bluuebunny/crossref_metadata_2025 huggingface dataset:
Outpatient healthcare costs associated with overweight and obesity in Italy
Authors: Atella Vincenzo , Belotti Federico , Cricelli Claudio , Giaccherini Matilde , Medea Gerardo , Nicolucci Antonio , Piano Mortari Andrea , Sbraccia Paolo
Published: June 2023

Background

To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations.

Methods

The study is based on a representative national sample of adults, with data obtained from electronic clinical records of 900 Italian general practitioners. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2, and 3) and glucose metabolism status (normoglycemia – NGT; impaired fasting glucose – IFG; diabetes mellitus – DM). Outpatient health expenditures include diagnostic tests, specialist visits, and drugs.

Results

Data relative to 991,917 adults were analyzed. Annual per capita expenditure rose from 252.2 Euro among individuals with normal weight to 752.9 Euro among those with class 3 obesity. The presence of obesity determined an excess cost, particularly among younger individuals. Within each BMI class, the presence of IFG or DM2 identified subgroups of individuals with substantially higher healthcare expenditures.

Conclusions

Outpatient healthcare costs markedly increased with increasing BMI in all age categories, particularly among individuals below 65. Addressing the double burden of excess weight and hyperglycemia represents a significant challenge and a healthcare priority.
Predictors of readmission in a medical department of a tertiary university hospital in the Philippines
Authors: Balane Janika Adrienne L. , Yap Celina Daia DG. , Villanueva Cary Amiel G. , Palileo-Villanueva Lia Aileen M. , Tamondong-Lachica Diana R.
Published: June 2023

Background

Identifying factors that increase the risk for hospital readmission helps in determining potential targets for quality improvement efforts. The main objective of this study was to examine factors that predict increased risk of hospital readmission within 30 days of hospital discharge of patients under the General Medicine service of a tertiary government hospital in Manila, Philippines.

Methods

We performed a retrospective cohort study which included service patients 19 years old and above readmitted within 30 days following discharge. A total of 324 hospital readmissions within 30 days of discharge from January 1 to December 31, 2019 were reviewed. We estimated the rate of 30-day readmission and identified factors associated with preventable readmissions using multivariable logistic regression.

Results

Of the 4,010 hospitalizations under General Medicine service in 2019, 602 (18%) were readmissions within 30 days of discharge, majority of which were related to the index admission (90%) and unplanned (68%). Predictors of preventable readmission were emergency readmission (OR 3.37, 95% CI 1.72 to 6.60), having five to ten medications at discharge (OR 1.78, 95% CI 1.10 to 2.87), and presence of nosocomial infection (OR 1.86, 95% CI 1.09 to 3.17). The most frequent reason for readmission among preventable ones is health-care related infection (42.9%).

Conclusions

We identified factors which increased the likelihood of preventable readmissions such as type of readmission, number of medications per day, and presence of nosocomial infections. We propose that these issues be addressed to improve healthcare delivery and reduce readmission-related expenditures. Further studies should be pursued to identify impactful evidence-based practices.
Novel compound heterozygous variants in the RPL3L gene causing dilated cardiomyopathy type-2D: a case report and literature review
Authors: Yang Qi , Zhang Qiang , Qin Zailong , Zhang Shujie , Yi Sheng , Yi Shang , Zhang Qinle , Luo Jingsi
Published: June 2023

Background

Dilated cardiomyopathy type-2D (CMD2D) is a rare heart disease causing a severe cardiomyopathy with neonatal onset and rapid progression to cardiac decompensation and death in untreated patients. CMD2D is an autosomal recessive disease resulting from variants in the RPL3L gene, which encodes the 60 S ribosomal protein exclusively expressed in skeletal and cardiac muscle and plays an essential role in myoblast growth and fusion. Previous reports have only associated CMD2D with a small duplication and seven nucleotide substitution in the RPL3L gene.

Case presentation

In this study, we report the case of a 31 days old Chinese infant patient with severe dilated cardiomyopathy (DCM) and rapid decompensation along with other cardiac malformations. In addition to previously reported clinical features, the patient showed the previously unreported complication of occasional premature atrial contractions and a first-degree atrioventricular block. Whole-exome sequencing (WES) revealed compound heterozygous variants (c.80G > A (p.Gly27Asp) and c.1074dupA (p.Ala359fs*6)) in RPL3L (NM_005061.3). The latter novel variant may result in the absence of protein production with a significant decrease in mRNA level, suggesting it is a loss-of-function mutation.

