bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene signature based on glycolysis is closely related to immune infiltration of patients with osteoarthritis
Authors: Chen Ziyi , Wang Wenjuan , Hua Yinghui
Published: October 2022

Background:Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant metabolism such as shifting from oxidative phosphorylation to glycolysis is a response to changes in the inflammatory micro-environment and may play a key role in cartilage degeneration and OA progression. Therefore, there is a pressing need to identify glycolysis regulators in the diagnosis of OA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis.
Methods: We systematically studied glycolysis patterns mediated by 141 glycolysis regulators in 74 samples and discussed the characteristics of the immune microenvironment modified by glycolysis. The random forest was applied to screen candidate glycolysis regulators to predict the occurrence of OA. RT-qPCR was performed to validate these glycolysis regulators. Then two distinct glycolysis patterns were identified and systematic correlation between these glycolysis patterns and immune cell infiltration was analyzed. The glycolysis score was constructed to quantify glycolysis patterns together with immune infiltration of individual OA patient.
Results: 56 differentially expressed genes (DEGs) of glycolysis were identified between OA and normal samples. STC1, VEGFA, KDELR3, DDIT4 and PGAM1 were selected as candidate genes to predict the risk of OA using the random forest (RF) method. Two glycolysis patterns in OA were identified and glycolysis scoring system was constructed to show distinct individual immune characteristics. Glycolysis cluster A and higher glycolysis score was revealed to be related to an inflamed phenotype.
Conclusions: Taken together, these results established a genetic signature for OA based on glycolysis, which has reference significance for the in-depth study of the metabolic mechanism of OA and the exploration of new clinical treatment strategies.
Selection of Genipa americana L. seed trees by genetic divergence in fruits, seeds, and seedlings
Authors: Cola Raquel Elvira , Gonçalves Maria da Penha Moreira , Maciel Maria Inês Sucupira , Ralph Lidiana Nayara , Ordonho Ritt , Gallo Ricardo
Published: October 2022

Analyses with phenotypic characters are more practical to implement in forest nurseries, considering that genetics should be examined in forest restoration projects. Genipa americana L. is an essential species in producing seedlings for this purpose. This study aimed to select G. americana seed trees, for seed collection, in an area of Atlantic Forest, through the genetic divergence study in fruits, seeds, and seedlings. The study was conducted in the Saltinho Biological Reserve in Tamandaré - PE, Brazil. The ripe fruits of 11 G. americana seed trees were collected. The physical and physicochemical characterization of the fruits, biometric characterization of the seeds, and seed emergence analysis were performed. For the genetic analyses, the model used was the 81 of the Selegen REML/BLUP software and the cluster analysis made by the UPGMA method. The seed trees selection index was also created. The coefficients of determination of the seed trees’ effects were low because there is considerable interaction between the sites in which each one is inserted. It is possible to state that all variables contribute to explaining the genetic dissimilarity between the seed trees. Seed trees 1, 4, and 6 had the best average ranks for the variables collected concerning genotypes. The Saltinho Biological Reserve is a good source of genetic and reproductive material for the species G. americana for forest restoration purposes.
Heavy Metals in Soils Associated with Fertilizers in Trinidad
Authors: Beharry Rosanna , Joseph Andrea , Gordon Andre , Voutchkov Mitko
Published: October 2022

Heavy metals in agricultural soil poses human health risks through food consumption. In a novel study for Trinidad, concentration and pollution index levels of heavy metals were assessed from 18 agricultural farms using the X-Ray fluorescence technique, then to evaluate the Geo-accumulation and Nemerow’s Integrated Pollution indexes. Toxic elements Pb and As were present but soil quality due to anthropogenic input was found as unpolluted. Overall heavy metal pollution was classified at a precautionary level for 33% of farms, slightly polluted for 61% and moderately polluted for 6% of the farms assessed, thus, regular monitoring and mitigation measures are important for food safety and human health in Trinidad.
Multi-environment genomic selection in rice elite breeding lines
Authors: Nguyen Van Hieu , Morantte Rose Imee Zhella , Lopena Vitaliano , Verdeprado Holden , Murori Rosemary , Ndayiragije Alexis , Katiyar Sanjay , Islam Md Rafiqul , Juma Roselyne U. , Galvez Hayde , Glaszmann Jean-Christophe , Cobb Joshua N. , Bartholomé Jérôme
Published: October 2022

