bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of S122 in ERα is important for the skeletal response to estrogen treatment in male mice
Authors: Horkeby Karin , Farman Helen H. , Movérare-Skrtic Sofia , Lionikaite Vikte , Wu Jianyao , Henning Petra , Windahl Sara , Sjögren Klara , Ohlsson Claes , Lagerquist Marie K. 
Published: December 2022

AbstractEstrogen receptor alpha (ERα) signaling has beneficial skeletal effects in males. ERα signaling also affects other tissues, and to find bone-specific treatments, more knowledge regarding tissue-specific ERα signaling is needed. ERα is subjected to posttranslational modifications, including phosphorylation, which can influence ERα function in a tissue-specific manner. To determine the importance of phosphorylation site S122 (corresponding to human ERα site S118) for the skeleton and other tissues, male mice with a S122A mutation were used. Total areal bone mineral density was similar between gonadal intact S122A and WT littermates followed up to 12 months of age, and weights of estrogen-responsive organs normalized for body weight were unchanged between S122A and WT males at both 3 and 12 months of age. Interestingly, 12-month-old S122A males had decreased body weight compared to WT. To investigate if site S122 affects the estrogen response in bone and other tissues, 12-week-old S122A and WT males were orchidectomized (orx) and treated with estradiol (E2) or placebo pellets for four weeks. E2 increased cortical thickness in tibia in both orx WT (+ 60%, p < 0.001) and S122A (+ 45%, p < 0.001) males. However, the E2 effect on cortical thickness was significantly decreased in orx S122A compared to WT mice (− 24%, p < 0.05). In contrast, E2 affected trabecular bone and organ weights similarly in orx S122A and WT males. Thus, ERα phosphorylation site S122 is required for a normal E2 response specifically in cortical bone in male mice, a finding that may have implications for development of future treatments against male osteoporosis.
Clinical characteristics, management strategies and outcomes of patients with recurrent venous thromboembolism in the real world
Authors: Yamashita Yugo , Morimoto Takeshi , Kadota Kazushige , Takase Toru , Hiramori Seiichi , Kim Kitae , Oi Maki , Akao Masaharu , Kobayashi Yohei , Toyofuku Mamoru , Inoko Moriaki , Tada Tomohisa , Chen Po-Min , Murata Koichiro , Tsuyuki Yoshiaki , Nishimoto Yuji , Sakamoto Jiro , Togi Kiyonori , Mabuchi Hiroshi , Takabayashi Kensuke , Kato Takao , Ono Koh , Kimura Takeshi 
Published: December 2022

AbstractThere is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P < 0.001). Among 110 patients with first recurrent VTE during anticoagulation therapy, 84 patients (76%) received warfarin at recurrent VTE with the median prothrombin time-international normalized ratio (PT-INR) value at recurrent VTE of 1.6, although patients with active cancer had a significantly higher median PT-INR value at recurrent VTE compared with those without active cancer (2.0 versus 1.4, P < 0.001). Within 90 days after recurrent VTE, 23 patients (20.9%) during anticoagulation therapy and 24 patients (20.7%) after discontinuation of anticoagulation therapy died. Active cancer was a major cause of recurrent VTE during anticoagulation therapy as a patient-related factor, while sub-optimal intensity of anticoagulation therapy was a major cause of recurrent VTE during anticoagulation therapy as a treatment-related factor, particularly in patients without active cancer.
Unexpected self-lofting and dynamical confinement of volcanic plumes: the Raikoke 2019 case
Authors: Khaykin S. M. , de Laat A. T. J. , Godin-Beekmann S. , Hauchecorne A. , Ratynski M. 
Published: December 2022

