bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulsational Studies of δ Scuti Stars with TESS and K2: Discovery of New Variables and Insights into Stellar Structure
Authors: Zhou Ai-Ying
Published: July 2023

With TESS and Kepler K2 light curve archive, 13 known $\delta$ Scuti stars were reanalyzed and a small region survey of 1 deg radius centered on V1821 Cyg in the open cluster NGC 26871 was carried out. We discovered 45 new variables which include: 11 eclipsing binaries with pulsating components, 9 $\gamma$ Doradus stars, 8 $\delta$ Scuti stars, and other types. AD Ari is now reclassified as an eclipsing binary. The strong beating caused by two close frequencies present in the $\delta$ Sct star CD-54 7154. We can resolve at least 53 pulsation frequencies in $\iota$ Boo. At the same time, V1821 Cyg, V2238 Cyg and other stars pulsate with a couple of dozen frequencies, which is a significant improvement from the previous ground photometry results of a few. In particular, K2 data greatly increased the number of pulsation frequencies of three $\delta$ Sct stars: BU and BV from six to 27, and BN Cnc from five to ten. EX Cnc is an enticing asteroseismic target for its three groups of pulsation frequencies. Only a few stars can exhibit rich and regular pulsation patterns in their frequency spectra. With high-precision and long-term space-borne photometry, we can discern the pulsational contents of these stars more clearly and enhance our knowledge of them. The true nature of a star’s variability can be revealed by advanced photometry. The current small survey deserves to be continued and further expanded. The H--R diagram using the largest amount of member stars shows both $\delta$ Scuti and $\gamma$ Doradus stars occupy almost the same region; this would suggest a united pulsation mechanism.
Unveiling the therapeutic potential of Ponatinib and Imatinib against Aurora Kinase A in gastric cancer cells
Authors: Varshney Nidhi , Kashyap Dharmendra , Saini Vaishali , Singh Siddharth , Kumar Sachin , Elangovan Manivannan , Brás Natércia F. , Jha Hem Chandra
Published: July 2023

Aurora kinase A (AURKA) is considered a promising therapeutic target because of its abnormal expression pattern in multiple cancers. Since AURKA possesses a high similarity in active binding site with other kinases, we attempted to investigate and rationalize several kinase inhibitors that are currently under preclinical and clinical settings. All such inhibitors were selected based on sequence and structural similarity of AURKA with other kinases. Molecular docking revealed that Ponatinib, Imatinib, GSK-2334470, CFI-400945, MK2 inhibitor 3, and Vemurafenib bound to AURKA with high affinity. Molecular Dynamic (MD) simulations were carried out to assess pocket druggability, and stability of the potential inhibitors with respect to binding free-energy calculations. The findings suggested stable binding, particularly, for Ponatinib and Imatinib with AURKA via Van der Waals interactions. We identified Leu139, Val147, Lys162, Tyr212, Gly216, Leu263, and Asp274 as hotspot residues for binding of the inhibitors. Further, in vitro analyses of Ponatinib and Imatinib along with positive control MLN8237 realized decrease in AURKA expression at genomic as well as protein level studies even after ectopic transfection of AURKA. Notably, these compounds also reduced the expression of related signaling molecules β-catenin, STAT3 and its phosphorylation and NF-𝜿B and its phosphorylation. Beside the negative influence exercised by inhibitors on the oncogenic effect such as cell proliferation and genomic instability, Ponatinib and Imatinib also induced apoptosis rescue by AURKA and enhanced the protein expression of apoptotic markers like Caspase 9, 8, 3 and PARP1. Our results suggest these compounds as promising molecules to be used against AURKA.
Translation and Validation of a Chinese Version of the Body Talk Scale for Women and Men
Authors: He Jinbo , Lu Yining , Barnhart Wesley R. , Tang Chanyuan , Zhang Hengyue , Zhao Yiqing , Lin Linda
Published: July 2023

Research on body talk has received increasing research interest in recent years, with accumulating evidence supporting the link between body talk and body image and eating disturbances. However, research on body talk in China is still relatively scarce and is generally focused on fat talk, especially for women, and much remains unknown about muscle talk and positive body talk for both Chinese women and men. To promote a better understanding of body talk in the Chinese context, the present study aimed to translate the Body Talk Scale (BTS) into Chinese Mandarin (i.e., C-BTS) and evaluate the factor-structure and psychometric properties of the C-BTS in Chinese adult women and men. The English version of the BTS was translated into Chinese Mandarin with standard procedures. With 300 Chinese women (Mage = 29.48 years, SD = 7.26) and 300 men (Mage = 29.36 years, SD = 6.81), we examined the factor structure and gender invariance of the C-BTS, as well as internal consistency reliability, test-retest reliability, and construct validity including convergent, concurrent, and incremental validity of the C-BTS. The results indicated that the C-BTS had three subscales (Negative Fat Talk, Negative Muscle Talk, and Positive Body Talk) and had good reliability and validity. The findings demonstrate that the C-BTS is a useful measure of body talk in both Chinese women and men.
Experiences of healthcare personnel on the efficacy of artemisinin-based combination therapies and malaria diagnosis in hospitals in Uganda
Authors: Ocan Moses , Bakubi Racheal , Tayebwa Mordecai , Basemera Joan , Nsobya Sam
Published: July 2023

