bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Shock Transcription Factor B2b Acts as a Transcriptional Repressor of Vin3, a Gene Induced by Long-term Cold for Flowering
Authors: Lee Ilha , Jeong Goowon , Shin Jinwoo
Published: March 2022

Vernalization, an acceleration of flowering after long-term winter cold, is an intensively studied flowering mechanism in winter annual plants. In Arabidopsis, Polycomb Repressive Complex2 (PRC2)-mediated suppression of the strong floral repressor, FLOWERING LOCUS C (FLC), is critical for vernalization and a PHD finger domain protein, VERNALIZATION INSENSITIVE 3 (VIN3), recruits PRC2 on FLC chromatin. The level of VIN3 was found to gradually increase in proportion to the length of cold period during vernalization. However, how plants finely regulate VIN3 expression according to the cold environment has not been completely elucidated. As a result, we performed EMS mutagenesis using a transgenic line with a minimal promoter of VIN3 fused to the GUS reporter gene, and isolated a mutant, hyperactivation of VIN3 1 (hov1), which showed increased GUS signal and endogenous VIN3 transcript levels. Using positional cloning combined with whole-genome resequencing, we found that hov1 carries a nonsense mutation, leading to a premature stop codon on the HEAT SHOCK TRANSCRIPTION FACTOR B2b (HsfB2b), which encodes a repressive heat shock transcription factor. HsfB2b directly binds to the VIN3 promoter, and HsfB2b overexpression leads to reduced acceleration of flowering after vernalization. Collectively our findings reveal a novel fine-tuning mechanism to repress undesirable vernalization responses.
Experiences of and recommendations on clinical trial design in Alzheimer’s disease from the participant’s point of view
Authors: Ottenhoff Lois , Vijverberg Everard G.B. , Visser Leonie N.C. , Verijp Merike , Prins Niels D. , Flier Wiesje M. van der , Sikkes Sietske A.M.
Published: March 2022

Introduction.
In the context of the development of pharmaceutical interventions, expectations and experiences of participants are essential. Their insights may be particularly helpful to address the challenges of recruiting and retaining participants for Alzheimer’s disease (AD) clinical trials. We examined clinical trial participants’ experiences to optimize trial design in Alzheimer’s disease (AD).
Method.
In this mixed-methods study, we included adults who participated in sponsor-initiated AD trials at Brain Research Center, a clinical trial organization in the Netherlands. Participants (N = 71, age 69 ± 6.5, 54%F, 19 cognitively normal (CN), 19 Mild Cognitive Impairment (MCI) and 33 AD dementia) first completed an online survey. Next, a subsample (N = 12; 8 = CN, 4 = MCI) participated in focus groups to gain in-depth insight into their views on optimizing trial design. Audio recordings from focus group interviews were transcribed verbatim and analysed by thematic content analysis by two independent researchers.
Results.
To benefit future generations was most frequently (34%) reported as a motive for enrolment. The lumbar puncture (40%) and memory assessments (15%) were most often experienced as being of high burden. Structurally receiving individualized test results and smaller chance to get placebo, increased willingness to participate. Two main themes emerged from the focus groups: “trials design”, such as follow-up visit(s) after participating, and “trial center”, including the relevance of a professional and empathic staff.
Conclusion.
Relevant factors include expectation management and careful planning of high burden assessments, provision of individual feedback and prioritizing professionalism and empathy throughout conduct of the trial. Our findings provide insight into participants’ priorities to increase willingness to participate and can be used to optimize trial success.
3-D Printed BCP Blocks with Different Pore Sizes for Regeneration in Rabbit Calvarial Defects
Authors: Seo Young-Wook , Park Jin-Young , Lee Da-Na , Jin Xiang , Cha Jae-Kook , Paik Jeong-Won , Choi Seong-Ho
Published: March 2022