Conclusions

This is the first case report of RPL3L-associated neonatal dilated cardiomyopathy in China. The molecular confirmation of the patient expands the genetic spectrum of CMD2D, and the clinical manifestation of CMD2D in the patient provides additional clinical information regarding this disease.
Flavonoids target different molecules of autophagic and metastatic pathways in cancer cells
Authors: Hosseinzadeh Aysooda , Poursoleiman Faezeh , Biregani Akram Naghdipour , Esmailzadeh Ahmad
Published: June 2023

Despite the success of cancer therapy, it has encountered a major obstacle due to the complicated nature of cancer, namely resistance. The recurrence and metastasis of cancer occur when anti-cancer therapeutic agents fail to eradicate all cancer cells. Cancer therapy aims to find the best agent that targets all cancer cells, including those sensitive or resistant to treatment. Flavonoids, natural products from our diet, show anti-cancer effects in different studies. They can inhibit metastasis and the recurrence of cancers. This review discusses metastasis, autophagy, anoikis in cancer cells, and their dynamic relationship. We present evidence that flavonoids can block metastasis and induce cell death in cancer cells. Our research suggests that flavonoids can serve as potential therapeutic agents in cancer therapy.
HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis
Authors: Li Ke , Gong Quan , Xiang Xu-Dong , Guo Gang , Liu Jia , Zhao Li , Li Jun , Chen Nan , Li Heng , Zhang Li-Juan , Zhou Chun-Yan , Wang Zhi-Yong , Zhuang Li
Published: June 2023

Background

Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A “reader” has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC).

Methods

The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses.

Results

We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC.

Conclusions

Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.
Varicella-zoster virus proteome-wide T-cell screening demonstrates low prevalence of virus-specific CD8 T-cells in latently infected human trigeminal ganglia
Authors: van Gent Michiel , Ouwendijk Werner J. D. , Campbell Victoria L. , Laing Kerry J. , Verjans Georges M. G. M. , Koelle David M.
Published: June 2023

Background

Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to control virus reactivation, their protective role at the site of latency remains uncharacterized.

Methods

Paired blood and TG specimens were obtained from ten latent VZV-infected adults, of which nine were co-infected with herpes simplex virus type 1 (HSV-1). Short-term TG-derived T-cell lines (TG-TCL), generated by mitogenic stimulation of TG-derived T-cells, were probed for HSV-1- and VZV-specific T-cells using flow cytometry. We also performed VZV proteome-wide screening of TG-TCL to determine the fine antigenic specificity of VZV reactive T-cells. Finally, the relationship between T-cells and latent HSV-1 and VZV infections in TG was analyzed by reverse transcription quantitative PCR (RT-qPCR) and in situ analysis for T-cell proteins and latent viral transcripts.

Results

VZV proteome-wide analysis of ten TG-TCL identified two VZV antigens recognized by CD8 T-cells in two separate subjects. The first was an HSV-1/VZV cross-reactive CD8 T-cell epitope, whereas the second TG harbored CD8 T-cells reactive with VZV specifically and not the homologous peptide in HSV-1. In silico analysis showed that HSV-1/VZV cross reactivity of TG-derived CD8 T-cells reactive with ten previously identified HSV-1 epitopes was unlikely, suggesting that HSV-1/VZV cross-reactive T-cells are not a common feature in dually infected TG. Finally, no association was detected between T-cell infiltration and VZV latency transcript abundance in TG by RT-qPCR or in situ analyses.

Conclusions

The low presence of VZV- compared to HSV-1-specific CD8 T-cells in human TG suggests that VZV reactive CD8 T-cells play a limited role in maintaining VZV latency.
Chinese genetic variation database of inborn errors of metabolism: a systematic review of published variants in 13 genes
Authors: Guo Yongchao , Jiang Jianhui , Xu Zhongyao
Published: June 2023

Background

Population-specific variation database of inborn errors of metabolism (IEMs) is essential for precise genetic diagnosis and disease prevention. Here we presented a systematic review of clinically relevant variants of 13 IEMs genes reported among Chinese patients.

Methods

A systematic search of the following electronic databases for 13 IEMs genes was conducted: PubMed-NCBI, China national knowledge infrastructure and Wanfang databases. Patient data was extracted from articles eligible for inclusion and recorded in Excel electronic form using a case-by-case approach.

Results

A total of 218 articles, 93 published in English and 125 in Chinese, were retrieved. After variant annotation and deduplication, 575 unique patients (241 from articles published in Chinese) were included in the population-specific variation database. Patients identified by newborn screening and symptomatic presentation were 231 (40.17%) and 344 (59.83%), respectively. Biallelic variants were observed in 525/575 (91.3%). Among the 581 unique variants identified, 83 (14.28%) were described ≥ 3 times and 97 (16.69%) were not recorded in Clinvar or HGMD. Four variants were reclassified as benign and dozens of confusing variants deserved further research.