Background
The risk of widespread resistance to artemisinin-based combination therapies (ACTs) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed Artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACTs in management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda.
Methods
This was a qualitative study in which data was collected from healthcare personnel in hospitals using key informant interviews. The key informant interview guide was developed, pre-test prior to use and covered the following areas, (i) sociodemographic characteristics, (ii) malaria diagnosis (clinical and parasite based), (iii) quality assured artemisinin-based combination therapy, (iv) malaria patient follow-up, (v) artemisinin resistance, (vi) antimalarial self-medication. Data was entered in Atlas.ti ver 9.0 and analysis done following a framework criterion.
Results
A total of 22 respondents were interviewed of which 16 (72.7%) were clinicians. Majority, 81.8% (18/22) of the respondents were male. The following themes were developed from the analysis, malaria diagnosis (procedures and challenges), use of malaria laboratory test results, malaria treatment in hospitals, use of quality assured ACTs (QAACTs) in malaria treatment, and efficacy of ACTs in malaria treatment.
Conclusion
Most healthcare personnel-initiated malaria treatment after a positive laboratory test. Malaria patients who report remaining symptomatic after taking a full course of ACTs are common especially in high malaria transmission settings in Uganda. There is need for regular monitoring of artemisinin resistance emergence and spread in the country.
Demystification of CLSPN multiple potentialities in hepatocellular carcinoma: insight into individualized diagnosis and precision therapeutics
Authors: Shi Yanlong , Wang Yizhu , Niu Kaiyi , Zhang Wenning , Zhang Yewei
Published: July 2023

CLSPN, an essential molecule of the S-phase checkpoint in DNA replication stress, have not been elucidated in hepatocellular carcinoma (HCC). In this study, we firstly discovered and systematically verified CLSPN expression using RT-qPCR and western blotting assay, and its high expression was an independent prognostic factor in HCC. Patients with CLSPN low-expression had higher infiltration levels of T cell CD4 + memory resting, monocyte, mast cell activated, dryness index and lower immune response in HCC. Then, CLSPN silencing inhibited the proliferation, migration, invasion and cell cycle progression of HCC cells proved by CCK-8, transwell and cell cycle assay. We established a key lncRNA PSMA3-AS1/hsa-miR-101-3p/CLSPN regulator axis in HCC. Furthermore, CLSPN-mediated ubiquitination or deubiquitination may regulate post-transcriptional modifications in HCC. The emerging CLSPN potentialities might be mediated by the β-catenin-mediated Wnt signaling pathway. In addition, we detected CLSPN interaction protein profile, which further confirmed CLSPN involved in posttranscriptional modification, protein turnover, and biogenesis locating in cytoplasm, secreted, and mitochondrion. Therefore, it was the first time to discover and verify expression, prognosis, immunotherapy, RNAs regulator, posttranscriptional modification, and molecular mechanisms of CLSPN in HCC. These novel insights might accelerate the process of individualized diagnosis and precision therapeutics for patients with HCC.
mRNA sequencing provides new insights into the pathogenesis of Hirschsprung's disease in mice
Authors: Yang Qiwen , wang fuwen , Wang Zhaofei , Guo Jiajun , Chang Tingjin , Dalielihan Baligen , Yang Ge , Lei Chuzhao , Dang Ruihua
Published: July 2023

Hirschsprung's disease (HSCR) is an intestinal development defect caused by multiple gene mutations. Under natural circumstances, the incidence in newborns is approximately 1/5000. It has been confirmed that Hirschsprung's disease is a neurocrest-derived disease, and disorders in the development and migration of neural crest cells may lead to the disease. To explore the key susceptibility genes in the development of Hirschsprung's disease, 8354 differentially expressed genes were identified by RNA sequencing in the colon tissues of EDNRBm1yzcm and wild mice, including 4346 upregulated genes and 4005 downregulated genes. Correspondingly, the results of RT–qPCR analysis showed good correlation with the transcriptome data. In addition, GO and KEGG enrichment results suggested that there were 8103 terms and 320 pathways in all DEGs. When P < 0.05, 1081 GO terms and 320 KEGG pathways reached a significant level. Finally, through the existing studies and the enrichment results of differentially expressed genes, it was determined that axon guidance and the focal adhesion pathway may be closely related to the occurrence of HSCR. This study analyzed and identified the differential genes in colonic tissues between EDNRBm1yzcm mice and wild mice, which provided new insight for further mining the potential pathogenic genes of Hirschsprung's disease.
From waste to growth: tea residue recycling through Trichoderma's solid-state fermentation for tea cuttings
Authors: Meng Zhen , Lv Zijian , Wang Xue , Zhang Jian , Bai Guoxin , Liu Hongjun , Li Rong , Shen Qirong
Published: July 2023

