bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between HER2 and ATM predicts poor survival in bladder cancer patients
Authors: Albarakati Nada , Al‐Shareeda Alaa , Ramadan Majed , Al‐Sowayan Batla , Negm Ola , Nedjadi Taoufik 
Published: September 2022

AbstractHuman Epidermal Growth Factor Receptor 2 (HER2) overexpression is considered one of the interesting prognostic biomarkers in bladder cancer. However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2‐Ataxia telangiectasia mutated (ATM) kinase interaction and their impact on patient survival and cancer aggressiveness. Using the Cancer Genome Atlas (TCGA) cohorts, we demonstrated that ATM expression (protein/mRNA) is increased in HER2 deficient compared with proficient HER2 patients. This finding was then validated using the Gene Expression Omnibus database (GEO). Correlation analysis (using low expression vs high expression as a discriminator) revealed a significant association of ATM low and HER2 high status with several clinicopathological variables such as high tumour grade, late disease stage and tumour shape. Kaplan–Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease‐free survival (DFS). Furthermore, using bioinformatics and protein/protein interaction analyses, we identified 66 putative overlapping proteins with direct link between HER2 and ATM most of which are functionally involved in transcription regulation, apoptotic process and cell proliferation. Interestingly, the results showed that these proteins are strongly linked with PI3K‐Akt pathway, p53 pathway and microRNAs in cancer. Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.
Transcription factors are potential therapeutic targets in epilepsy
Authors: Sun Qihan , Xu Wenbo , Piao Jingjing , Su Jingyun , Ge Tongtong , Cui Ranji , Yang Wei , Li Bingjin 
Published: September 2022

AbstractAcademics generally believe that imbalance between excitation and inhibition of the nervous system is the root cause of epilepsy. However, the aetiology of epilepsy is complex, and its pathogenesis remains unclear. Many studies have shown that epilepsy is closely related to genetic factors. Additionally, the involvement of a variety of tumour‐related transcription factors in the pathogenesis of epilepsy has been confirmed, which also confirms the heredity of epilepsy. In this review, we summarize the existing research on a variety of transcription factors and epilepsy and present relevant evidence related to transcription factors that may be targets in epilepsy. This information is of great significance for revealing the in‐depth molecular and cellular mechanisms of epilepsy.
Clinical characteristics and outcomes of newly diagnosed patients with HIV‐associated aggressive B‐cell NHL in China
Authors: Wang Chaoyu , Liu Jun , Lei Haike , Li Yu , Wu Jian , Guo Bingling , Hu Renzhi , Liu Tingting , Wu Jing , Ding Yao , Hu Chongling , Liang Shunsi , Xiao Chunyan , Liang Xiping , Huang Dehong , Yang Tao , Zhang Wenjun , Yang Zailin , Li Jieping , Nan Yingyu , Li Qiying , Xiang Ying , Li Zhenhua , Wu Yongzhong , Liu Yao 
Published: September 2022

AbstractLittle is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV‐negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV‐associated aggressive B‐cell non‐Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV‐associated aggressive B‐cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23–87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3–5) (62.7%) at diagnosis. Median CD4+ T‐cell count at diagnosis was 191/μl (range, 4–1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122–4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027–19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589–1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500–6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347–0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti‐lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV‐associated DLBCL and BL.
Real‐world effectiveness and safety of tildrakizumab in long‐term treatment of plaque psoriasis: Results from the non‐interventional, prospective, multicentre study TILOT
Authors: Tsianakas Athanasios , Schwichtenberg Uwe , Pierchalla Peter , Hinz Torsten , Diemert Sebastian , Korge Bernhard 
Published: September 2022

