bluuebunny/crossref_metadata_2025 huggingface dataset:
Lynch syndrome: influence of additional susceptibility variants on cancer risk
Authors: VIBERT Roseline , Hasnaoui Jasmine , Lefebvre Alexandra , Colas Chrystelle , Dhooge Marion , Basset Noemie , Chansavang Albain , Desseignes Camille , Duval Alex , Farelly Solenne , Hamzaoui Nadim , Laurent-Puig Pierre , Metras Julie , Moliere Diane , Muleris Martine , Netter Jeanne , Nicolle Romain , Perkins Géraldine , Perrier Alexandre , Warcoin Mathilde , Coulet Florence , Benusiglio Patrick
Published: October 2022

Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines. We made the hypothesis that additional germline variants in cancer susceptibility genes (CSG) could explain some of these phenotypes. We compared the prevalence of additional CSG variants in LS patients with a cancer diagnosis before age 30 (early-onset, EO group) and after 40 (usual-onset, UO group). While there was no overall difference, we did find an excess of pathogenic variants and variants of unknown significance in EO cases when only gastrointestinal CSG were considered (OR 2.25; 95%CI: 1.01–5.06, p-value = 0.04). Four EO cases stood out: two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion. Additional germline variants should be considered in future screening recommendations, as they might influence cancer risk.
PLATO’s signal and noise budget
Authors: Börner Anko , Paproth Carsten , Perez Juan Cabrera , Pertenais Martin , Rauer Heike , Mas-Hesse J. Miguel , Pagano Isabella , Alvarez Jose Lorenzo , Erikson Anders , Denis Grießbach , Levillain Yves , Magrin Demetrio , Mogulsky Valery , Niemi Sami Mathias , Prod'homme Thibaut , Regibo Sara , De Ridder Joris , Rockstein Steve , Samadi Reza , Serrano-Velarde Dimitri , Smith Alan , Verhoeve Peter , Walton Dave
Published: October 2022

ESA’s PLATO mission aims the detection and characterization of terrestrial planets around solar-type stars as well as the study of host star properties. The noise-to-signal ratio (NSR) is the main performance parameter of the PLATO instrument, which consists of 24 Normal Cameras and 2 Fast Cameras. In order to justify, verify and breakdown NSR-relevant requirements the software simulator PINE was developed. PINE models the signal pathway from a target star to the digital output of a camera based on physical models and considers the major noise contributors. In this paper, the simulator’s coarse mode is introduced which allows fast performance analyses on instrument level. The added value of PINE is illustrated by exemplary applications.
Effects of arbuscular mycorrhizal fungus on sodium and chloride ion channels of Casuarina glauca under salt stress
Authors: Wang Yihan , Dong Fengxin , Chen Hui , Xu Tingying , Tang Ming
Published: October 2022

Arbuscular mycorrhizal fungi (AMF) can promote the growth and salt tolerance of plants under salt stress. However, the effects of AMF on the distribution of Na+ and Cl− and the expression of related genes in plants under salt stress need to be further explored. This study explored the effects of Rhizophagus irregularis on plant biomass, the distribution of Na+ and Cl−, and the expression of related genes in Casuarina glauca under NaCl stress. R. irregularis could promote salt dilution of C. glauca by increasing biomass and the content of K+, compartmentalizing Na+ and Cl− in vacuoles. These processes were associated with the expression of CgNHX1, CgNHX2-1, CgCLCD, CgCLCF, and CgCLCG. This phenomenon may explain why C. glauca with R. irregularis grows better than that without under the same level of NaCl stress.
Effect of light quality on polyphenol biosynthesis in three varieties of mung bean sprouts with different color seed coats
Authors: Cheng Yaoyao , Chen Honglin , Zhao Yihan , Cheng Xuzhen , Wang Lixia , Guo Xinbo
Published: October 2022

Mung bean (Vigna radiata) sprouts are a popular sprouting vegetable all over the world and are an excellent source of polyphenols with high antioxidant activity. This study investigated the effects of light qualities on the kinetic changes and metabolic regulation mechanism of light signal mediating polyphenols in three mung bean sprout cultivars. Experimental results showed that white light particularly enhanced the contents of caffeic acid, rutin and delphinidin 3-glucoside. Interestingly, ferulic acid and vitexin responded selectively to blue light and red light, severally. Most genes involved in polyphenol biosynthesis were activated under different light quality conditions, resulting in an overaccumulation of phenylpropanoids. Pearson correlation analysis showed that PAL, F3H, F3’H and F3’5’H expression correlated highly with rutin, whereas ANS expression paralleled anthocyanin biosynthesis. Moreover, MYB111, MYB3, MYB4, MYB1 and MYC2 were critical regulators of polyphenol biosynthesis in mung bean sprouts. These changes were likely due to the changes in expression of the photoreceptor genes CRY-D, PHOT2, PHYE and light response genes (PIF3 and HY5). Our results provide insights into polyphenol biosynthesis in sprouts and microgreens.
Bletilla striata polysaccharides protect against mercury-induced oxidative damage to Drosophila midguts via modulation of sestrin
Authors: Chen Zhi , Wen Di
Published: October 2022

