bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of the value of amide proton transfer-weighted imaging and diffusion kurtosis imaging in evaluating the histological grade of cervical squamous carcinoma
Authors: Hou Mengyan , Song Kai , Ren Jipeng , Wang Kaiyu , Guo Jinxia , Niu Yongchao , Li Zhenyu , Han Dongming
Published: January 2022

Background

Uterine cervical cancer (UCC) was the fourth leading cause of cancer death among women worldwide. The conventional MRI hardly revealing the microstructure information. This study aimed to compare the value of amide proton transfer-weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) in evaluating the histological grade of cervical squamous carcinoma (CSC) in addition to routine diffusion-weighted imaging (DWI).

Methods

Forty-six patients with CSC underwent pelvic DKI and APTWI. The magnetization transfer ratio asymmetry (MTRasym), apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were calculated and compared based on the histological grade. Correlation coefficients between each parameter and histological grade were calculated.

Results

The MTRasym and MK values of grade 1 (G1) were significantly lower than those of grade 2 (G2), and those parameters of G2 were significantly lower than those of grade 3 (G3). The MD and ADC values of G1 were significantly higher than those of G2, and those of G2 were significantly higher than those of G3. MTRasym and MK were both positively correlated with histological grade (r = 0.789 and 0.743, P <  0.001), while MD and ADC were both negatively correlated with histological grade (r = − 0.732 and - 0.644, P <  0.001). For the diagnosis of G1 and G2 CSCs, AUC (APTWI+DKI + DWI) > AUC (DKI + DWI) > AUC (APTWI+DKI) > AUC (APTWI+DWI) > AUC (MTRasym) > AUC (MK) > AUC (MD) > AUC (ADC), where the differences between AUC (APTWI+DKI + DWI), AUC (DKI + DWI) and AUC (ADC) were significant. For the diagnosis of G2 and G3 CSCs, AUC (APTWI+DKI + DWI) > AUC (APTWI+DWI) > AUC (APTWI+DKI) > AUC (DKI + DWI) > AUC (MTRasym) > AUC (MK) > AUC (MD > AUC (ADC), where the differences between AUC (APTWI+DKI + DWI), AUC (APTWI+DWI) and AUC (ADC) were significant.

Conclusion

Compared with DWI and DKI, APTWI is more effective in identifying the histological grades of CSC. APTWI is recommended as a supplementary scan to routine DWI in CSCs.
Presurgical time and associated factors as predictors of acute perforated appendicitis: a prospective cohort study in a teaching pediatric hospital in Colombia
Authors: Castro Paula , Rincón Julián , Sánchez Cristian , Molina Iván , Buitrago Giancarlo
Published: January 2022

Background

We aim to determine the association between out and in-hospital factors with time, from the beginning of the symptoms to the surgery, in patients with acute appendicitis treated at Fundación Hospital Pediatrico La Misericordia (HOMI) in Colombia.

Methods

Eleven month prospective cohort study of pediatric patients at HOMI with acute appendicitis diagnosis taken to surgery. Data from the out-of-hospital phase was collected by surveying parents, and the data regarding the in-hospital phase was completed with medical records. We analyzed the association between the time from the beginning of the symptoms to the surgery, and out and in-hospital factors associated with this time using generalized linear models.

Results

Eight hundred three patients were included in the study. Total pre-surgical time was longer in perforated appendicitis (PA) group (2.65 days, standard deviation (SD) 1.88 vs. 2.04 days, SD 1.45) (p < 0.01). Factors associated with longer total and out-of-hospital presurgical times were age under 4 years old, lower socioeconomic status, father as a caregiver, self-medication, and underestimating disease severity.

Conclusions

Out-of-hospital timing determines the longer pre-surgical time in complicated appendicitis. Younger age and lower socioeconomic status affect time significantly. We suggest the implementation of strategies in order to lower prehospital time, rates, and costs of complicated appendicitis.
Neonatal acute ethanol intoxication during the epidemic of COVID-19: a case report
Authors: Sun Chao , Nie Yanyan , Cui Xiaoyu , Zhang Fang , Liu Yang
Published: January 2022

Background

After the outbreak of COVID-19, many families equip with 75% ethanol to inactivate the SARS-CoV-2, which increases the risk of exposure to ethanol.

Case presentation

We reported a 25-day-old newborn who was diagnosed with neonatal acute ethanol intoxication with a presenting complaint of accidental consumption about 15 ml formula milk containing 75% ethanol. His main clinical manifestations were irritability, flushed skin, tachycardia, tachypnea, and toxicology analysis detected ethanol. After timely gastric lavage and intravenous fluid replacement, he was cured and discharged.