Conclusion

This review provides a unique resource of the well-characterized diseases and causative variants that have accumulated in Chinese population and is a preliminary attempt to build the Chinese genetic variation database of IEMs.
Expanding genotype–phenotype correlations in FOXG1 syndrome: results from a patient registry
Authors: Brimble Elise , Reyes Kathryn G. , Kuhathaas Kopika , Devinsky Orrin , Ruzhnikov Maura R. Z. , Ortiz-Gonzalez Xilma R. , Scheffer Ingrid , Bahi-Buisson Nadia , Olson Heather ,   the FOXG1 Research Foundation
Published: June 2023

Background

We refine the clinical spectrum of FOXG1 syndrome and expand genotype–phenotype correlations through evaluation of 122 individuals enrolled in an international patient registry.

Methods

The FOXG1 syndrome online patient registry allows for remote collection of caregiver-reported outcomes. Inclusion required documentation of a (likely) pathogenic variant in FOXG1. Caregivers were administered a questionnaire to evaluate clinical severity of core features of FOXG1 syndrome. Genotype–phenotype correlations were determined using nonparametric analyses.

Results

We studied 122 registry participants with FOXG1 syndrome, aged < 12 months to 24 years. Caregivers described delayed or absent developmental milestone attainment, seizures (61%), and movement disorders (58%). Participants harbouring a missense variant had a milder phenotype. Compared to individuals with gene deletions (0%) or nonsense variants (20%), missense variants were associated with more frequent attainment of sitting (73%). Further, individuals with missense variants (41%) achieved independent walking more frequently than those with gene deletions (0%) or frameshift variants (6%). Presence of epilepsy also varied by genotype and was significantly more common in those with gene deletions (81%) compared to missense variants (47%). Individuals with gene deletions were more likely to have higher seizure burden than other genotypes with 53% reporting daily seizures, even at best control. We also observed that truncations preserving the forkhead DNA binding domain were associated with better developmental outcomes.

Conclusion

We refine the phenotypic spectrum of neurodevelopmental features associated with FOXG1 syndrome. We strengthen genotype-driven outcomes, where missense variants are associated with a milder clinical course.
Oral findings in patients with cartilage-hair hypoplasia - cross-sectional observational study
Authors: Arponen Heidi , Vakkilainen Svetlana , Rautava Jaana , Mäkitie Outi
Published: June 2023

Background and objectives

Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia with associated primary immunodeficiency. The aim of this cross-sectional study was to examine oral health indicators in individuals with CHH.

Methods

In total, 23 individuals with CHH, aged between 4.5 and 70 years, and 46 controls aged between 5 and 76 years were clinically examined for periodontal disease, presence of oral mucosal lesions, tooth decay, masticatory system function, and malocclusions. A chairside lateral flow immunoassay test of active-matrix metalloproteinase was obtained from all the adult participants with a permanent dentition. Laboratory signs of immunodeficiency were recorded for individuals with CHH.

Results

Individuals with CHH and controls had similar prevalence of gingival bleeding on probing (median 6% vs. 4%). Oral fluid active-matrix metalloproteinase concentration was greater than 20 ng/ml in 45% of study subjects in both groups. However, deep periodontal pockets, 4 mm or deeper, were more common in individuals with CHH as compared to the controls (U = 282.5, p = 0.002). Similarly mucosal lesions were significantly more common in individuals with CHH (30% vs. 9%, OR = 0.223, 95%CI 0.057–0.867). The median sum of the number of decayed, missing due to caries, and filled teeth was nine for the individuals with CHH and four for controls. In the CHH cohort, 70% displayed an ideal sagittal occlusal relationship. Malocclusion and temporomandibular joint dysfunction prevalence were similar in both study groups.