AbstractRecent research has provided evidence of the self-lofting capacity of smoke aerosols in the stratosphere and their self-confinement by persistent anticyclones, which prolongs their atmospheric residence time and radiative effects. By contrast, the volcanic aerosols—composed mostly of non-absorptive sulphuric acid droplets—were never reported to be subject of dynamical confinement. Here we use high-resolution satellite observations to show that the eruption of Raikoke volcano in June 2019 produced a long-lived stratospheric anticyclone containing 24% of the total erupted mass of sulphur dioxide. The anticyclone persisted for more than 3 months, circumnavigated the globe three times, and ascended diabatically to 27 km altitude through radiative heating of volcanic ash contained by the plume. The mechanism of dynamical confinement has important implications for the planetary-scale transport of volcanic emissions, their stratospheric residence time, and atmospheric radiation balance. It also provides a challenge or “out of sample test” for weather and climate models that should be capable of reproducing similar structures.
CD46 protects the bladder cancer cells from cetuximab-mediated cytotoxicity
Authors: Do Manh-Hung , Thanh Hien Duong , To Phuong Kim , Kim Min Soo , Moon Changjong , Jung Chaeyong 
Published: December 2022

AbstractEpidermal growth factor receptor (EGFR) is an effective target for those patients with metastatic colorectal cancers that retain the wild-typeRASgene. However, its efficacy in many cancers, including bladder cancer, is unclear. Here, we studied the in vitro effects of cetuximab monoclonal antibodies (mAbs) targeting EGFR on the bladder cancer cells and role of CD46. Cetuximab was found to inhibit the growth of both colon and bladder cancer cell lines. Furthermore, cetuximab treatment inhibited AKT and ERK phosphorylation in the bladder cancer cells and reduced the expression of CD46 membrane-bound proteins. Restoration of CD46 expression protected the bladder cancer cells from cetuximab-mediated inhibition of AKT and ERK phosphorylation. We hypothesized that CD46 provides protection to the bladder cancer cells against mAb therapies. Bladder cancer cells were also susceptible to cetuximab-mediated immunologic anti-tumor effects. Further, cetuximab enhanced the cell killing by activating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in bladder cancer cells. Restoration of CD46 expression protected the cells from both CDC and ADCC induced by cetuximab. Together, CD46 exhibited a cancer-protective effect against both direct (by involvement of PBMC or complement) and indirect cytotoxic activity by cetuximab in bladder cancer cells. Considering its clinical importance, CD46 could be an important link in the action mechanism of ADCC and CDC intercommunication and may be used for the development of novel therapeutic strategies.
Phase separation of rotor mixtures without domain coarsening driven by two-dimensional turbulence
Authors: Hrishikesh Bhadra , Takae Kyohei , Mani Ethayaraja , Tanaka Hajime 
Published: December 2022

AbstractUnlike in thermodynamic systems, phase separation can occur without a thermodynamic driving force in active systems. How phase separation of purely hydrodynamic origin proceeds is an intriguing physical question. To this end, we study the phase separation of a binary mixture of oppositely rotating disks in a two-dimensional (2D) viscous fluid at an athermal condition by hydrodynamic simulations, focusing on the inertia effect. At symmetric and off-symmetric compositions, phase separation forms the oppositely flowing bands and a circular rotating droplet in the disordered matrix phase. In both cases, phase separation creates the largest structure directly from a chaotic state without gradual domain coarsening, unlike in the thermodynamic and corresponding dry rotor mixtures. We show that this unusual behaviour results from the nonlinear convective acceleration, i.e., the inverse cascade phenomena characteristic of 2D turbulence. Our finding reveals nontrivial nonlinear hydrodynamic effects on the self-organisation of active/driven particles in a fluid.
The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part II: In Vitro and In Vivo Evaluations
Authors: Xi Quan , Cao Zhen , Miao Jia-Ying , Wang Hao 
Published: December 2022

