bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Proportion of APOE4 Carriers Among Non-Demented Individuals: A Pooled Analysis of 389,000 Community-Dwellers
Authors: Wang Ya-Yu , Ge Yi-Jun , Tan Chen-Chen , Cao Xi-Peng , Tan Lan , Xu Wei 
Published: April 2021

Background: The apolipoprotein E epsilon 4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). Its carriage percentage in non-demented population varies across geographic regions and ethnic groups. Objective: To estimate the proportion of APOE4 (2/4, 3/4, or 4/4) carriers in non-demented community-dwellers. Methods: PubMed, EMBASE, and China National Knowledge Infrastructure were searched from inception to April 20, 2020. Community-based studies that reported APOE polymorphisms with a sample of≥500 non-demented participants were included. Random-effects models were used to pool the results. Meta-regression and subgroup analyses were performed to test the source of heterogeneity and stratified effects. Age-standardized pooled proportion estimates (ASPPE) were calculated by direct standardization method. Results: A total of 121 studies were included, with a pooled sample of 389,000 community-dwellers from 38 countries. The global average proportion of APOE4 carriers was 23.9% (age-standardized proportion: 26.3%; 2.1% for APOE4/4, 20.6% for APOE3/4 and 2.3% for APOE2/4), and varied significantly with geographical regions (from 19.3% to 30.0%) and ethnic groups (from 19.1% to 37.5%). The proportion was highest in Africa, followed by Europe, North America, Oceania, and lowest in South America and Asia (p < 0.0001). With respect to ethnicity, it was highest in Africans, followed by Caucasians, and was lowest in Hispanics/Latinos and Chinese (p < 0.0001). Conclusion: APOE4 carriers are common in communities, especially in Africans and Caucasians. Developing precision medicine strategies in this specific high-risk population is highly warranted in the future.
Study assessing the efficacy of herbal teas on bone health and quality of life in a population with osteopenia: rooibos actions on melatonin and tulsi actions on quality of life.
Authors: Munmun Fahima , Linden Alyssa , Hanlon Hunter , Enderby Hannah , Witt-Enderby Paula 
Published: April 2021

The purpose of the OsTea translational study was to assess the efficacy of teas (tulsi, rooibos, oolong) compared to placebo (coriander) on markers of bone health and quality of life (QOL) in those with osteopenia and on human mesenchymal stem cell (hMSC) differentiation into osteoblasts to identify potential mechanisms of action. Following consumption of tea (3 times/day; 90 days), participants collected a urine sample during the night (10pm-6am) and filled in questionnaires before and after the study. Rooibos consumption demonstrated a significant decrease in urinary CTX levels vs placebo; trended towards increases in nocturnal melatonin levels (p=0.06); significantly decreased serotonin-producing microbes in the gut; and demonstrated trends towards improvements (p=0.09) in QUALIOST emotional parameters. Tulsi consumption primarily affected subjective measures, such as significantly improved scores for PSS, STAI-trait anxiety, and osteoporosis/osteopenia-related parameters in the QUALIOST. To further identify potential mechanisms underlying these actions of rooibos on CTX and melatonin (urinary and gut), rooibos and melatonin effects on human osteoblastogenesis were carried out for 21 days under oxidative stress conditions to mimic osteopenia. Although both rooibos and melatonin protected against oxidative stress-induced loss of osteoblasts in vitro, their underlying mechanisms were different. Melatonin, like tulsi and oolong, demonstrated the greatest protection against oxidative stress at days 10-11 of exposure, which was due to effects on hMSC viability and through melatonin receptors. Rooibos, on the other hand, demonstrated protection at days 10-11 and 20-21, which was through signaling mechanisms involved in differentiation processes and not on cell viability. These findings suggest that the clinical actions of rooibos on decreasing CTX levels in a population with osteopenia may be through a cooperative effort between melatonin and rooibos by protecting hMSC viability against oxidative stress-induced loss and by promoting osteoblast differentiation, respectively. This study also supports the use of tulsi for improving quality of life in a population susceptible to osteoporosis.
Countering Subtractive Bilingualism with Additive Bilingualism in the Albanian Language
Authors: DORAMBARI Diedon 
Published: April 2021

The English language is the lingua franca of education, trade, and employment. However, with such a global influence, the English language sometimes interferes with the native languages via subtractive bilingualism. The aim of this essay is to explain the negative effects of subtractive bilingualism on a global scale in general, elaborate on its negative effects on the Albanian language in particular, and propose solutions to the problem.
To achieve such an aim, research related to the macroscopic model of determinants of additive and subtractive bilingualism (MMDASB) was consulted. Based on the research findings, I conclude that the school milieu should lead by example in using additive bilingualism to counter subtractive bilingualism. In doing so, the school milieu would counter subtractive bilingualism on the sociological, socio-psychological, and psychological levels as predicted in the MMDASB (Landry & Allard, 1993) model. Following the conclusion, concrete proposals for promoting additive bilingualism by the higher education in the school milieu are recommended.
Criminal Law Reform Toward Deprivation of Property Resulting from Corruption Criminal Acts
Authors: WEDHA Yogi Yasa , NURCAHYO Edy 
Published: April 2021