Conclusions

Individuals with CHH have more frequently deep periodontal pockets and oral mucosal lesions than general population controls. Routine intraoral examination by a dentist at regular intervals should be recommended to all individuals with CHH.
Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years’ multi-stakeholder dialogue on improving access in Europe via MoCA
Authors: Cavaller-Bellaubi Maria , Hughes-Wilson Wills , Kubinová Šárka , Van de Casteele Marc , Van Lente Evert Jan , Degortes Emanuele , Pontén Johan , Eichler Hans-Georg , Le Cam Yann , Boselli Simone , Bucsics Anna
Published: June 2023

Background

The Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA) was established in 2013 with the intention of developing a coordinated mechanism between volunteering EU stakeholders and developers of Orphan Medicinal Products (OMPs) to support the exchange of information aimed at enabling informed decisions on pricing and reimbursement at Member State level and to evaluate the value of an OMP based on a Transparent Value Framework. The objective of the collaborative approach was to support more equitable access to authorised therapies for people living with rare diseases, rational prices for payers and more predictable market conditions for OMP developers. Over the past 10 years, the MoCA has conducted a series of pilot projects, examining a variety of different products and technologies at different stages of development; and with contributions from a variety of patient representatives, participation from EU payers from a range of Member States and, recently, with EUnetHTA members and the European Medicines Agency participating in the meetings as observers.

Results

10 years on from the establishment of the MoCA, the European landscape has significantly evolved, not only in the field of drug development with increasingly transformative therapies based on novel technologies, but also in terms of larger numbers of approved treatments, increased budget impact and the resulting associated uncertainties; as well as in terms of stakeholder collaboration and interactions. The value of early dialogue with OMP developers, including the EU payer community via their national decision-making authorities, is a key element within this early interaction and contributes to identifying, managing and reducing uncertainties allowing a prospectively planned approach earlier in development and, consequently, to support more timely, sustainable and equitable access to new OMPs, particularly where there is a high unmet medical need.

Conclusions

The voluntary, informal nature of the MoCA interactions creates a flexible framework for non-binding dialogue. A forum for such interactions is needed to achieve the aims of the MoCA and both to support healthcare systems in planning as well as to underpin timely, equitable and sustainable access to new therapies for patients with rare diseases within the EU.
Quality of life and physical/psychosocial factors in children and adolescents with orthostatic intolerance
Authors: Shigeyasu Yoshie , Okada Ayumi , Fujii Chikako , Tanaka Chie , Sugihara Akiko , Horiuchi Makiko , Yorifuji Takashi , Tsukahara Hirokazu
Published: June 2023

Background

Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI.

Methods

A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9–15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression.

Results

Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 ± 13.5 vs. 67.9 ± 13.4, p < 0.001) and junior high schools (51.8 ± 14.6 vs. 61.3 ± 12.6, p < 0.001). This finding was observed in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (β =  − 3.2, 95% confidence interval [CI] =  − 5.8 to − 0.5, p = 0.022) and poor relationship with school (β =  − 5.0, 95% CI =  − 9.8 to − 0.4, p = 0.035).

Conclusions

These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI.
Firm performance over innovation cycle: evidence from a small European economy
Authors: Baláž Vladimír , Jeck Tomáš , Balog Miroslav
Published: June 2023

Innovation is seen as a key capability for maintaining competitive advantage, creating value for customers, and capturing a larger share of the market. Yet, empirical evidence on the impact of innovation on firm performance is mixed. This research adds to the current debate on the relationship between innovation and the economic performance of firms. It brings new evidence from a small European economy (i.e., the Slovak Republic). We use a unique data set on 170 firms supported by the European Structural and Cohesion Funds (ESCF). Actual economic data reported in companies’ annual accounts, rather than self-reported information, is used to follow firm performance over a longer term horizon. The most significant finding is that the company’s innovation strategy was a key mediator of capability development and, ultimately, economic performance. The importance of specific innovation strategies varied over the innovation cycle. Simple process and organisational innovations were perceived to be important when assessing the immediate effects of European assistance. Investment in and cooperation on R&D&I became important when assessing firm performance over the longer term. The research expands the current body of literature on innovation capabilities and economic performance. It accentuates the need for a long-term perspective on innovation capabilities. To maintain a competitive advantage, a company's innovation capabilities must be constantly aligned with the changing environment.
CT-based radiomics models may predict the early efficacy of microwave ablation in malignant lung tumors
Authors: Zhu Fandong , Yang Chen , Xia Yang , Wang Jianping , Zou Jiajun , Zhao Li , Zhao Zhenhua
Published: June 2023

Purpose

To establish and validate radiomics models for predicting the early efficacy (less than 3 months) of microwave ablation (MWA) in malignant lung tumors.

Methods

The study enrolled 130 malignant lung tumor patients (72 in the training cohort, 32 in the testing cohort, and 26 in the validation cohort) treated with MWA. Post-operation CT images were analyzed. To evaluate the therapeutic effect of ablation, three models were constructed by least absolute shrinkage and selection operator and logistic regression: the tumoral radiomics (T-RO), peritumoral radiomics (P-RO), and tumoral-peritumoral radiomics (TP-RO) models. Univariate and multivariate analyses were performed to identify clinical variables and radiomics features associated with early efficacy, which were incorporated into the combined radiomics (C-RO) model. The performance of the C-RO model was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). The C-RO model was used to derive the best cutoff value of ROC and to distinguish the high-risk group (Nomo-score of C-RO model below than cutoff value) from the low-risk group (Nomo-score of C-RO model higher than cutoff value) for survival analysis of patients.