Background: Assessing the performance of elite lines in target environments is essential for breeding programs to select the most relevant genotypes. One of the main complexities in this task resides in accounting for the genotype by environment interactions. Genomic prediction models that integrate information from multi-environment trials and environmental covariates can be efficient tools in this context. The objective of this study was to assess the predictive ability of different genomic prediction models to optimize the use of multi-environment information. We used 111 elite breeding lines representing the diversity of the International Rice Research Institute (IRRI) breeding program for irrigated ecosystems. The lines were evaluated for three traits (days to flowering, plant height, and grain yield) in 15 environments in Asia and Africa and genotyped with 882 SNP markers. We evaluated the efficiency of genomic prediction to predict untested environments using seven multi-environment models and three cross-validation scenarios.
Results: The elite lines were found to belong to the indica group and more specifically the indica-1B subgroup which gathered improved material originating from the Green Revolution. Phenotypic correlations between environments were high for days to flowering and plant height (33% and 54% of pairwise correlation greater than 0.5 ) but low for grain yield (lower than 0.2 in most cases). Clustering analyses based on environmental covariates separated Asia’s and Africa's environments into different clusters or subclusters. The predictive abilities ranged from 0.06 to 0.79 for days to flowering, 0.25 to 0.88 for plant height, and -0.29 to 0.62 for grain yield. We found that models integrating genotype-by-environment interaction effects did not perform significantly better than models integrating only main effects (genotypes and environment or environmental covariates). The different cross-validation scenarios showed that, in most cases, the use of all available environments gave better results than a subset.
Conclusion: Multi-environment genomic prediction models with main effects were sufficient for accurate phenotypic prediction of elite lines in targeted environments. The recommendation for the breeders is to use simple multi-environment models with all available information for routine application in breeding programs.
A male case of primary mediastinal choriocarcinoma accompanying with lung metastasis A case report
Authors: Zhou Yang , Kong Li , Yang Chao , Xu Lingzhi , Li Na , Zhao Xiangpeng , Luo Ning , Wang Bing , Zhang AoDan , SUN WeiHang , Kong ZiXuan
Published: October 2022

Introduction:Choriocarcinoma is a highly invasive gestational trophoblastic tumor,which is quite rare. In this case report, we analyzed the CT image features in a case of primary choriocarcinoma in the anterior mediastinum accompanying with lung metastasis.
Patient concerns:A 24-year-old male patient had recurrent chest pain for over 20 days, fever, expectoration with blood-stained sputum for over 10 days.
Diagnosis:chest CT revealed a huge mass in the anterior mediastinum and several quasi-circular nodules in bilateral lungs.The pathological diagnosis conformed to non-gestational choriocarcinoma.
Interventions:Chemotherapy using EP regimen: VP-16 0.2g d1-5, DDP 40mg d1-5 ivgtt, 21 days cycle.
Outcomes:Symptoms such as chest pain，fever，cough improved significantly. The condition is stable.
Conclusions：For young male patients with mediastinal mass and single or multiple lung nodules, accompanying with elevated B-HCG contents in urine and serum,primary choriocarcinoma should be vigilant.
cTBS over the pre-SMA in schizophrenia and comorbid substance use disorder: preliminary clinical data
Authors: Pallanti Stefano , Ponzio Michele Di , Makris Nikos , Kubicki Marek
Published: October 2022

Schizophrenia (SZ) is a debilitating disorder, which tremendously impacts psychological, social, and financial aspects of patients’ life. Frequently, SZ patients present with poor insight, which can even worse the symptomatology. Antipsychotic medications frequently result in suboptimal outcomes, especially the ones concerning negative and cognitive symptoms. Accordingly, new therapeutic options are warranted. Transcranial magnetic stimulation (TMS) has been adopted in SZ with promising results. Continuous Theta burst stimulation (cTBS) is a particularly brief and effective form of TMS. It has been successfully applied in patients with poor cognitive control (e.g., gambling disorder’s patients) targeting the pre-Supplementary Motor Area (pre-SMA). Given that poor cognitive control has been regarded as a core deficit in SZ, 11 patients with SZ were included in this study and treated with continuous TBS for a total of 10 sessions during a two-week period. Patients were divided into two groups: patients with a diagnosis of SZ in comorbidity with Substance Use Disorder (SZ + SUD) vs SZ. Patients were evaluated before and after treatment, assessing executive functions, awareness and nicotine craving. Within-group comparisons showed a significant reduction in the Scale to assess Unawareness in Mental Disorders (SUMD) scores (p < 0.05) and in the test of Fagerstrom (to assess nicotine dependence) scores (p < 0.001) before and after treatment in the SZ + SUD group. These results showed the efficacy of cTBS for craving reduction as well as in improving awareness of illness and of treatment. This can considered a remarkable result since a better insight has been previously associated with a better quality of life in SZ.
A qualitative exploration of the reasons and influencing factors for pregnancy termination among young women in Soweto, South Africa: a Socio-ecological perspective
Authors: Mabetha Khuthala , Soepnel Larske , Ssewanyana Derrick , Draper Catherine E , Norris Shane A
Published: October 2022

Background: In Southern Africa, an estimated 24% of all pregnancies end in termination of pregnancy, against a backdrop of high rates of unintended pregnancies and unsafe pregnancy terminations. Understanding of the reasons for termination may remain incomplete if seen in isolation of interpersonal (including family, peer, and partner), community, institutional, and public policy factors. This study therefore aimed to qualitatively explore young women’s reasons for terminating their pregnancy, in Soweto, South Africa, with a focus on the impact of socio-ecological factors on their experience.
Methods: In-depth interviews were conducted with ten (10) participants who underwent a termination of pregnancy since being enrolled in the Bukhali trial, set in Soweto, South Africa. A semi-structured interview guide, based on the socioecological domains, was used. The data was analysed using reflexive thematic analysis, and a deductive approach.
Results: The majority of the direct reasons to terminate a pregnancy fell into the individual and interpersonal domains of the socioecological framework. Key reasons included financial dependence and insecurity, feeling unready to have a child (again), and a lack of support from family and partners. However, factors that influenced the participants’ decision and experience, such as the available of social support and (lack of) accessibility to termination services, were identified across all domains. The COVID-19 pandemic and resultant lockdown policies also indirectly impacted participants’ decisions through detrimental changes in interpersonal support and financial situation.
Conclusions: Amongst the South African women included in this study, the decision to terminate a pregnancy was made within a complex structural and social context. Insight into the reasons why women choose to terminate helps to better align legal termination services with women’s needs across multiple sectors, for example by reducing judgement within healthcare settings and improving access to social and mental health support.
Corticosteroid Activation of Atlantic Sea Lamprey Corticoid Receptor: Allosteric Regulation by the N-terminal Domain
Authors: Katsu Yoshinao , Lin Xiaozhi , Ji Ruigeng , Chen Ze , Kamisaka Yui , Bamba Koto , Baker Michael E.
Published: October 2022