Conclusions

During the COVID-19 epidemic, high concentration ethanol used for inactivating SARS-COV-2 should be placed reasonably and neonatal feeding safety should be emphasized. Timely diagnosis and symptomatic treatment are essential for the prevention and management of acute ethanol intoxication in newborns.
A school-based program to prevent depressive symptoms and strengthen well-being among pre-vocational students (Happy Lessons): protocol for a cluster randomized controlled trial and implementation study
Authors: Rombouts Marieke , Duinhof Elisa L. , Kleinjan Marloes , Kraiss Jannis T. , Shields-Zeeman Laura , Monshouwer Karin
Published: January 2022

Background

Depression is one of the leading causes of illness and disability among young people. In the Netherlands, one in twelve Dutch adolescents has experienced depression in the last 12 months. Pre-vocational students are at higher risk for elevated depressive symptoms. Effective interventions, especially for this risk group, are therefore needed to prevent the onset of depression or mitigate the adverse long-term effects of depression. The aim of this study is to examine the effectiveness and implementation of a school-based program Happy Lessons (HL), that aims to prevent depression and promote well-being among pre-vocational students.

Methods

A cluster randomized controlled trial (RCT) with students randomized to HL or to care as usual will be conducted. Pre-vocational students in their first or second year (aged 12 to 14) will participate in the study. Subjects in both conditions will complete assessments at baseline and at 3- and 6-months follow-up. The primary outcome will be depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D) at 6-months follow-up. Secondary outcomes are well-being using the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) and life satisfaction (Cantril Ladder) measured at 6-months follow-up. Alongside the trial, an implementation study will be conducted to evaluate the implementation of HL, using both quantitative and qualitative methods (interviews, survey, and classroom observations).

Discussion

The results from both the RCT and implementation study will contribute to the limited evidence base on effective school-based interventions for the prevention of depression and promotion of well-being among pre-vocational adolescents. In addition, insights from the implementation study will aid identifying factors relevant for optimizing the future implementation and scale-up of HL to other schools and contexts.

Trial registration

This study was registered on 20 September 2021 in the Dutch Trial Register (NL9732).
Risk of SARS-CoV-2 infection in migrants and ethnic minorities compared with the general population in the European WHO region during the first year of the pandemic: a systematic review
Authors: Jaljaa Anissa , Caminada Susanna , Tosti Maria Elena , D’Angelo Franca , Angelozzi Aurora , Isonne Claudia , Marchetti Giulia , Mazzalai Elena , Giannini Dara , Turatto Federica , De Marchi Chiara , Gatta Angela , Declich Silvia , Pizzarelli Scilla , Geraci Salvatore , Baglio Giovanni , Marceca Maurizio
Published: January 2022

Background

Migrants and ethnic minorities have suffered a disproportionate impact of the COVID-19 pandemic compared to the general population from different perspectives. Our aim was to assess specifically their risk of infection in the 53 countries belonging to the World Health Organization European Region, during the first year of the pandemic.

Methods

We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42021247326). We searched multiple databases for peer-reviewed literature, published on Medline, Embase, Scisearch, Biosis and Esbiobase in 2020 and preprints from PubMed up to 29/03/2021. We included cross-sectional, case-control, cohort, intervention, case-series, prevalence or ecological studies, reporting the risk of SARS-CoV-2 infection among migrants, refugees, and ethnic minorities.

Results

Among the 1905 records screened, 25 met our inclusion criteria and were included in the final analysis. We found that migrants and ethnic minorities during the first wave of the pandemic were at increased exposure and risk of infection and were disproportionately represented among COVID-19 cases. However, the impact of COVID-19 on minorities does not seem homogeneous, since some ethnic groups seem to be more at risk than others. Risk factors include high-risk occupations, overcrowded accommodations, geographic distribution, social deprivation, barriers to access to information concerning preventive measures (due to the language barrier or to their marginality), together with biological and genetic susceptibilities.

Conclusions

Although mixed methods studies will be required to fully understand the complex interplay between the various biological, social, and cultural factors underlying these findings, the impact of structural determinants of health is evident. Our findings corroborate the need to collect migration and ethnicity-disaggregated data and contribute to advocacy for inclusive policies and programmatic actions tailored to reach migrants and ethnic minorities.
Synchronous lung and multiple soft tissue metastases developed from osteosarcoma of tibia: a rare case report and genetic profile analysis
Authors: Zheng Chuanxi , Wang Yitian , Luo Yi , Pang Zongguo , Zhou Yong , Min Li , Tu Chongqi
Published: January 2022

Background

Osteosarcoma is the most common primary malignant bone tumor with a highly metastatic propensity in children and young adolescents. The majority of metastases develope in the lung, while metastases to the extrapulmonary locations have rarely been discussed, especially in skeletal muscle.