Background
Trichoderma is a widely recognized plant growth-promoting fungus (PGPF) that has been extensively utilized in various agricultural applications. However, the effects of Trichoderma on the growth of tea cuttings and the changes in the fungal community are still unclear. This study produced T. guizhouense NJAU 4742 (NJAU 4742) via solid-state fermentation using tea residue and evaluated its potential to promote the growth of tea cuttings.
Results
The optimal conditions for spore yield were determined as a 7:3 (w/w) ratio of tea residue to rice bran, a material thickness of 3 cm, an inoculum concentration of 15%, and an incubation time of 4 days, resulting in a spore count of 1.83×109 CFU/g. The application of NJAU 4742 spore products significantly increased the biomass of tea cuttings and influenced the fungal community composition. Moreover, the application of higher NJAU 4742 spore concentrations resulted in better growth performance, and the application of nursery substrate with 1×107 CFU/mL spores was the most economically viable option. Notably, among the top ten fungal genera with the highest relative abundances, Trichoderma showed a positive correlation with the fresh weight of tea cuttings, while the other nine genera exhibited a negative correlation.
Conclusions
This study showed that utilizing tea residue for solid-state fermentation of NJAU 4742 is a feasible approach, and the application of NJAU 4742 spores enhances the growth of tea cuttings by increasing the relative abundance of Trichoderma.
Comprehensive analysis of the role of pyroptosis-related genes in predicting prognosis in hepatocellular carcinoma
Authors: Tian Lin , He Jia , Yang Ronghua , Zhou Jie
Published: July 2023

Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Pyroptosis is an inflammatory form of programmed cell death closely related to tumor formation and development. However, the functional role and significance of pyroptosis in HCC remain unclear.
Methods
RNA-sequencing and clinical data for HCC patients were obtained from TCGA and GEO databases. We first explored the 49 pyroptosis-related genes (PRGs) expression patterns in HCC. The univariate Cox regression analysis and consensus clustering by PRGs were then performed to divide TCGA-HCC patients into two subtypes, C1 and C2. Based on prognostic PRGs, the LASSO Cox regression method was employed to construct a prognostic model. The predictive value was evaluated by generated nomogram and decision curve analysis (DCA). GSEA and immune infiltration analysis evaluated immune status. Additionally, regulating networks of prognostic PRGs were predicted with Networkanalyst online tools. Finally, the expression of the prognostic genes was validated by qRT-PCR.
Results
HCC patients in subtype C2 exhibited a larger proportion of grade III-IV, higher immune scores, more genetic mutations, and increased expression of immune factors. A prognostic model was developed based on four prognostic PRGs and classified HCC patients into high- and low-risk groups. Patients in the low-risk group showed better prognostic survival. The risk score of this model was an independent prognostic factor and had a good predictive ability. Besides, immune status showed a difference between the two risk groups. We drew the regulating networks between the mRNA of 4 prognostic PRGs and TFs, miRNAs, or chemicals. The qRT-PCR results demonstrated PRGs highly expressed in paracancerous tissues and lowly expressed in carcinoma.
Conclusions
The prognostic model based on four PRGs has significant implications for prognosis assessment and provides a new idea for HCC treatment.
Antinociceptive and Anti-Urolithiatic Effects of Ensete glaucum (Roxb.) Cheesman Seed Aqueous Extract in Mice
Authors: Le Van Minh , Ly Hai Trieu , Le Kim Oanh
Published: July 2023

Ensete glaucum seeds, being known as one of traditional medicine, are commonly used in folk medicine to treat urinary stones, edema, and osteoarthritis-related problems. However, no scientific evidence has been reported to support these uses. This study focused on investigating the antinociceptive and antiurolithiatic activities of E. glaucum seed aqueous extract (EGE). The antinociceptive effect of EGE was evaluated in mice using thermal (hot plate test) and chemical (acetic acid and formalin-induced nociception test) pain models at various doses (50, 100, 200, 400 mg/kg; p.o.). The anti-urolithiatic activity of the EGE (200, 400 mg/kg; p.o.) was assessed in the sodium glyoxylate-induced urolithiasis in mice and in vitro nucleation and aggregation assays. The analgesic effect of EGE was detected at several doses via peripheral and central antinociceptive mechanisms in the acetic acid-induced writhing (50-400 mg/kg), hot plate (100-200 mg/kg), and formalin-induced licking (200-400 mg/kg) tests. EGE had potential against urolithiasis through its ability to modify several serum and urine biochemical parameters on glyoxylate-induced nephrolithiasis. The extract at the dose of 400 mg/kg significantly improved the inflammatory cells, kidney tissue structure, and renal calcification. The extract also exhibited significant anti-urolithiatic, anti-inflammatory, and antioxidant activities in some in vitro models. These outcomes suggest that E. glaucum aqueous seed extract possesses antinociceptive activity and may aid in the prevention of urinary stones. Further studies are needed to elucidate the effectiveness of E. glaucum seeds in the analgesic activity and management of urolithiasis disease.
Algorithm for the solution of Hammerstein
integral typ e of equation in a Banach Spaces
Authors: Mendy John T , Shukla Rahule , Mendy Furmose , Mendy Gabriel J
Published: July 2023

