bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate Diagnostic Tissue Segmentation and Concurrent Disease Subtyping with Small Datasets
Authors: Frank Steven
Published: June 2022

· Purpose: pathology slides of malignancies are segmented based on small training datasets; the segmentations may be used to visualize diseased regions and to guide subtyping analysis.· Approach: an ensemble of lightweight convolutional neural networks (CNNs) is trained on different subsets of a small dataset derived from annotated whole-slide histopathology images (WSIs). The WSIs are first reduced in scale to preserve anatomic features critical to analysis but also facilitate convenient handling and storage. They are then decomposed into tiles, which are sifted using various criteria and used to train the CNNs to distinguish diseased from undiseased tissue. For subtyping, a similar procedure is used to train an ensemble of CNNs to distinguish among subtypes. A segmentation is generated by downsampling and tiling a candidate image, sifting the tiles, and classifying each tile with the ensemble of CNNs. The CNN predictions are combined using a function to favor a selected similarity metric, and a segmentation mask or map is produced from tiles whose combined predictions exceed a decision boundary. For subtyping, the resulting mask is applied to the downsampled candidate image, and new tiles are derived from the unmasked regions. These are classified by the subtyping CNNs to produce an overall subtype prediction.· Results and conclusion: this approach was applied successfully to two very different datasets of large WSIs, one (PAIP2020) involving multiple subtypes of colorectal cancer and the other (CAMELYON16) single-type breast-cancer metastases. Scored using standard similarity metrics, the segmentations outperformed more complex models typifying the state of the art.
Intra-corporeal hand-sewn gastroduodenostomy in totally laparoscopic distal gastrectomy: Preliminary Experience with 21 Cases
Authors: Zhang Ren-Chao , Cen Gang , Huang Chen , Mou Yi-Ping
Published: June 2022

Purpose
Various procedures of intra-corporeal gastroduodenostomy in totally laparoscopic distal gastrectomy(TLDG) have been devised, but an optimal method has not yet been standardized. Studies of intra-corporeal hand-sewn gastroduodenostomy in TLDG are limited. In this study, we present our experience of intra-corporeal hand-sewn gastroduodenostomy in TLDG.
Methods
From December 2018 to October 2021, 21 patients underwent TLDG using intra-corporeal hand-sewn gastroduodenostomy for gastric cancer. The data of the patient demographics, intraoperative variables, postoperative hospital stay, morbidity, mortality, pathologic findings and follow-up were collected.
Results
All patients were successfully operated on without conversion to open- or laparoscope-assisted surgery. The median operative time was 175 min (range, 152-240min), with a reconstruction duration of 21 min (range, 15- 34min) .The time until first flatus was 4 days (range,2-6d). The time to starting a soft diet was 7 days (range,3-16d). There were no anastomotic complications. The morbidity rate was 4.76% with one case of delayed gastric emptying. There was no postoperative 30-day mortality and reoperation. The median postoperative hospital stay was 8 days(range,6-19d). Median follow-up time was 15 months (range,3-36m), no anastomotic strictures were encountered.
Conclusions
Intra-corporeal hand-sewn gastroduodenostomy in TLDG is a safe and feasible procedure. This method with lower surgical costs could be a good option for performing intracorporeal gastroduodenostomy with an advanced laparoscopic suture technique.
New extensions of (2+1)-dimensional BLMP models with soliton solutions
Authors: Darvishi M. T. , Najafi Mohammad , Rezazadeh Hadi , Bekir Ahmet , Cevikel Adem
Published: June 2022

Searching for soliton solutions of NPDEs is one of the most interesting and important areas of science in the field of nonlinear phenomena. Soliton is a localized wave with exponential wings or is a localized wave with an infinite support. In this work, we study two extensions of (2+1)-dimensional Boiti-Leon-Manna-Pempinelli (BLMP) equation. Based on the simplified Hirota’s method (HM) and the Cole-Hopf transformation (CHT) method, new multiple front wave solutions are obtained for both versions.
Cross-layer Balance of Visuo-hippocampal Functional Connectivity Is Associated With Episodic Memory Recognition Accuracy
Authors: CHANG Wei-Tang , Langella Stephanie , Seo Min Sung , Huynh Khoi , Yap Pew-Thian , Lin Weili ,   Kelly Giovanello1
Published: June 2022

Episodic memory is supported by the hippocampus and widespread cortical areas. However, little is known about how hippocampal subregions connect with different cortical layers or how layer-dependent cortico-hippocampal functional connectivity (FC) correlates with memory performance. Inspired by cross-frequency coupling between the hippocampus and neocortex in intracranial electrophysiological studies, we hypothesized that the balance of cortico-hippocampal FC strengths between deep and superficial layers would be associated with recognition memory accuracy. To test this hypothesis, we developed laminar-resolution fMRI, achieving whole-brain coverage, 1-mm isotropic resolution, and 2-second temporal resolution on a 7T scanner by integrating multiple advanced methods. Our results showed that the balance of cortico-hippocampal FC between superficial and deep layers in visual cortex was more highly correlated with recognition accuracy than conventional layer-averaged FC. Such findings open a new avenue for layer-dependent FC research, with clear implications for future investigations into clinical populations.
Microglial-oligodendrocyte interactions in myelination and neurological function recovery after traumatic brain injury
Authors: Song Shanshan , Hasan Md Nabiul , Yu Lauren , Paruchuri Satya S. , Bielanin John P. , Metwally Shamseldin , Fischer Sydney G. , Fiesler Victoria M. , Sen Tanusree , Gupta Rajaneesh K. , Foley Lesley M. , Hitchens T. Kevin , Dixon C. Edward , Cambi Franca , Sen Nilkantha , Sun Dandan
Published: June 2022