Oxidative stress was one of the major causes of heavy metal-induced toxicity in organisms including Drosophila melanogaster. Bletilla striata polysaccharide (BSP) with anti-oxidative property has been recently recognized as a novel player in the management of oxidative stress response in organisms. Here, we took Drosophila midgut as a model to evaluate the protective effects of BSP (50 µg/mL) on mercury chloride-induced gastrointestinal adversities. As a result, BSP was found to significantly improve the survival rates and climbing ability of flies exposed to mercury. Further study demonstrated that BSP significantly alleviated the mercury-induced injury to midgut epithelium, at least partly, through increasing antioxidant enzyme activity (glutathione-S-transferase and superoxide dismutase), decreasing reactive oxidative species production, inhibiting cell apoptosis, restoring intestinal epithelial barrier and regulating stem cell-mediated tissue regeneration. Additionally, oxidative stress responsive gene sestrin was involved in the protection of BSP against mercury-induced oxidative damage to midguts. This study suggested that BSP has great potential for future application in the treatment and prevention of heavy metal-induced gastrointestinal adversities in mammals.
Early removal of a permanent catheter during the acute management of the unstable pediatric hemato-oncology patient with suspected catheter-related bloodstream infection: a multi-disciplinary survey and review of the literature
Authors: Cohen Neta , Rosenberg Tom , Rimon Ayelet
Published: October 2022

Purpose
There are no guidelines for the optimal manner and timing of permanent central catheter removal in the hemodynamically unstable pediatric hemato-oncology patient with suspected catheter related bloodstream infections (CRBSI). Our goals were to examine current practices of permanent central catheter management and choice of removal in the hemodynamically unstable pediatric patient with suspected CRBSI among practitioners in diverse subspecialties.
Methods
We performed a literature review on the subject, and conducted a multi-disciplinary survey included pediatric oncologists, pediatric emergency medicine physicians, and pediatric intensive care physicians whom we queried about their choice of permanent central catheter management and removal while treating the hemodynamically unstable pediatric patient with suspected CRBSI.
Results
Most of the 78 responders (n = 47, 59%) preferred to utilize the existing permanent central catheter for initial intravenous access rather than an alternative access. There were no significant differences between physician subspecialties (p = 0.29) or training levels (p = 0.14). Significantly more pediatric emergency medicine physicians preferred not to remove the permanent central catheter at any time point compared to the pediatric hemato-oncologists, who preferred to remove it at some point during the acute presentation (44.4% vs. 9.4%, respectively, p = 0.02).
Conclusions
Our study findings reflect the need for uniform guidelines on permanent central catheter use and indications for its removal in the hemodynamically unstable pediatric patient. We suggest that permanent central catheter removal should be urgently considered in a deteriorating patient who failed to be stabilized with medical treatment.
Recovery-Model: a model for CAR T-cell-related thrombocytopenia in relapsed/refractory Multiple myeloma
Authors: Li Zhe , Que Yimei , Wang Di , Lu Jie , Li Chunhui , Xu Menglei , Wang Zhiqiong , Yu Qiuxia , Long Xiaolu , An Ning , Xiao Yi , Li Chunrui
Published: October 2022

Background: Multiple myeloma (MM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy tend to have delayed platelet recovery
Patients and methods: This was a single-center retrospective observational study, which included a cohort of MM patients treated with anti-BCMA CAR-T in ChiCTR-OPC-16009113, ChiCTR1800018137, and ChiCTR1900021153.
Results: 58 MM patients treated with anti-BCMA CAR-T were included, and delayed platelet recovery (platelet not recovered to 50×109 /L within 28 days) could be observed in 36% of patients. The regression analysis identified factors influencing platelet recovery such as baseline platelet counts (p < 0.0001, r = -0.59) and the Recovery-Model was created. High Recovery- Model score indicated a greater risk of delayed platelet recovery after CAR-T infusion and reflected the risk of hematologic toxicity. Predictive biomarkers of the model included baseline platelet count, baseline hemoglobin, logarithm of baseline ferritin, and cytokine release syndrome grade. Finally, survival analysis showed the significant relationship between overall survival, delayed platelet recovery (p = 0.0457) and a high Recovery-Model score (P = 0.0011).
Conclusions: Inflammation-related factors and hematopoietic reserve were associated with delayed platelet recovery. We developed a model to predict the risk of platelet recovery and hematological toxicity in R/R MM patients after anti-BCMA CAR-T treatment.
Discrete semigroups of bounded linear operators on non-archimedean Banach spaces
Authors: Ettayb Jawad
Published: October 2022

In this paper, we give a new necessary and sufficient conditions on the resolvent of a spectral operator A so that the discrete semigroup consisting of powers of A is contractions on non-archimedean Banach spaces over Cp.
One-pot synthesis of indole-fused diketopiperazine through an Ugi 4-CR condensation and N-annulation under mild conditions
Authors: Shourkaei Fatemeh Ahmadi , Ranjbar Parviz Rashidi , mahdavi mohammad
Published: October 2022

This communication describes two-step approach to the synthesis of indole-fused diketopiperazine derivatives based on no metal catalyst cyclization of the Ugi adducts in the presence of trimethylamine. The reaction was initiated by simple Ugi condensation, followed by nucleophilic intramolecular attack in one-pot under mild conditions. This report is an excellent strategy for the preparation of new biological compounds containing indole-fused diketopiperazine
Penalized Model-based Clustering of Complex Functional Data
Authors: Pronello Nicola , Ignaccolo Rosaria , Ippoliti Luigi , Fontanella Sara
Published: October 2022