Results

Four radiomics features were selected from the region of interest of tumoral and peritumoral CT images, which showed good performance for evaluating prognosis and early efficacy in three cohorts. The C-RO model had the highest AUC value in all models, and the C-RO model was better than the P-RO model (AUC in training, 0.896 vs. 0.740; p = 0.036). The DCA confirmed the clinical benefit of the C-RO model. Survival analysis revealed that in the C-RO model, the low-risk group defined by best cutoff value had significantly better progression-free survival than the high-risk group (p<0.05).

Conclusions

CT-based radiomics models in malignant lung tumor patients after MWA could be useful for individualized risk classification and treatment.
Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda
Authors: Tabuti John R. S. , Obakiro Samuel Baker , Nabatanzi Alice , Anywar Godwin , Nambejja Cissy , Mutyaba Michael R. , Omara Timothy , Waako Paul
Published: June 2023

Background

Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance of Plasmodium species to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda.

Methods

An ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor.

Results

A total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species were Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica and Mangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed.

Conclusion

This study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.
Understanding polycystic ovary syndrome in light of associated key genes
Authors: Bhimwal Tanisha , Puneet  , Priyadarshani Anjali
Published: June 2023

Background

Polycystic ovary syndrome (PCOS) is an endocrinopathy affecting women of reproductive age group at a global level. According to many community-based studies, the prevalence of PCOS in India ranges from 3.7 to 22.5% due to the country's enormous population. Upon ultrasound, it shows multiple cysts arranged in a bead of necklace-like appearance causing irregular menstrual cycles and infertility in most cases. It is manifested with abnormally raised testosterone and insulin levels and increased luteinizing hormone (LH)-to-follicle-stimulating hormone (FSH) ratio. Phenotypically, it is presented as obesity, hirsutism, acne and male pattern baldness, which impacts the self-esteem of young girls leading to depression and compromised quality of life.

Aim

Numerous potential genes have been shown to contribute to PCOS, and the genetic linkage of PCOS has been investigated in many studies. In this study we are looking into the candidate genes, the variants, and other responsible factors behind the genesis of PCOS. This will help in better understanding of its pathogenesis and, as a result, deciphering the mechanism by proper medication.

Method of the study

We comprehensively searched for publications including PCOS-relevant keywords in different areas in five different electronic databases: PubMed, Google Scholars, Elsevier, Springer Link and Science Direct up to March 2023 focusing on the new ones. We excluded non-English articles, conference papers and studies that were overlapping. Chosen articles were carefully read and further articles that were retrieved from their references were also reviewed so as to make the search complete with the inclusion criterion.

Result

This review summarizes PCOS as an polygenic and a multifactorial complex disease in which a vast array of genetic and environmental factors are involved. Genes that affect steroidogenesis (ovarian and adrenal), gonadotropin action and regulation, insulin action and secretion, body mass index and chronic inflammation are directly or indirectly associated with PCOS.

Conclusion

In this study, research of the genetic propensity to PCOS was made, though not in-depth. With the acquired knowledge of array of genes involved, targeted efforts can be made for the potential therapeutic management of the PCOS patients via the novel discovered routes. Moreover, understanding more about PCOS would be beneficial in prevention of the associated metabolic disorders, life-threatening morbidities, restoring fertility and raising the self-esteem of the young women.
Clinical features, laboratory characteristics, and outcome of ETP and TCRA/D aberrations in pediatric patients with T-acute lymphoblastic leukemia
Authors: Ashry Mona S. El , Radwan Enas , Abdellateif Mona S. , Arafah Omar , Hassan Naglaa M.
Published: June 2023

Background

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few accepted prognostic factors that limit the efficiency of therapy. The aim of the current study was to assess the clinical and laboratory features of T-cell receptor (TCR) aberrations and early T-cell precursor (ETP) subtype as well as their outcome to therapy.

Methods

Sixty-three newly diagnosed pediatric T-ALL patients were assessed for the ETP status using immunophenotyping. Screening of TCRA/D aberrations was done by fluorescent in situ hybridization (FISH). The data were correlated to the patients’ clinical features, response to treatment, and survival rates.