Differential microglial inflammatory responses play a role in regulation of differentiation and maturation of oligodendrocytes (OLs) in brain white matter. How microglia-OL crosstalk is altered by traumatic brain injury (TBI) and its impact on axonal myelination and neurological function impairment remain poorly understood. In this study, we investigated roles of a Na+/H+ exchanger (NHE1), an essential microglial pH regulatory protein, in microglial proinflammatory activation and OL survival and differentiation in a murine TBI model induced by controlled cortical impact. Similar TBI-induced contusion volumes were detected in the Cx3cr1-CreERT2 control (Ctrl) mice and selective microglial Nhe1 knockout (Cx3cr1-CreERT2;Nhe1flox/flox, Nhe1 cKO) mice. Compared to the Ctrl mice, the Nhe1 cKO mice displayed increased resistance to initial TBI-induced white matter damage and accelerated chronic phase of OL regeneration at 30 d post-TBI. The cKO brains presented increased anti-inflammatory phenotypes of microglia and infiltrated myeloid cells, with reduced proinflammatory transcriptome profiles. Moreover, the cKO mice exhibited accelerated post-TBI sensorimotor and cognitive functional recovery than the Ctrl mice. These phenotypic outcomes in cKO mice were recapitulated in C57BL6J wild-type TBI mice received treatment of a potent NHE1 inhibitor HOE642 for 1-7 days post-TBI. Taken together, these findings collectively demonstrated that blocking NHE1 protein stimulates restorative microglial activation and oligodendrogenesis, which contributes to accelerated white matter repair and neurological function recovery after TBI.
WITHDRAWN: Mathematical modeling of transport phenomena in chemical reactors
Authors: Chen Junjie
Published: June 2022

Endothermic reactions performed in thermally integrated microchannel reactors are driven using heat from an external source. However, the temperature of the gas stream providing the heat is limited by constraints imposed by the materials of construction. This study relates to a thermochemical process for producing hydrogen by the catalytic endothermic reaction of methanol with steam in a thermally integrated microchannel reforming reactor. Computational fluid dynamics simulations are conducted to better understand the consumption, generation, and exchange of thermal energy between endothermic and exothermic processes in the reactor. The effects of wall heat conduction properties on heat transfer characteristics and reactor performance are investigated. Processes of conducting reactions in integrated combustion reactors are described and the results are presented. Particular reactor designs are also described. The results indicate that asymmetric operation requires spatial distribution of the feed for the exothermic reaction in order to prevent excess temperatures and to ensure stable operation. The peak reaction heat flux increases with the channel dimensions while maintaining the flow rates. The change in specific enthalpy is positive for the exothermic reaction and negative for the endothermic reaction. The change in specific sensible enthalpy is always positive. The thermal conductivity of the channel walls is fundamentally important. Materials with high thermal conductivity are preferred for the channel walls. Thermally conductive ceramics and metals are well-suited. The application of autothermal reactor concepts can be extended to endothermic high temperature reactions. Advantages are the compact design which allows fast start-up and load changes. Drawbacks include the dilution of the reforming product with nitrogen if air is used as oxidant.
Schulübergreifende Lehrpersonenkooperation im Kontext digitalisierter Lernangebote
Authors: Demski Denise , Bellenberg Gabriele , Im Brahm Grit
Published: June 2022

Bereits seit 2002 besteht an ausgewählten Schulen des Zweiten Bildungsweges für erwachsene Lernende die Möglichkeit, das (Fach-)Abitur im Lehrgang Abitur-Online in einer Kombination aus schulischen Präsenzphasen und Distanzlernen zu erwerben. Der Beitrag fokussiert die Zusammenarbeit im Kontext digitalisierter Lernangebote und betrachtet dabei insbesondere sog. Materialentwicklungsgruppen im Lehrgang Abitur-Online, die Materialien konzipieren und auf einer Plattform verfügbar machen, die im Zweiten Bildungsweg von Kolleg:innen – auch aus anderen Bildungsgängen – sowie von Schüler:innen als Selbstlernmaterialien genutzt werden können. Dazu wurden im BMBF-Projekt «DigiGO» Gruppeninterviews mit Personen aus der Materialentwicklung in drei Fächern durchgeführt, die inhaltsanalytisch ausgewertet wurden. Die Befunde zeigen, dass die Arbeitsteilung die vorherrschende Form der Zusammenarbeit in den Gruppen darstellt und sich die Interviewten vorrangig als Dienstleistende für die Kollegien der Einzelschulen verstehen. Die konkrete Verwendung der Materialien in den Schulen bleibt allerdings unbestimmt, da kaum Feedback erfolgt; hier wird zudem die pädagogische Autonomie von Lehrpersonen betont. Schulentwicklungsbezogene Aspekte und ein Innovationstransfer stehen bei der Konzeption der Materialien nicht im Vordergrund; zudem wird ein deutlich grösseres Augenmerk auf Fragen der Digitalisierung als der Digitalität gelegt.
‹Hätten wir keinen Digitalpakt, hätten wir eine bessere Ausstattung›
Authors: Krein Ulrike
Published: June 2022