High dimensional data, large-scale data, imaging and manifold data are all fostering new frontiers of statistics. These type of data are commonly considered in Functional Data Analysis (FDA) where they are viewed as infinite-dimensional random vectors in a functional space. The rapid development of new technologies has generated a flow of complex data that have led to the development of new modeling strategies by scientists. In this paper, we basically deal with the problem of clustering a set of complex functional data into homogeneous groups. Working in a mixture model-based framework, we develop a flexible clustering technique achieving dimensionality reduction schemes through an L1 penalization. The proposed procedure results in an integrated modelling approach where shrinkage techniques are applied to enable sparse solutions in both the means and the covariance matrices of the mixture components, while preserving the underlying clustering structure. This leads to an entirely data-driven methodology suitable for simultaneous dimensionality reduction and clustering. The proposed methodology is evaluated through a Monte Carlo simulation study and an empirical analysis of real-world datasets showing different degrees of complexity.
Novel markers to evaluate the disease activity of rheumatoid arthritis based on some intestinal flora imbalance, abnormal immune cells and cytokines
Authors: Chi shuhong , Jiang chunlei , Wang fengkui , Wu lihua , Yang xiaojuan , Liu miao , Ma bin , Ubaid Syed , Su chunxia , Duan xiangguo
Published: October 2022

Objective: We aimed to investigate the changes of gut microbiota and analyze the correlation of gut microbiota with lymphocyte subsets, cytokines and clinical indicators in RA patients with active and remission stage, and to find new makers to evaluate disease activity of RA.
Method: The intestinal flora of subjects was collected for 16SrRNA gene sequencing. Flow cytometry to detect the number of lymphocyte subsets and their ability to secrete cytokines. ELISA was used to test the serum levels of cytokines.
Result: The richness and diversity of gut microbiota were significantly decreased in active and remission stages of RA patients compared to HCs. Most importantly, at the phylum level, the relative abundance of Bacteroidetes and Actinobacteria was decreased in RA patients with remission stage, while the relative abundance of Fusobacteria was increased in RA patients with active compared to HCs. At the genus level, the relative abundance of Ruminococcaceae_Ruminococcus and Bacteroides was decreased, while the abundance of Megamonas was increased in RA patients with active and remission stage compared to HCs. Intestinal flora was directly correlated with lymphocytes, cytokines and clinical indicators in active and remission stages of RA patients.
Conclusion: These results suggest that the changes of gut microbiota can lead to imbalances of CD4+T, CD8+T, memory B-cell subsets and cytokines that influence disease activity of RA patients. Interestingly, some intestinal flora may be used as markers to evaluate disease activity in RA patients.
Factors affecting the total occlusion time in eyes with hyperopic anisometropic amblyopia
Authors: Utamura Keisuke , Wakayama Akemi , Matsumoto Fumiko , Shiraishi Yukari , Narita Ikumi , Tanabe Fumi , Kusaka Shunji
Published: October 2022

Purpose To investigate the factors that affected the total occlusion time (TOT) in eyes with hyperopic anisometropic amblyopia.
Methods Subjects were 58 patients (26 boys and 32 girls; age range, 3.6-9.2, average, 5.8 ± 1.3 years) with hyperopic anisometropic amblyopia. All the subjects had initially visited and completed occlusion therapy with improved visual acuity (VA) of 1.0 (0.0 logMAR equivalent) or better in the amblyopic eye at Kindai University Hospital between January 2007 and March 2017. Using the subjects’ medical records, five factors for the TOT were evaluated retrospectively: the age at treatment, the initial VA of the amblyopic eye, refraction of the amblyopic eye, anisometropic disparity, and the presence of microstrabismus.
Results The initial VA of the amblyopic eye ranged from 0.1 to 0.9 (median, 0.4). The TOT ranged from 140 to 1795 (median, 598) hours with an average daily occlusion time of 7 hours. The initial VA of the amblyopic eye and presence of microstrabismus were the influential factors for the TOT (p< 0.01). To achieve VA of 1.0 or better, patients with initial VA of ≤ 0.3 in the amblyopic eye required a longer TOT. Moreover, patients with concomitant microstrabismus required a 1.7-fold longer TOT compared to those without microstrabismus.
Conclusion Patient’s initial VA and the presence of microstrabismus are the significant factors that affect the TOT.
Characterizations of derivations on spaces of smooth functions
Authors: Fechner Włodzimierz , Świątczak Aleksandra
Published: October 2022

We provide a list of equivalent conditions under which an additive operator acting on a space of smooth functions on a compact real interval is a multiple of the derivation.
Mathematics Subject Classification (2010). Primary: 39B42; Secondary: 39B72, 39B82, 47B47.
Effect of fidget spinners in enhancement of cognitive skills in healthy individuals: An interventional study
Authors: Biswas Ratnadeep , Kumar Yogesh , Rani Ruchi
Published: October 2022