AbstractBackgroundPlaque psoriasis is a chronic inflammatory disorder affecting the skin and impacting quality of life. Tildrakizumab (TIL) is an IL‐23 inhibitor licensed for moderate‐to‐severe plaque psoriasis. Regulatory approval of medicinal products is based on safety and efficacy data from randomized controlled trials (RCTs) which impose stringent selection criteria. Long‐term non‐interventional studies (NIS) are needed to establish effectiveness and safety in daily practice bridging the gap between RCTs and the real‐world setting.ObjectivesThis analysis of the NIS TILOT seeks to evaluate effectiveness and safety of TIL in patients with moderate‐to‐severe plaque psoriasis in a real‐world setting. Secondary objectives include the assessment of the Dermatology Life Quality Index (DLQI), treatment satisfaction and course of scalp and nail disease using Physician Global Assessment (PGA).MethodsInterim analysis at 52 weeks (W) of the ongoing non‐interventional, prospective, long‐term multicentre study TILOT.ResultsThe effectiveness analysis included 412 patients. The mean [standard deviation, SD] Psoriasis Area and Severity Index (PASI) score was 16.0 [9.1] at baseline improving by 82.4% (95% confidence interval [CI], 78.9–86.0) to 2.1 [2.9] at W52. The proportion of patients achieving PASI scores of <3 and <5 increased over time peaking at 74.6% (95% CI, 69.3–79.4) and 88.4% (95% CI, 84.3–91.8) at W52. Scalp‐PGA and nail‐PGA improved by 79.8% (95% CI, 75.6–84.0) and 72.7% (95% CI, 63.9–81.6), respectively. DLQI of 0/1 was achieved by 48.2% (95% CI, 42.3–54.2). Nine out of 10 physicians and patients expressed a high level of treatment satisfaction. No new safety signals were observed.ConclusionsThis prospective cohort study demonstrates a high degree of effectiveness and a reassuring safety profile of TIL in a real‐world setting over 52 weeks. Patients with scalp and nail involvement or pruritus showed marked improvements.
A New Bayesian Person‐Fit Analysis Method Using Pivotal Discrepancy Measures
Authors: Combs Adam 
Published: September 2022

AbstractA common method of checking person‐fit in Bayesian item response theory (IRT) is the posterior‐predictive (PP) method. In recent years, more powerful approaches have been proposed that are based on resampling methods using the popular statistic. There has also been proposed a new Bayesian model checking method based on pivotal discrepancy measures (PDMs). A PDM T is a discrepancy measure that is a pivotal quantity with a known reference distribution. A posterior sample of T can be generated using standard Markov chain Monte Carlo output, and a p‐value is obtained from probability bounds computed on order statistics of the sample. In this paper, we propose a general procedure to apply this PDM method to person‐fit checking in IRT models. We illustrate this using the and measures. Simulation studies are done comparing these with the PP method and one of the more recent resampling methods. The results show that the PDM method is more powerful than the PP method. Under certain conditions, it is more powerful than the resampling method, while in others, it is less. The PDM method is also applied to a real data set.
An artificial neural network‐hydrodynamic coupled modeling approach to assess the impacts of floods under changing climate in the East Rapti Watershed, Nepal
Authors: Bhattarai Roshika , Bhattarai Utsav , Pandey Vishnu Prasad , Bhattarai Pawan Kumar 
Published: September 2022

AbstractRecurring floods have devastating consequences on the East Rapti Watershed (ERW), but effective mitigation/adaptation measures are lacking. This article aims at establishing a rainfall‐runoff (RR) relationship; estimating depth and extent of inundation under climate change scenarios; assessing impacts on the socio‐economy; and identifying and evaluating adaptation strategies in the ERW. Artificial Neural Network (ANN) was used to generate peak flows which were then entered into a hydraulic model to simulate inundation. Results were validated with field survey. The calibrated and validated RR and hydraulic models were fed with projected future climate (2021–2050) derived from multiple regional‐climate‐models to assess the changes in inundation. Results showed the peak discharge likely exceeds 10,500 m3/s at the ERW outlet in the extreme future flood scenario with corresponding inundation of 80 km2 and up to a depth of 11 m sweeping away over 1000 houses and 19 km2 of agricultural land in the critical areas. Constructing a 17 km long embankment in the critical areas along the right bank of the East Rapti River could reduce the flood spread by 35%, safeguarding 78% of the houses and saving 51% agricultural land compared with the scenarios without the embankment.
Response to COVID‐19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose
Authors: Shiga Hisashi , Kakuta Yoichi , An Kumiko , Abe Yuko , Fujimaki Shinichi , Shimoyama Yusuke , Naito Takeo , Moroi Rintaro , Kuroha Masatake , Khor Seik‐Soon , Kawai Yosuke , Tokunaga Katsushi , Kinouchi Yoshitaka , Masamune Atsushi 
Published: September 2022