Lampreys are jawless fish that evolved about 550 million years ago at the base of the vertebrate line. Modern lampreys contain a corticoid receptor (CR), the common ancestor of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which first appear in cartilaginous fish, such as sharks. Until recently, 344 amino acids at the amino terminus of adult lamprey CR were not present in the lamprey CR sequence in GenBank. A search of the recently sequenced lamprey germline genome identified two CR sequences, CR1 and CR2, containing the 344 previously un-identified amino acids at the amino terminus. CR1 also contains a novel four amino acid insertion in the DNA-binding domain (DBD). We studied corticosteroid activation of CR1 and CR2 and found their strongest response was to 11-deoxycorticosterone and 11-deoxycortisol, the two circulating corticosteroids in lamprey. Based on steroid specificity, both CRs are close to elephant shark MR and distant from elephant shark GR. HEK293 cells transfected with full-length CR1 or CR2 and the MMTV promoter have about 3-fold higher steroid-mediated activation compared to HEK293 cells transfected with these CRs and the TAT3 promoter. Deletion of the amino-terminal domain (NTD) of lamprey CR1 and CR2 to form truncated CRs decreased transcriptional activation by about 70% in HEK293 cells transfected with MMTV, but increased transcription by about 6-fold in cells transfected with TAT3, indicating that the promoter has an important effect on NTD regulation of CR transcription by corticosteroids.
Time-period Measurements of Reversible Pendulum Using Arduino
Authors: Wadhwa Adya , Kumar Kuldeep , Wadhwa Ajay
Published: October 2022

We present an experiment to demonstrate the utility of Arduino microcontroller in the undergraduate Physics laboratory. The experiment is the traditional reversible (Kater’s) pendulum which is usedfor the determination of acceleration due to gravity ‘g’. We use the IR sensor with Arduino as an interface to determine accurately the time intervals. This work is inspired by the feedback received from undergraduate students who wanted to improve upon the traditional way of measuring the time periods of oscillations.
Regulatory roles of ACSL5 in anti-tumor function of Palmitic acid (C16:0) via ERK signaling pathway
Authors: Lv Jiapei , Wang Yanting
Published: October 2022

Background
Non-small cell lung cancer (NSCLC), accounting for 85% of all types of lung cancer cases, is a malignant disease with high incidence worldwide. Meanwhile, mounting evidence indicates this lesion is easily susceptible to the perturbation of lipids metabolism. Our team identified palmic acid (C16:0) as a novel treatment to interact with NSCLC for the first time and the expression patterns of ACSL5 stimulated by C16:0, however, its pathogenesis remains poorly understood in NSCLC.
Methods
A549 cells were treated with a different dose of palmitic acid. Then, CCK-8 assay, annexin V-FITC/PI double staining assay, wound healing assay and Transwell assay were performed to evaluate the effects of PA on proliferation, apoptosis, migration and invasion of A549 cells. Further, the expression levels of ACSL5 and the related proteins were detected by qPCR and Western blotting. Tumor volume assay and hematoxylin-eosin staining were used to detect tumor growth in vivo.
Results
The trend toward proliferation, apoptosis, migration and invasion can be substantially flattened by PA in A549 cells. Meanwhile, compared with the control group, a significant increase in expression levels of ACSL5 and related proteins has been observed in PA-treated A549 cells. Moreover, the knockdown of ACSL5 reversed the anti-tumor effect, resulting in an increase in the rate of above malignant phenotype in tumor. In addition, the expression of ERK phosphorylated protein was inhibited dramatically with the increased concentration of C16:0 in A549 cells.
Conclusion
C16:0 decreases the rate of proliferation and apoptosis, inhibits cell migration and invasion of NSCLC cells, and its mechanism may be related to the targeted regulation of ACSL5 and activation of the ERK pathway.
Evaluación de la percepción de la calidad de los servicios de salud y de la cooperación internacional durante la pandemia COVID-19 en un hospital del caribe colombiano
Authors: Vega Salinas Marianela , Gonzalez Rubio Altamar Carlos , Uribe Calderón Laura Marcela
Published: October 2022