Case presentation

We reported a young patient with pathologically diagnosed osteosarcoma of the right tibia who was initially treated with standard chemotherapy and complete surgical resection. However, pulmonary metastases and multiple soft tissue masses in skeletal muscle developed four years after the index surgical resection. Subsequently, a targeted next-generation sequencing assay based on an 806 oncogenes and tumor suppressor genes panel was performed to analyze genetic alterations in this patient with rare metastatic pattern. The genetic analysis revealed canonical somatic mutations of RB1 and germline variants of ALK (c.862 T > C), BLM (c.1021C > T), PTCH1 (c.152_154del), MSH2 (c.14C > A), RAD51C (c.635G > A). Using silico prediction programs, the germline variants of the MSH2 and RAD51C were predicted as “Possibly Damaging” by Polymorphism Phenotyping v2 (PolyPhen-2) and “Tolerated” by Sorting Intolerant from Tolerant (SIFT); BLM was classified as “Tolerated”, while the germline variant of ALK was predicted to be pathogenic by both PolyPhen-2 and SIFT.

Conclusions

Osteosarcoma with extrapulmonary metastases is rare, especially located in the skeletal muscle, which predicts a worse clinical outcome compared with lung-only metastases. The several novel variants of ALK, BLM, PTCH1 in this patient might expand the mutational spectrums of the osteosarcoma. All the results may contribute to a better understanding of the clinical course and genetic characteristics of osteosarcoma patients with metastasis.
Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells
Authors: Brandão Douglas C. , Lima Paula M. A. P. , Martins Isabella C. , Cordeiro Carina S. , Cordeiro Antonielle O. , Vecchi Lara , Guerra Joyce F. C. , Orsolin Priscila C. , Gazolla Matheus C. , Costa Danilo S. , da Silva Filho Ademar A. , Araújo Thaise G.
Published: January 2022

Background

Breast Cancer (BC) is the most common cancer in women worldwide and, although 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients’ survival is comprised by resistance to endocrine therapy. Brazilian flora, especially the Amazon biome, is one of the richest global sources of native species with potentially bioactive compounds. Arrabidaea chica is a plant native to the Amazon that has been used in the treatment of different diseases. However, its action on BC remains unclear.

Methods

Herein the biological effects of the chloroform extract of A. chica (CEAC) were evaluated on BC cells and in in vivo model. After confirmation of CEAC antioxidant capacity, cells were treated with CEAC and Tam, alone and with CEAC+Tam. The cell viability was evaluated by MTT and hormone receptor transcripts levels were assessed (ESR1, ESR2 and AR). Finally, anticarcinogenicity of CEAC was recorded in Drosophila melanogaster through Epithelial Tumor Test (ETT).

Results

The study confirmed the antioxidant activity of CEAC. CEAC was selective for MCF-7, downregulating ESR2 and AR transcripts and upregulating ESR2 expression. The modulatory effects of CEAC on ERs did not differ between cells treated with Tam and with CEAC+Tam. Interestingly, previous treatment with CEAC, followed by treatment with Tam promoted a significant decrease in cell viability. The extract also presented anticarcinogenic effect in in vivo assay.

Conclusion

The bioassays on breast tumor cells demonstrated the antiproliferative activity of the extract, which modulated the expression of hormone receptors and sensitized luminal tumor cells to Tam. These results suggest that CEAC could be a complementary treatment for BC.
How an EPA-based curriculum supports professional identity formation
Authors: Bremer Anne E. , van de Pol Marjolein H. J. , Laan Roland F. J. M. , Fluit Cornelia R. M. G.
Published: January 2022

Background

Entrustable professional activities (EPAs) are widely used in medical education, and they might be an important incentive to stimulate professional identity formation (PIF) of medical students, by actively encouraging participation in the workplace. The goal of this study was to explore the effects of an EPA-based curriculum on the PIF of medical students in undergraduate curricula.

Methods

In this study at the Radboud University Medical Center in Nijmegen, the Netherlands, the authors interviewed twenty-one medical students in three focus group interviews (November 2019), and conducted a thematic analysis based on both the synthesizing concepts PIF, communities of practice and EPAs, and newly defined themes.