AbstractBackgroundCoronavirus disease 2019 (COVID‐19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two‐dose and additional dose of messengerRNA COVID‐19 vaccine.MethodsAfter measuring high‐affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA‐1273), time from second/third vaccination, molecular‐targeted agent (anti‐tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular‐targeted agents), thiopurine, steroid, and 5‐aminosalicylic acid.ResultsAmong 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non‐carriers of HLA‐A24 associated with severe disease during COVID‐19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti‐TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers.ConclusionsOur findings further support the recommendation for COVID‐19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti‐TNF agents and/or thiopurine or tofacitinib.
Automated particle recognition for engine soot nanoparticles
Authors: Haffner‐Staton E. , Avanzini L. , La Rocca A. , Pfau S. A. , Cairns A. 
Published: September 2022

AbstractA pre‐trained convolution neural network based on residual error functions (ResNet) was applied to the classification of soot and non‐soot carbon nanoparticles in TEM images. Two depths of ResNet, one 18 layers deep and the other 50 layers deep, were trained using training‐validation sets of increasing size (containing 100, 400 and 1400 images) and were assessed using an independent test set of 200 images. Network training was optimised in terms of mini‐batch size, learning rate and training length. In all tests, ResNet18 and ResNet50 had statistically similar performances, though ResNet18 required only 25–35% of the training time of ResNet50. Training using the 100‐, 400‐ and 1400‐image training‐validation sets led to classification accuracies of 84%, 88% and 95%, respectively. ResNet18 and ResNet50 were also compared for their ability to categorise soot and non‐soot nanoparticles via a fivefold cross‐validation experiment using the entire set of 800 images of soot and 800 images of non‐soot. Cross‐validation was repeated 3 times with different training durations. For all cross‐validation experiments, classification accuracy exceeded 91%, with no statistical differences between any of the network trainings. The most efficient network was ResNet18 trained for 5 epochs, which reached 91.2% classification after only 84 s of training on 1600 images. Use of ResNet for classification of 1000 images, the amount suggested for reliable characterisation of soot sample, requires <4 s, compared with >30 min for a skilled operator classifying images manually. Use of convolution neural networks for classification of soot and non‐soot nanoparticles in TEM images is highly promising, particularly when manually classified data sets have already been established.
Characterization of natural killer cells in the blood and airways of cynomolgus macaques during Mycobacterium tuberculosis infection
Authors: Diedrich Collin R. , Rutledge Tara , Baranowski Tonilynn M. , Maiello Pauline , Lin Philana Ling 
Published: September 2022

AbstractBackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and kills more than 1.5 million people each year.MethodsWe examine the frequency and function of NK cells in the blood and airways over the course of Mtb infection in a TB macaque model and demonstrate differences in NK marker expression between the two compartments. Flow cytometry and intracellular cytokine staining were utilized to identify NK cell subsets (expressing NKG2A, CD56, or CD16) and function (IL‐10, TNF, IL‐2, IFN‐g, IL‐17, and CD107a).ResultsBlood and airway NK cell frequencies were similar during infection though there were differences in subset populations between blood and airway. Increased functional (cytokine/CD107a) parameters were observed in airway NK cells during the course of infection while none were seen in the blood.ConclusionsThis study suggests that NK cells in the airway may play an important role in TB host response.
Recognising the potential of large animals for modelling neuromuscular junction physiology and disease
Authors: Cahalan Stephen D. , Boehm Ines , Jones Ross A. , Piercy Richard J. 
Published: September 2022

AbstractThe aetiology and pathophysiology of many diseases of the motor unit remain poorly understood and the role of the neuromuscular junction (NMJ) in this group of disorders is particularly overlooked, especially in humans, when these diseases are comparatively rare. However, elucidating the development, function and degeneration of the NMJ is essential to uncover its contribution to neuromuscular disorders, and to explore potential therapeutic avenues to treat these devastating diseases. Until now, an understanding of the role of the NMJ in disease pathogenesis has been hindered by inherent differences between rodent and human NMJs: stark contrasts in body size and corresponding differences in associated axon length underpin some of the translational issues in animal models of neuromuscular disease. Comparative studies in large mammalian models, including examination of naturally occurring, highly prevalent animal diseases and evaluation of their treatment, might provide more relevant insights into the pathogenesis and therapy of equivalent human diseases. This review argues that large animal models offer great potential to enhance our understanding of the neuromuscular system in health and disease, and in particular, when dealing with diseases for which nerve length dependency might underly the pathogenesis.
Retinoic acid induces the osteogenic differentiation of cat adipose tissue‐derived stromal cells from distinct anatomical sites
Authors: Ferreira‐Baptista Carla , Queirós André , Ferreira Rita , Fernandes Maria Helena , Gomes Pedro Sousa , Colaço Bruno 
Published: September 2022