Background
Alveolar ridge augmentation is frequently performed in the deficient alveolar ridge to facilitate the placement of dental implants. Severe resorption of the bony ridge may occur because of aging or periodontal and periapical pathologies. When faced with this situation, a block bone graft might be indicated, since the block bone provides structural stability to the augmented site. The aim of this study was to compare three-dimensionally printed biphasic calcium phosphate (BCP) block bone substitutes with different pore sizes (0.8, 1.0 and 1.2 mm) for regeneration rabbit calvarial defects.
Material & Methods
Four circular defects were formed on the calvaria of ten rabbits. Each defect was randomly allocated to the following study groups: 1) Control group, 2) 0.8 mm group, 3) 1.0 mm group, and 4) 1.2 mm group. All specimens were harvested at 2 and 8 weeks postoperatively, and the samples were analyzed radiographically and histomorphometrically.
Results
Histologically, the BCP blocks remained unresorbed up to 8 weeks, and new bone formation occurred within the porous structure of the blocks. At the early healing period of 2 weeks, histomorphometric analysis revealed significantly greater new bone formation in the BCP groups compared to the control (p < 0.05). However, there were no significant differences between the groups with different pore sizes (p > 0.05). At 8 weeks, only the 1.0 mm group (3.42 ± 0.48 mm2) showed a significantly greater area of new bone compared to the control group (2.26 ± 0.59 mm2) (p < 0.05). Among the BCP block groups, 1.0 mm and 1.2 mm groups exhibited significantly greater area of new bone compared to the 0.8 mm group (3.42 ± 0.48 and 3.04 ± 0.66 vs 1.60 ± 0.70 mm2, respectively).
Conclusions
Within the limitations of this study, 1.0 mm pore diameter of the BCP block bone substitute was the most optimal size for bone regeneration. The BCP block bone substitutes can be applied in bone defects for successful bone regeneration, and further study should be performed in more challenging defect configurations prior to the clinical application.
An integrated cell atlas of the human lung in health and disease
Authors: Luecken Malte , Sikkema Lisa , Strobl Daniel , Zappia Luke , Madissoon Elo , Markov Nikolay , Zaragosi Laure-Emmanuelle , Ansari Meshal , Arguel Marie-Jeanne , Apperloo Leonie , Becavin Christophe , Berg Marijn , Chichelnitskiy Evgeny , Chung Mei-i , Collin Antoine , Gay Aurore , Kashani Baharak Hooshiar , Jain Manu , Kapellos Theodore , Kole Tessa , Mayr Christoph , von Papen Michael , Peter Lance , Ramírez-Suástegui Ciro , Schniering Janine , Taylor Chase , Walzthoeni Thomas , Xu Chuan , Bui Linh , de Donno Carlo , Dony Leander , Guo Minzhe , Gutierrez Austin , Heumos Lukas , Huang Ni , Río Ignacio Ibarra Del , Jackson Nathan , Murthy Preetish Kadur Lakshminarasimha , Lotfollahi Mohammad , Tabib Tracy , Talavera-Lopez Carlos , Travaglini Kyle , Wilbrey-Clark Anna , Worlock Kaylee , Yoshida Masahiro , Desai Tushar , Rozenblatt-Rosen Orit , Falk Christine , Kaminski Naftali , Krasnow Mark , Lafyatis Robert , Nikolic Marko , Powell Joseph , Rajagopal Jay , Seibold Max , Sheppard Dean , Shepherd Douglas , Teichmann Sarah , Tsankov Alexander , Whitsett Jeffrey , Xu Yan , Banovich Nicholas , Barbry Pascal , Duong Thu , Meyer Kerstin , Kropski Jonathan , Pe'er Dana , Schiller Herbert , Tata Purushothama Rao , Schultze Joachim , Berge Maarten van den , Chen Yuexin , Hagood James , Hassan Ahmed , Horvath Peter , Lundeberg Joakim , Leroy Sylvie , Marquette Charles , Pryhuber Gloria , Samakovlis Christos , Sun Xin , Ware Lorraine , Zhang Kun , Misharin Alexander , Nawijn Martijn , Theis Fabian
Published: March 2022

Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.
The Histone H2B Arg95 residue links the Pheromone Response Pathway to Rapamycin-Induced G1 Arrest in Yeast
Authors: Sulaiman Abdallah , Ali Reem , Aouida Mustapha , Ramotar Dindial
Published: March 2022

Rapamycin is an immunosuppressant used for treating many types of diseases such as kidney carcinomas. In yeast, rapamycin inhibits the TORC1 kinase signaling pathway causing rapid alteration in gene expression and ultimately cell cycle arrest in G 1 through mechanisms that are not fully understood. Herein, we screened a histone mutant collection and report that one of the mutants, H2B R95A, is strikingly resistant to rapamycin due to a defective cell cycle arrest. We show that the H2B R95A causes defects in the expression of a subset of genes of the pheromone pathway required for α factor-induced G 1 arrest. The expression of the STE5 gene and its encoded scaffold protein Ste5, required for the sequential activation of the MAPKs of the pheromone pathway, is greatly reduced in the H2B R95A mutant. Similar to the H2B R95A mutant, cells devoid of Ste5 are also resistant to rapamycin. Rapamycin-induced G 1 arrest does not involve detectable phosphorylation of the MAPKs, Kss1 and Fus3, as reported for α factor-induced G 1 arrest. However, we observed a sharp induction of the G 1 cyclin Cln2 (~ 3- to 4-fold) in the ste5Δ mutant within 30 mins of exposure to rapamycin. Our data provide a new insight whereby rapamycin signaling via the Torc1 kinase may exploit the pheromone pathway to arrest cells in the G 1 phase.
Evolution of naive non exudative type 1 macular neovascularization detected by OCT angiography
Authors: Lorusso Massimo , Ferrari Luisa Micelli , Gigante Domenico Antonio , Monteleone Giuseppina , Cicinelli Maria Vittoria , Nikolopoulou Eleni , Ferrari Tommaso Micelli
Published: March 2022

Background: The aim of the study was to explore the features of eyes with non exudative macular neovascularization (NE-MNV) . OCT angiography (OCTA) was used to evaluate the natural history of NE-MNV.Methods: Retrospective case series. Patients with intermediate AMD (iAMD) were imaged using OCTA. Patients with NE-MNV were selected. The en face choriocapillaris slab was used to calculate the area and the flow of MNV. Results: From October 2016 through October 2020, 211 patients with iAMD underwent OCTA. OCTA showed NE-MNV in 18 eyes. Nine eyes developed an exudative MNV during the follow-up. We considered the sensitivity and specificity of the area and flow measurements to predict exudation by the area under the receiver operating characteristic (AUROC). The AUROC of the basal area was 0,91 (0.78-0.99) and the the AUROC of the basal flow was 0,86 (0.68-0.99), showing discriminable ability for predicting exudation.Conclusion: Based on our results, we found at high risk of exudation those eyes with larger areas of neovascularization. We recommend more frequent follow-up in those eyes and prompt treatment when exudation occurs.retrospectively registeredBari ethics committee approved the study protocol. Reference number is 7176
Student dispositions towards learning: A cross-sectional analysis
Authors: Spray Erika , Holbrook Allyson , Scevak Jill , Cantwell Robert
Published: March 2022