Results

Seven patients (11%) had ETP-ALL. The ETP-ALL patients were older (P = 0.013), presented with lower white blood cell (WBC) count (P = 0.001) and lower percentage of peripheral blood (PB) blast cells (P = 0.037), more likely to have hyperdiploid karyotype (P = 0.009), and had been associated with TCRA/D gene amplification (P = 0.014) compared to other T-ALL patients. Of note, the same associations had been significantly observed in patients with TCRA/D gene amplification. Patients with TCRA/D amplification frequently coincided with TCRβ aberrations (P = 0.025). TCR-β aberrations were significantly associated with negative MRD at the end of induction compared to TCR-β-negative patients. There was a nonsignificant trend of ETP-positive cases to have lower overall survival (OS) (P = 0.06). Patients with TCR aberrations had no significant differences regarding disease-free survival (DFS) or OS rates compared to those with normal TCR.

Conclusion

ETP-ALL patients tend to have increased mortalities. There was no significant impact of TCR aberrations on the survival rates of the patients.
Determinants of targeted cancer therapy use in community oncology practice: a qualitative study using the Theoretical Domains Framework and Rummler-Brache process mapping
Authors: Ellis Shellie D. , Brooks Joanna Veazey , Birken Sarah A. , Morrow Emily , Hilbig Zachary S. , Wulff-Burchfield Elizabeth , Kinney Anita Y. , Ellerbeck Edward F.
Published: June 2023

Background

Precision medicine holds enormous potential to improve outcomes for cancer patients, offering improved rates of cancer control and quality of life. Not all patients who could benefit from targeted cancer therapy receive it, and some who may not benefit do receive targeted therapy. We sought to comprehensively identify determinants of targeted therapy use among community oncology programs, where most cancer patients receive their care.

Methods

Guided by the Theoretical Domains Framework, we conducted semi-structured interviews with 24 community cancer care providers and mapped targeted therapy delivery across 11 cancer care delivery teams using a Rummler-Brache diagram. Transcripts were coded to the framework using template analysis, and inductive coding was used to identify key behaviors. Coding was revised until a consensus was reached.

Results

Intention to deliver precision medicine was high across all participants interviewed, who also reported untenable knowledge demands. We identified distinctly different teams, processes, and determinants for (1) genomic test ordering and (2) delivery of targeted therapies. A key determinant of molecular testing was role alignment. The dominant expectation for oncologists to order and interpret genomic tests is at odds with their role as treatment decision-makers’ and pathologists’ typical role to stage tumors. Programs in which pathologists considered genomic test ordering as part of their staging responsibilities reported high and timely testing rates. Determinants of treatment delivery were contingent on resources and ability to offset delivery costs, which low- volume programs could not do. Rural programs faced additional treatment delivery challenges.

Conclusions

We identified novel determinants of targeted therapy delivery that potentially could be addressed through role re-alignment. Standardized, pathology-initiated genomic testing may prove fruitful in ensuring patients eligible for targeted therapy are identified, even if the care they need cannot be delivered at small and rural sites which may have distinct challenges in treatment delivery. Incorporating behavior specification and Rummler-Brache process mapping with determinant analysis may extend its usefulness beyond the identification of the need for contextual adaptation.
Kinetic modeling of wealth distribution with saving propensity, earnings growth and Matthew effect
Authors: Cui Lijie , Lin Chuandong , Huang Xinfei
Published: June 2023

A kinetic model is presented for a closed economic market with random transactions involving the saving interest, earnings growth, and Matthew principle. Furthermore, the deviation (overlap) degree is defined to quantify the dissimilarity (similarity) between two arbitrary wealth distributions. It is interesting to find that the tendency of the entropy is similar to that of the particular overlap degree which measures the coincidence between the monetary distribution and the Boltzmann-Gibbs exponential function. In addition, both the Gini coefficient and Kolkata index decrease with increasing saving propensity, which helps to enhance wealth equality by raising the middle-class population and reducing the proportion of the rich and the poor. However, the economic profit and Matthew effect contribute to dispersion in the wealth distribution and exacerbate wealth inequality.
Containing the Unnamable
Authors: Amoretti Valerio
Published: June 2023

This essay uses W. R. Bion’s object-relations theory to argue that the formal experiments in Samuel Beckett’s The Unnamable demand a distinctive kind of psychic work from readers. It describes this work in terms of containment, an unconscious mechanism that supports the psyche’s capacity to think. The concept of containment reveals the continuities between the psychological breakdowns that occur in psychosis, trauma, and ordinary development, as well as the relationship between these breakdowns and the emergence of the ability to represent and narrate experience. Analyzing the affective configuration generated by The Unnamable through the prism of containment deepens our understanding of the challenges posed by the text and of the text’s historical situatedness.
The Pot Still Boils
Authors: Anderman Nicholas , Hicks Zachary
Published: June 2023