Schulen sehen sich vor dem Hintergrund einer voranschreitenden Digitalisierung (in) der Schule (nicht erst seit der Coronapandemie) verschiedenen pädagogischen wie strukturellen Herausforderungen gegenüber. Damit sie als aktive pädagogische Handlungseinheiten in einer digitalen Welt agieren können, bedarf es einer angemessenen, kontinuierlichen Schulentwicklungsarbeit. Unterstützung sollen Schulen hierbei u. a. durch politische Initiativen wie den «DigitalPakt Schule» erfahren. Doch obwohl der DigitalPakt Schule bereits im Mai 2019 verabschiedet wurde, wurden bislang nur wenige Mittel abgerufen. Worin dies begründet liegt und welche Herausforderungen in diesem Kontext bestehen, wird meist nur spekulativ verhandelt. Der Beitrag setzt an dieser Stelle an und beleuchtet am Beispiel von Rheinland-Pfalz Herausforderungen bei Schulentwicklungsprozessen im Kontext des DigitalPakts. Herangezogen werden hierfür bestehende Studienergebnisse sowie explizierende Expert:inneninterviews mit Schulleitungen, die Einblicke in prozessinhärenten Herausforderungen im Rahmen von Schulentwicklungsarbeit unter Perspektivität von Digitalisierung bieten. Anhand der Ergebnisse werden Ambivalenzen äusserer Schulentwicklungsinstrumente und einer Steuerungsperspektive auf Schule sowie damit einhergehende Herausforderungen für die Kooperation verschiedener Akteur:innen deutlich. Diese werden im Rahmen des Beitrages diskutiert.
ANALYSIS OF TRANSFORMATION OF ENTREPRENEURIAL FORMS OF AGRICULTURAL COOPERATIVES IN UKRAINE
Authors: Ponomarenko I. , Lebid N. , Ihnatchenko A. , Khymchenko Yu. , Kovalov B.
Published: June 2022

This article considers the process of development of agricultural cooperatives in Ukraine. The data of the indicators of the State Statistics Service of Ukraine, the Unified State Register of Enterprises and Organizations of Ukraine by organizational and legal forms were taken as a basis. Data from the official report of the Ministry of Agrarian Policy and Food of Ukraine were also taken. The study was conducted in several stages. First, with the help of data from the State Statistics Service, a table of the number of cooperatives in Ukraine to date was constructed with a breakdown into production, service, consumer, agricultural production and agricultural service. However, the percentage of cooperatives compared to the total number of registered legal entities was calculated. After that, a diagram of changes in the number of cooperatives from 2013 to 2021, with a breakdown into production and service cooperatives. At the second stage, according to the report of the Ministry of Agrarian Policy and Food of Ukraine for 2019, a table was built with the number of agricultural cooperatives by region, broken down by species and their condition. The results of the study showed that 47.7% of agricultural cooperatives do not actually function. After that, it was considered on the regulatory framework that regulates and regulates the process of creating and maintaining a cooperative form of economy, namely the amendments to the Law of Ukraine "On Agricultural Cooperation" № 819-IX from 21.07.2020. In the fourth stage, the problem of lack of professional cooperative managers was analyzed, and the possibility of implementing and using foreign experience in managing cooperatives was considered. In countries such as the United States, the Netherlands and Japan. The fifth stage was the analysis of cooperative financing. To date, 63% of all agricultural cooperatives are financed by grants, 27% by borrowed funds, and only 9% by the cooperative’s own funds. The conclusion summarizes all the problematic aspects.
Relação entre as características do comitê de auditoria e a evidenciação do imobilizado: estudo nas empresas da BM&FBovespa
Authors: Monteiro Feijó Amanda , Bruna Teixeira  , Ernesto Fernando Rodrigues Vicente
Published: June 2022

O estudo tem como objetivo identificar as características do comitê de auditoria que estão relacionadas com a evidenciação do imobilizado de companhias pertencentes a todos os setores de atuação da BM&FBovespa. Realizou-se uma pesquisa conduzida por meio de análise de conteúdo e abordagem quantitativa, com a utilização de estatística descritiva. A amostra é composta por 114 empresas, referente aos anos de 2013 e 2014. As características do comitê de auditoria avaliadas foram: tamanho do comitê, expertise, independência, gênero e idade dos membros, além de outras relacionadas com as atividades desenvolvidas pelo comitê de auditoria. A evidenciação do imobilizado foi mensurada por meio da verificação da conformidade das DFP’s com as práticas contábeis do ativo imobilizado (CPC 27), incluindo o arrendamento mercantil financeiro (leasing) (CPC 06) e ao teste de recuperabilidade (CPC 01). Os resultados apontaram que dentre as empresas com maior nível de adequação do imobilizado 76% (2013) e 69% (2014) possuem comitê de auditoria. Também se constatou que as características gênero feminino, membros que possuem expertise, empresas que disponibilizam o relatório do comitê de auditoria, que autorizam/opinam contratação, que possuem relatório específico encaminhado, que supervisionam a elaboração e a divulgação da DFP, que estabelece e divulga códigos internos, que verificam o cumprimento dos regulamentos e normas e, que tratam de resoluções de conflitos, estão relacionadas com melhores evidenciação do imobilizado, isto é, empresas com comitês de auditoria que possuem estas características tendem a evidenciar o imobilizado com maior adequação às normas contábeis.
Development of business architecture of the banking sector based on public-private partnership
Authors: Kuznyetsova Аnzhela , Boiarko Іryna , Rudevska Viсtoria , Maslov Vladyslav
Published: June 2022