El proceso de mejora continua es clave en la calidad de los servicios de salud, por lo cual es necesario realizar evaluaciones constantes, que permitan controlar las acciones como un engranaje perfecto para mejorar las capacidades entre actores del sistema de salud. Objetivo: evaluar la percepción de la calidad de los servicios de salud a través del modelo SERVQUAL y la actuación de la cooperación internacional durante la pandemia COVID-19 en un hospital de baja de complejidad en el caribe colombiano. Metodología: se realizó de un estudio observacional de tipo descriptivo en temporalidad prospectiva, el análisis de los datos se realizó a través del programa estadístico informático SPSS. La encuesta se aplicó a 107 personas seleccionadas en un muestreo aleatorio simple que recibieron atención médica durante el año 2020. Resultados: las dimensiones mejor puntuadas fueron empatía y seguridad, mientras que capacidad de respuesta presentó la menor puntuación. El promedio de la percepción general sobre la calidad del servicio de salud se estimó en 4,90 lo que corresponde a una percepción positiva regular considerando que el valor máximo posible de calificación por los usuarios era de 7,0. Con lo que respecta a la cooperación internacional el 30% de los sujetos manifestaron haber escuchado ocasionalmente sobre la participación de la misma. Conclusión: la pandemia COVID-19 afectó sin lugar a dudas las dimensiones propuestas para la calidad de la atención en salud y la cooperación internacional tuvo una imagen positiva en beneficio de la respuesta y la ayuda durante la emergencia sanitaria.
Palabras clave: Servicios de salud; Virus; Cooperación internacional; Percepción; Salud.
Sobrepeso y obesidad en menores de cinco años
Authors: Escobar Velasquez Katty , Hernández Álvarez Guiomar , López Sáleme Rossana
Published: October 2022

Objetivos: Determinar los factores sociales, culturales, familiares y patrones alimentarios relacionados con el exceso de peso en la primera infancia en la ciudad de Cartagena
Metodología: Estudio analítico cross-sectional, con una muestra de 440 niñas y niños, muestreo por conglomerados, valoración del estado nutricional por medidas antropométricas y los factores socioculturales, familiares y los hábitos alimentarios a través de cuestionario de ENSIN 2015 y la ficha de AIEPI clínico.
Se aplicaron técnicas de estadística descriptiva y de medidas de asociación chi cuadrado.
Resultados: En los niños y niñas menores de 5 años se encontró una prevalencia de sobrepeso de 7,79%, obesidad 6,23%, y una prevalencia de exceso de peso de 14,03%.
Se encontró asociación con el sobrepeso en factores como: No tener estudio por parte del padre (p0,012) y pertenecer a un estrato socioeconómico alto (p 0,04).
En cuanto a la obesidad fueron significativa las asociaciones con: El cuidador no tiene estudios (p0,021), estrato socioeconómico bajo y el niño de 2 años come solo (p0,013).
No se encontró asociación con el consumo de alimentos específicos.
Conclusiones: El exceso de peso va en aumento en la población mayor de 2 años, los factores sociales y familiares mantienen relevancia en la malnutrición por exceso
Palabras clave: Obesidad; Primera infancia; Nutrición; Dinámica familiar; Niñez; Unesco; Clacso.
Constraints and enablements on quality improvement in higher education
Authors:   , Browning Leanne Elizabeth
Published: October 2022

This study contributes to the literature on quality improvement in higher education by examining the structural, cultural and agential constraints and enablements on a quality process at a university in South Africa. It examined four cases and developed an understanding of the complex interaction of structure, culture and agency and the mechanisms that enable or constrain quality improvement in higher education. The study drew on the literature on higher education quality for the theoretical basis for what is known contributes to the way in which quality assurance and improvement is implemented and its impact on the higher education context. Critical Realism provided the ontological framework and conceptual tools to understand and explore the complex social world within which the quality process took place. The literature on the morphogenetic approach provided the analytical framework for the data analysis and findings. The data consisted of a set of documents from a quality process that took place over a five-year period. The data analysis revealed that different departmental contexts impact on how mechanisms are activated. Each school context shapes the way in which people engage with the review process and consequently, processes and procedures are mediated in each context. This research therefore adds to the understanding of the way in which quality processes take place at a micro-level within an institutional context and informs the approach to quality improvement more broadly, nationally and internationally. The research contributes to the knowledge that will inform planning, policies and practices in quality improvement processes in higher education and the findings identify a number of factors (mechanisms) that should inform the way in which a quality process is facilitated, will enable effective self-evaluation and review processes, and consequently are more likely to lead to quality improvement.
Promoting azo dye decomposition in natural molybdenite activated peroxymonosulfate process by low concentration of ferrous ions
Authors: Qin Yingzhi , Zhang Xin , Yuan Guang-En
Published: October 2022

In this study, low concentration of ferrous ions (Fe2+) was added into natural molybdenite (MDN) activated peroxymonosulfate (PMS) process to degrade a typical azo dye, orange G (OG). It was found that the addition of Fe2+ promoted OG degradation and simultaneously reduced the leaching of toxic Mo ions significantly. Further, the utilization efficiency of MDN was improved immensely, which was estimated from reuse experiment. MDN mainly acted as the reductant to promote cycling of Fe3+/Fe2+ redox couple through reducible sulfur and Mo(IV) on its surface. Sulfate radicals (SO4•-), hydroxyl radical (•OH) and singlet oxygen (1O2) were verified as the main reactive oxygen species responsible for OG degradation by scavenging tests and electron paramagnetic resonance. Some experiment parameters, such as MDN dosage, Fe2+ concentration, PMS concentration, initial solution pH and coexisting anion, all affected OG degradation efficiency. In a word, this work provides a new method of enhancing PMS activation by MDN using low concentration of Fe2+ for degradation of organic pollutants in water.
Insights into activated sludge/Chlorella consortia under dark condition compared with light condition
Authors: Fan Jie , Zhang Xujie , Du Xingyu , Cai Zhenlei
Published: October 2022

