glycogen synthase kinase (GSK)‐3 promotes the proliferation of neonatal rat cardiomyocytes (NRCMs) and human iPS cell‐derived cardiomyocytes (hiPSC‐CMs). Additionally, Yes‐associated protein (YAP) induces cardiomyocyte proliferation. The purpose of this study was to address the importance of YAP activity in cardiomyocyte proliferation induced by GSK‐3 inhibitors (GSK‐3Is) to develop a novel strategy for cardiomyocyte amplification. Immunofluorescent microscopic analysis using an anti‐Ki‐67 antibody demonstrated that the treatment of NRCMs with GSK‐3Is, such as BIO and CHIR99021, increased the ratio of proliferative cardiomyocytes. YAP was localized in the nuclei of more than 95% of cardiomyocytes, either in the presence or absence of GSK‐3Is, indicating that YAP was endogenously activated. GSK‐3Is increased the expression of β‐catenin and promoted its translocation into the nucleus without influencing YAP activity. The knockdown of YAP using siRNA or pharmacological inhibition of YAP using verteporfin or CIL56 dramatically reduced GSK‐3I‐induced cardiomyocyte proliferation without suppressing β‐catenin activation. Interestingly, the inhibition of GSK‐3 also induced the proliferation of hiPSC‐CMs under sparse culture conditions, where YAP was constitutively activated. In contrast, under dense culture conditions, in which YAP activity was suppressed, the proliferative effects of GSK‐3Is on hiPSC‐CMs were not detected. Importantly, the activation of YAP by the knockdown of α‐catenin restored the proproliferative activity of GSK‐3Is. Collectively, YAP activation potentiates the GSK‐3I‐induced proliferation of cardiomyocytes. The blockade of GSK‐3 in combination with YAP activation resulted in remarkable amplification of cardiomyocytes.
Dental hygienists’ use of motivational interviewing and perceptions of effectiveness in changing patient behaviors
Authors: Rogers Kelly M. , Arnett Michelle C. , Mays Keith A. , Wang Qi , Blue Christine M. 
Published: March 2022

AbstractBackgroundThe University of Minnesota (UMN) Dental Hygiene (DH) program devotes considerable time developing students’ competency using motivational interviewing (MI). However, the extent to which graduates use MI in clinical practice and their perceptions of MI effectiveness in changing behavior is unknown.MethodsA cross‐section of UMN dental hygiene classes from 2010–2019 were emailed an electronic survey using Qualtricsxm software (n = 208). The survey instrument collected demographic information and queried respondents’ current MI use and perceptions of its effectiveness in changing patients’ behavior. Survey questions were aligned with the constructs of the Theory of Planned Behavior (TPB): attitudes, subjective norms, and perceived behavioral control. Data analyses included descriptive statistics, cross‐tabulations, and one‐way ANOVA tests.ResultsThere were 73 responses for a 35% response rate and 58 surveys (28%) included in data analysis. Respondents (95%) used MI, held positive attitudes toward MI and perceived MI to be an effective behavior counseling method (98%). However, respondents expressed concerns about patients’ abilities to change behaviors. The three TPB constructs were found to be predictors of MI use in the clinical environment. A significant association was found between age and the TPB construct: behavioral control (p = 0.02).ConclusionThe majority of respondents reported using MI in clinical practice. According to the TPB, respondents exhibited strong behavioral intentions to use MI. Respondents held favorable attitudes toward MI and believed it to be effective in motivating positive behavior change. Respondents were confident in their MI skills and felt supported to use MI in their work environments.
Uniformly connected graphs
Authors: Göring Frank , Hofmann Tobias , Streicher Manuel 
Published: March 2022