AbstractThe mometasone furoate (MF) and formoterol fumarate dihydrate (FF) inhalable microparticles prepared by different methods, such as micronized active pharmaceutical ingredients (APIs), microparticles of APIs prepared by spray-freeze drying technique (SFD APIs), and phospholipid microparticles of APIs prepared by SFD (SFD Lip-APIs), showed different inhaled drug delivery characteristics. Study on the physicochemical characteristics of those microparticles and the effect of matrix excipients on pharmacokinetic (PK) behaviors of inhalable microparticles is helpful for the development of new methods for inhalable microparticles with excellent performance of inhalation characteristics. In this study, the crystal state of the microparticles was investigated by powder X-ray diffraction and differential scanning calorimetry. The density was investigated by a bulk density method. The suspension and dispersion characteristics were determined by observing its state in hydrofluoroalkane (HFA). Meanwhile, the PK behaviors of SFD Lip-APIs in beagle dogs were also investigated by airway administration to evaluate the effect of phospholipids on drug release. The results indicated that the presence of phospholipids prevents the formation of solid bridges bonding to each other during SFD of pure drug solutions. In comparison to the conventional micronized microparticles, inhalable drug–phospholipid microparticles were easily dispersed and suspended in HFA. The embedded drugs were in a crystal state that endowed a better physical stability, and most interestingly, have similar PK behavior to the control (a mixed solution of MF/FF), suggesting that the phospholipids, as matrix excipients, had no effect on absorption. Given above, our designed SFD phospholipid microparticles may represent an efficient carrier for pulmonary delivery of MF and FF for further clinical treatment.
Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study
Authors: Rønnow Sand Jakob , Troelsen Frederikke Schønfeldt , Nagy Dávid , Farkas Dóra Körmendiné , Erichsen Rune , Christiansen Christian Fynbo , Sørensen Henrik Toft 
Published: December 2022

Background Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients.
Objectives To examine the cancer risk in patients with kidney disease following a VTE.
Methods We conducted a nationwide population-based cohort study in Denmark (1996–2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease.
Results We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6–5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3–5.8), with a SIR of 2.9 (95% CI: 2.5–3.4) when compared with the general population, and 2.0 (95% CI: 1.8–2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3–1.6) when compared with the general population, and 1.1 (95% CI: 0.9–1.2) compared with VTE patients without kidney disease.
Conclusion Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.
The role of social value orientation in modulating vaccine uptake in the COVID-19 pandemic: A cross-sectional study
Authors: Moosa Sheena , Abdul Raheem Raheema , Riyaz Aminath , Musthafa Hawwa Shiuna , Naeem Aishath Zeen 
Published: December 2022

AbstractCOVID-19 vaccination is the only pharmaceutical measure available to control the pandemic and move past the current crisis. As such, the Maldives, a small island country, invested heavily on securing and vaccinating the eligible population through an intensive risk communication campaign to create awareness on vaccination benefits. This paper reports on the vaccine coverage after a year of COVID-19 vaccine being introduced into the country, based on data obtained from the Values in Crisis Survey – Wave Two among Maldivian adults (n = 497). The findings show a vaccine coverage of 94%, with only 2.2% of the respondents indicating they will not get vaccinated. No significant differences were observed by age, gender, income earning, educational status or residential area. No significant relationship was observed in vaccine behaviour and confidence in government, health sector and experts. Social value orientations, particularly conservation and self-transcendence value orientations determined positive vaccine behaviour (rs = 0.180,p < 0.01 and 0.136p < 0.01 respectively), yet conservation was the only predictor that contributed significantly to the regression model (B = 0.158,p < 0.01). The findings indicate that, despite the uncertainties around COVID-19 vaccinations, the prosocial value orientations were instrumental in achieving a high COVID-19 vaccine coverage. Further theoretical and conceptual exploration of vaccine behaviour in crisis situations is needed to inform future pandemic situations. The vaccination rollout and behaviour change strategies also need an examination of social value orientations in order to achieve a high coverage and sustain pro-vaccine behaviour post-pandemic.
Relationship Between Obesity and Hypertension From Bioinformatics Analysis
Authors: Fan Ji-lin , Zhu Ting-ting , Tian Xiao-ling , Xue Zhen-yu , Guo Jing-qi , Ren Wen-qing , Zhang Shi-liang 
Published: December 2022

Abstract

Background
To explore the relationship between obesity and hypertension using bioinformatics analyses.