This special-issue introduction historicizes and seeks to move beyond the antinomy between totality and culture that is today a mainstay of much contemporary critical theory. The introduction proceeds in three parts. The first examines a midcentury crisis of Marxism that, concomitant with major shifts in global capitalism, set the scene for subsequent scholarly accounts of culture that have privileged the fragment, the supplement, the remainder, the site, the margins, and the like over against the totality. The second part consists of an analysis of two works of art—by the American visual artists Allan Sekula and Ellen Gallagher, respectively—which we take to be exemplary of the affordances of art, literature, and other forms of cultural expression for accessing totality anew. The third part briefly surveys recent theoretical work that aims to put a revitalized concept of totality at the center of cultural critique. The introduction concludes with summaries of the seven articles included herein. The special issue covers a lot of ground in terms of subject matter, theoretical milieu, disciplinary framework, and style. What binds the articles together is, in effect, a shared working method, which involves thinking through the relationship between a specific cultural object (or set of objects) and the social whole in and through which it emerged.
Inverted Propositions
Authors: Chan Roy
Published: June 2023

Nikolai Chernyshevsky (1828–89) is best known for his utopian realist novel What Is to Be Done? (1863). However, he was perhaps most celebrated as a literary thinker in China as a result of the Soviet canonization of the nineteenth-century “democratic critics.” This essay discusses two Chinese critics’ engagement with Chernyshevsky’s treatise The Aesthetic Relation of Art to Reality (1853). Here Chernyshevsky advanced the proposition “Beauty is life.” In the 1930s and 1940s the literary theorist Zhou Yang read Chernyshevsky and produced a Chinese translation in 1942. In 1963 the philosopher Zhu Guangqian published the History of Western Aesthetics, in which he devoted a chapter to Chernyshevsky. This article explores how both Zhou and Zhu responded to Chernyshevsky’s proposition on beauty and life, with particular attention to all three thinkers’ engagement with Ludwig Feuerbach’s “transformative method” in his critique of Christianity, which sought to invert the relation between subject and predicate. Both Zhou and Zhu alighted on how Chernyshevsky’s reliance on Feuerbach led to a one-sided interpretation that needed further articulation; they marshaled the insights of Marx and Hegel to reinterpret Chernyshevsky. Finally, the essay considers the issue of transnational Bildung between Russia and China and the teacher-student relation as expressions of totality along the lines of both Feuerbachian transformative critique and Hegelian speculative retrieval.
Aggregation-prone Tau impairs mitochondrial import, which affects organelle morphology and neuronal complexity
Authors: Needs Hope I. , Wilkinson Kevin A. , Henley Jeremy M. , Collinson Ian
Published: June 2023

Mitochondrial protein import is essential for organellar biogenesis, and thereby for the sufficient supply of cytosolic ATP – which is particularly important for cells with high energy demands like neurons. This study explores the prospect of import machinery perturbation as a cause of neurodegeneration instigated by the accumulation of aggregating proteins linked to disease. We found that the aggregation-prone Tau variant (TauP301L) reduces the levels of components of the import machinery of the outer (TOM20, encoded by TOMM20) and inner membrane (TIM23, encoded by TIMM23) while associating with TOM40 (TOMM40). Intriguingly, this interaction affects mitochondrial morphology, but not protein import or respiratory function; raising the prospect of an intrinsic rescue mechanism. Indeed, TauP301L induced the formation of tunnelling nanotubes (TNTs), potentially for the recruitment of healthy mitochondria from neighbouring cells and/or the disposal of mitochondria incapacitated by aggregated Tau. Consistent with this, inhibition of TNT formation (and rescue) reveals Tau-induced import impairment. In primary neuronal cultures, TauP301L induced morphological changes characteristic of neurodegeneration. Interestingly, these effects were mirrored in cells where the import sites were blocked artificially. Our results reveal a link between aggregation-prone Tau and defective mitochondrial import relevant to disease.
A fundamental propulsive mechanism employed by swimmers and flyers throughout the animal kingdom
Authors: Costello John H. , Colin Sean P. , Gemmell Brad J. , Dabiri John O. , Kanso Eva A.
Published: June 2023