The purpose of the paper is to identify promising areas of business architecture of the banking sector of Ukraine’s economy based on public-private partnerships. Business architecture integrates risks due to the predominance in a certain period of development of the banking sector of different business models. Its development should involve the subordination of private interests of the banking business to national and public needs to achieve economic growth. Such a public-private partnership should become an institutional tool for the formation and functioning of a business architecture, based on socially responsible banking.Development directions of business architecture of the Ukrainian banking sector based on public-private partnership are determined by the results of correlation and regression assessment of the impact of business architecture on economic growth in 2015–2020.The generalization of the effects on gross investment and gross consumption allows identifying the following areas for targeted changes in business architecture of the banking sector in Ukraine’s economy: 1) reducing the lending activity of banks with retail, corporate, and universal business models; 2) incitement the lending activity of banks with a corporate business model with retail financing and a business model of limited credit intermediation.The paper substantiates the feasibility of transition to mesoprudential banking regulation and supervision. The main priority of this approach is to reduce systemic risks, which is determined by the propensity for similar risks within groups of financial institutions with the same business models.
Study on factors affecting audit fees and audit quality through auditors’ perceptions: Evidence from an emerging economy
Authors: Nguyen Van Hau , Thanh Hai-Phan , Nguyen Thanh Cuong , Nguyen Ngoc Diep , Ha Hai Giang
Published: June 2022

Audit fees and audit quality have received the attention of stakeholders, clients, audit firms, and third parties. Each subject has its own opinion on determining influencing factors and their relationship. This study aims to investigate the determining factors of audit fees and audit quality in Vietnam. Using random data collection, a questionnaire was created on Google forms and sent to auditors from the 4th quarter of 2020 to the end of the 1st quarter of 2021. 267 valid auditors’ responses in 28 audit firms were used for data analysis. Exploratory factor analysis (EFA) was used to determine relationships between observed variables and factors. The measurement model and recommended hypotheses were confirmed by structural equation modeling (SEM) using SPSS 26 and AMOS 26. The study results show that contract types and audit complexity, audit firms’ reputation, size, and risk significantly impact audit fees and audit quality. In addition, the specialization of the audit firms does not have a positive effect on audit quality but on audit fees. The audit tenure has no statistical impact on audit fees and audit quality. Notably, audit fees statistically affected audit quality. Several implications can be applied, such as increasing the firm size, performing the procedures in response to audit risk, separating audit contract types, and determining the complexity of audit projects and specialties.
Influence of Refinery Asphalt Residue Addition on Flow: A Study Using Waxy Model-System
Authors: Valente Ana Carla , Nunes Rita , Lucas Elizabete
Published: June 2022

One of the main phenomena causing problems in the oil industry is the precipitation of waxes, which can crystallize and form deposits, clogging lines and reducing flows. Many studies have been conducted seeking to overcome this problem, mainly through application of chemical to increase flow. Some studies have shown that the asphaltenes present in crude oil can also be involved in the process of wax deposition. In this study, model systems were investigated to determine the influence of a natural additive, a chemical additive and their combined use on the fluidity of the samples. The natural additive, consisting of a refinery asphalt residue (ASPR), was studied in relation to the influence of its aggregation states on the fluidity of the wax model systems. All samples were evaluated through the pour point test, according to the ASTM D-97 standard. The results indicated that both the ASPR and the commercial poly(ethylene-co-vinyl acetate) can improve the fluidity. Synergistic effect, using both together, was verified by the significant reduction of pour point for model systems with wax content as high as 13% m v-1. That action was closely related to the concentration of ASPR and its aggregation state, as indicated by tests with different wax concentrations.
Isolation and identification of potentially pathogenic free-living amoeba in dental-unit water samples
Authors: Khatoonaki Hadi , Solhjoo Kavous , Rezanezhad Hassan , Armand Belal , Abdoli Amir , Taghipour Ali
Published: June 2022

Although the presence of free-living amoebae (FLAs) in various water sources has been reported, few studies have been surveyed on their abundance in medical-unit and dental-unit water samples. The current study aimed to identify morphological and molecular characteristics of FLA isolates in the water samples of the dental unit in Iran. A total of 232 water samples were collected from 17 dental units. Then, filtration and cultivation were conducted on a non-nutrient agar (NNA) medium. Also, polymerase chain reaction (PCR) assay and sequencing were performed by using the genus/species-specific primers plus a common primer set on positive samples. One hundred and sixty-six samples were positive for FLA by the microscopic method, whereas 114 samples were positive by the molecular method with a common primer set. Considering the PCR assay with genus/species-specific primers, 23.27% (54/232) samples were identified as Acanthamoeba spp. (belonging to T4 genotype), 36.63% (85/232) as Vermamoeba vermiformis, and 1.72% (4/232) as Vahlkampfiidae family (Naegleria lovaniensis). These results highlight a need to improve filtration systems in dental units and periodic screenings for FLA in dental-unit water.
Fuzzy risk-based allocation of pollution load using extended trading-ratio system
Authors: Monfared Ali , Reza Rabieifar Hamid , Ebrahimi Hossein
Published: June 2022