This pap er investigates the convergence of iterative methods for solving functional equations of the form u + KF u = 0 in a normed linear space E. The equations under consideration include nonlinear integral equations of Hammerstein type, where F and K are maps between E and its dual E∗. The article explores diffrent extensions of monotonicity and accretivity concepts for operators in Banach spaces and highlighting their connections with minimax theory. Building upon previous results on iterative approximation schemes, we present new iterative algorithms that yield strong convergence to the unique solution of
the Hammerstein equation.
Selbstverständnis Diversität = Diversität selbstverständlich? – Erfahrungen aus einem sächsischen Kooperationsprojekt
Authors: Brenner Franziska , Henschler Julia
Published: July 2023

In diesem Beitrag wird aufgezeigt, wie das Thema „Diversität“ im sächsischen Verbundprojekt „Digitale Hochschulbildung in Sachsen“ als Querschnittsthema verstanden und wie Barrierefreiheit als ein zentraler Aspekt diversitätssensibler Hochschullehre thematisiert und umgesetzt werden kann. Als Grundlage dient hierfür das gemeinsam formulierte Selbstverständnis von Diversität, welches von der projektinternen A G Diversität in konkrete Maßnahmen überführt und regelmäßig von allen Projektmitarbeitenden reflektiert werden soll. Zudem verdeutlichen Ergebnisse einer anonymen Befragung aller Mitarbeitenden sowie Teilnehmenden eines Digital Workspace Erfahrungen und Einschätzungen zum Thema „Barrierefreiheit im Hochschulkontext“, welche Implikationen für die weitere Arbeit im Projekt aufzeigen.
Live-Transkription für Zoom-Meetings – Ein Praxisbericht der Universität Bern
Authors: Hohermuth Jessica , Reichel Sibylle
Published: July 2023

Personen mit Hörbeeinträchtigung haben bei Online-Meetings oft Schwierigkeiten, wenn durch eine schlechte Videoübertragung oder bei Präsentationen mit verkleinertem oder gar keinem Sprecher*innenvideo das Lippenlesen erschwert oder unmöglich ist. Eine Live-Transkription des gesprochenen Vortrags kann hilfreich sein. Eine solche ist in Zoom und Teams zwar integriert, jedoch mit verschiedenen Einschränkungen. Um ein deutsches Transkript zu erhalten, wurde daher in Zusammenarbeit dreier Stellen (SWITCH, aiconix, Unibe) eine Lösung entwickelt, die den Ton eines Zoom-Meetings via Stream auf eine Website umleitet, auf der der Input transkribiert und das Ergebnis dann via A P I wieder in das Zoom-Meeting eingespeist wird. Seit November 2021 ist diese Lösung an der Universität Bern im Einsatz. Dabei sind verschiedene Schwierigkeiten zu bewältigen, wie etwa der Umgang mit konkurrierenden Zielen, Qualität und Geschwindigkeit des Transkripts sowie die Berücksichtigung passender Lexika, um eine gute Transkription auch wenig frequenter Fachbegriffe zu ermöglichen sowie die Erkennung schweizerdeutsch gesprochener Texte. Im Beitrag wird aus Anwender*innen- und Entwickler*innensicht die technische Lösung vorgestellt, technische und systematische Herausforderungen werden beleuchtet, Erfahrungen mit der Anwendung beschrieben und ein Ausblick gegeben, wie die Möglichkeit der Speech-to-Text-Konvertierung in verschiedenen Szenarien noch eingesetzt werden kann (Live-Transkription vs. nachträgliche Transkription, Verbesserung der Transkription durch Erweiterung der Lexika, Integration weiterer Sprachen).
Sustainable Development: Problems in Understanding and Implementation
Authors: Radonjić Ognjen
Published: July 2023

From the perspective of the dominant economic theory, as long as economic growth brings more benefits than costs expressed in monetary units, such growth should be supported. On the other hand, this theoretical approach ignored not only the natural environment's limited capacities but also anomalies in economic growth that lead to increased inequality in the distribution of income and wealth, as well as poverty. The topic of this study is the definition of sustainable development, which aims to encompass the economic, social, and ecological dimension of human activities as well as problems in the implementation of sustainable development policies at the supranational, national, and local level.
A simple theory for quantum quenches in the ANNNI model
Authors: Robertson Jacob , Senese Riccardo , Essler Fabian
Published: July 2023

In a recent numerical study by Haldar et al. [Phys. Rev. X 11, 031062] it was shown that signatures of proximate quantum critical points can be observed at early and intermediate times after certain quantum quenches. Said work focused mainly on the case of the axial next-nearest neighbour Ising (ANNNI) model. Here we construct a simple time-dependent mean-field theory that allows us to obtain a quantitatively accurate description of these quenches at short times, which for reasons we explain remains a fair approximation at late times (with some caveats). Our approach provides a simple framework for understanding the reported numerical results as well as fundamental limitations on detecting quantum critical points through quench dynamics. We moreover explain the origin of the peculiar oscillatory behaviour seen in various observables as arising from the formation of a long-lived bound state.
3d $\mathcal{N}=4$ mirror symmetry with 1-form symmetry
Authors: Nawata Satoshi , Sperling Marcus , Wang Hao Ellery , Zhong Zhenghao
Published: July 2023