Results

Four central themes proved crucial for understanding the influence of EPAs on PIF: creating learning opportunities, managing feedback, dealing with supervision in context and developing confidence. EPAs helped students to create learning opportunities and to choose activities purposefully, and the use of EPAs stimulated their feedback-seeking behavior. The context and way of supervision had a great impact on their development, where some contexts offer better learning opportunities than others. EPAs helped them develop trust and self-confidence, but trust from supervisors hardly appears to result from using EPAs.

Conclusions

An EPA-based curriculum does stimulate PIF in the complex context of working and learning by supporting participation in the workplace and by encouraging feedback-seeking behavior. Striking the right balance between participation, feedback-seeking behavior and choosing learning activities is essential.

Trial registration

This study was approved by the ethics committee of the Netherlands Association of Medical Education (NVMO, case number 2019.5.12).
Periostin promotes the proliferation and metastasis of osteosarcoma by increasing cell survival and activates the PI3K/Akt pathway
Authors: Xu Chaojian , Wang Ziyue , Zhang Long , Feng Yi , Lv Jia , Wu Zhuangzhuang , Yang Rong , Wu Taiyong , Li Jian , Zhou Ruhao , Tian Zhi , Bai Junjun , Zhang Huadong , Lan Yanping , Lv Zhi
Published: January 2022

Background

Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear.

Methods

We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein–protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes.

Results

The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway.

Conclusions

Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.
Core policies disparity response to COVID-19 among BRICS countries
Authors: Jiao Jun , Shi Leiyu , Zhang Yuyao , Chen Haiqian , Wang Xiaohan , Yang Manfei , Yang Junyan , Liu Meiheng , Sun Gang
Published: January 2022

Objective

To provide experience for formulating prevention and control policies, this study analyzed the effectiveness of the Coronavirus disease 2019(COVID-19) prevention and control policies, and evaluated health equity and epidemic cooperation among BRICS countries.

Methods

This study summarized the pandemic prevention and control policies in BRICS countries and evaluated the effectiveness of those policies by extracting COVID-19 related data from official websites.

Result

As of May 4, 2021, responding to COVID-19. China adopted containment strategies. China’s total confirmed cases (102,560) were stable, without a second pandemic peak, and the total deaths per million (3.37) were much lower than others. India and South Africa who adopted intermediate strategies have similar pandemic curves, total confirmed cases in India (20,664,979) surpassed South Africa (1,586,148) as the highest in five countries, but total deaths per million (163.90) lower than South Africa (919.11). Brazil and Russia adopted mitigation strategies. Total confirmed cases in Brazil (14,856,888) and Russia (4,784,497) continued to increase, and Brazil’s total deaths per million (1,936.34) is higher than Russia (751.50) and other countries.

Conclusion

This study shows BRICS countries implemented different epidemic interventions. Containment strategy is more effective than intermediate strategy and mitigation strategy in limiting the spread of COVID-19. Especially when a strict containment strategy is implemented in an early stage, but premature relaxation of restrictions may lead to rebounding. It is a good choice to combat COVID-19 by improving the inclusiveness of intervention policies, deepening BRICS epidemic cooperation, and increasing health equities.
High remnant cholesterol level is relevant to diabetic retinopathy in type 2 diabetes mellitus
Authors: Shan Yongyan , Wang Qian , Zhang Yitong , Tong Xuewei , Pu Shengdan , Xu Yuxin , Gao Xinyuan
Published: January 2022

Background

Diabetic retinopathy (DR) is the primary oculopathy causing blindness in diabetic patients. Currently, there is increasing interest in the role of lipids in the development of diabetic retinopathy, but it remains controversial. Remnant cholesterol (RC) is an inexpensive and easily measurable lipid parameter; however, the relationship between RC and DR in type 2 diabetes mellitus (T2DM) has not been elucidated. This research investigates the relevance between RC levels and DR severity while building a risk prediction model about DR.

Methods

In this single-centre retrospective cross-sectional study. Each hospitalised T2DM patient had no oral lipid-lowering drugs in the past three months, and coronary angiography showed epicardial coronary artery stenosis of less than 50% and completed seven-field stereo photographs, fluorescein fundus angiography, and optical coherence tomography detection. The RC value is calculated according to the internationally recognised formula. Binary logistic regression was used to correct confounding factors, and the receiver operating characteristic (ROC) analysis was used to identify risk factors and assess the nomogram’s diagnostic efficiency.