This article reports the dispositional profile of 880 Masters students in Australia, based on their responses to an online survey. Learners’ dispositional attributes form the foundations for learning behaviour and therefore academic outcomes. The profile of the cohort overall was as expected for an elite academic group, yet there was substantial variation between individuals. Cluster analysis identified three groups of students with meaningfully different dispositional profiles. These profiles related to academic achievement, with participants’ academic achievement most closely related to their epistemic attributes. It is argued that students at the Masters level typically possess the agentic attributes necessary for effective self-regulation. Epistemic attributes are therefore more relevant for differentiating between higher and lower achieving students at this level. The importance of sophisticated epistemic attributes is in line with the stated goals of postgraduate education around the world. Collectively, this evidence supports the explicit teaching of metacognitive and epistemic skills within postgraduate coursework degrees.
Effectiveness of CoronaVac in children 3 to 5 years during the omicron SARS-CoV-2 outbreak
Authors: Araos Rafael , Jara Alejandro , Undurraga Eduardo , Zubizarreta Jose , Gonzalez Cecilia , Acevedo Johanna , Pizarro Alejandra , Vergara Veronica , Marchant Mario Soto , Gilabert Rosario , Flores Juan Carlos , Suarez Pamela , Leighton Paulina , Eguiguren Pablo , Rios Juan Carlos , Fernandez Jorge , Garcia-Escorza Heriberto
Published: March 2022

The outbreak of the B.1.1.529 lineage of SARS-CoV-2 (omicron) has caused an unprecedented number of Covid-19 cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but the evidence is sparse or non-existing. Leveraging a population-based cohort of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of CoronaVac using inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between December 6, 2021, and February 26, 2022, during the omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95%CI, 36.5–39.9) against Covid-19, 64.6% (95%CI, 49.6–75.2) against hospitalization, and 69.0% (95%CI, 18.6–88.2) to prevent intensive care unit admission. The effectiveness was modest; however, protection against severe disease remained high.
Characterization of Pleurotus Citrinopileatus Hydrolysates Obtained from Actinomucor Elegans Proteases Compared with That by Commercial Proteases
Authors: Zhang Weiwei , Shi Kexin , Han Yaqian , Wang Jianming , Yang Chen , Xu Xu , Li Bingye
Published: March 2022

Pleurotus citrinopileatus, the nutritious and palatable edible mushroom, can be taken as an appropriate material to prepare high-grade flavoring agents. Based on this, this study aimed to investigate the feasibility of productive proteases system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The A. elegans crude protease (AECP) was prepared from the solid state fermentation product of P. citrinopileatus by A. elegans. AECP and four commercial proteases (Alcalase, Neutrase, Papain, and Protamex) were applied to acquire five kinds of PCHs respectively. The physical-chemical properties of PCHs as well as its concentration and composition of non-volatile compounds were comparatively analyzed. Electronic tongue was utilized to evaluate sensory characteristics. AECP was found to be the most effective protease with the top hydrolysis degree of 35.91% and protein recovery of 81.46%. The result of molecular weight distribution indicated that below 500 Da peptides were observed to be the main fraction of AECP hydrolysates, meanwhile AECP hydrolysates showed the highest content of MSG-like (20.23 ± 0.16 mg/g) and flavor 5'-nucleotide (4.30 ± 0.07 mg/g). Besides, the AECP hydrolysates exhibited favorable aftertaste-umami, in which peptides below 500 Da showed a higher correlation with aftertaste-umami by results of partial least-squares regression. These results indicated the feasibility for PCHs application as flavor additives or seasoning in food industry. The AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency.
Case Report of Breakthrough Long COVID and the Use of Nirmatrelvir-Ritonavir
Authors: Geng Linda N. , Bonilla Hector F. , Shafer Robert W. , Miglis Mitchell G. , Yang Phillip C.
Published: March 2022

Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID, is a major public health problem. Encouraging data suggest that vaccination can reduce the risk of PASC. We report a cautionary case of breakthrough PASC and its resolution following a course of the novel combination antiviral nirmatrelvir-ritonavir.
Patient Clinical Outcomes in Standalone Versus a Combined Ophthalmology-Rheumatology Uveitis Clinic
Authors: Ross Bing X. , Habhab Samantha , Syeda Sarah , Baiyasi Ahmad , Benchaala Ilyes , Okeagu Chinwenwa , Barbosa Joshua , Im Jacob , Le Kim , Lin Xihui
Published: March 2022