The study of 3d mirror symmetry has greatly enhanced our understanding of various aspects of 3d \mathcal{N}=4𝒩=4 theories. In this paper, starting with known mirror pairs of 3d \mathcal{N}=4𝒩=4 quiver gauge theories and gauging discrete subgroups of the flavour or topological symmetry, we construct new mirror pairs with non-trivial 1-form symmetry. By providing explicit quiver descriptions of these theories, we thoroughly specify their symmetries (0-form, 1-form, and 2-group) and the mirror maps between them.
Genotoxic Impurities in Critical Analysis of Product Development: Recent
Advancements, Patents, and Current Challenges
Authors: Swain Suryakanta , Jena Bikash Ranjan , Rao Areti Anka , Malothu Narender , Kothakota Naga Jogayya , Tripathy Satya Narayan
Published: July 2023

The current review intends to regulate and accurately evaluate genotoxic contaminants
in drug substance and drug product method and formulation process development, validation, and
degradation pathways. The Quality by Design (QbD) principles can be applied to the systematic
evaluation and control of impurities enabled by the development of modern analytical techniques,
including the performance of risk assessment, the screening of Critical Process Parameters (CPPs),
and the identification of the most influential variables in the optimization of the evaluation and
control methods. Current difficulties in removing genotoxic contaminants and the procedures for
doing so have been outlined in this review, along with the steps necessary to acquire optimum
techniques and the most acceptable formulations. In addition to this, division, characterization,
assessment, quantification, and formation of genotoxic impurities sources and control strategy
for genotoxic impurities, handling of nitrosamine assay content of drug products in different industrial
methodologies and their chemometric prospects and associated recent patents are also explored.
Co-Crystallization: A Novel Technique to Improvise the Pharmaceutical Characteristics of API’s
Authors: Kumar Aditay , Kumar Mahesh
Published: July 2023

Background:

The poor water solubility of an active pharmaceutical ingredient leads to a lower dissolution profile that in turn results in poor bioavailability of drugs. Various approaches like solid dispersion, nano-technology, complexation, and micronization techniques, etc. are frequently used by pharmaceutical researchers to overcome these issues. In this context, crystal engineering emerges as a viable technique.

Objective:

This review endeavors to cover the latest developments in the field of solubility enhancement using crystal engineering techniques.

Methods:

Extensive literature survey was conducted in order to gain information on the past and present developments in the field of crystal engineering.

Results:

In the co-crystallization process, the API and coformer interact with each other in a fixed stoichiometric ratio. The backbone of co-crystals is structurally repeating units called supramolecular synthons. These synthons provide the flexibility of transfer from one co-crystal system to another, making crystal engineering a viable approach for physicochemical property modification. Further, the availability of a large number of food and drug grade coformers with a diverse functional group and a range of preparation methods provide an excellent opportunity for tuning up desired physicochemical properties of an API.

Conclusion:

This review focuses on the latest developments in the field of crystal engineering in the context of screening, preparation methods, characterization, and their application in the pharmaceutical field. Also, the concern over scale-up and regulatory guidelines are covered.
Base–modified Tunisian Smectite: Efficient Catalysts for Ultrasound-
Assisted Knoevenagel Condensation under Mild Reaction Conditions
Authors: Chtourou Manef
Published: July 2023

This research work presents the use of base-modified Tunisian Smectite as catalysts for the
condensation of Knoevenagel. The prepared clay-catalysts were characterized via FTIR and XRD
studies. A series of condensation reactions based on ultrasonic irradiation of various types of active
methylene compounds and a variety of aryl aldehydes have shown the high efficacy of prepared catalysts.
The stability and catalytic performance of the clay-catalysts were excellent since they could be
reused four times without considerable loss in catalytic activity
Premature Thelarche: An Updated Review
Authors: Leung Alexander K.C. , Lam Joseph M. , Hon Kam L.
Published: July 2023

Background:

Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment.

Objective:

The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty.

Methods:

A search was conducted in September 2022 in PubMed Clinical Queries using the key term "Premature thelarche". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article.

Results:

Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty.

Conclusion:

Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow-up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.
Quality of Life and Disability in Chikungunya Arthritis
Authors: Amaral Jose Kennedy , Taylor Peter C. , Weinblatt Michael E. , Bandeira Ícaro , Schoen Robert T.
Published: July 2023

Background:

Chikungunya virus infection, transmitted by Aedes mosquito vectors, causes outbreaks of chikungunya fever (CHIKF), throughout the tropical and subtropical world. Following acute infection, many CHIKF patients develop a second phase, chronic and disabling ar-thritis.

Objective:

To evaluate the impact of chikungunya arthritis (CHIKA) on quality of life and disability in a cohort of Brazilian CHIKA patients.

Methods:

We conducted a descriptive, non-interventionist, retrospective cross-sectional study ana-lysing data collected from the medical records of chikungunya virus-infected patients treated be-tween June 1, 2022, and June 30, 2022, in the Brazilian rheumatology clinic of one of us (JKA). To assess disability, quality of life, and pain, patients were evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI), 12-Item Short-Form Health Survey (SF-12), and Visual Analog Scale (VAS) pain.