Bacteria–algae consortia in the light bring the benefit of O2 production and CO2 reduction for wastewater treatment, while the bottleneck for application is how it behaves in the dark. In this study, inoculum ratio and sludge retention time (SRT) affected nutrient removal rather than chemical oxygen demand (COD) removal. Dark conditions (with a sludge/Chlorella inoculum ratio of 1:2 at a SRT of 15 d) achieved comparable performance to those of light conditions, due to bacteria contribution and mechanical aeration. Compared with light conditions, the ratio of Chla/Chlb decreased and Caro/(Chla + Chlb) increased to response oxidative stress. In the dark, algae were associated with Nitrosomonas and Dechloromonas. Flavobacterium disassociated with Chlorella in the dark but associated with Chlorella in the light. Moreover, nitritation genes (amo and Hao) and denitrifying gene (narH) were up-regulated, while P metabolism genes (PPX and PPK) were down-regulated. It is proposed to enrich Nitrosomonas in the night and denitrify polyphosphate accumulating organisms (DPAO) in the daytime to establish short-cut nitrification and denitrifying phosphorus removal in practical applications.
Surfactant modified waste ash for the removal of chloro and nitro group substituted benzene from wastewater
Authors: Mushtaq Sadiya , Aslam Zaheer , Ali Rizwan , Aslam Umair , Naseem Sana , Ashraf Muhammad , Bello Mustapha Mohammed
Published: October 2022

A surfactant-modified coal fly ash was developed as a multifunctional adsorbent for the removal of organic pollutants from wastewater. Sodium dodecyl sulfate (SDS) was used to modify the surface of coal fly ash (CFA). The modified CFA was characterized using scanning electron microscopy (SEM), surface porosity analyzer, thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. The results showed that loading CFA with SDS not only improved the functionality and surface morphology of the raw ash for the adsorption of organic pollutants, but also enhanced its thermal stability. The efficiency of the modified fly ash was tested in terms of removal of two non-polar organic pollutants namely chlorobenzene (CB) and nitrobenzene (NB) from aqueous phase. The maximum uptake capacity of chlorobenzene and nitrobenzene with SDS-modified coal fly ash (SCFA) was 225 mg/g and 90 mg/g, respectively. The kinetic analysis was done by controlled kinetic models, i.e., pseudo first and second order kinetic models. The results showed that adsorption of CB and NB onto SCFA followed a pseudo second order kinetic model. The adsorption of chlorobenzene was exothermic over the modified adsorbent while nitrobenzene showed an endothermic behavior. The isotherm analysis depicted the multilayer adsorption of both pollutants onto the surface of the surfactant modified adsorbent. This work has shown that surface modification using surfactants can be a viable option to enhance the adsorption capacity of fly ash for pollutants removal.
Carnitine Palmitoyltransferase: A Viable Target for the Treatment of
NIDDM?
Authors: Anderson Robert C.
Published: October 2022

Inhibition of fatty acid oxidation is well recognized as a potentially effective mechanism for controlling glycemia in non-insulin-dependent diabetes mellitus (NIDDM). However, a direct targeting of inhibition cif the intramitochondrial -oxidation pathway or an indirect modulation of fatty acid oxidation by inhibition of substrate release from adipose stores has been fraught with lack of efficacy, unacceptable side­ effects or both. Focus has therefore recently been directed towards the carnitinc
palmitoyltransferase (CPT) system, a three-component system necessary for the transfer
of long-chain fatty acids into the intramitochondrial matrix. This article will briefly review the background for fatty acid oxidation inhibition in NIDDM and then focus on the progress in the biological understanding and drug discovery targeting of the CPT system for the treatment of NIDDM. Based upon the review, it is concluded that mechanism-based hepatic and myocardial toxicities in normal animals and a potential for a lack of human efficacy may pose insurmountable hurdles for the development of CPT inhibitors for the treatment of NIDDM.
The Fluorinated Quinolones
Authors: Kidwai M. , Misra P. , Kumar R.
Published: October 2022

Following the discovery of nalidixic acid in 1962, numerous structural modifications have been made to the quinolone nucleus to increase antimicrobial activit> and improve pharmacokinetic performance. A major advance occured during the 1980\ with the discovery that a fluorine at position-6 conferred broad and potent antimicrobial activity, (e.g. norfloxacin) but still with relatively less activity for Gram-positive and antiaerobic organisms than Gram-negative bacteria. Subsequent developments produced quinolones with further improvements, predominantly in either solubility (e.g. ofloxacin), antimicrobial activity (e.g. ciprotloxacin) or prolonged serum half-life (e.g.
pefloxacin). Recent modifications have attempted to achieve an optimal blend of favourable prupcn1c, together with minimal potential for undesirable side-effects. The mode of action of quinolones is by blocking of the bacterial enzyme gyrase. This enzyme is responsible for the coiling and supercoiling of the DNA within the cell. When this enzyme is inhibited, DNA transcription, which results in protein synthesis, and DNA replication, which results in cell division, are inhibited.
Improvements in antimicrobial activity combined with adequate blood and tissue concentrations do offer expectancy of enhanced therapeutic efficacy for new derivatives in those infections by organisms which are 'marginally' sensitive to currently used quinolones. The possibility of resistance emerging in these organisms during treatment should also be reduced.
Cytotoxics Derived from Distamycin A and Congeners
Authors: Cozzi P. , Mongelli N.
Published: October 2022