Methods
Disease databases (GeneCards, OMIM, CTD, TTD, DisGeNET, and Drugbank) were used to obtain hypertension and obesity-related targets. The intersection targets of obesity and hypertension were constructed using Venn diagrams. STRING online platform was used to obtain protein–protein interaction networks of common targets, and Cytohubba plug-in was used to screen the core targets. Gene ontology (GO) analysis and the enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) were carried out using DAVID database.

Results
A total of 459 and 551 targets were obtained for obesity and hypertension, respectively. Among them, 135 were targets for both obesity and hypertension in which tumor necrosis factor (TNF), cell tumor antigen p53 (TP53), chemokine 2 (CCL2), Toll-like receptor 4 (TLR4), interleukin (IL) 1B, nitric oxide synthase 3 (NOS3), IL-6, and serine/threonine protein kinase 1 (AKT1) were key targets for regulating obesity and hypertension. Enrichment analysis yielded 306 GO entries [P &lt; 0.05, false discovery rate (FDR) &lt;0.05], which were involved in positive regulation of mitogen-activated protein kinase (MAPK) cascade, positive regulation of nitric oxide biosynthetic process, cilium basal body, hormone activity, and RNA polymerase II repeating transcription factor binding. The 86 enriched KEGG entries (P &lt; 0.05, FDR &lt;0.05) included adipocytokine signaling pathway, regulation of lipolysis in adipocytes, PI3K–Akt signaling pathway and forkhead transcription factor O (FoxO) signaling pathway.

Conclusions
TNF, TP53, CCL2, TLR4, IL-1B, NOS3, IL-6, AKT1, and the key pathways including adipocytokine signaling pathway, regulation of adipocyte lipolysis, PI3K–Akt and FoxO signaling pathway play a regulatory role in interactions between obesity and hypertension. These findings provide new insights into the complex interactions between obesity and hypertension.
HCovDock: an efficient docking method for modeling covalent protein–ligand interactions
Authors: Wu Qilong , Huang Sheng-You 
Published: December 2022

Abstract
Covalent inhibitors have received extensive attentions in the past few decades because of their long residence time, high binding efficiency and strong selectivity. Therefore, it is valuable to develop computational tools like molecular docking for modeling of covalent protein–ligand interactions or screening of potential covalent drugs. Meeting the needs, we have proposed HCovDock, an efficient docking algorithm for covalent protein–ligand interactions by integrating a ligand sampling method of incremental construction and a scoring function with covalent bond-based energy. Tested on a benchmark containing 207 diverse protein–ligand complexes, HCovDock exhibits a significantly better performance than seven other state-of-the-art covalent docking programs (AutoDock, Cov_DOX, CovDock, FITTED, GOLD, ICM-Pro and MOE). With the criterion of ligand root-mean-squared distance &lt; 2.0 Å, HCovDock obtains a high success rate of 70.5% and 93.2% in reproducing experimentally observed structures for top 1 and top 10 predictions. In addition, HCovDock is also validated in virtual screening against 10 receptors of three proteins. HCovDock is computationally efficient and the average running time for docking a ligand is only 5 min with as fast as 1 sec for ligands with one rotatable bond and about 18 min for ligands with 23 rotational bonds. HCovDock can be freely assessed at http://huanglab.phys.hust.edu.cn/hcovdock/.
Logistic tensor decomposition with sparse subspace learning for prediction of multiple disease types of human–virus protein–protein interactions
Authors: Ma Yingjun , Zhong Junjiang 
Published: December 2022