Introduction
Fidget spinners have gained explosive popularity. Polarizing anecdotal accounts of their effects have been given but very few studies have been conducted to assess their effect. Thus, this study was undertaken to observe the effect of using fidget spinners on various aspects of cognition.
Methods
We selected 30 healthy individuals and following the recording of baseline scores in various cognitive function tests, they took these tests before & after a particular intervention (i.e., using fidget spinners) daily for a total of 9 days over the course of three weeks, at the end of which, an end-assessment was done. A follow-up was conducted after a period of 3 weeks post-discontinuation of fidget spinners.
Results
Significant improvement was observed in digit symbol matching, picture pairs, multiple object tracking, and fast choice tests (p < 0.001). A sustained effect was observed when the follow-up scores were compared to baseline and end-assessment scores.
Conclusion
While there was little to no change in fluid intelligence and response speed, using fidget spinners resulted in sustained improvement in processing speed, visual episodic memory, working memory, visuospatial attention, and inhibitory control. Regular use of fidget spinners might improve various aspects of cognition and benefit countless individuals.
Early experience of adopting a generative diffusion model for the synthesis of fundus photographs
Authors: Yoo Tae Keun , Ryu Ik Hee , Kim Hong Kyu
Published: October 2022

The generative diffusion model has been highlighted as a state-of-the-art artificial intelligence technique for image synthesis. Here, we show that a denoising diffusion probabilistic model (DDPM), which is currently a popular diffusion technique, can be used for a domain-specific task generating fundus photographs. Because the DDPM has disadvantages, including difficulty in training and low image quality compared with generative adversarial networks, further studies are needed to improve diffusion models.
Assessment of COVID-19 vaccines side effects among Health workers in Damascus Hospital: cross-sectional study
Authors: Bibars Marwa , alikhtyar Abdullatif , Al-bardan Hossam
Published: October 2022

Background
Severe Acute Respiratory Syndrome Coronavirus 2 continues to spread in the world, and in the absence of an effective treatment, the vaccine remains the best hope for controlling this disease. In this study, we seek to evaluate the side effects of vaccines among health workers in Damascus Hospital.
Methods
A cross-sectional study was conducted among health sector workers at Al-Mujtahid Hospital in Damascus using an appropriate sampling pattern. Written informed consent was obtained from all participants. A self-administered, paper-based, self-filling questionnaire that has been used in previous studies. The study included 299 participants from employees, students or students who had previously received the corona vaccine. Ethical approval was obtained from the Institutional Review Board (IRB), Faculty of Medicine, Syrian Private University.
Results
Out of the 299 participants, 54.5% were male and 45.5% were female. With an average age of 26.7 years. 61.9% of the participants stated that they had taken the vaccine in its complete program with two doses, and 24.4% had taken the vaccine in its complete program with its single dose only. Most of the participants received the vaccine inside Syria (96.3%). Pain at the injection site was the most prominent symptom, especially after receiving the first dose of the vaccine. 44.8% of the participants had mild side effects, while 40.1% of the participants reported having moderate side effects. Most of those who received the Sputnik vaccine showed 38.1% mild side effects. Notable against the rest of the types of vaccines, most of those who received another vaccine (Pfizer, Moderna or Johnson) had greater side effects compared to the rest of the vaccines provided in the hospital, namely Sputnik, Sinopharm and AstraZeneca.
Conclusion
This study revealed that nearly all the side effects that occurred were similar to those reported in the literature, indicating that most COVID-19 vaccines` side effects are almost known at this time. The majority of them are non-life threatening, with most cases being mild to moderate in intensity and resolving in a few days. statistically significant between the type of vaccine and the various side effects. More comprehensive studies should be conducted and others also to investigate the possible causes.
Road extraction based on dynamic scale MSR and improved Canny in vague aerial images
Authors: wang w , Feng Sheng , Tu Angyan
Published: October 2022

Road extraction in vague aerial or remote sensing images is hard but significant. In this paper, a road extraction method for vague aerial images is studied. The method consists of four main algorithms: (1) a modified MSR algorithm to enhance a vague aerial road image, in which, the logarithm transform is applied first, then the scales for Retinex are determined in light on the image depth by using the method of dark channel prior; (2) the enhanced image is roughly segmented based on the improved Canny edge detector with edge region expansion, then, edge image is thresholded by Otsu; (3) a number of post processing functions in a binary image is applied for gap linking and noise removal; and (4) the extracted roads are regulated by using the road shape features. In experiments, a number of vague aerial images of multiple roads were selected, and the algorithm comparison results show that the studied method is satisfactory for the road extraction in a vague aerial image, and it is much better than other traditional algorithms.
The Impact of Stockmarket Development on Economic Growth in Singapore. Econometric Study Based on an Autoregressive Distribution Lag (Ardl) Model Covering the Period From 1990 to 2020
Authors: Bekhti Djamila , Bakbak Leila Ismahane , Bouchetara Mehdi
Published: October 2022