AbstractMesenchymal stromal cells‐based regenerative orthopedic therapies have been used in cats as a promising and innovative therapeutic approach to enhance the repair of bone defects. Adipose tissue‐derived stromal cells (ADSCs) can be obtained from two main sites—subcutaneous and visceral—with established differences regarding structure, composition, cell content, and functionality. However, in cats, to the best of the authors' knowledge, no studies have been conducted to compare the functional activity of the ADSCs isolated from the two sites, and the impact of these differences on the induced osteogenic potential. Additionally, retinoic acid has been recently regarded as a new osteogenic inducer within cells of distinct species, with undisclosed functionality on cat‐derived cell populations. Thus, the present study aimed to evaluate the functional activity of ADSCs isolated from the subcutaneous and visceral adipose sites (SCAT and VAT, respectively) of the cat, as well as the effects of two osteogenic‐inducing conditions—the classic dexamethasone, β‐glycerophosphate and ascorbic acid‐supplemented media (Dex + β + AAM), and Retinoic Acid‐supplemented media (RAM). The adipose tissue of subcutaneous and visceral origin was isolated, characterized, and ADSCs were isolated and grown in the presence of the two osteogenic‐inducing conditions, and characterized in terms of proliferation, metabolic activity, morphology, and osteogenic activity. Our results demonstrated a distinct biological profile of the two adipose tissue sites regarding cell size, vascularization, and morphology. Further, osteogenic‐induced ADSCs from both sites presented an increased expression of alkaline phosphatase activity (ALP) and cytochemical staining, as compared with control. Overall, RAM induced higher levels of ALP activity than Dex + β + AAM, supporting an increased osteogenic activation. Additionally, VAT was the tissue with the best osteogenic potential, showing higher levels of ALP expression, particularly with RAM. In conclusion, different characteristics were found between the two adipose tissue sites—SCAT and VAT, which probably reflect the differences found in the functionality of isolated ADSCs from both tissues. Furthermore, for cat, VAT shows a greater osteogenic‐inductive capacity than SCAT, particularly with RAM, which can be of therapeutic relevance for regenerative medicine applications.
Comparison of the efficacy of carboxytherapy versus fractional CO2 laser therapy for the treatment of periorbital dark circles: A randomized clinical trial
Authors: Zaheri Hooman , Beyzaee Amir Mohammad , Rokni Ghasem Rahmatpour , Patil Anant , Golpour Masoud , Goldust Mohamad 
Published: September 2022

AbstractBackgroundPeriorbital dark circles (PDC) is one of the most common cosmetic issues in today's society. Only moderate degree of improvement has been achieved by various available treatment options. The present study aimed to compare the clinical efficacy of carboxytherapy and fractional CO2 laser therapy in the management of PDC.MethodsIn this split face study, 30 patients with bilateral PDC aged between 23 and 52 years were recruited who underwent carboxytherapy (n = 30) on PDC of one side of the face and fractional CO2 laser therapy (n = 30) on the PDC of other side. The entire treatment comprised of four sessions of each therapy with an interval of 2 weeks each time. The assessment was based on both subjective methods (patients' satisfaction and physician's judgment) and objective method (based on digital standard photographs). The degree of improvement from the patient's point of view (patient satisfaction) and physician's point of view (physician satisfaction) was assessed in different therapy sessions in comparison with the improvement after first session.ResultsThe study included 30 patients with mean age of 38.22 ± 8.3 years. The mean disease duration was 45 ± 12.3 months. After the second therapy session, patients' satisfaction was remarkably better in the fractional CO2 laser therapy group than the carboxytherapy group, over the time. According to the physician satisfaction, the improvement rate was higher after the second and sixth weeks in the fractional CO2 laser therapy group than the carboxytherapy group; whereas in other sessions, there were no statistically significant differences. There were no significant side effects observed in either group post‐treatment each time.ConclusionFractional CO2 laser therapy is a better option to treat PDC than carboxytherapy. Also, mild side effects (including erythema, pain, and discomfort) were reported in both groups; with no significant difference between the groups.