Results

A total of 456 T2DM patients were included in the study. The RC levels in the DR team was higher [0.74 (0.60–1.12) mmo/l vs 0.54 (0.31–0.83) mmol/l P < 0.001] in the non-DR team. After adjusting for confounding elements, RC levels are still associated with DR risk (OR = 5.623 95%CI: 2.996–10.556 P < 0.001). The ratio of DR in every stage (except mild non-proliferative diabetic retinopathy) and DME in the high RC level team were further increased compared to the low-level team (all P < 0.001). After ROC analysis, the overall risk of DR was predicted by a nomogram constructed for RC, diabetes duration, and the neutrophil-lymphocyte ratio as 0.758 (95%CI 0.714–0.802 P < 0.001).

Conclusions

High RC levels may be a potential risk factor for diabetic retinopathy, and the nomogram does better predict DR. Despite these essential findings, the limitation of this study is that it is single-centred and small sample size analysis.
The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China
Authors: He Jiaoyu , Li Qiufu , Ma Shiyu , Li Tianjun , Chen Yuning , Liu Yiran , Cui Yanru , Peng Jianying , Shi Yunfan , Wei Xia , Ding Xianping
Published: January 2022

Background

The Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein.

Methods

Cell samples were collected by cervical scraped for HPV detecting and typing.
HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB.

Results

α-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site.

Conclusions

HPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.
Comparison of clinical behavior between mucinous ovarian carcinoma with infiltrative and expansile invasion and high-grade serous ovarian carcinoma: a retrospective analysis
Authors: Hada Taira , Miyamoto Morikazu , Ishibashi Hiroki , Matsuura Hiroko , Kakimoto Soichiro , Iwahashi Hideki , Tsuda Hitoshi , Takano Masashi
Published: January 2022

Background

The aim of this study was to evaluate the clinicopathological factors and prognosis of mucinous carcinoma (MC) with infiltrative invasion, MC with expansile invasion, and high-grade serous carcinoma (HGSC).

Methods

Cases of MC and HGSC between 1984 and 2019 were identified. The clinicopathological factors and prognosis of MC with infiltrative invasion or expansile invasion and HGSC were retrospectively compared. Although our present study included cases in our previous studies, we extended observational period when analysis was performed. Accordingly, our study added increased cases and survival analysis was newly conducted.

Results

After pathological review, 27 cases of MC with infiltrative invasion, 25 cases of MC with expansile invasion, and 219 cases of HGSC were included. MC had a better prognosis in terms of progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than HGSC for all International Federation of Gynecology and Obstetrics (FIGO) stages; however, multivariate analysis did not show statistical differences in PFS and OS. There were no statistically significant differences in PFS and OS for all FIGO stages between MC with infiltrative invasion and HGSC. However, in cases with FIGO stages II to IV, MC with infiltrative invasion had worse PFS (p < 0.01) and OS (p < 0.01) than HGSC. In univariate analysis, MC with infiltrative invasion was a worse prognostic factor for PFS (hazard ratio [HR] 2.83, p < 0.01) and OS (HR 3.83, p < 0.01) than HGSC. Compared with HGSC, MC with expansile invasion had better PFS (p < 0.01) and OS (p < 0.01). Multivariate analysis demonstrated that MC with expansile invasion was a better prognostic factor for PFS (HR 0.17, p < 0.01) and OS (HR 0.18, p = 0.03) than HGSC.

Conclusions

Compared to the prognosis of HGSC, that of MC was different according to the invasive pattern and FIGO stage. Therefore, future study may be needed to consider this association.
The boosting effects of melatonin on the expression of related genes to oocyte maturation and antioxidant pathways: a polycystic ovary syndrome- mouse model
Authors: Nikmard Fatemeh , Hosseini Elham , Bakhtiyari Mehrdad , Ashrafi Mahnaz , Amidi Fardin , Aflatoonian Reza
Published: January 2022

Background

Melatonin, as a free radical scavenger exhibiting genomic actions, regulates the antioxidant genes expression and apoptosis mechanisms. In polycystic ovary syndrome (PCOS) patients, an imbalance between free radicals and antioxidants in follicular fluid leads to oxidative stress, aberrant folliculogenesis, and intrinsic defects in PCOS oocytes. In this experimental mouse model study, oocytes of PCOS and the control groups were cultured in different melatonin concentrations (10− 5, 10− 6, and 10− 7 M) to investigate the expression of oocyte maturation-related genes (Gdf9/Bmp15), antioxidant-related genes (Gpx1/Sod1), apoptotic biomarkers (Bcl2/Bax) and total intracellular ROS levels.