Even casual observations of a crow in flight or a shark swimming demonstrate that animal propulsive structures bend in patterned sequences during movement. Detailed engineering studies using controlled models in combination with analysis of flows left in the wakes of moving animals or objects have largely confirmed that flexibility can confer speed and efficiency advantages. These studies have generally focused on the material properties of propulsive structures (propulsors). However, recent developments provide a different perspective on the operation of nature's flexible propulsors, which we consider in this Commentary. First, we discuss how comparative animal mechanics have demonstrated that natural propulsors constructed with very different material properties bend with remarkably similar kinematic patterns. This suggests that ordering principles beyond basic material properties govern natural propulsor bending. Second, we consider advances in hydrodynamic measurements demonstrating suction forces that dramatically enhance overall thrust produced by natural bending patterns. This is a previously unrecognized source of thrust production at bending surfaces that may dominate total thrust production. Together, these advances provide a new mechanistic perspective on bending by animal propulsors operating in fluids – either water or air. This shift in perspective offers new opportunities for understanding animal motion as well as new avenues for investigation into engineered designs of vehicles operating in fluids.
Overdue taxdebt in Greece
Authors: Karavitis Nicholas , Paipetis Kosmas , Priniotaki Maria
Published: June 2023

Accumulation of overdue tax debts has been a thorn in the side of Greek fiscal policy in the past two decades. The dramatic accumulation of tax debts during the crisis of 2008 called for urgent reforms and measures to tackle the problem. Under the pressure of three Economic Adjustment Programmes, the MOU governments embarked on an effort to reform Greek Tax Administration, with emphasis on independence, depoliticization and wider digital transformation. This has been a slow process yet to be completed and the strains to the system introduced by the ongoing health crisis, make the need for reform even more urgent. The present paper puts overdue tax debts into perspective, analyzes the process of accumulation and brings out its main features, assesses the efficiency of Tax Administration and comes up with several policy recommendations. After we profile overdue debts stock and its characteristics, we compile an input-output table, which leads us to the composition of a series of indicators, which help assess the efficiency of tax administration in the context of the fiscal policies of the last two decades. The results of the research indicate poor quality of debts accumulated over time, as well as low efficiency of the Tax Administration, but with some improvement in recent years.
The use of Cause and Effect Diagram (Fishbone) and its impact on Personal Quality Management: Case Study in a classroom during the pandemic of COVID – 19
Authors: Deliou Cleopatra , Malagkoniari Maria
Published: June 2023

Personal quality and total quality management (TQM) are key success factors for organizational performance. The combination of individual and team quality management actions leads to motivated people in the workplace and can create high quality processes, relationships and outputs. The Cause and Effect Diagram (Fishbone) is one of the seven most known quality tools and it provides a systematic way of looking at effects and the causes that create or contribute to those effects. It helps an organization to identify, analyze and improve quality issues.

This study examines the use of the Cause and Effect Diagram (Fishbone) quality tool in a classroom during the pandemic of COVID – 19. After the use of the tool by the class participants on personal and team level, students were also asked to assess its impact and provide feedback over the connection of this tool application to personal quality development.

The researchers concluded that on a team basis, the Cause and Effect Diagram helped the team members visually diagram the problems and allowed them to truly diagnose the problem, to separate a problem's content from its history, and facilitated team consensus around its causes. Finally, it is well – known that by team action are cultivated skills such as cooperation, team – thinking, determination, persuasion, creativity, inspiration, fast problem solving, synergy, immediate decision making and direct communication.

EL Classification: Μ19

Keywords: Total Quality Management, Personal Quality, Cause and Effect Diagram, Personal and Team Projects
The impact of Non-Performing Loans on the Banks’ Profitability
Authors: Diakomihalis Mihail , Economakou Sofia
Published: June 2023

The global financial system after and during the financial crisis had to face the major issue which has extremely influence their profitability: The Non-Performing Loans portfolio (NPLs).

The present study aims to reveal the interrelation and the possible impact of the NPLs to the profitability indicators of the Greek banks and specifically how they affect the profitability of the banks.

The empirical investigation of included a comparative study of Financial ratios of certain Greek banks were calculated in order to reveal the impact of Non-Performing loans to their profitability for the year 2017.

Interest income on loans is positive for all Banks but with a wide variation, while Interest-Expenses show an asymmetric distribution. Overdue loans for more than 90 days show uniformity with the exception of Piraeus Bank which shows an extreme price. The correlation between ROA and ROE with loans is not statistically significant.

The effect on the Equity of loans in all forms except regulated is considered statistically significant. The negative effect of NPLs for more than 90 days on Net Profit before Tax is considered statistically significant.

 

JEL Classifications: G210, D140, G300, O160

Key words: Non- Performing loans, Greek Banks, Profitability, Credit risk, Legal frame of NPLs