Today, one of the most important aspects of urban planning and management is the issue of environmental protection. It is necessary to consider the effects of urban development on the environment in urban planning to achieve sustainable economic and industrial development. In this paper, an optimal planning structure has been developed to reduce the pollution load of Khorramabad River, Lorestan Province, Iran. The developed fuzzy trading-ratio system was programmed based on risk-based fuzzy analysis for nine dischargers of biochemical oxygen demand (BOD5) as a water quality index and optimized using a genetic algorithm. The calibrated and verified model was utilized to simulate the BOD5 concentration at checkpoints of the river using four data sets of water quality collected from 2018 to 2021 in August (2018, 2019 and 2020 for calibration and 2021 for verification). The results showed that BOD5 exchange in the downstream stations is in critical condition. Optimization to reduce the cost of wastewater treatment showed that the proposed model could be economically improved by about 11%. The feasible domain of risk changes was assessed at three levels of 30, 60 and 90%, with the maximum value of the objective function calculated for the alcohol factory and the minimum value obtained for the flour factory.
Gardens of the Bible as a Place of Encounter between Man and God
Authors: Wawrzyniak Justyna
Published: June 2022

This article combines two goals. The first is to show the gardens of the Bible as the background settings for the most important encounters between God and man, and the second is to define the genius loci of these places. The challenge was to isolate the physical features of the gardens of the Bible as carriers of spiritual aspects. The introduction presents the role of nature and the garden as the theatre of God’s Glory (mentioned by Calvin). It explores moreover the sacred aspects of historical gardens and then describes the nature of individual gardens of the Bible and the events that took place there, closing with the results of observations ordered by parameters that make up the western-defined genius loci (spirit of the place), such as: things, earth, sky, order, and character. At the end of each description of a garden, the challenge of defining its spirit was taken for the first time. The inspiring phenomenon of gardens and the conscious use of selected elements will meet not only aesthetic expectations but also the spiritual exploration of contemporary people.
Cross-Talk between Obesity and Diabetes: Introducing Polyphenols as an Effective Phytomedicine to Combat the Dual Sword Diabesity
Authors: Shah Muhammad Ajmal , Haris Muhammad , Faheem Hafiza Ishmal , Hamid Ayesha , Yousaf Rimsha , Rasul Azhar , Shah Ghulam Mujtaba , Khalil Atif Ali Khan , Wahab Abdul , Khan Haroon , Alhasani Reem Hasaballah , Althobaiti Norah A.
Published: June 2022

Obesity-associated diabetes mellitus, a chronic metabolic affliction accounting for 90% of all diabetic patients, has been affecting humanity extremely badly and escalating the risk of developing other serious disorders. It is observed that 0.4 billion people globally have diabetes, whose major cause is obesity. Currently, innumerable synthetic drugs like alogliptin and rosiglitazone are being used to get through diabetes, but they have certain complications, restrictions with severe side effects, and toxicity issues. Recently, the frequency of plant-derived phytochemicals as advantageous substitutes against diabesity is increasing progressively due to their unparalleled benefit of producing less side effects and toxicity. Of these phytochemicals, dietary polyphenols have been accepted as potent agents against the dual sword “diabesity”. These polyphenols target certain genes and molecular pathways through dual mechanisms such as adiponectin upregulation, cannabinoid receptor antagonism, free fatty acid oxidation, ghrelin antagonism, glucocorticoid inhibition, sodium-glucose cotransporter inhibition, oxidative stress and inflammation inhibition etc. which sequentially help to combat both diabetes and obesity. In this review, we have summarized the most beneficial natural polyphenols along with their complex molecular pathways during diabesity.
The Promising Role of Natural Exosomal Nanoparticles in Cancer Chemoimmunotherapy
Authors: Premnath Archana , Benny Sonu , Presanna Aneesh Thankappan , Mangalathillam Sabitha
Published: June 2022

Exosomal nanoparticles are cell-derived nano-sized vesicles in the size range of 30-150nm formed by the
inward infolding of the cell membrane. They are encased in a lipid bilayer membrane and contain various proteins
and nucleic acids according to the characteristics of their parent cell. They are involved in intercellular communication.
Their specific structural and inherent properties are helpful in therapeutics and as biomarkers in diagnostics.
Since they are biomimetic, these small-sized nanoparticles pose many advantages if used as a drug carrier vehicle. In
cancer, the exosomal nanoparticles have both stimulatory and inhibitory activity towards immune responses; hence,
they are used in immunotherapy. They can also carry chemotherapeutic agents to the target site minimizing their
targetability concerns. Chemoimmunotherapy (CIT) is a synergistic approach in which chemotherapy and immunotherapy
are utilized to benefit each other. Exosomal nanoparticles (NPs) are essential in delivering CIT agents into
tumor tissues. Most advanced studies in CIT take place in the stimulator of interferon genes (STING) signaling
pathway, where the STING activation supported by chemotherapy-induced an increase in immune surveillance
through the help of exosomal NPs. Dendritic cell(DC) derived exosomes, as well as Mesenchymal stem cells (MSC),
are abundantly used in immunotherapy, and hence their support can be used in chemoimmunotherapy (CIT) for
multifaceted benefits.
Saikosaponin B4 Suppression Cancer Progression by Inhibiting SW480
and SW620 Cells Proliferation via the PI3K/AKT/mTOR Pathway in
Colon Cancer
Authors: Sui Hong , Fu Xueyan , Zhang Yiwei , Lin Lizhen , Wang Yushu , Liu Zhenzhen , Xia Wenxin
Published: June 2022

Background:

Colon cancer is a gastrointestinal malignancy with high incidence and poor
prognosis.

Objective:

Saikosaponin B4 (SSB4) is a monomeric component of the Traditional Chinese medicine
(TCM), Bupleurum. The current study investigates the therapeutic effect and mechanisms of SSB4 in
colon cancer.

Methods:

The proliferation of two colon cancer cell lines, SW480 and SW620, were assessed using
CCK8 and expression of regulatory molecules, including Bax, Caspase3, Caspase9, Cleaved Caspase3,
Cleaved Caspase9 and Bcl2 by flow cytometry and Western blotting.