Results

Gdf9 and Bmp15, Gpx1 and Sod1 were up-regulated in PCOS and control oocytes cultured in all melatonin concentrations compared to those cultured in IVM basal medium (P < 0.05). A significant decrease in the total ROS level was observed in all groups cultured in the supplemented cultures. Melatonin increased Bcl2 and decreased Bax gene expression in PCOS and control oocytes compared to non-treated oocytes.

Conclusions

Melatonin increased antioxidant gene expression and regulated the apoptosis pathway, effectively reducing the adverse effects of culture conditions on PCOS oocytes. Furthermore, it influenced the expression of oocyte maturation-related genes in PCOS, providing valuable support during the IVM process.
Covid-19 and spirometry in this age
Authors: Klain Angela , Indolfi Cristiana , Dinardo Giulio , Decimo Fabio , Miraglia Del Giudice Michele
Published: January 2022

In the last year, many countries adopted a plan to contain hospital infections by Sars-Cov-2 also limiting pulmonary function tests (PFTs), exclusively to indispensable cases. All the recommendations of the major scientific societies regarding the use of PFTs, in particular spirometry, in the Covid era were formulated in the initial period of the pandemic. Currently, the new scientific knowledge about Sars-Cov-2 and the vaccination among healthcare workers, shown new insight to start doing PFTs again to help the investigation and monitoring of patients with respiratory pathology. In this article, we sum up the recommendations of major International Respiratory Societies, and we shared our experience about PFTs in a Pediatric Respiratory Disease Unit during the pandemic.
The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex
Authors: Singleton E. H. , Pijnenburg Y. A. L. , Gami-Patel P. , Boon B. D. C. , Bouwman F. , Papma J. M. , Seelaar H. , Scheltens P. , Grinberg L. T. , Spina S. , Nana A. L. , Rabinovici G. D. , Seeley W. W. , Ossenkoppele R. , Dijkstra A. A.
Published: January 2022

Background

The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD.

Methods

VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss.

Results

The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5.

Discussion

VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.
Clinical characteristics and CT features of hepatic epithelioid haemangioendothelioma and comparison with those of liver metastases
Authors: Wang Xiaopeng , Liang Pan , Lv Peijie , Li Rui , Hou Ping , Gao Jianbo
Published: January 2022

Background

To analyse clinical characteristics and computer tomography (CT) findings of hepatic epithelioid haemangioendothelioma (HEH) and to determine differential features compared with liver metastasis (LM).

Methods

This retrospective study included 80 patients with histopathologically confirmed HEH (n = 20) and LM (n = 60) of different primary tumours who underwent dynamic contrast-enhanced CT scans. CT findings included the location, contour, size, number, margin, and density of lesions, the patterns and degree of contrast enhancement of lesions, vascular invasion and changes in other organs. The enhancement ratio (ER) and tumour-to-normal parenchyma ratio (TNR) were calculated. Receiver operating characteristic curves (ROCs) were used to determine areas under the curve (AUCs).

Results

About 65% of HEH lesions were located in submarginal areas. Significant differences were observed between HEH and LM patients in age, sex, and tumour marker positivity (p < 0.05). HEH showed minimal to slight enhancement, thin ring-like enhancement in arterial phase, and slight, homogeneous, progressive enhancement in the portal phase. HEH presented capsule retraction, and the “target” sign and the “lollipop” sign were significantly more frequent than in LM (p < 0.05). The ER and TNR in the arterial phase of HEH were lower than those of LM (p < 0.05). AUCs of ER and TNR in the arterial phase were 0.74 and 0.73, respectively.

Conclusion

Lesions in subcapsular locations, capsular retraction, slight and thin ring-like enhancement, “target” and “lollipop” signs and lower ER and TNR in the arterial phase may represent important features of HEH compared with LM.
The use of disaggregate data in evaluations of public health interventions: cross-sectional dependence can bias inference
Authors: Halkjelsvik Torleif , Gasparrini Antonio , Hart Rannveig Kaldager
Published: January 2022

Higher availability of administrative data and better infrastructure for electronic surveys allow for large sample sizes in evaluations of national and other large scale policies. Although larger datasets have many advantages, the use of big disaggregate data (e.g., on individuals, households, stores, municipalities) can be challenging in terms of statistical inference. Measurements made at the same point in time may be jointly influenced by contemporaneous factors and produce more variation across time than suggested by the model. This excess variation, or co-movement over time, produce observations that are not truly independent (i.e., cross-sectional dependence). If this dependency is not accounted for, statistical uncertainty will be underestimated, and studies may indicate reform effects where there is none. In the context of interrupted time series (segmented regression), we illustrate the potential for bias in inference when using large disaggregate data, and we describe two simple solutions that are available in standard statistical software.
Small-sized type A thymoma with pulmonary metastasis: a case report
Authors: Kawagishi Sachi , Maniwa Tomohiro , Watari Hirokazu , Sakata Ryuhei , Omura Akiisa , Tanaka Ryo , Kimura Toru , Honma Keiichiro , Okami Jiro
Published: January 2022