Background: To evaluate uveitis care outcomes in standalone versus a combined ophthalmology-rheumatology clinic.Methods: Participants were patients aged 18 years and older with a minimum 12-month history of chronic uveitis prior to being referred to the combined uveitis clinic at Kresge Eye Institute and who were treated in the combined clinic for at least 6 months. Best corrected visual acuity (BCVA), objective markers of inflammation, and achieving targeted dose of immunomodulatory therapy (IMT) were compared in the cohort of uveitis patients 6 months prior to and after the initial evaluation in the combined clinic. Results: Sixty-six percent of study participants were female with a mean age of 51.5 years. BCVA improved from 0.58 logMAR (Snellen: ~20/74) at the initial combined clinic visit to 0.50 logMAR (Snellen: ~20/63) 6 months after the first combined visit (p=0.0137). The establishment of the combined uveitis clinic led to higher frequency of patients at target dose of IMT: an increase from 49.0% at 6 months prior to the combined visit to 70.1.4% and 79.8% at the initial combined visit and 6 months after the combined visit, respectively.Conclusion: A combined model of management for chronic uveitis patients wherein rheumatological services are coupled with ophthalmic care leads to improvement in patient clinical outcomes and achieving target therapy.
Surgical Resection for Esophageal Adenosquamous Carcinoma: an Analysis of 56 Cases
Authors: Chen Shao-bin , Liu Di-tian , Chen Yu-ping
Published: March 2022

Background: Esophageal adenosquamous carcinoma (EASC) is a rare disease. The biological behavior and treatment of this malignancy are not well studied. Methods: Data from 56 patients with EASC who underwent esophagectomy were retrospectively analyzed and compared with 5028 patients with esophageal squamous cell carcinoma (ESCC). The impact of clinicopathological factors on the survival of patients with EASC was analyzed. The survival differences between patients with EASC and ESCC were also compared. Results: There were 43 males and 13 females with a mean age of 59.7 ± 1.3 years (range, 39-79 years). Only one of the 43 patients who received preoperative esophagoscopic biopsy was diagnosed with EASC. The median survival time for patients with EASC was 32.0 months, and the 1-, 3- and 5-year overall survival rates were 78.3%, 46.1% and 29.6%, respectively. Resection margin, pN category, and adjuvant chemotherapy were found to be independent predictors. After 1:1 propensity score matching, the 5-year overall survival rate of 29.6% for patients with EASC was similar to that of 42.5% for patients with ESCC (P=0.179). Conclusions: EASC is a rare disease and is easily misdiagnosed by esophagoscopic biopsy. The prognosis of EASC was similar to that of ESCC. Postoperative adjuvant chemotherapy may improve the survival of patients with EASC after esophagectomy.
PEG-modified Copper Cysteine for Photodynamic Therapy in Alzheimer's Disease
Authors: Ma Zhihao , Song Chenglong , Yang Kaitong , Wang Jie
Published: March 2022

As a progressive neurodegenerative disease, Alzheimer's disease (AD) is characterized by the accumulation and misfolding of amyloid polypeptides (Aβ) which result in irreversible brain damages, cognitive decline and behavioral impairment. Photodynamic therapy (PDT) has received much attention as a potential approach for AD treatment. In this study, we investigated a novel multifunctional theranostic photosensitizer, copper cysteine (Cu-Cy). By performing PEG modification on nanoparticles’ surface, the particle size and cytotoxicity were significantly reduced. Under UV irradiation, Cu-Cy-PEG can produce reactive oxygen species (ROS) and could degrade Aβ(1-40) aggregates efficiently. This is the first case for Cu-Cy-PEG being used for degrading Aβ aggregates in vitro. The macroscopic amyloid aggregates were photodegraded by Cu-Cy-PEG into amorphous particles. This study firstly proved that Cu-Cy-PEG may serve as a potential treatment in AD therapy.
Surgical and anaesthetic outcomes of paediatric splenectomies at a tertiary care institution in South India – A retrospective cohort
Authors: DCunha Aureen Ruby , Rai Ekta , Jacob Tarun John K , Devasia Anup J , Rebekah Grace
Published: March 2022

PurposeSplenectomies though well-established in the successful management of several resistant haemoglobinopathies, have not been studied in detail in the paediatric population to assess the outcomes. We conducted this review to primarily assess the surgical and anaesthetic outcomes of paediatric splenectomies and secondarily highlight factors predictive for a high-risk splenectomy.MethodsA 5 year retrospective chart review was made, and patient follow-up was done jointly using the hospital electronic medical records and telephonic calls. A p value of <0.05 was considered significant.ResultsAmong the 69 splenectomised children, 61% were male and the overall mean age was 10.2 years. The cohort consisted of thalassemia’s(46%), ITP’s(30%), haemolytic anemias(19%) and 1 child each with lymphoma, splenic cyst and Kassabach Meritt syndrome. Most(96%) were electively operated and 23% were performed laparoscopically. 61% received intravenous analgesia and the mean volume of fluid administered intra-operatively was 21ml/kg. There was no documented OPSI, and there was one mortality. The mean follow-up period was 43 months.ConclusionSplenectomy was associated with a promising overall outcome with a survival rate of 98.5%. A greater pre-operative transfusion requirement, a larger sized spleen and increased fluid administration intra-operatively, were associated with a worse outcome.
Risk Factors of Enterostomy in Neonates With Hirschsprung Disease
Authors: Liu Zhaozhou , Zhang Yanan , Li Shuangshuang , Yang Shen , Zhao Jiawei , Yang Ting , Li Siqi , Chen Yongwei , Guo Weihong , Hou Dawei , Du Jingbin , Li Yingzi , Huang Jinshi
Published: March 2022