Results:

Survival rates, assessed by CCK8, of SW480 and SW620 cells decreased significantly when
the SSB4 concentration was in the range 12.5–50 μg/ml. Flow cytometry measurements indicated
apoptosis rates of 55.07% ± 1.63% for SW480 cells and 33.07% ± 1.28% for SW620 cells treated with
25 μg/ml SSB4. Western blotting revealed upregulation of the proapoptotic proteins, Bax, Caspase3,
Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and downregulation of the anti-apoptotic protein,
Bcl2, in the presence of SSB4. Network pharmacology and molecular docking predicted that the
PI3K/Akt/mTOR pathway might be the main regulatory target for the antitumor effect of SSB4. Further
Western blotting experiments showed that SSB4 downregulated (p < 0.01) expression of PI3K,
Akt, mTOR and the phosphorylated proteins, P-PI3K, P-Akt and P-MTOR. Expression of PI3K, Akt
and mTOR mRNA was found to be downregulated by SSB4 (P < 0.01) as the result of RT-PCR measurements.

Conclusion:

SSB4 is a potent anti-colon cancer agent. Its effects are likely to be mediated by suppression
of the PI3K/AKT/mTOR pathway.
The Effectiveness of Counseling and Mung Bean (Vigna radiata L) Premix
Cookies as Complementary Food to Prevent Stunting
Authors: Nasution Zuraidah , Nurhayati Ida , Mahdiyah
Published: June 2022

Some factors that cause malnutrition in 1-2 year old children are inadequate provision of complementary food and early/late weaning. Appropriate complementary feeding from the age of 6 months and breastfeeding until at least the age of 2 years, are considered as the best feeding patterns for child’s growth and development. Education and the right food choices are needed to fulfill children’s nutritional needs in this period to prevent malnutrition which can lead to stunting. This research was conducted on 52 mothers with 1-2 years old children using quasi-experimental design by counseling and providing premix cookies that were produced using mung bean (Vigna radiata l) as intervention for 3 months. Datas were analyzed using Chi-Square correlation test and T-test. This research objective was to determine the effectiveness of counseling and premix cookies as complementary food to prevent stunting. The result shows that premix cookies were 82.14% effective in increasing the children’s body weight and achieving good nutritional status, therefore preventing the incidence of stunting. This condition was also supported by the improvement of their mothers’ knowledge and attitude (p = 0.011) in their concern about complementary feeding. Consuming the given premix cookies can fulfill children’s nutritional needs as follows: 27.69% protein, 56.59% fat, 24.04% carbohydrates and 56.89% energy. These findings conclude that mung bean premix cookies are considered effective as complementary food in reducing the incidence of stunting.
A Systematic Review of Arterial Dissections in COVID-19 Patients
Authors: Abraham Betsy , Mathew Sherman David , Sridharan Kannan
Published: June 2022

COVID-19 is often seen presenting with a myriad of signs and symptoms of multiorgan dysfunction including arterial dissection. Various theories have been proposed such as endothelial dysfunction triggered by hyper-inflammatory response that results in rupture of atherosclerotic plaque and subsequent dissection. However, the exact incidence is unknown and only case reports and case series have been published till date. Here we carried out a systematic analysis of published case reports/series related to dissection of the aorta, coronary, cerebral, vertebral, cervical, renal, and splanchnic arteries.
Intra-Observational and Inter-Observer Agreement of The Radiographic
Humerus Union Measurement (RHUM) in Patients Treated with Dynamic
Compression Plate for Humeral Shaft Nonunion
Authors: Yüce Ali , Karahan Gokhan , Kucuk Levent
Published: June 2022

Background:

It is important for orthopedic surgeons to follow the union of the fracture after surgery. This becomes even more important after nonunion surgery. The radiological union scale is popular in the follow-up of unions. However, the intraobserver and interobserver agreement of this scale in humeral nonunion surgery is still not found in the literature.

Objective:

This study aimed to reveal the intra/interobserver agreement of the Radiographic Union scale (RHUM) for the humerus as well as the relationship between this agreement, plate placement characteristics, and the number of plates in cases where plates were used for surgical treatment of humeral diaphysis nonunion.

Material and Methods:

Twenty patients who received surgical treatment for aseptic humeral nonunion at our hospital between 2010-2019 were studied retrospectively. Two observers scored the patients' anteroposterior and lateral radiographs in the postoperative 12th week according to RHUM. The data obtained were statistically analyzed.

Results:

The mean age was 52.05±15.88 years. While a single plate was used in 14 cases, a double plate was used in 6 cases. Interobserver agreement was fair-moderate. The interobserver agreement values of the single plate group were significantly higher than those of the double plate group (p<0.05). Interobserver agreement in cases with lateral plate was significantly higher than in the group in which the lateral + posterior plate was applied (p:0.01).