Background

Type A thymomas comprise a homogenous population of neoplastic epithelial cells that are characterized by a spindle/oval shape without nuclear atypia. They may be accompanied by few non-neoplastic lymphocytes. Most type A thymomas are detected in the earlier Masaoka stages. Compared to other thymoma subtypes, they rarely metastasize or recur. There have been some reports of patients with type A thymomas with pulmonary metastasis; however, these thymomas were 20 mm or more in size. Herein, we report the case of a patient who underwent surgical resection for a small-sized type A thymoma (12 mm) with pulmonary metastasis.

Case presentation

A 62-year-old patient presented with an abnormal shadow in the left lung on plain chest radiography during a medical checkup. Chest computed tomography revealed a 12-mm tumor in the anterior mediastinum and a 13-mm nodule in the left lower lobe. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed uptake in the anterior mediastinal tumor, but did not show a significant uptake in the pulmonary nodule. The patient underwent surgical resection on two separate occasions, and was diagnosed with an atypical type A thymoma and pulmonary metastasis. The TNM classification was p-T1aN0M1b stage IVb, and it was stage IVb according to the Masaoka staging system. No recurrence was observed during the follow-up.

Conclusions

We report a case of the smallest type A thymoma with pulmonary metastasis. Pulmonary metastasis secondary to a type A thymoma should be considered even if the thymoma is small in size (< 20 mm).
The role of knowledge economy in Asian business
Authors: Zeb Shumaila
Published: January 2022

The study examines the role of the knowledge economy (KE) in Asian businesses in 45 countries for 2000–2019. KE indicators include education, economic incentives, innovation, institutional regime, and information and communication technology. The business indicators used in the study are starting, doing, and closing business. The empirical analysis is carried out by applying principal component analysis (PCA) and instrument variable panel fixed effects estimator. The results proved that the KE indicators are essential to improve businesses in Asia. They help the economies to boost their business sector and help to fight against poverty and unemployment.
The metabolic changes that effect fruit quality during tomato fruit ripening
Authors: Zhu Feng , Wen Weiwei , Cheng Yunjiang , Fernie Alisdair R.
Published: January 2022

As the most valuable organ of tomato plants, fruit has attracted considerable attention which most focus on its quality formation during the ripening process. A considerable amount of research has reported that fruit quality is affected by metabolic shifts which are under the coordinated regulation of both structural genes and transcriptional regulators. In recent years, with the development of the next generation sequencing, molecular and genetic analysis methods, lots of genes which are involved in the chlorophyll, carotenoid, cell wall, central and secondary metabolism have been identified and confirmed to regulate pigment contents, fruit softening and other aspects of fruit flavor quality. Here, both research concerning the dissection of fruit quality related metabolic changes, the transcriptional and post-translational regulation of these metabolic pathways are reviewed. Furthermore, a weighted gene correlation network analysis of representative genes of fruit quality has been carried out and the potential of the combined application of the gene correlation network analysis, fine-mapping strategies and next generation sequencing to identify novel candidate genes determinants of fruit quality is discussed.
Validation of the Greek version of the Affiliate Stigma Scale among mothers of children with autism spectrum disorder
Authors: Papadopoulos Angelos , Tafiadis Dionysios , Tsapara Angeliki , Skapinakis Petros , Tzoufi Meropi , Siafaka Vassiliki
Published: January 2022

Background

Caregivers of children with autism spectrum disorder (ASD) are sensitive to the internalisation of the stigma, known as affiliate stigma, resulting in reduced self-esteem, isolation and poor psychological well-being.

Aims

This study aims to validate the Greek version of the Affiliate Stigma Scale (ASS) among mothers of children with ASD.

Method

The translated version of ASS in Greek was administered to 53 mothers of children newly diagnosed with ASD in two time periods: 1–6 months from diagnosis (time point 1) and 12 months from the initial assessment (time point 2). The control group consisted of 62 mothers of typically developing children.

Results

The ASS total mean score revealed a moderate level of stigma to the ASD group in both assessments. The reliability measures by item showed a satisfactory composite reliability (affective 0.828, cognitive 0.833, behaviour 0.857). Cronbach's alpha revealed that the estimated internal consistency was excellent (α= 0.888), and it found a high positive item-total correlation. Receiver operating characteristic analysis results indicated a statistically significant positive discrimination (area under the curve 0.849,P= 0.000) between the groups. The cut-off point was 31.00, with a sensitivity of 0.849 and a 1 – sensitivity of 0.258.