Distamycin A is an antibiotic, characterised by an oligopeptidic pyrrolocarbamoyl frame ending with an amidino moiety, which binds reversibly to DNA minor groove with high selectivity for TA-rich sequences and shows antiviral and antiprotozoal activity. Distamycin was used as DNA sequence selective vector of alkylating functions, leading to a substantial increase of cytotoxicity in comparison to that, very weak, of distamycin itself. The benzoyl nitrogen mustard derivative of desformyldistamycin, tallimustine, was selected as a candidate antineoplastic drug in view
of its strong activity against a series of experimental tumors. Tallimustine, like distamycin, shows DNA selective binding to TA-rich sequences but its cytotoxicity is not associated with DNA strand breaks and interstrand crosslinking, at variance with classical phenyl nitrogen mustards. Tallimustine represents an important model for the design of new minor groove alkylating agents derived from distamycin and analogues, including the so-called lexitropsins, sequence-reading oligopeptides in which one or more N-methyl-pyrrole units of distamycin are replaced by imidazole or other rings. The structural features of the alkylating moieties and binding frames, the antitumor activities and the mechanism of action of most representative cytotoxics derived from distamycin and congeners are discussed. Some of these, recently reported, show an activity profile apparently superior to tallimustine. Finally, a concise survey of representative hybrid compounds in which known non-alkylating cytotoxic agents or their active moieties have been tethered to distamycin and congeners is presented and briefly discussed. These compounds witness the attention paid to this approach on the basis of the interest for the DNA binding features of distamycin A.
The Protein Kinase ABC's of Signal Transduction as Targets for Drug Development
Authors: Glazer Robert I.
Published: October 2022

Signal transduction plays a key regulatory role in the growth and metastatic potential of tumor cells. These signaling pathways form an interconnecting grid that serves to regulate the homeostatic, survival and invasive functions of the cell. Among the key regulatory molecules in these pathways are the serine/threonine-protein kinases A, B and C, also known respectively as cyclic AMP-dependent protein kinase (PKA), Akt (PKB) and protein kinase C (PKC). These protein kinases modulate pathways associated with tumor proliferation, cell survival and multidrug resistance, and at a molecule level
are likely to serve as effective targets for drug design. The unique structural features of each protein kinase have been deduced from their crystallographic structures and form unique opportunities for structure-based drug design. In addition, these. protein kinases are potentially important targets for antisense oligonucleotide therapy, and therefore may provide a means of selectively inhibiting tumor proliferation and inducing apoptosis with minimal nonspecific cytotoxicity.
New Approaches to Rapid Onset Antidepressants
Authors: Briner Karin , Dodel Richard C.
Published: October 2022

The challenges for the design of new antidepressant drugs are threefold: rapid onset of antidepressant response, broader efficacy, and fewer adverse effects. While progress has been made to reduce side-effects, the currently available drugs show no convincing evidence for a shorter delay of onset nor for improved efficacy. This review summarizes some of the hypotheses that try to explain the delayed onset and that are currently used for antidepressant drug design. These approaches include combinations of SSRI activity with either NA reuptake inhibition or 5-HT1 A-, 5-HT2-, or a.2-adrenergic receptor specificity, as well as targeting interactions with specific receptor subtypes (5-HT1A, 5-HTJA/5-HT2, 5-HTJB/D, a.2/5-HT2, D2/D3). Structure activity relationship studies to obtain molecular entities with the desired pharmacological profile are discussed. Many structural modifications have exploited successfully the acquired knowledge on structural features that are necessary for monoamine reuptake inhibition as well as for affinities at various receptors. Most of the current drug design efforts are focused on these approaches, which are based on the monoamine theory of depression; however, novel biological concepts of depression involving other receptor systems or intracellular targets are briefly mentioned. Although their impact on the onset of antidepressant response is only a matter of speculation at this moment, they may lead to the identification of targets for truly novel antidepressants.
The Inhibitory Glycine Receptor: Prospects for a Therapeutic Orphan?
Authors: Breitinger H.-G. , Becker C.-M.
Published: October 2022

The inhibitory glycine receptor is a member of the ligand-gated ion channel superfamily. It mediates inhibitory synaptic transmission in mammalian spinal cord and brainstem. Structure and function of the receptor, as well as its chromosomal localization and genetic structure, have •been extensively studied. While hereditary and acquired receptor dysfunctions can be identified, selective and specific modulation of receptor function is still lacking. The preponderance of current literature regarding the inhibitory glycine receptor raises the prospect that adequate methods for the treatment of glycine receptor-mediated disorders might be developed.
Inhibitors of Tryptase for the Treatment of Mast Cell-Mediated Diseases
Authors: Rice Kenneth D. , Tanaka Richard D. , Katzt Bradley A. , Numeroftt Robert P. , Moore William R.
Published: October 2022