Conclusion:

In cases of humeral diaphyseal fracture nonunion, the number and location of the plate following surgery have a negative impact on the evaluation of RHUM scores. Given the importance of the union's follow-up and the decision to proceed with additional treatment in these cases, it may be necessary to develop a new method for determining and monitoring the union if a plate was used in the surgical treatment of humeral nonunion.
Lipid-based Nanocarriers via Nose-to-Brain Pathway for Alzheimer's and
Parkinson's Disease
Authors: Wairkar Sarika , Tambe Varunesh Sanjay
Published: June 2022

Neurodegenerative disorders are characterized by the progressive, irreversible deterioration of functions of the central nervous system, especially neurons, that lead to cognitive, motor, and intellectual impairment. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent forms of neurodegenerative disorders and are predicted to be leading causes of mortality. Although conventional formulations are available for symptomatic treatment of AD and PD, many novel formulations and routes of administration are persistently studied for their better management and nose-to-brain delivery is one of them. This platform has been explored with various nanoformulations for targeted brain delivery. Lipid nanocarriers are known for bypassing the blood-brain barrier (BBB) through nasal delivery, and several drugs have been evaluated in the lipid carrier system. This review focuses on various lipid-based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsions, nanoemulsions, micelles and cubosomes reported to treat and alleviate the symptoms of AD and PD via nasal route. It gives an overview of key findings of nasal lipid-based nanocarriers and their improved pharmacokinetic parameters and enhanced neuroprotection that may be utilized in the future to explore it commercially.
First Human Report of Relief of Lumbar and Cervical Discogenic and
Arthritic Back Pain after Epidural and Facet Joint Mesenchymal Stem
Cell Injection: A Case Report
Authors: Sharan Joshua , Barmada Amir , Prodromos Chadwick , Candido Kenneth
Published: June 2022

Introduction:

Back pain causes tremendous patient suffering and high financial cost to the
healthcare system. Mesenchymal Stem Cells (MSCs) have demonstrated the ability to enhance healing
and reduce inflammation and pain without the deleterious side effects of corticosteroids and nonsteroidal
anti-inflammatory drugs in numerous clinical series for peripheral joint arthritis. We hypothesized that
translaminar MSC injection into the epidural space would effectively treat disc arthritis without the burden
of sedation and the risks of disc space injection. We further hypothesized that MSC injection into the
facet joints would effectively and safely treat facet joint-induced back pain. The combination of epidural
and facet joint injection would potentially treat the most recognized low back pain generators with virtually
complete safety.

Objective:

We present the initial results for the first patient enrolled in phase 1 clinical trial of the efficacy
and safety of allogeneic MSCs when injected translaminarly and into the facet joints for the treatment of
recalcitrant discogenic and arthritic back pain.

Case Report:

A 47-year-old male presented with complaints of 13-year-long chronic lower back pain
resistant to conservative treatment. The decision was made to treat the patient with umbilical cord-derived
MSCs. 87 million MSCs were infused intravenously. Simultaneously, 1 million cells were injected into
each of the 8 lumbar epidural facet joints and 5 million cells into the lumbar epidural space. The patient
had no adverse events or complications related to the treatment. Five days after treatment, most of his
lumbar pain was gone, and his back spasms stopped. He no longer needed to take acetaminophen or ibuprofen
and had no difficulty sleeping without medications. The patient also reported his residual cervical
radicular pain to be 98% resolved due to the injection.

Conclusion:

We have demonstrated for the first time that MSC injection into the lumbar facet joints and
epidural space results in significant improvement of lower back pain and can improve symptoms in other
spinal regions without engendering the risks associated with intradiscal injections or epidural use of corticosteroids.
Current Insights into the Role of BRAF Inhibitors in Treatment of Melanoma
Authors: Kumar Pradeep , Singh Ankit Kumar , Kumar Adarsh , Thareja Suresh
Published: June 2022

Melanomas represent only 4% of all skin cancers, but their mortality rate is more than 50 % of any other
skin cancer. Alteration in genetic and environmental factors are the risk factors for melanoma development. The
RAS/RAF/MEK/ERK or Mitogen-activated protein kinase (MAPK) pathway is activated in melanoma. BRAF activation
is necessary to govern differentiation, proliferation, and survival. Mutations in BRAF were found in 80–90% of all
melanomas. Over 90% of BRAF mutations occur at codon 600, and over 90% of them are BRAFV600E other common
mutations are BRAFV600K, BRAFV600R, BRAF V600′E2′, and BRAF V600D. Based on αC-helix and DFG motif
(αC-helix-IN/DFG-IN), (αC-helix-IN/DFG-OUT), (αC-helix-OUT/DFG-IN) and (αC-helix-OUT/ DFG-OUT) are four
structural types of inhibitors for targeting BRAF. Sorafenib, Vemurafenib, Dabrafenib, and Encorafenib are FDAapproved
for the treatment of BRAF. Understanding melanoma pathogenesis, RAS/RAF/MEK/ERK or MAPK pathway,
and BRAF conformations, mutations, the problems with FDA approved BRAF inhibitors will be important for
new drug discovery, modification of existing BRAF barriers to improve target specific action, and prevent increasing
response levels while minimizing toxicity.
Microbiome Medicine: Microbiota in Development and Management of Cardiovascular Diseases
Authors: Garg Yogesh , Kanwar Navjot , Chopra Shruti , Tambuwala Murtaza M. , Dodiya Hemraj , Bhatia Amit , Kanwal Abhinav
Published: June 2022