AbstractIn this article, we investigate the structure of uniformly ‐connected and uniformly ‐edge‐connected graphs. Whereas both types have previously been studied independent of each other, we analyze relations between these two classes. We prove that any uniformly ‐connected graph is also uniformly ‐edge‐connected for and demonstrate that this is not the case for . Furthermore, uniformly ‐connected and uniformly ‐edge‐connected graphs are well understood for and it is known how to construct uniformly 3‐edge‐connected graphs. We contribute here a constructive characterization of uniformly 3‐connected graphs that is inspired by Tutte's Wheel Theorem. Eventually, these results help us to prove a tight bound on the number of vertices of minimum degree in uniformly 3‐connected graphs.
A Biodegradable Multifunctional Film as a Tissue Adhesive for Instant Hemostasis and Wound Closure
Authors: Huang Wen‐Can , He Yongjun , Wang Wei , Mao Xiangzhao 
Published: March 2022

AbstractHere, a multifunctional film (MFF) as an alternative tissue adhesive in the form of an interpenetrating network consisting of self‐crosslinked aldehyde‐functionalized chitosan (AC) and crosslinked poly(acrylic acid) (PAA) further coordinated with Ag+ is reported. The MFF combines enhanced toughness and stretchability, which is attributed to the synergistic effects of the double‐network design. Covalent crosslinking maintains the overall integrity of the MFF matrix, while noncovalent crosslinking dissipates energy under deformation. Upon contact, the MFF quickly dries the tissue surface followed by instant physical crosslinking to the tissue. Subsequent covalent crosslinking between the aldehyde groups of the MFF and the primary amine groups on the surface of the tissue further stabilizes the adhesion. Meanwhile, Ag+ provides strong antibacterial properties to the MFF. Notably, in vivo studies demonstrate that the MFF allows facile and tough attachment to the wet and dynamic surface of rabbit liver and presents superior hemostasis and sealing properties. Furthermore, the MFF can be safely degraded without causing abnormal defects in vivo. The outstanding physicochemical properties of the MFF can potentially be a good alternative to existing sutures or staples and has potential for use in clinical practice.
The interplay between fractional damping and nonlinear memory for the plate equation
Authors: D'Abbicco Marcello , Longen Luis Gustavo 
Published: March 2022

In this paper, we study the interplay between a fractional damping (− Δ)θut with θ ∈ [0, 1/2), and a nonlinear memory term applied to a plate equation:

in space dimension
. In different scenarios, we prove the global existence of small data solutions in
for supercritical powers, where the critical exponent is determined by the fractional power of the damping term and by the order of the fractional integration in the memory term. In one case, we also feel the influence of the regularity‐loss type decay, which is due to the presence of the rotational inertia term −Δutt in the plate equation.
Diet Supplementation with NUTRIOSE, a Resistant Dextrin, Increases the Abundance of Parabacteroides distasonis in the Human Gut
Authors: Thirion Florence , Da Silva Kévin , Plaza Oñate Florian , Alvarez Anne‐Sophie , Thabuis Clémentine , Pons Nicolas , Berland Magali , Le Chatelier Emmanuelle , Galleron Nathalie , Levenez Florence , Vergara Coralie , Chevallier Hélène , Guérin‐Deremaux Laetitia , Doré Joël , Ehrlich Stanislav D. 
Published: March 2022

ScopeAn imbalance of the gut microbiota (“dysbiosis”) is associated with numerous chronic diseases, and its modulation is a promising novel therapeutic approach. Dietary supplementation with soluble fiber is one of several proposed modulation strategies. This study aims at confirming the impact of the resistant dextrin NUTRIOSE (RD), a soluble fiber with demonstrated beneficial health effects, on the gut microbiota of healthy individuals.Methods and resultsFifty healthy women are enrolled and supplemented daily with either RD (n = 24) or a control product (n = 26) during 6 weeks. Characterization of the fecal metagenome with shotgun sequencing reveals that RD intake dramatically increases the abundance of the commensal bacterium Parabacteroides distasonis. Furthermore, presence in metagenomes of accessory genes from P. distasonis, coding for susCD (a starch‐binding membrane protein complex) is associated with a greater increase of the species. This suggests that response to RD might be strain‐dependent.ConclusionSupplementation with RD can be used to specifically increase P. distasonis in gut microbiota of healthy women. The magnitude of the response may be associated with fiber‐metabolizing capabilities of strains carried by subjects. Further research will seek to confirm that P. distasonis directly modulates the clinical effects observed in other studies.