Results:

Forty-two women with a mean (± SD) age of 57.83 (± 13.05) years had CHIKF confirmed by chikungunya-specific serology. The mean (± SD) time between the onset of chikungunya sym-ptoms and the first clinic visit was 55.19 (± 25.88) days. At this visit, the mean (± SD) VAS pain score and DAS28-ESR were 77.26 (± 23.71) and 5.8 (± 1.29), respectively. The mean (± SD) HAQ-DI score was 1.52 (± 0.67). The mean (± SD) SF-12 PCS-12 was 29.57 (± 8.62) and SF-12 MCS-12 was 38.42 (± 9.85).

Conclusion:

CHIKA is often highly disabling. As the mosquito vectors that transmit this illness ha-ve spread to every continent except Antarctica, there is a potential for widespread public health im-pact from CHIKA and the need for more effective, early intervention to prevent CHIKA.
Bioactivity and Therapeutic Applications of Punica granatum L. Peel:
Evidence and Prospects
Authors: Noor Uroosa , Soni Shashi , Gupta Ena
Published: July 2023

Background:

Inclination of the world towards natural and super foods has intended researchers
and nutritionists to develop foods that are highly nutritious, feasible, eco-friendly along
with immuno-boosting potential. Massive amounts of agro-industrial waste are generated across the
world which can be turned-up into a functional ingredient by utilization and transformation of these
wastes into wealth. An Indian balanced diet consists of foods from all food categories, with fruits
and vegetables constituting one-fourth of the diet. Since ancient times, pomegranate (Punica granatum)
and its various parts have been well-known for their therapeutic properties and delicious flavor.
Worldwide approximately million tons of pomegranate peels are produced per annum which
are a considerable source of vitamins, minerals, and numerous bioactive compounds such as phenolics,
flavonoids (anthocyanins, flavonols, flavones) and tannins. Consequently, it has many health
benefits, including antioxidative, anticancer, antidiabetic, anti-inflammatory, anti-microbial, antimutagenic,
cardio-protective, hepato-protective, nephro-protective properties as well as it is also
helpful in the prevention of many other chronic diseases. Its safety and efficacy for consumption
have been proved by incorporating it in food products and industrial applications. The main aim of
this review is to focus on the vital bioactive compounds present in pomegranate peel and their positive
health benefits on human health.
Discrimination between Benign and Malignant Lung Lesions using Volumetric
Quantitative Dynamic Contrast-enhanced MRI
Authors: Wei Fang , Weidong Fu , Wenming Zhou , Lei He , Xiaosan Cheng , Zhongliang Mao , Qianyun Liu , Huashan Lin
Published: July 2023

Background:

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is considered a promising method in lung lesion assessment.

Methods:

Sixty-four patients with single pulmonary lesions (SPLs) received DCE-MRI at 3.0 T. Of them, 49 cases were diagnosed with lung cancer, and 15 with benign pulmonary nodules (8 inflammatory nodules, 5 tuberculosis, and 2 abscesses). SPLs were quantitatively analyzed to determine the pulmonary lesions-related perfusion parameters, including reflux constant (Kep), volume transfer constant (Ktrans), the maximum slope of increase (MaxSlope), extravascular extracellular space volume fraction (Ve), apparent diffusion coefficient (ADC), the initial area in the signal intensity-time curve (IAUGC), and contrast-enhancement ratio (CER). In addition, a Student’s t-test was conducted to calculate statistical significance regarding the quantitatively analyzed perfusion parameters in benign SPLs compared to malignant SPLs. The area under (AUC) the receiver operating characteristic (ROC) curve was studied to investigate the performance of perfusion parameters in diagnosing lung cancer.

Results:

Values of Ktrans, Kep, Ve, MaxSlope, and IAUGC increased within malignant nodules relative to benign nodules (Ktrans: 0.21 ±0.08 vs. 0.73 ±0.40, P = 0.0001; Kep: 1.21 ±0.66 vs. 1.83 ±0.90, P = 0.0163; Ve: 0.24 ±0.08 vs. 0.47 ±0.18, P < 0.0001; MaxSlope: 0.09 ±0.14 vs. 0.28 ±0.29, P = 0.0166; IAUGC: 0.18 ±0.09 vs. 0.55 ±0.34, P = 0.0001). Meanwhile, malignant nodules presented higher ADC than benign nodules (0.0016 ±0.0006 vs. 0.0012 ±0.0003, P = 0.0019). Ktrans and IAUGC showed the best diagnostic performance with AUCs [1.0, 95%CI (0.99–1.0); 0.93, 95%CI(0.85–1.0), respectively].