Criminal law reform is part of criminal law policy and is closely related to law enforcement policies, criminal policies and social policies. One of the forms of national legal development reform is the Reform of the Criminal Justice System (SPP) which is an integral part of a sub-system, namely legal substance, legal structure, and legal culture. Corruption as an organized crime in Indonesia is categorized as extra ordinary crimes that have an impact on the creation of injustice in society. One of the injustices referred to is related to the non-return of state losses stolen by corruptors. Whereas efforts to recover state losses are closely related to legal instruments in force in a country. In Indonesia, the Criminal Code and the Law on the Eradication of Corruption places the confiscation of proceeds of corruption only as an additional punishment and does not have a clear formula for the mechanism of deprivation of properties, resulting in unclarity/obscurity of norms. This condition should not occur, therefore it is necessary to reform the criminal law immediately by studying the criminal perpetrators of a criminological perspective, which is related to the factors that cause people to commit criminal acts of curruption. This article is a study of the author concerning the importance of making legal arrangements regarding the deprivation of properties from the proceeds of corruption to mitigate the state losses. This article is compiled by applying normative legal research using statutory approaches, historical approaches, conceptual approaches and comparative approaches. It is concluded that there must be immediate reform of criminal law in Indonesia, especially regarding the deprivation of properties from the criminal act of corruption based on the development of criminal behavior (criminology) and the development of international criminal law concerning corruption.
O impacto da medida socioeducativa de liberdade assistida na auto-organização do projeto de vida de jovens em conflito com a lei
Authors: Campos Rafael Garcia , Machado Dinair Ferreira , Quinelatto Rubia Fernanda , Conceição Willian Lazaretti da 
Published: April 2021

A prática de atos infracionais por jovens vem se configurando cada vez mais como questão de saúde pública, dado o impacto na vida dos/as adolescentes e da sociedade em geral. A presente pesquisa investigou o impacto da medida socioeducativa de Liberdade Assistida na auto-organização do projeto de vida de adolescentes autores/as de ato infracional. Trata-se de um estudo de natureza qualitativa, de caráter descritivo-exploratório com a colaboração de 13 adolescentes, com idade entre 12 a 18 anos incompletos. Os dados foram coletados por meio de um questionário de caracterização sociofamiliar e entrevistas individuais com roteiro semiestruturado, as quais foram gravadas e transcritas integralmente. O roteiro de entrevista contemplou questões norteadoras, as quais abordaram as experiências vivenciadas pelos/as adolescentes durante e depois do cumprimento da medida socioeducativa. Os resultados apontaram para quatro categorias significativas para auto-organização dos/as jovens na ocasião da medida: 1) Vínculos familiares e afetivos; 2) O trabalho e o estudo; 3) As relações interpessoais; 4) A relação com o/a Orientador/a. Constatou-se, nesta pesquisa, que a abordagem ampliada da medida socioeducativa conforme previsto pelo ECA e pelo SINASE impacta positivamente na auto-organização do/a adolescente e contribui para a estruturação do projeto de vida.
The Absence of PTEN in Breast Cancer Is a Driver of MLN4924 Resistance
Authors: Du Meng-ge , Peng Zhi-qiang , Gai Wen-bin , Liu Fan , Liu Wei , Chen Yu-jiao , Li Hong-chang , Zhang Xin , Liu Cui Hua , Zhang Ling-qiang , Jiang Hong , Xie Ping 
Published: April 2021

Background: Numerous studies have indicated that the neddylation pathway is closely associated with tumor development. MLN4924 (Pevonedistat), an inhibitor of the NEDD8-activating E1 enzyme, is considered a promising chemotherapeutic agent. Recently, we demonstrated that neddylation of the tumor suppressor PTEN occurs under high glucose conditions and promotes breast cancer development. It has been shown, however, that PTEN protein levels are reduced by 30–40% in breast cancer. Whether this PTEN deficiency affects the anti-tumor function of MLN4924 is unknown.Methods: In the present study, cell counting kit-8 and colony formation assays were used to detect cell proliferation, and a transwell system was used to quantify cell migration. A tumor growth assay was performed in BALB/c nude mice. The subcellular location of PTEN was detected by fluorescence microscopy. The CpG island of the UBA3 gene was predicted by the Database of CpG Islands and UCSC database. Western blotting and qRT-PCR were used to measure the expression of indicated proteins. The Human Protein Atlas database, the Cancer Genome Atlas and Gene Expression Omnibus datasets were used to validate the expression levels of UBA3 in breast cancer.Results: Our data show that the anti-tumor efficacy of MLN4924 in breast cancer cells was markedly reduced with the deletion of PTEN. PI3K/Akt signaling pathway activity correlated positively with UBA3 expression. Pathway activity correlated negatively with NEDP1 expression in PTEN-positive breast cancer patients, but not in PTEN-negative patients. We also demonstrate that high glucose conditions upregulate UBA3 mRNA by inhibiting UBA3 promoter methylation, and this upregulation results in the overactivation of PTEN neddylation in breast cancer cells.Conclusion: These data suggest a mechanism by which high glucose activates neddylation. PTEN is critical, if not indispensable, for MLN4924 suppression of tumor growth; PTEN status thus may help to identify MLN4924-responsive breast cancer patients.
Psychometric Properties of a Chatbot Version of the PHQ-9 With Adults and Older Adults
Authors: Dosovitsky Gilly , Kim Erick , Bunge Eduardo L. 
Published: April 2021