Conclusions

The proposed version of the ASS has good psychometric properties and is valid and reliable for measuring affiliate stigma among caregivers of children with ASD in Greece. Health professionals can use it to assess and understand the stigma experienced by caregivers of children with ASD, and design appropriate interventions to reduce their affiliate stigma.
Real-World Analysis of Off-Label Use of Molecularly Targeted Therapy in a Large Academic Medical Center Cohort
Authors: Upadhyay Vivek A. , Johnson Bruce E. , Landman Adam B. , Hassett Michael J.
Published: January 2022

PURPOSE

The primary objective of this study is to quantify the use of off-label molecularly targeted therapy and describe the clinical situations in which off-label targeted therapy are used. A key secondary objective is to report the outcomes of patients treated with off-label use of targeted therapy.

PATIENTS AND METHODS

We searched the electronic health record between 2000 and 2020 at our center to characterize the volume, clinical settings, and outcomes associated with off-label use of targeted therapies in different types of solid tumors.

RESULTS

Among 46,712 patients who received targeted therapies, we identified 119 instances of off-label use of targeted therapy. Colon cancer was the most common cancer type to receive off-label targeted therapy in 18 patients (15.1%), followed by 13 with non–small-cell lung cancer (10.9%), eight with cholangiocarcinoma (6.7%), and seven with glioblastoma (5.9%). The most frequent molecular rationale for off-label therapy came from a comprehensive next-generation sequencing test (53.7%). The most frequently mutated gene that provided the rationale for targeted therapy was BRAF (20.1%), with BRAFV600E being the most common molecular alteration overall (15.1%). The median duration of off-label targeted therapy was 3.58 months, and the overall survival of treated patients was 7.59 months. There were 37 patients (31.1%) treated for longer than 6 months, 23 patients (19.3%) who survived ≥ 2 years, and 13 patients who were still on therapy as of June 2020.

CONCLUSION

In this large cohort study of patients with solid tumors, off-label use of targeted therapy was uncommon. With that said, a notable proportion of patients had treatment durations ≥ 6 months and survivals of ≥ 2 years.
Implementing the Design of Experiments (DoE) Concept into the Development Phase of Orodispersible Minitablets (ODMTs) Containing Melatonin
Authors: Hejduk Arkadiusz , Teżyk Michał , Jakubowska Emilia , Krüger Klaudia , Lulek Janina
Published: January 2022

Development of orodispersible minitablets (ODMTs) requires consideration of aspects related to small dimensions, while ensuring short disintegration time with sufficient mechanical stability. In order to meet these and other critical quality attributes (CQAs), quality by design is encouraged. According to this approach, formulation and compression process factors were systematically studied using design of experiments (Plackett-Burman for screening purposes, full and fractional factorial design for in-depth characterization) to understand their influence on CQAs of orodispersible minitablets containing melatonin. Mathematical models describing the relationships between processing variables and attributes such as resistance to crushing and disintegration time were successfully developed, characterized by high coefficients of determination (R2adj = 0.90–0.97) and prediction errors in the range (+2.4 to −10.8%). In conclusion, based on these models, the design space was created for melatonin ODMTs, ensuring the product’s quality and process robustness. Moreover, the study demonstrated the suitability of texture analysis as an alternative to compendial measurement methods of resistance to crushing and disintegration time.
Surface plasmonic catalysis based on molecular optomechanics
Authors: Liu Jian , He Fei , Zhu Ka Di
Published: January 2022

Nowadays, researchers find that the surface plasmons can mediate some chemical reactions through the generation of the confined plasmonic field, excited electrons, and local heating effect. In this article we suggest a new surface plasmonic photocatalysis mechanism based on the molecular optomechanics which is not considered before. A reaction kinetic model was established to achieve a quantitative study of catalytic efficiency. The catalytic mechanism is not limited to a specific chemical reaction, all molecules with Raman activity can be accelerated dramatically in reaction. For molecules with different mechanical properties, the corresponding optomechanical catalytic pathway needs to be selected. We hope that this work will provide guidance for achieving strong or even ultrastrong catalyses under specific optical conditions. We further demonstrate that the optomechanical effects can also be used for the deceleration, which provides the possibility to design a highly tunable chemical reaction system. We believe that the quantum photochemistry will be further developed and widely used in future research.