Purpose
To explore the risk factors of enterostomy in neonates with Hirschsprung disease (HD) to provide reference for clinicians to make treatment decisions.
Methods
The medical records of 284 patients who were diagnosed with HD during the neonatal period were retrospectively analyzed. The patients were retrospectively divided into 2 groups according to whether or not they had an enterostomy before radical surgery. Univariate and multivariable logistic regression analysis were performed to identify risk factors of enterostomy.
Results
The incidence of enterostomy was 18.5% (34/284) in neonates with HD. Univariate and multivariate logistic regression analysis showed that serum albumin < 25.4 g/L, radiographic results as subphrenic free air and level of aganglionosis with long-segment or total colonic aganglionosis (TCA) were independent risk factors of enterostomy in neonates, with OR of 42.045 (6.131, 288.319), 285.558 (26.651, 3059.694) and 15.573 (4.319, 56.157), respectively.
Conclusions
The low serum albumin level, bowel perforation and level of aganglionosis with long-segment or TCA could influence the occurrence of enterostomy in neonates with HD.
Investigation of Common Source Amplifier Circuit Application Using Gate Stack Based Gate-all-around Charge Plasma Nanowire FET
Authors: SOLAY LEO RAJ , KUMAR PRADEEP , AMIN S INTEKHAB , ANAND SUNNY
Published: March 2022

The reported work demonstrates the application of common source amplifier circuit using gate-all-around gate stacked charge plasma nanowire field effect transistor (GAA GS CP NW FET). Primarily, the impact of the gate stacking (GS) technique upon the Gate-All-Around Charge Plasma Nanowire Field Effect Transistor (GAA CP NW FET) structure is explored. In which GAA GS CP NW FET structure resulted in excellent electrostatic control over the channel by incorporating the advantages of GAA structures. The transfer characteristics have been enhanced with the gate stacking (SiO2 + high k) technique when employed at the dielectric region of the structure. The charge plasma concept which is applied in the proposed device helped in reducing the threshold voltage fluctuations. A contrast is drawn between GAA CP NW FET and GAA GS CP NW FET structures in terms of analog and RF analysis. Linearity parametric analysis were made to examine the distortion less digital communication and a comparison is made between the structures. The proposed structure is then utilized for designing a common source amplifier circuit and contrasted with the GAA CP NW FET structure. With the applied gate stacking technique, the proposed structure resulted in improved ON-current, reduced OFF-current, enhanced current ratio. The CS amplifier circuit application resulted in improved Vout and gain attributes with the proposed GAA GS CP NW FET structure when compared with Metal Oxide Semiconductor FET (MOSFET), Tunnel FET (TFET) and GAA CP NW FET structure proving its capability for forthcoming nanoscale circuit applications.
Deficit Financing Components, Inflation and Capital Formation in Nigeria: Evidence from A Direct and Indirect Analysis
Authors: Aladejare Samson Adeniyi
Published: March 2022

Deficit financing occasioned by low domestic savings and low capital formation, have characterised the Nigerian economy since the 1970s with attendant increase in inflation. Empirical studies on Nigeria have shown that deficit financing directly affects inflation and capital formation when examined independently. However, little attention has been paid to a simultaneous investigation of the direct and indirect effects of deficit financing components on inflation and capital formation in Nigeria. Consequently, this study was designed to fill this gap through time series data and the instrumental variable approach. The study found that deficit financing components indirectly impacted on inflation and capital formation in Nigeria from 1970 to 2017; as against the direct effects reported in empirical studies. Also, inflation was found to have had adverse effect on capital formation. Hence, better synergy of fiscal and monetary policies to effectively tame inflation and ensure growth of capital formation was recommended.
Entanglement wedge in flat holography and entanglement negativity
Authors: Basu Debarshi , Chandra Ashish , Raj Vinayak , Sengupta Gautam
Published: March 2022

We establish a construction for the entanglement wedge in asymptotically flat bulk geometries for subsystems in dual (1+1)-dimensional Galilean conformal field theories in the context of flat space holography. In this connection we propose a definition for the bulk entanglement wedge cross section for bipartite states of such dual non relativistic conformal field theories. Utilizing our construction for the entanglement wedge cross section we compute the entanglement negativity for such bipartite states through the generalization of an earlier proposal, in the context of the usual AdS/CFT scenario, to flat space holography. The entanglement negativity obtained from our construction exactly reproduces earlier holographic results and match with the corresponding field theory replica technique results in the large central charge limit.
A COMPARATIVE STUDY OF HEMOGLOBIN STATUS AMONG TRIBAL INHABITANTS OF DOOARS IN NORTH BENGAL
Authors:   Assistant Professor, Department of Physical Education Ananda Chandra College, Jalpaiguri., Adhikary Bhusan
Published: March 2022

The study was carried out to know the relationship of blood hemoglobin status among tribal inhabitants of Dooars. For the present study two hundred and forty male ranging between 17 to 23 years from four different tribes of Dooars were selected randomly from the whole population of the selected tribes.
Segundo Simposio Internacional de la Red Amigoniana de Innovación Social-RAIS
Authors: Sierra Hernández María Isabel , Osorio Atehortúa Ubeimar Aurelio , Malavera Pineda Sandra Milena , Aristizábal Velásquez Mónica Eliana
Published: March 2022