The gut microbiome consists of trillions of bacteria and other microbes whose metabolic activities and interactions with the immune system go beyond the gut itself. We are all aware that bacteria and other microorganisms have a significant impact on our health. Also, the health of the bacteria directly reflects the health status of the body where they reside. Eventually, alterations in the microbiome at different sites of a body are associated with many different diseases such as obesity, IBD, malnutrition, CVD, etc. Microbiota directly or indirectly affects the heart with the formation of plaques in the blood vessels, and cell walls become prone to lesion development. This ultimately leads to heightening the overall inflammatory status via increased bacterial translocation. Metabolites derived from the gut microbial metabolism of choline, phosphatidylcholine, and L-carnitine directly contribute to CVD pathology. These dietary nutrients have trimethylamine (TMA) moiety, which participates in the development of atherosclerotic heart disease. The objective of this review was to examine various metabolic pathways regulated by the gut microbiome that appear to alter heart function and lead to the development and progression of cardiovascular diseases, as well as how to target the gut microbiome for a healthier heart. In this review, we also discussed various clinical drugs having crosstalk between microbiota and heart and clinical trials for the gut-heart microbiome.
Correlation Between Vitamin B12 Deficiency and Autoimmune Thyroid
Diseases
Authors: Kacharava Tinatin , Giorgadze Elene , Janjgava Shota , Lomtadze Nino , Taboridze Iamze
Published: June 2022

Background:

Autoimmune thyroid diseases (AITD) are the most prevalent organ-specific
autoimmune disorders. Vitamin B12 plays an important role in the proper functioning of the
immune system. The aim of this study was therefore to investigate the correlation between vitamin
B12 deficiency and AITD.

Methods and Materials:

A total of 306 patients (aged 18-65 years, mean – 37.6 ± 11.3 years and
comprising 87 males and 219 females) were studied retrospectively (observational study). Patients
were divided into groups: with and without vitamin B12 deficiency, and with and without AITD.
Differences between groups were evaluated by Fisher’s exact test for qualitative variables and by
Student’s t-test for quantitative variables. Correlations for quantitative factors were determined by
the Pearson correlation coefficient and for qualitative factors by Spearman correlation analysis. The
sensitivity and specificity of vitamin B12 deficiency for AITD were calculated by ROC analysis.

Results:

The vitamin B12 level was significantly lower in patients with AITD (and 200.70 + 108.84)
compared to controls (393.41+150.78 p<0.0001). Patients with vitamin B12 deficiency were characterized
by significantly higher mean values of anti-TPO (236.60+455.74) compared to controls
(39.51+165.57 p<0.0001). Vitamin B12 levels were inversely correlated to anti-TPO levels (r=–
0.233, p<0.001). Roc analysis of vitamin B12 as a diagnostic test for AITD gave the area under
curve as 0.881 (95% CI: 0.839-0.924), a sensitivity of – 0.947, a specificity of – 0.768, and a cutoff
value of – 178.9.

Conclusions:

The vitamin B12 level correlates significantly to AITD. The concentration of vitamin
B12 should therefore be determined in patients with autoimmune thyroiditis as a diagnostic test with
high sensitivity and good specificity.
Synthesis and Photocatalytic Activity of Si-doped TiO2 Nanotube/SnS Hybrids
for Environmental Decontamination
Authors: Ma Ning , He Hai-Yan
Published: June 2022

Background:

Heterostructures with nanoscale sizes have great superiorities in photocatalytic environment decontaminant because of their efficient interface charge transfer and great surface area.

Objective:

This work reports the facile fabrication of nano-tubular TiO2 and Si-doped TiO2 (NTs) hybridizing SnS nanocrystallites and their high-efficient photocatalytic activity.

Methods:

The modified hydrothermal processes were used to synthesize the nanotubes. A chemical bath deposition process was used to hybridize SnS nanocrystallines with the nanotubes.

Results:

The fabricated nanostructures show wide light absorption in the UV-visible region. The SBET, light absorption, hydrophilicity, and photo-induced super hydrophilicity were enhanced by Si-doping and SnS modification. Moreover, high-efficient interface charge transfer was produced after the SnS modification and further enhanced by the Si doping because of band structure modulation.

Conclusion:

Thus, the Si-doped TiO2 nanotubes/SnS heterostructures showed remarkably enhanced photocatalytic and Fenton-like photocatalytic activity in dye wastewater treatment than the TiO2 NTs. This work suggests potential materials and their facile fabrication process for the photocatalytic application of environmental decontamination.
Mechanism, Pathophysiology and Herbal Management-A Review on
Irritable Bowel Syndrome
Authors: Wal Ankita , Wal Pranay , Verma Neha , Rai Awani Kumar , Vatsha Piyush
Published: June 2022

Background:

The global distribution of IBS is surprisingly uniform, affecting men and women of all ages. Its deep-rooted character, symptoms that fluctuate from moderate to extreme, have several detrimental effects on the sufferer's standard of living; consequently, proper treatment of these patients is necessary. The etiology of IBS is unknown. Although several explanations were also proposed, the specific etiology of irritable bowel syndrome remains unknown. Clinical trials using stabilized therapies and new active medications have shown symptom reduction over placebo.

Objective:

IBS has long been linked to visceral sensitivity and gastrointestinal motor abnormalities. The pathophysiology of IBS appears to be multifaceted. However, several of the following elements are vital in forming IBS. This paper aims to provide a complete, scientific proof assessment of the prognosis, pathogenesis, and therapy choices to assist clinicians in successfully treating their patients.

Method:

The report's information was compiled by combining numerous review articles and research papers from multiple sources, including Hindawi, Elsevier, NCBI [National Centre for Biotechnology Information], and Research Gate, from 1981 to 2021, using keywords such as IBS, Brain-gut axis, postinfectious IBS, Microbiota, low-grade inflammation, and so on.

Conclusion:

The acute symptom influences the selection of medical techniques and therapy (IBS with diarrhoea, IBS with constipation, or mixed IBS). Current research demonstrates both pharmaceutical and non-pharmaceutical treatment has a positive impact (in comparison to a placebo) on irritable bowel syndrome (IBS) problems, discomfort relief, and improved health status.