The main objective of this paper is to discuss and examine the relationship between the development of stock market and economic growth and to show if the economic growth is positively influenced by stock market development in Singapore. Theoretically, some economists postulate a bidirectional relationship between financial development and economic growth, while others consider that growth drives finance, but that financial development is only a minor growth factor. We used an econometric study based on an autoregressive distribution lag (ARDL) model covering the period from 1990 to 2020 which is supported by the Asian financial crisis of 1997, obtained from various sources, in particular World Bank data and International Monetary Fund reports. Economic growth is expressed by GDP per capita, while stock market development is measured by market capitalization of domestic listed companies (% of GDP), shares traded total value (% of GDP) and stocks traded turnover ratio of domestic shares (%). The results show that the capitalization of domestic listed companies and the turnover ratio of domestic stocks have a positive and significant effect on gross domestic product per capita in the short and long run. However, shares traded total value hasa negative impact on gross domestic product per capita in short and long term. The contribution of our results suggests that stock market development promotes short and long-run growth in Singapore. Our findings can be of direct value to developed or emerging countries while they are of indirect value to less developed economies that may be committed to certain policy or regulatory decisions.
METAIS EM SEDIMENTOS DA INTERFACE TALUDE-PLATAFORMA CONTINENTAL DA BACIA POTIGUAR EM ÁREA DE EXPLORAÇÃO DE PETRÓLEO E GÁS NATURAL OFFSHORE, NE BRASIL
Authors: Lacerda Luiz , Godoy Jose , Gonçalves Rodrigo , Rocha Marcia , Dutra Breno
Published: October 2022

METALS IN SEDIMENTS FROM THE SHELF-SLOPE INTERFACE OFF THE POTIGUAR BASIN OFFSHORE OIL EXPLORATION AREA, NE BRAZIL. Marine sediments collected in November 2009 and July 2011 at depths ranging from 150 m to 2,000 m in the Potiguar Basin, northeastern Brazil, were analyzed for their main sedimentological characteristics (contents of carbon, nitrogen and their stable isotopes) and metals (Al, Fe, Mn, As, Cr, Cu, Ni, Pb, V and Zn) concentrations and their spatial distribution. Sediments were relatively rich in organic matter (C-org: 0.21% to 0.56%) and metals concentrations increased with depth, suggesting an accumulation of fine and terrigenous sediments eroded and transported from the continental shelf to the slope region. Metals concentrations were higher than those observed in coarser shelf sediments, because of sorting of fine-grained sediments. Iron (Fe), Cr and Cu distribution, although presenting this general pattern, also suggests some changes along the transport. Fe and Cr, probably in discrete minerals, are less affected by accumulation in deeper sediments. The high enrichment in Cu, however, suggests additional sources directly to slope sediments, probably by biological productivity and deposition through the water column. The concentrations of all metals are lower or fall close to the lowest range of concentrations reported for slope sediments from other marine regions worldwide and no evidence of anthropogenic contribution was evident.
KMnO4 modified biochar derived from swine manure for tetracycline removal
Authors: Fu Zan , Chen Yurong , Lu Yanyan , Wang Yue , Chen Jiahui , Zhao Youxin , Yang Mengya , Tian Xiaofei
Published: October 2022

Tetracycline (TC) is widely used in the livestock industry, but undigested TC is excreted with livestock waste and accumulates in the environment. In this study, swine manure-derived biochar (SBC) was modified with KMnO4 (MnOx-SBC), and used to remove TC. SEM-EDS, FTIR, XPS and elemental analysis all indicated that ultrafine MnOx particles were attached to the biochar surface. The surface properties and composition of the oxygen-containing functional groups were enhanced by KMnO4 modification. Batch sorption experiments showed that MnOx-SBC's TC-adsorption capacity was 105.9 mg·g−1, 46.4% higher than SBC's. The TC-adsorption onto MnOx-SBC agreed well with the pseudo-second-order model and Freundlich isotherm. A new platform is proposed for reusing swine manure while solving the livestock industry's antibiotic pollution risk by ‘treating waste with waste’.
Inhibitors of Tyrosine Kinases Involved in Inflammation and Autoimmune Disease
Authors: Myers Michael R. , He Wei , Hulme Christopher
Published: October 2022

The study of tyrosine kinases involved in cellular signaling associated with inflammation and autoimmune disease is rapidly progressing. Lessons learned from recent successes in identifying novel, potent, and selective tyrosine kinase inhibitors for the treatment of cancer and cardiovascular disease can be applied toward developing selective tyrosine kinase inhibitors for targets associated with diseases such as rheumatoid arthritis, sepsis and autoimmune disease. The design of new selective tyrosine kinase inhibitors will be aided by the very recent successes in solving X-ray crystal structures of
the catalytic domains of several kinases. This paper summarizes the literature on inhibitors of several non- receptor and receptor tyrosine kinases thought to be involved in cellular signaling associated with infl_ammatory diseases.
State-of-the-art Tools to Elucidate the Therapeutic Potential of TAT-peptide (TP) Conjugated Repurposing Drug Against SARS-CoV-2 Spike Glycoproteins
Authors: Ansari Mohammad Azam , Alomary Mohammad N. , Jamal Qazi Mohammad Sajid , Almoshari Yosif , Salawi Ahmed , Almahmoud Suliman A. , Khan Johra
Published: October 2022

Background:

In late 2019, a highly infectious and pathogenic coronavirus was recognized as Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), which causes acute respiratory disease, threatening human health and public safety. A total of 448,327,303 documented cases and 6,028,576 deaths have been reported as of March 8th 2022. The COVID-19 vaccines currently undergoing clinical trials or already in use should provide at least some protection against SARS-CoV-2; however, the emergence of new variations as a result of mutations may lessen the effectiveness of the currently available vaccines. Since the efficacy of available drugs and vaccines against COVID-19 is notably lower, there is an urgent need to develop a potential drug to treat this deadly disease. The SARS-CoV-2 spike (SCoV-SG) is the foremost drug target among coronaviruses.