Conclusion:

Malignant pulmonary lesions had higher values of Ktrans, Ve, Kep, MaxSlope, and IAUGC compared to benign pulmonary lesions. Overall, perfusion parameters of DCE-MRI facilitate discrimination between benign from malignant pulmonary nodules.
Anti-Inflammatory Potential of Curcumin: From Chemistry and Mechanistic
Insight to Nanoformulations
Authors: Aggarwal Diwakar , Chaudhary Mayank , Bajaj Nandini , Sharma Deepika , Upadhyay Sushil Kumar , Garg Vivek Kumar , Abdulabbas Hadi Sajid , Tuli Hardeep Singh , Rani Isha
Published: July 2023

Background:

Curcumin is a natural compound obtained from Curcuma longa that possesses a vast therapeutic potential for disease treatment. It is a potent anticancer, anti-inflammatory, antioxidant, and anti-aging phytochemical as evident from numerous studies. Curcumin's anti-inflammatory and antioxidant properties are thought to be more potent than its other biological actions. Curcumin's anti-inflammatory properties can lead to an improvement in symptoms and make it a viable candidate for the treatment and prevention of pro-inflammatory disorders.

Objective:

The goal of this review is to analyse curcumin's anti-inflammatory properties and mechanisms in the treatment of various disorders. The effect of different curcumin-based nanoformulations on anti-inflammatory potential is also reviewed, as the therapeutic use of curcumin is influenced by its solubility, bioavailability, and pharmacokinetic profile.

Methodology:

The literature searched during the last ten years using keywords such as curcumin, anti-inflammatory mechanisms, cytokines, and nanoformulations from multiple databases, such as PubMed, Science Direct, Scopus, and others. The quality research and review articles containing the aforementioned keywords were chosen for this review article.

Conclusion:

This review focuses on the anti-inflammatory properties of curcumin against a variety of inflammatory disorders that arise over the course of various illnesses. It also emphasises the importance of developing alternative nanoformulations to address the limitations of curcumin usage. Further, it will aid the scientific community's understanding of curcumin and its anti-inflammatory mechanisms, prompting them to devise innovative treatment options.
Peanut Resveratrol Inhibits COX-2 in Ehrlich Ascites Carcinoma In vivo
Model
Authors: Abosharaf Hamed A. , Habib Aliaa A. , Gad Abdul Aziz M. , Mohamed Tarek M.
Published: July 2023

Background:

The primary goal of researchers interested in the field of oncology continues to
be the development of a new anti-cancer medicine with minimal side effects. Due to their minimal toxicity
and impressive performance, natural source-mediated anti-cancer treatments are attracting a lot of
attention.

Objective:

The purpose of the current work was to extract and purify resveratrol from local Leguminosae,
such as peanut, beans, cowpea, lupine, fava bean, and soybean, and then assess its cyclooxygenase-
2 (COX-2) inhibition. The aim was then to evaluate the anticancer potential of extracted resveratrol
individually or combined with doxorubicin against Ehrlich ascites carcinoma (EAC) model.

Methods:

Resveratrol was extracted and purified using a silica gel column. The inhibition study of extracted
resveratrol was conducted against COX-2 in vitro. Then, the anti-proliferation impact of resveratrol
alone or combined with doxorubicin was evaluated against the previously established EAC model.
Apoptotic/anti-apoptotic genes and cell cycle arrest were investigated.

Results:

After being extracted from peanuts, resveratrol inhibited COX-2 in vitro competitively with an
inhibition constant (Ki) of 0.545 μM, which is extremely close to the theoretically predicted value (0.48
μM) from molecular docking. Further, resveratrol obviously inhibited COX-2 in vivo. Importantly,
resveratrol was able to cause apoptosis by upregulating Bax and downregulating the anti-apoptotic gene
Bcl-2, either by itself or in combination with doxorubicin. Additionally, resveratrol's ability to stop the
cell cycle is evidence of its COX-2-inhibiting antiproliferative properties.

Conclusion:

Resveratrol exhibits anticancer potential via inhibition of COX-2, and it could be appropriate
for combinational therapy in vivo.
Dual Role of Exosome in Neurodegenerative Diseases: A Review Study
Authors: Sheykhhasan Mohsen , Heidari Fatemeh , Eslami Farsani Mohsen , Azimzadeh Maryam , Kalhor Naser , Ababzadeh Shima , Seyedebrahimi Reihaneh
Published: July 2023

Introduction:

Extracellular vesicles (EVs) are one of the crucial means of intercellular communication,
which takes many different forms. They are heterogeneous, secreted by a range of cell types,
and can be generally classified into microvesicles and exosomes depending on their location and function.
Exosomes are small EVs with diameters of about 30–150 nm and diverse cell sources.

Methods:

The MEDLINE/PubMed database was reviewed for papers written in English and publication
dates of recent years, using the search string "Exosome" and "Neurodegenerative diseases."

Results:

The exosomes have attracted interest as a significant biomarker for a better understanding of
disease development, gene silencing delivery, and alternatives to stem cell-based therapy because of their
low-invasive therapeutic approach, repeatable distribution in the central nervous system (CNS), and high
efficiency. Also, they are nanovesicles that carry various substances, which can have an impact on neural
plasticity and cognitive functioning in both healthy and pathological circumstances. Therefore, exosomes
are conceived as nanovesicles containing proteins, lipids, and nucleic acids. However, their composition
varies considerably depending on the cells from which they are produced.