Human tryptase is a structurally unique and mast cell specific trypsin-like serine protease. Recent biological and immunological investigations have implicated tryptase as a mediator in the pathology of numerous allergic and inflammatory conditions including rhinitis, conjunctivitis, and most notably asthma. A growing body of data further implicates tryptase in certain gastrointestinal, dermatological, and cardiovascular disorders as well. The recent availability of potent, and selective tryptase inhibitors, though, has facilitated the validation of this protease as an important therapeutic target as well.
Herein, we describe the design and potency of four classes of selective tryptase inhibitors, of which the first
three types are synthetic and the fourth is natural in origin: 1) peptidic inhibitors (e.g., APC-366), 2) dibasic inhibitors (i.e., pentamidine-like), 3) Zn2+-mediated inhibitors (i.e., BABIM-like), and 4) heparin antagonists
(e.g., lactoferrin). These inhibitors have been tested in the airways and skin of allergic sheep. Aerosol administration of tryptase inhibitors from each structural class 30 minutes before, and 4 hours and 24 hours after allergen challenge, abolishes late phase bronchoconstriction and airway hyperresponsiveness in a dose­ dependent manner. Moreover, intradermal injection of APC-366 blocks the cutaneous response to antigen. These studies provide the essential proof-of-concept for the further pursuit of tryptase inhibitors for the treatment of asthma, and perhaps other allergic diseases. Results from clinical studies with the first generation tryptase inhibitor APC-366, currently in phase II trials for the treatment of asthma, provide additional support for a pathological role for tryptase in this disease.
Notable advances in the area of tryptase inhibitor design at Axys Pharmaceuticals, Inc. include a novel, zinc­ mediated, serine protease inhibitor technology (described herein), and the discovery of a unique class of extremely potent and selective dibasic tryptase inhibitors. Independently, an X-ray crystal structure of active tryptase tetramer complexed with 4-amidinophenyl pyruvic acid has been reported. It is anticipated that these discoveries will further accelerate the design of structurally novel tryptase inhibitors as well as the development of new drugs for the treatment of mast cell tryptase-mediated disorders.
Cell Adhesion Molecule CD99 in Cancer Immunotherapy
Authors: Yu Feng , Liu Guodong , Zhang Hailing , Wang Xiaoyan , Wu Zhi , Xu Qinggang , Wu Yan , Chen Dongfeng
Published: October 2022

The CD99 antigen is a transmembrane protein expressed in a broad variety of tissues, particularly in hematopoietic cells, thymus, endothelial cells, etc. It participates in several crucial biological processes, including cell adhesion, migration, death, differentiation, and inflammation. CD99 has shown oncogenic or tumor suppressor roles in different types of cancer. Therefore, it has been used as a biomarker and therapeutic target for several types of cancer. Moreover, it has also been reported to be involved in several critical immune processes, such as T cell activation and differentiation, dendritic cell differentiation, and so on. Hence, CD99 may have potential values in cancer immunotherapy. Anti-CD99 antibodies have shown therapeutic effects on certain types of cancer, especially on Ewing sarcoma and T cell acute lymphoblastic leukemia (ALL). This review summarizes the recent progress of CD99 in cancer research and targeting therapies, especially in cancer immunotherapy, which may help researchers understand the crucial roles of CD99 in cancer development and design new therapeutic strategies.
Case Report: A Novel Mutation Leading to 11-β Hydroxylase Deficiency in
a Female Patient
Authors: Ozbas Burak , Demir Mikail , Dursun Huseyin , Sahin Izem , Hacioglu Aysa , Karaca Zuleyha , Dundar Munis , Unluhizarci Kursad
Published: October 2022

Background:

11β hydroxylase deficiency (11βOHD) ranks as the second most common
enzyme deficiency that causes congenital adrenal hyperplasia. Depending on the severity of the enzyme
deficiency, it can lead to cortisol deficiency, androgen excess and hypertension due to increased
mineralocorticoid precursor levels. Many different types of mutations in the CYP11B1 gene located on
chromosome 8q24.3 have been shown to cause 11βOHD. Here, we report a novel missense mutation
that leads to 11βOHD in a female patient.

Case Presentation:

A 35-year-old female patient was admitted to the Endocrinology Department with
a complaint of abdominal pain. The patient had a history of genital reconstruction surgery twice in
childhood. On physical examination, an abdominal mass was detected. Laboratory examination of the
patient revealed low levels of cortisol, potassium and high levels of ACTH, 11-deoxycortisol and
androstenedione, suggesting 11βOHD. Genotyping showed a novel homozygous missense mutation
(c.1385T>C L462P variant) detected on the 8th chromosome where the CYP11B1 gene is located.
Glucocorticoid therapy was commenced for the patient whose diagnosis of 11βOHD was confirmed by
both hormonal and genetic tests. A mass originating from the left adrenal gland with the largest diameter
of 7 cm was compatible with myelolipoma.

Conclusion:

In this case report, we aimed to contribute to the literature by reporting a new missense
mutation in the CYP11B1 gene, leading to classic type 11βOHD that has not been described before.
Antimicrobial agent containing absorbable gelatin sponge to prevent dry socket: A systematic review
Authors: Sadeghi Shalaleh Hosseini , Sharifi Simin , Dizaj Solmaz Maleki , Ghavimi Mohammad Ali , Shahi Shahriar , Ghoreishizadeh Arezou , Negahdari Ramin
Published: October 2022

Background:

The use of absorbable gelatin sponges (AGSs) as a hemostatic surgical material resulted in a reduction of dry sockets occurrence. The systemic use of antibiotics and antimicrobial agents can also reduce the infection of extracted teeth, and therefore, it may show pain-relieving effects on the dry socket as well.