ObjectiveL:

The major objectives of the current study are to conduct a molecular docking study investigation of TAT-peptide47–57(GRKKRRQRRRP)-conjugated remodified therapeutics such as ritonavir (RTV), lopinavir (LPV), favipiravir (FPV), remdesivir (RMV), hydroxychloroquine (HCQ), molnupiravir (MNV) and nirmatrelvir (NMV) with (SCoV-SG) structure.

Methods:

Molecular docking analysis was performed to study the interaction of repurposed drugs and drugs conjugated with the TAT-peptide with target SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) using Auto- Dock. Further docking investigation was completed with PatchDock and was visualized by the discovery of the studio visualizer 2020.

Results:

TAT-peptides are well-characterized immune enhancers that are used in intracellular drug delivery. The results of molecular docking analysis showed higher efficiency and significantly enhanced and improved interactions between TP-conjugated repurposed drugs and the target sites of the SCoV-SG structure.

Conclusion:

The study concluded that TP-conjugated repurposed drugs may be effective in preventing COVID- 19, and therefore, in vitro, in vivo, and clinical trial studies are required in detail.
Advances in Exercise Therapy in Hemodialysis: A Systematic Review
Authors: Li Yu , Wang Xin , Pei Zuowei
Published: October 2022

Background:

The main and common treatment of renal replacement therapy (RRT) for
chronic kidney disease (CKD), especially in end-stage kidney disease (ESKD) patients, is hemodialysis
(HD). Many reports have shown that exercise therapy is good for HD patients. This review aims to
describe recent advances in exercise therapy in HD patients.

Objective:

Our key opinions have focused on varied types of exercise therapy and identified barriers
to exercise therapy among HD patients. Exercise implementation includes aerobic exercise training,
resistance exercise training, combined exercise training, and novel exercise interventions. Barriers
include internal and external distress, such as HD patients' restrictions and environmental problems.

Methods:

This review is based on the novel/ most findings in PubMed, Web of Science, Google
Scholar, and MEDLINE from the inception of every database until August 2022.

Results:

The systematic search strategy identified 6 articles that met the inclusion criteria. Four were
specific to exercise therapy in HD, and three were to exercise barriers in HD. Massive evidence has
demonstrated exercise therapy for HD has specific benefits and neglectful causes of exercise barriers.

Conclusion:

In this review, we aimed to summarize recent advances in individual exercise therapy
recommendations (type, intensity, time, and frequency) and exercise barriers in HD patients. In conclusion,
Low/moderate-intensity exercise trained for at least thirty minutes five times per week, including
aerobic exercise (Walking, Jogging, Swimming, and Health Exercises), resistance training
(Dumbbells, Band training, and Knee extension), and combination exercise (both) during the first 2
hours of dialysis treatment or non-dialysis days is advisable treatment recommendation.
A Review on Proniosomes: A Propitious Outlook to the Provesicular Drug
Delivery System
Authors: Saxena Anamika , Apurvi Pragya , Aslam Ramsha
Published: October 2022

Currently, various kinds of research are going in the evolution of the Novel Drug Delivery
System. NDDS mainly emphasizes the development of a system with improved sustained, controlled,
and targeted drug delivery with minimum toxicity. Proniosomes are dry free-flowing formulation that
minimizes the drawbacks associated with liposomes and niosomes. Proniosomes are carrier particles
that are water-soluble and covered with a surfactant which, upon hydration in a hot aqueous medium
with agitation, gives niosomal dispersion. Proniosomes derived niosomes are superior substitutes as
compared to other vesicular delivery due to preferable physicochemical properties and improved chemical
stability. The proniosomes deliver additional convenience of transportation, storage, distribution,
and dosing, which makes dry niosomes a versatile commercial product. This illustrated review emphasizes
the components, method of preparation, factors affecting the formation of proniosomes, characterization,
and various routes of administration of proniosomes. This review will help to explore the efficacy
and functionality of proniosomes in different fields for their upcoming supremacy in the field of drug
delivery.
Machine-Based Learning Shifting to Prediction Model of Deteriorative
MCI Due to Alzheimer’s Disease - A Two-Year Follow-Up Investigation
Authors: Zhao Xiaohui , Sui Haijing , Yan Chengong , Zhang Min , Song Haihan , Liu Xueyuan , Yang Juan
Published: October 2022

Objective:

The aim of the present work was to investigate the features of the elderly population
aged ≥65 yrs and with deteriorative mild cognitive impairment (MCI) due to Alzheimer’s disease
(AD) to establish a prediction model.

Method:

A total of 105 patients aged ≥65 yrs and with MCI were followed up, with a collection of
357 features, which were derived from the demographic characteristics, hematological indicators (serum
Aβ1-40, Aβ1-42, P-tau and MCP-1 levels, APOE gene), and multimodal brain Magnetic Resonance
Imaging (MRI) imaging indicators of 116 brain regions (ADC, FA and CBF values). Cognitive
function was followed up for 2 yrs. Based on the Python platform Anaconda, 105 patients were randomly
divided into a training set (70%) and a test set (30%) by analyzing all features through a random
forest algorithm, and a prediction model was established for the form of rapidly deteriorating
MCI.