AbstractViral infection involves a large number of protein–protein interactions (PPIs) between the virus and the host, and the identification of these PPIs plays an important role in revealing viral infection and pathogenesis. Existing computational models focus on predicting whether human proteins and viral proteins interact, and rarely take into account the types of diseases associated with these interactions. Although there are computational models based on a matrix and tensor decomposition for predicting multi-type biological interaction relationships, these methods cannot effectively model high-order nonlinear relationships of biological entities and are not suitable for integrating multiple features. To this end, we propose a novel computational framework, LTDSSL, to determine human–virus PPIs under different disease types. LTDSSL utilizes logistic functions to model nonlinear associations, sets importance levels to emphasize the importance of observed interactions and utilizes sparse subspace learning of multiple features to improve model performance. Experimental results show that LTDSSL has better predictive performance for both new disease types and new triples than the state-of-the-art methods. In addition, the case study further demonstrates that LTDSSL can effectively predict human-viral PPIs under various disease types.
Efficacy of a multicomponent singing intervention on communication and psychosocial functioning in chronic aphasia: a randomized controlled crossover trial
Authors: Siponkoski Sini-Tuuli , Pitkäniemi Anni , Laitinen Sari , Särkämö Essi-Reetta , Pentikäinen Emmi , Eloranta Heidi , Tuomiranta Leena , Melkas Susanna , Schlaug Gottfried , Sihvonen Aleksi J , Särkämö Teppo 
Published: December 2022

Abstract
The ability to produce words through singing can be preserved in severe aphasia, but the benefits of group-based singing rehabilitation in aphasia are largely unknown. Our aim was to determine the efficacy of a multicomponent singing intervention on communication and speech production, emotional-social functioning and caregiver well-being in aphasia. Fifty-four patients with acquired brain injury and chronic aphasia and their family caregivers (n = 43) were recruited. Using a crossover randomized controlled trial design, participants were randomized to two groups who received a 4-month singing intervention either during the first or second half of the study in addition to standard care. The intervention comprised weekly group-based training (including choir singing and group-level melodic intonation therapy) and tablet-assisted singing training at home. At baseline, 5- and 9-month stages, patients were assessed with tests and questionnaires on communication and speech production, mood, social functioning, and quality of life and family caregivers with questionnaires on caregiver burden. All participants who participated in the baseline measurement (n = 50) were included in linear mixed model analyses. Compared with standard care, the singing intervention improved everyday communication and responsive speech production from baseline to 5-month stage, and these changes were sustained also longitudinally (baseline to 9-month stage). Additionally, the intervention enhanced patients’ social participation and reduced caregiver burden. This study provides novel evidence that group-based multicomponent singing training can enhance communication and spoken language production in chronic aphasia as well as improve psychosocial wellbeing in patients and caregivers.
https://www.clinicaltrials.gov, Unique identifier: NCT03501797.
Selective extinction and habitat nestedness are the main drivers of lizard nestedness in the Zhoushan Archipelago
Authors: Zhang Minchu , Tang Chaonan , Zhang Qing , Zhan Chengxiu , Chen Chuanwu , Wang Yanping 
Published: December 2022

Abstract
Nested subset pattern (nestedness) is an important part of the theoretical framework of island biogeography and community ecology. However, most previous studies often used nestedness metrics or randomization algorithms that are vulnerable to type I error. In this study, we investigated the nestedness of lizard assemblages on 37 islands in the Zhoushan Archipelago, China. We used the line-transect method to survey species occurrence, abundance, and habitat types of lizards on 37 islands during 2 breeding seasons in 2021 and 2022. We applied the nested metric WNODF and the conservative rc null model to control for type I error and quantify the significance of nestedness. Spearman rank correlations were used to evaluate the role of 4 habitat variables (island area, 2 isolation indices, and habitat diversity) and 4 ecological traits (body size, geographic range size, clutch size, and minimum area requirement) in generating nestedness. The results of WNODF analyses showed that lizard assemblages were significantly nested. The habitat-by-site matrix estimated by the program NODF was also significantly nested, supporting the habitat nestedness hypothesis. The nestedness of lizard assemblages were significantly correlated with island area, habitat diversity, clutch size, and minimum area requirement. Overall, our results suggest that selective extinction and habitat nestedness were the main drivers of lizard nestedness in our system. In contrast, the nestedness of lizard assemblages was not due to passive sampling or selective colonization. To maximize the number of species preserved, our results indicate that we should protect both large islands with diverse habitats and species with large area requirement and clutch size.