Esta segunda versión del Simposio Internacional RAIS se propuso direccionar los ejes temáticos hacia las realidades actuales del medio y de las instituciones de educación superior, tomando como base el resultado del primer simposio que actuó como piloto de lo que hoy es una red más amplia que abre sus puertas a la comunidad internacional y que centra su interés en el estudio de la innovación social y la relación con la cultura solidaria.
Selective reversible JAK1 inhibitor in the treatment of moderate and severe atopic dermatitis
Authors: Kovaleva Yu. S. , Orobei M. V. , Zyablitskaya N. K.
Published: March 2022

In recent decades, industrialized countries have recorded a steady increase in the incidence of atopic dermatitis (AD). The pathogenesis of AD is complex and diverse and includes hereditary determinism leading to a disruption of the skin barrier, as well as the Th2 immune response, which is supported by a wide range of pro-inflammatory mediators released by immunocompetent and epithelial cells, which play a key role in the activation and maintenance of inflammation in the skin. Progress in the treatment of immunoinflammatory diseases, including in the skin, has been achieved with the advent of a new class of targeted synthetic oral immunomodulatory drugs, Janus kinase inhibitors. Janus kinases are part of the JAK – STAT intracellular signaling system; STAT proteins are responsible for signaling more than 60 cytokines, hormones and growth factors that regulate key cellular processes. Currently, second generation JAK inhibitors have been developed, such as upadacitinib (trade name Rinvoq), which distinguish them from non-selective JAK inhibitors by their selectivity for certain JAK isoforms. In June 2021, the Ministry of Health of the Russian Federation approved the use of upadacitinib (UPA) for the indication “treatment of moderate to severe atopic dermatitis in adults and children aged 12 years and older who are indicated for treatment with systemic drugs”; the drug can be used in monotherapy or in combination with topical therapy in adults at a dose of 15 or 30 mg per day depending on the individual characteristics of the course, in adolescents weighing at least 40 kg – at a dose of 15 mg per day. Results from a Phase 3 clinical trial program involving more than 2500 patients worldwide in three global key studies: Measure Up 1, Measure Up 2 (UPA monotherapy at a dose of 15 mg or 30 mg per day) and AD Up (UPA in the same doses in combination with topical glucocorticosteroids (TGCS) demonstrated high efficacy and favorable benefit/risk profile of UPA both in monotherapy and in combination with TGCS in patients with moderate to severe AD.
Immune mechanisms of atopic dermatitis and new approaches to targeted biological therapy
Authors: Potekaev N. N. , Tereshchenko G. P. , Khanferyan R. A. , Savastenko A. L.
Published: March 2022

This review presents current data on immunopathogenesis, the role of cytokines in inflammation in atopic dermatitis (AD). The pathogenetic phenotypes of the disease associated with various abnormalities of immune mechanisms and dysfunction of the epidermal barrier are considered. The inflammatory processes in atopic dermatitis were shown to be implemented mainly through Th2-lymphocytes and IL-4 and IL-13 produced by these cells, which play a key role in the allergic cascade. It is the effects of IL-4 and IL-13 cytokines that determine the main pathophysiological mechanisms, such as decreased expression of epidermal barrier proteins and suppression of terminal differentiation of keratinocytes, microbiota disturbances, tissue remodelling, immunoglobulin isotype switching by B-lymphocytes and IgE synthesis, degranulation of mast cells and basophils, trafficking of inflammatory cells into tissues, itching. Moderate and severe forms of AD require administration of systemic therapy, which has been represented until recently by non-selective immunosuppressive drugs with moderate efficacy and pronounced side effects if they are used for a long time. Modern targeted therapy of atopic dermatitis provides for the use of monoclonal antibodies against both pro-inflammatory cytokines and their receptors. Directional action on the key mechanisms and targets of immune inflammation can minimize possible side effects of immunosuppressive therapy. Clinical trials on the efficacy and safety of IL-4 and IL-13 inhibitors in the treatment of atopic dermatitis are described.
Infectious complications of atopic dermatitis
Authors: Dvoriankova E. V. , Denieva M. I. , Shevchenko G. А.
Published: March 2022

Atopic dermatitis is a chronic inflammatory skin disease linked to a genetic predisposition and accompanied by acute inflammatory manifestations that develop due to abnormality of skin barrier properties and changes in both innate and adaptive immune responses. The high risk of developing complications of this disease caused by skin and systemic infections is one of the most urgent problems of modern health care. However, infectious complications of atopic dermatitis may include skin and soft tissue infections, herpetic eczema, bacteremia, osteoarthritis, myelitis, septic arthritis, and endocarditis. Skin barrier defects, type 2 immune-mediated inflammation, Staphylococcus aureus colonization, and skin dysbiosis are main predisposing factors for an increased incidence of infectious complications of atopic dermatitis. The development of infectious complications of atopic dermatitis may be prevented by comprehensive treatment of exacerbations of the underlying disease, sanitation of chronic infection foci, as well as restoration and maintenance of the skin barrier function. The use of special moisturizers and emollients for skin care during exacerbation and remission is an important and integral part of therapeutic and preventive measures.