Results:

Of the 105 patients enrolled, 41 deteriorated, and 64 did not come within 2 yrs. Model 1 was
established based on demographic characteristics, hematological indicators and multi-modal MRI image
features, the accuracy of the training set being 100%, the accuracy of the test set 64%, sensitivity
50%, specificity 67%, and AUC 0.72. Model 2 was based on the first five features (APOE4 gene, FA
value of left fusiform gyrus, FA value of left inferior temporal gyrus, FA value of left parahippocampal
gyrus, ADC value of right calcarine fissure as surrounding cortex), the accuracy of the training set
being 100%, the accuracy of the test set 85%, sensitivity 91%, specificity 80% and AUC 0.96. Model
3 was based on the first four features of Model 1, the accuracy of the training set is 100%, the accuracy
of the test set 97%, sensitivity100%, specificity 95% and AUC 0.99. Model 4 was based on the first
three characteristics of Model 1, the accuracy of the training set being 100%, the accuracy of the test
set 94%, sensitivity 92%, specificity 94% and AUC 0.96. Model 5 was based on the hematological
characteristics, the accuracy of the training set is 100%, the accuracy of the test set 91%, sensitivity
100%, specificity 88% and AUC 0.97. The models based on the demographic characteristics, imaging
characteristics FA, CBF and ADC values had lower sensitivity and specificity.

Conclusion:

Model 3, which has four important predictive characteristics, can predict the rapidly deteriorating
MCI due to AD in the community.
Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A
Systematic Review of the Current Literature
Authors: Mosca Alessio , Chiappini Stefania , Miuli Andrea , Mancusi Gianluca , Santovito Maria Chiara , Di Carlo Francesco , Pettorruso Mauro , Corkery John M. , Canessa Carlos , Martinotti Giovanni , Di Giannantonio Massimo
Published: October 2022

Background:

Ibogaine and noribogaine are psychedelic substances with dissociative properties
naturally occurring in plants of the Apocynaceae family. Research has shown their efficacy in
treating substance use disorders (SUD), particularly in opiate detoxification, but their efficacy and toxicity
are still unclear.

Objective:

This review aims to assess the anti-addictive role of ibogaine and evaluate its side effects.

Methods:

A systematic literature review was conducted on the 29th of November 2021 using PubMed,
Scopus and Web of Science databases through the following search strategy: ("Ibogaine" OR "Noribogaine")
AND ("SUD" OR "substance use disorder" OR "craving" OR "abstinence" OR "withdrawal"
OR "addiction" OR "detoxification") NOT animal NOT review NOT "vitro." The Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed for data gathering
purposes. Research methods were registered on PROSPERO (CRD42021287034).

Results:

Thirty-one articles were selected for the systematic revision, and two were considered for
analysis. The results were organised according to the type of study: case reports/case series, randomised-
controlled trials (RCTs), open-label, survey and observational studies. The main outcomes were
related to the anti-addictive effect of ibogaine and its cardiac toxicity. A meta-analysis of side effects
was conducted using RevMan 5.4 software, showing a significant risk of developing headaches after
ibogaine/noribogaine treatment.

Conclusion:

The results show some efficacy of ibogaine in the treatment of SUDs, but its cardiotoxicity
and mortality are worrying. Further studies are needed to assess its therapeutic efficacy and actual
safety.
Does Folic Acid Supplementation Affect Body Weight or Body Mass
Index? A Systematic Review and Meta-analysis of a Randomized
Controlled Trial
Authors: Aghakhani Ladan , Haghighat Neda , Nazarian Behzad , Clark Cain C. T.
Published: October 2022

Background & Aims:

Folic acid is a widely used supplement with numerous purported
health benefits. The purpose of this study was to evaluate the effect of folic acid on body
weight (BW) and body mass index (BMI).

Methods:

This systematic review and meta-analysis of 11 randomized controlled trials (RCTs)
evaluated the effects of folic acid supplementation BW or BMI in 514 participants. A systematic
search, current as of March 2021, was performed in PubMed/Medline, Scopus, Web of Science,
and Embase using relevant keywords to identify eligible studies. A fixed-effects model was used
to estimate the weighted mean difference (WMD) and 95% confidence intervals (CIs).

Results:

11 RCTs were included in this meta-analysis. The pooled analysis revealed that folic acid
supplementation did not affect BW (WMD: 0.16 kg; 95% CI: -0.77 to 1.10; p = 0.727, I²=
0.0%, p = 1.00) and BMI (WMD: 0.05 kg/m2; 95% CI: -0.08 to 0.19; p = 0.447, I²= 0.0%, p =
0.666).

Conclusions:

Folic acid supplementation did not significantly impact body weight or BMI. Future
large-scale RCTs, on various dosages and durations of intervention are needed to elucidate the
effects more clearly.
Synthesis and In vivo Evaluation of Hepatoprotective Effects of Novel
Sulfur-Containing 1,4-Dihydropyridines and 1,2,3,4-Tetrahydropyridines
Authors: Dotsenko Victor V. , Krivokolysko Bogdan S. , Bibik Elena Y. , Frolov Konstantin A. , Aksenov Nicolai A. , Aksenova Inna V. , Krivokolysko Sergey G.
Published: October 2022

Background:

Hepatoprotectors, currently used in clinical practice, often show low efficacy.
One of the promising goals in the therapy of liver diseases is the targeted synthesis of smallmolecule
drugs with hepatoprotective activity. Some heterocycles, such as 1,4-dihydropyridines,
are proven to be good hepatoprotectors.