Conclusion:

In the present review, we discuss several techniques for the isolation of exosomes from different
cell sources. Furthermore, reviewing research on exosomes' possible functions as carriers of bioactive
substances implicated in the etiology of neurodegenerative illnesses, we further examine them. We
also analyze the preclinical and clinical research that shows exosomes to have therapeutic potential.
Interleukin-2 and Oncolytic Virotherapy: A New Perspective in Cancer Therapy
Authors: Shiri Aghbash Parisa , Rasizadeh Reyhaneh , Yari Amir Hossein , Lahouti Shiva , MotieGhader Habib , Nahand Javid Sadri , Entezari-Maleki Taher , Baghi Hossein Bannazadeh
Published: July 2023

By triggering immune responses in malignancies that have generally been linked to poor outcomes, immunotherapy
has recently shown effectiveness. On the other hand, tumors provide an environment for cells that influence
the body’s immunity against cancer. Malignant cells also express large amounts of soluble or membrane-bound ligands
and immunosuppressive receptors. In this regard, the combination of oncolytic viruses with pro-inflammatory or inflammatory
cytokines, including IL-2, can be a potential therapy for some malignancies. Indeed, oncolytic viruses
cause the death of cancerous cells and destroy the tumor microenvironment. They result in the local release of threat
signals and antigens associated with tumors. As a result, it causes lymphocyte activity and the accumulation of antigenpresenting
cells which causes them to accumulate in the tumor environment and release cytokines and chemokines. In
this study, we reviewed the functions of IL-2 as a crucial type of inflammatory cytokine in triggering immune responses,
as well as the effect of its release and increased expression following combination therapy with oncolytic viruses in
the process of malignant progression, as an essential therapeutic approach that should be taken into consideration going
forward.
Design, Synthesis, and Antiproliferative Activity of Quinazolin-4-One/Chalcone
Hybrids via the EGFR Inhibition Pathway
Authors: Hisham Mohamed , Hassan Heba A. , Gomaa Hesham A. M. , Youssif Bahaa G.M. , Hayalah Alaa M. , Abdel-Aziz Mohamed
Published: July 2023

Background:

Quinazolinone scaffolds have drawn international attention due to their potent anticancer
activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide
range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize
and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted
quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor
(EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAFV600E) oncogene.

Objective:

All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new
hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules
within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis
were also investigated.

Method:

The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)-
quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2-
bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c,
and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and
doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against
EGFR and BRAF.

Result:

Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as
a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1
phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site.

Conclusion:

2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative
properties.
Unraveling the Role of Neuroligin3 in Autism Spectrum Disorders:
Pathophysiological Insights and Targeted Therapies
Authors: Yacoubi Fatima Azzahrae EL , Oukabli Mohamed , Ibrahimi Azeddine , Kisra Hassan , Bensaid Mounia
Published: July 2023

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social
and communication skills, repetitive behaviors, and/or restricted interests with a prevalence of as
high as 1% of children. Autism spectrum has strongly associated with genetic factors and exhibits
wide clinical and heterogeneous genetic architecture. Most genes associated with Autism are involved
in neuronal and synaptic development. The neuroligin3, the sex-linked gene on the X chromosome,
was the first gene to be associated with a monogenic form of Autism. Neuroligin3 is a postsynaptic
cell adhesion protein involved in synapse transmission, brain formation, and neuronal development. In
this review, we provide recent findings on different mutations in the Neuroligin3 gene linked to Autism
spectrum disorder and their molecular pathway effect. We also give the behavioral, and synaptic
alterations reported in the Neuroligin3 animal model of Autism and the potential therapeutic strategies
targeting the biological processes and the main symptoms of autism spectrum disorder. In addition, we
discuss the use of novel technologies like induced pluripotent stem cells from Autistic patients that
have the potential to differentiate in human neurons and therefore have a variety of applications in
therapy and biomedical studies to search specific biomarkers, and develop systems for screening
chemical molecules in human cells to discover target therapies.
Hypothetical Interventions to Prevent Acute Kidney Injury After
Humpnosed Pit Viper Bite
Authors: Sellahewa Kolitha Harischandra
Published: July 2023

Even though the Hump-nosed pit viper bite is the commonest venomous snake bite in Sri Lanka, antivenoms with specific activity against it are not available. Acute kidney injury (A.K.I.) is an important systemic complication accounting for mortality. Therapeutic plasma exchange (TPE) and fresh frozen plasma (F.F.P.) are two interventional options hypothesized to prevent A.K.I. This is by TPE at-tenuating venom antigenemia and F.F.P. by inhibiting nephrotoxic renal injury by immunomodulation, and the additional benefit of replenishment of depleted clotting factors triggered by venom-induced con-sumption coagulopathy implicated in the multifactorial mechanisms of renal injury. Routine interventions on all envenomed patients are not justifiable owing to the rarity and sporadic occurrence of systemic complications, and only patients with coagulopathy should be selected for interventions. The benefit of preventing A.K.I. is most likely with early intervention at the inception of coagulopathy.