Emollients are medical cosmetic products that are close to the natural lipid skin barrier in composition. They not only effectively soften and moisturize the skin, but also restore damaged protective properties. Additional components of emollients with anti-inflammatory and antimicrobial activity are an optional, but desirable condition to prevent recurrence of the disease and reduce the risk of developing a secondary infection. Thus, not only special skin care drugs, but also products for patients with atopic dermatitis, can contribute to the development of antibacterial protection and prevent the development of infectious complications.
Hand eczema: possible risks and choice of therapy
Authors: Sakaniya L. R. , Smolkina O. Yu. , Korsunskaya I. M.
Published: March 2022

Hand eczema is a common disease – up to 5% in the general population. In addition, eczema is closely related to atopy and, like atopic dermatitis, to a mutation in the FLG gene. In addition to genetic factors, eczema is caused by external irritants and toxic substances. Eczema often occurs in families with atopic diseases, including asthma, allergic rhinitis/hay fever (and food allergies), and atopic dermatitis. These diseases share a common pathogenesis and often occur together in the same person and/or family. Eczematous rashes are often accompanied by itching. This symptom can lead not only to sleep disturbances but also to secondary infections. According to some data, the rate of infections in eczema can be more than 70%. In such cases, the drugs of choice are combined glucocorticosteroids (GC), which in addition to GC contain an antimycotic and an antibiotic. Our practical experience shows the high effectiveness of the combination of beclomethasone dipropionate, gentamicin, and clotrimazole not only in cases of eczema complicated by secondary infection but also in patients with other infected chronic dermatoses. This article reviews these and other practical aspects and problems in the treatment of hand eczema, discusses the etiological factors that lead to the development of the disease, and presents current data from clinical recommendations and guidelines for the treatment of eczema.
Exposome factors in the acne pathogenesis
Authors: Smirnova I. O. , Zhelonkina A. O. , Zhelonkin A. R. , Petunova Y. G. , Shin N. V. , Bessalova A. Y. , Kulikova E. A. , Novikova N. E. , Ptashnikova P. D.
Published: March 2022

The concept of the exposome, formulated more than fifteen years ago, is increasingly discussed in the modern scientific literature. The term “exposome” is understood as a cumulative measure of the impact of environmental factors on an individual throughout his or her life (from the prenatal period to death) and the biological response associated with it. The sum of these factors has a significant impact on the occurrence, course, and treatment efficacy of multifactorial diseases. The skin is a border organ and is constantly exposed to environmental influences, i.e., it is a target for the exposome. The influence of the latter components has been described in skin aging, atopic dermatitis, and malignant skin neoplasms. Acne is one of the most common chronic inflammatory dermatoses. Over the past decade, the worldwide increase in the incidence of acne, its early onset and a prolonged course, affecting adult men and women, has been noted. The review presents an analysis of the data on the effects of the components of the exposome – diet, medications, stress, and pollutants - on the course of acne. Particular attention is paid to the few data on the nature of interaction between the components of the exposome and the skin microbiome, which, on the one hand, is involved in the pathogenesis of dermatoses, including acne, and, on the other hand, is changed under the influence of exposome factors, acting as an intermediary between the environment and the human body. The search for environmental factors has at least two objectives: the discovery of potential pathogenetic links, the strength of their relationship with the clinical manifestations of the disease to develop new therapies aimed at new targets; and the creation and recommendation of a protective regime for factors with a proven effect on the course of the disease, for patients suffering from acne.
Effective sorptive removal of five cationic dyes from aqueous solutions by using magnetic multi-walled carbon nanotubes
Authors: Song Guobin , Shi Yawei , Wang Haonan , Li Anqi , Li Wanran , Sun Ya , Ding Guanghui
Published: March 2022

The excellent properties of micro-nano materials and structures have attracted extensive attention especially in wastewater treatment. Based on this, magnetic multi-walled carbon nanotubes (MMWCNTs) have been prepared and used for the sorptive removal of five typical cationic dyes from aqueous solutions in the present study. Effects of several operational and environmental factors were investigated carefully, including initial pH values, common ions, contact time and temperature. The kinetics processes were well fitted by the pseudo-second-order kinetic model. The maximum adsorption capacities on MMWCNTs at 298.15 K for malachite green oxalate, auramine O, neutral red, crystal violet and rhodamine B were 442.2, 295.2, 183.4, 165.3 and 143.0 mg g−1, respectively. Differences in the size, structure and properties of these dyes led to the difference of adsorption amounts. ΔG0 were all negative within the temperature range tested, which meant the adsorption processes were spontaneous in nature. Moreover, the adsorption processes of targeted dyes, except auramine O, were exothermic and entropy decreasing. The regeneration studies indicated that the MMWCNTs showed high reusability and removal efficiencies above 75% can be achieved after four consecutive cycles. For the adsorption mechanism, electrostatic interaction, hydrogen bonds, π-π interaction together with hydrophobic interaction could coexist during the adsorption process.
Nonpolyglutamatable Antifolates as Inhibitors of Thymidylate Synthase (TS) and Potential Antitumour Agents
Authors: Bavetsias V. , Jackman A.L.
Published: March 2022