Objective:

This study aimed to prepare and investigate the hepatoprotective effects of some dihydro-
and tetrahydro pyridines using the experimental rat model of tetrachloromethane (CCl4)-
induced acute liver damage.

Methods:

Several 1,4-dihydropyridines and 1,2,3,4-tetrahydropyridines were synthesized by the
reaction of cyanothioacetamide with carbonyl compounds and active methylene compounds, such
as Meldrum’s acid, ethyl cyanoacetate or β-keto esters, followed by S-alkylation of intermediate
pyridine-2-thiolates. In silico prediction studies were performed to explore the possible protein
targets. Using virtual bioscreening tools, we selected the six most promising compounds from the
library of new partially saturated pyridines. Six novel compounds were characterized by IR, 1H,
13C DEPTQ NMR spectroscopy, 2D NMR experiments (1H–13C HSQC, 1H–13C HMBC), HRMS
(ESI), and elemental analysis. The hepatoprotective effects were studied in vivo on eighty white
rats with CCl4-induced liver damage. Biochemical studies, including thymol turbidity test and
measurements of levels of bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline
phosphatase in the blood of rats, were performed.

Results:

Five of six studied compounds showed a good hepatoprotective effect on a rat model of
tetrachloromethane (CCl4)-induced acute hepatitis. The blood of rats in the experimental groups
revealed significantly lower levels of total bilirubin, alanine aminotransferases, aspartate aminotransferases,
thymol turbidity and alkaline phosphatase compared to the control group of rats
with acute toxic tetrachloromethane hepatitis.

Conclusion:

Our results suggests that compound, (benzyl 4-(4-chlorophenyl)-5-cyano-6-({2-[(3,4-
dimethylphenyl)amino]-2-oxoethyl}thio)-2-methyl-1,4-dihydropyridine-3-carboxylate), can be considered
as candidate for further preclinical studies. Moreover, as per our knowledge, this is the
first report on the hepatoprotective effects of the 1,2,3,4-tetrahydropyridine series.
Cancer Stem Cells and Anti-tumor Immunity
Authors: Yılmaz Merve , Kaplan Fuat , Mender Ilgen , Gryaznov Sergei M. , Dikmen Z. Gunnur
Published: October 2022

Cancer stem cells (CSCs) are correlated with poor clinical outcome due to their contribution to chemotherapy resistance and formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used for the detection of these cells.

We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and anti-programmed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere targeted therapy 6-thio-2’deoxyguanosine (6-thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that, personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.
Assessment of Xylem Discs from Fruiting and Shading Plants in Tap
Water Desalination
Authors: Lubbad Said H. , Elfarram Atta
Published: October 2022

Aims and background:

The low rainwater recharge rate and high seawater intrusion into water aquifer present a dilemma of high ground-water salinity for the narrow coastal Gaza Strip. Thus, extremely saline water causes impairment to household appliances and deteriorates the performance of the reverse-osmosis desalination units.

Methods:

Accordingly, xylem discs of different plants, such as Mulberry, Pomegranate, Olives, Centroza, and Ficus, were investigated for desalination of tap-water by flow-through experimentation. Various parameters such as the total dissolved salt of the inflow water, disc thickness, flow-rate and the type of plant were investigated. Finally, the morphology of the xylem discs of the five plants were screened using optical microscope.

Result and discussion:

It was found that xylem of different plants showed dissimilar efficiencies in water desalination. Thus, Centroza established the highest desalination efficiency of 31%, followed by Olive and Ficus as 26 and 25%, respectively, while Pomegranate and Mulberry established the poorest salt removal of 17 and 14%, respectively. Successive three-disc set up established ~ 50% desalination of inflow-water of ~5000 ppm.

Conclusion:

Hence, disposable cost-effective xylem desalination unit is proposed as guard filter to be installed between the faucet and household desalination units and washing machines or dishwashers, in order to improve the performance and extend the life-time of these appliances.
Overview of 3D and 4D Printing Techniques and their Emerging
Applications in Medical Sectors
Authors: Kumar Rakesh , Kumar Santosh
Published: October 2022

Additive manufacturing is a highly effective and versatile technology, especially in the
medical sector, due to its customization, material complexity, design flexibility, waste minimization,
and ability to fabricate intricate shapes that are cumbersome to manufacture by conventional
manufacturing techniques. 4D printing plays a significant role in the medical field, especially in
the areas not covered by 3D printing technologies, such as smart implants, devices and tools. Also,
4D printing helps doctors to treat more patients with high accuracy and quality. Hence, this
manuscript aims to provide an overview of distinct 3D and 4D printing techniques and their
emerging applications in the medical sector. A study of 3D printing technologies is presented by
explaining the working principles of distinct 3D printing methods: stereo lithography, fusion deposition
modeling, inkjet printing, selective laser sintering, selective laser melting and electron
beam melting. In addition, the emerging applications of 3D printing in medical sectors (e.g., bioprinting,
surgical guides, pharmaceuticals, prostheses, medical devices, dentistry, physiotherapy,
etc.), as well as challenges and the future scope of 3D printing, are also discussed. Further, the
concept of 4D printing, the market for both 3D and 4D printing, the benefits of 4D printing, the
comparison of 3D and 4D printing, limitations, applications, and the future scope of 4D printing
in the medical sector are also covered.