Objective:

Given the high prevalence of dry sockets in the extracted teeth, the main objective of this review was a brief overview of AGSs, including antimicrobial agents to prevent dry sockets.

Methods:

The electronic search of the literature was done on the Pubmed and Google Scholar databases with the MESH keywords of Antimicrobials, Gelatin sponge, Gelfoam, Dry socket, Antibiotics, Alveolar osteitis. Only papers published in English were investigated. No limitations were put on the publication date.

Results:

Of the 279 electronic papers, 79 articles were found relevant to the study. All abstracts were reviewed, and only desired articles were selected. The final electronic and manual search led to 15 articles for use in this study. Among these studies, 5 studies were related to AGSs, including antimicrobial agents to prevent dry sockets.

Conclusion:

The reviewed literature showed that the systemic/topical use of antibiotics and antimicrobial agents can reduce infection and, therefore, may show pain-relieving effects on the dry socket. Besides, antimicrobial-loaded AGSs can be helpful in curing or preventing dry sockets. There were a limited number of clinical trials that used antimicrobial loaded AGSs for dry socket. More clinical studies are needed, especially in subgroups of patients with a high risk of infectious conditions, to validate the effectiveness of antimicrobial-loaded AGSs for dry socket.
Analysis of tensile strength and microstructure on GTAW- Aluminum 6061 welding results
Authors: Fakhri Ardani Ahsanul , Basyirun Basyirun , Fikrie Ahmad
Published: October 2022

The process of joining aluminum metal requires a special welding method. The use of GTAW welding is a suitable method for joining aluminum plates. This research is intended to analyze the tensile strength and microstructure of the GTAW Aluminum 6061 welding with various currents. The research method used in this research is experimental research. Welding current variations used in this study were 100A, 115A, and 130A, then tested using a destructive test, tensile test. The data analysis used in this study is descriptive analysis, where the data obtained are averaged and then described and concluded. The results of microstructure research on GTAW welding show that changes in the microstructure are very visible in the HAZ area and the weld metal, the greater the heat input, the more spread the Mg2Si grains will be. Good structural dispersion only occurs at 130A current. This is different from the base metal which does not change the material structure at all. Based on the tensile test, the tensile stress value is 80.9 MPa at 100 A current, 84.9 MPa at 115A current variation, and the highest tensile strength is 86.7 MPa at 130A current. So, it can be concluded that the higher the current used, the better the microstructure and tensile strength produced.
بونیادی گێڕانەوەی تەنزئامێزانە لە (ڕشتەى مرواری و ڕیسالەى دلگوشا) دا
Authors: Amin Muhammad Muhammad Dler , كەسنەزانی بوشرا قادر كاكە محەمەد
Published: October 2022

ئەم باسە بە ناونیشانى بونیادی گێڕانەوەی تەنزئامێزانە لە "ڕشتەى مرواری و ڕیسالەى دلگوشا دا"، لێکۆڵینەوەیەکی بەراوردکارییە لە نیوان هەردوو کتێبی پەخشانی "ڕشتەى مرواریی عەلائەدین سەجادی" و حیکایەتی نێو "ڕیسالەى دلگوشای عوبەید زاکانی"، کە خۆی لە حیکایەتە عەرەبی و فارسییەکاندا دەبینێتەوە. تەوەری سەرەکی باسەکە قسەکردنە لەسەر بونیادی گێڕانەوەی ساتیروگاڵتەجاڕانە لە نێو ئەو حیکایەتانەدا، کە هەندێکی بە مەبەستى ڕەخنەگرتنە لە ڕەفتار و کردارە ناپەسەندەکانى ناو کۆمەڵگا، هەندێکی تری حیکمەت و پەنددادانە. لەگەڵ ئەوەشدا بونیادەکە بەهۆی زمانێکی ڕەوان و سادەوە لە هەردوو ئەدەبی کوردی و فارسی دا پێکهاتووە، زۆرینەى خەڵک لێی تێگەیشتوون، بەڵام ئەم تێگەیشتنە نەبۆتە هۆی قبوڵکردن و وەرگرتنى، چونکە بەشێکی بونیادنانەکە لەسەر بنەمای تابووشکێنى کۆمەڵایەتى و ئایینى و سیاسییە، بۆیە هەردوو نووسەر ڕوبەرووی تانە و سەرزەنشتکردن بوونەتەوە، زۆرجاریش ئەدەبیاتەکەیان بە ئەدەبیاتى لاڕێ و لادەر و بێڕوو لە قەڵەم دراوە و لە زۆرێک لە چاپەکانی ئێراندا بە سانسۆرەوە بەرهەمەکان چاپ دەکرێنەوە.
گرنگی ئەم باسە، لەوەدا خۆی دەبینێتەوە، تا ئێستە لە ناو ئەدەبی کوردیدا کەمترین لێکۆڵینەوە لە بارەى گێڕانەوەکانى ناو کتێبی ڕشتەى مروارییەوە کراوە، هاوتا، هیچ باسێکمان بەرچاونەکەوتووە بەراوردی تەنزی گێڕانەوەی نێوان ئەو دوو ئەدەبەى کردبێت، بۆیە پێمان وایە جێی خۆی دەگرێت.