Thymidylate synthase (TS), an enzyme that catalyses the conversion of dUMP to dTMP, has been the focus of interest as a target in cancer chemotherapy for more than two decades. Over the last 10 years much research has been devoted to the design and development of nonpolyglutamatable inhibitors of TS as antitumour agents, mainly to over­ come resistance due to unfavourable expression of folylpolyglutamate synthetase (FPGS). Lipophilic inhibitors of the enzyme were expected not to depend on the reduced folate carrier transporter (RFC) for cellular uptake, thus avoiding resistance due to an impaired RFC. Compounds of this type can be classified in three groups: A: nonclassical lipophilic inhibitors of TS, mainly folate-based analogues lacking the glutamate side chain; B: folate-based analogues in which the glutamate side chain has been- modified in such a way that polyglutamation is precluded; and C: nonpolyglutamatable gluta.mate-containing inhibitors of TS. Compounds of group A included 5- or 6-substituted quinazolin-4-ones, benzo[flquinazolines, imidazotetrahydroquinoline- and benz[cd]indole-based inhibitors. The second group is mainly related to a series of γ-linked dipeptide derivatives of ICII98583, or analogues of this inhibitor where the glutamate residue was replaced with a range of α-amino acids. The third group is concerned with some 7-substituted derivatives of ICI198583 and the pyrrolo[3,2-d]pyrimidine-based inhibitor 175. A large number of structurally diverse nonpolyglutamatable inhibitors of TS were synthesised some of which were potent inhibitors of the enzyme (human or E. coli) and in vitro cell growth. Three compounds, i.e. 49 (AG 337), 83 (AG 331), 123 (ZD9331) have reached the stage of clinical evaluation.
Thrombin Inhibitor Design
Authors: Sanderson P. E. J. , Naylor-Oisen A. M.
Published: March 2022

Recently, iv formulated direct thrombin inhibitors have been shown to be safe and efficacious alternatives to heparin. These results have fueled the hopes for an orally active compound. Such a compound could be a significant advance over warfarin if it had predictable pharmacokinetics and a duration of action sufficient for once or twice a day dosing. In order to develop an orally active compound which meets these criteria, the deficiencies of the prototype inhibitor efegatran have had to be addressed. First, using a combination of structure based design and empirical structure optimization, more selective compounds have been identified by modifying the P1 group or by incorporating different peptidomimetic P2/P3 scaffolds. Secondly, this optimization has resulted in the development of potent and selective non-covalent inhibitors, thus bypassing the liabilities of the serine trap. Thirdly, oral bioavailability has been achieved while maintaining selectivity and efficacy through the incorporation of progressively less basic P1 groups. The duration of action of these compounds remains to be optimized. Other advances in thrombin inhibitor design have included the development of uncharged P1 groups and the discovery of two non-peptide templates.
Synthesis of SrCO3 Nanoparticles Supported on Montmorillonite as Efficient Catalyst in the Preparation of α, ά-bis(substituted benzylidene) cycloalkanones
Authors: Mohammadpour Azim , Sheikhhosseini Enayatollah
Published: March 2022

In the present study, the SrCO3@montmorillonite nanocomposite was synthesized by loading Sr(NO3)2 on natural bentonite using a controlled and facile microwave method. The SrCO3@montmorillonite nanoparticles’ characteristics are identified using advanced techniques, such as infrared spectroscopy (IR), energy‐dispersive X‐ray analysis (EDX), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and pore size distribution analysis. Crossed-aldol condensation of an aromatic aldehyde with cycloalkanone in the presence of these nanoparticles produced α, ά-bis(substituted-benzylidene) cycloalkanones in good yields without using any solvent. The present method is operationally simple and dose not use organic solvent, which makes the process environmentally benign.
Promising Effects of Naringenin and Melatonin against Hepatic Encephalopathy
Impairments Induced by Bile Duct Ligation in Male Rats
Authors: Raviz Elahe Karami , Noormand Fatemeh , Kermani Ali Sharifzadeh , Galedari Ali , Esmaeilpour Khadijeh , Maneshian Marzieh , Kalantaripour Taj Pari , Dabiri Shahriar , Asadi-Shekaari Majid
Published: March 2022

Background:

Bile duct ligation (BDL) is used for evaluating the protective effects of
different agents with anti-inflammatory and antioxidant properties against the liver and brain
damages. Naringenin (N) and melatonin (M) are used as protectants in various models of diseases.

Aim:

In the current research, the combinational effects of these well-known anti-inflammatory
and antioxidants agents were investigated against cerebral injuries induced by BDL in male rats.

Methods:

The animals were distributed into the following groups: Sham, BDL + Vehicle and
BDL+ N + M. Neuronal damages were evaluated using biochemical, motor behavioral tasks and
morphological assessments.

Results:

Based on the data, BDL resulted in decreasing locomotor activity, which was reversed by
N and M. Morphological study confirmed that BDL led to neurodegeneration in the cortex of the
rats, and the N and M treatment preserved cortical neurons. In addition, immunohistochemical
(IHC) study of the rat cortex showed that BDL resulted in increasing the activated astrocytes, and
the N and M treatment reduced the number of activated cells.

Conclusion:

These results obviously depicted combinational therapy with N and M to exert positive
effects in the BDL rats, probably due to their synergistic anti-inflammatory and antioxidant
activities.