Background: The Patient Health Questionnaire-9 (PHQ-9) is a brief depression measure that has been validated. A chatbot version of the PHQ-9 would allow the assessment of depressive symptoms remotely, at a large scale and low cost.Objective: The current study aims to: Assess the feasibility of administering the PHQ-9 in a sample of adults and older adults via chatbot, report the psychometric properties of and identify the relationship between demographic variables and PHQ-9 total scores.Methods: A sample of 3,902 adults and older adults in the US and Canada were recruited through Facebook from August 2019 to February 2020 to complete the PHQ-9 using a chatbot.Results: A total of 3,895 (99.82%) completed the PHQ-9 successfully. The internal consistency of the PHQ-9 was 0.896 (p &lt; 0.05). A one factor structure was found to have good model fit [X2 (27, N = 1,948) = 365.396, p &lt; 0.001; RMSEA = 0.080 (90% CI: 0.073, 0.088); CFI and TLI were 0.925 and 0.900, respectively, and SRMR was 0.039]. All of the demographic characteristics in this study were found to significantly predict PHQ-9 total score, however; their effect was negligible to weak.Conclusions: There was a large sample of adults and older adults were open to completing assessments via chatbot including those over 75. The psychometric properties of the chatbot version of the PHQ-9 provide initial support to the utilization of this assessment method.
Risk Stratification in Patients With Follicular Neoplasm on Cytology: Use of Quantitative Characteristics and Sonographic Patterns
Authors: Wu Ming-Hsun , Chen Kuen-Yuan , Hsieh Min-Shu , Chen Argon , Chen Chiung-Nien 
Published: April 2021

ObjectivesDifferentiating thyroid nodules with a cytological diagnosis of follicular neoplasm remains an issue. The goal of this study was to determine whether ultrasonographic (US) findings obtained preoperatively from the computer-aided detection (CAD) system are sufficient to further stratify the risk of malignancy for this diagnostic cytological category.MethodsFrom September 2016 to September 2018 in our hospital, patients diagnosed with Bethesda category IV (follicular neoplasm or suspicion of follicular neoplasm) thyroid nodules and underwent surgical excisions were include in the study. Quantification and analysis of tumor features were performed using CAD software. The US findings of the region of interest, including index of composition, margin, echogenicity, texture, echogenic dots indicative of calcifications, tall and wide orientation, and margin were calculated into computerized values. The nodules were further classified into American Thyroid Association (ATA) and American College of Radiology Thyroid Imaging Reporting &amp; Data System (TI-RADS) categories.Results92 (10.1%) of 913 patients were diagnosed with Bethesda category IV thyroid nodules. In 65 patients, the histological type of the nodule was identified. The quantitative features between patients with benign and malignant conditions differed significantly. The presence of heterogeneous echotexture, blurred margins, or irregular margins was shown to have the highest diagnostic value. The risks of malignancy for nodules classified as having very low to intermediate suspicion ATA, non-ATA, and high suspicion ATA patterns were 9%, 35.7%, and 51.7%, respectively. Meanwhile, the risks of malignancy were 12.5%, 26.1%, and 53.8% for nodules classified as TIRADS 3, 4, and 5, respectively. When compared to human observers, among whom poor agreement was noticeable, the CAD software has shown a higher average accuracy.ConclusionsFor patients with nodules diagnosed as Bethesda category IV, the software-based characterizations of US features, along with the associated ATA patterns and TIRADS system, were shown helpful in the risk stratification of malignancy.
Complications of Pregnancy and the Risk of Developing Endometrial or Ovarian Cancer: A Case-Control Study
Authors: Liu Yang , Chen Xingyu , Sheng Jiayi , Sun Xinyi , Chen George Qiaoqi , Zhao Min , Chen Qi 
Published: April 2021

BackgroundThe association of complications of pregnancy and the risk of developing gynecological cancer is controversial with the limited study. In this study, we investigated the association of preeclampsia, or gestational diabetes mellitus (GDM), or large for gestational age (LGA), or intrauterine growth restriction (IUGR) and the risk of endometrial or ovarian cancer.MethodsIn this case-control study, 189 women with endometrial cancer and 119 women with ovarian cancer were included. 342 women without gynecological cancers were randomly selected as a control group. Data on the history of pregnancy and age at diagnosis of gynecological cancer as well as the use of intrauterine devices (IUDs) were collected.ResultsWomen with a history of preeclampsia or IUGR did not have an increased risk of developing endometrial or ovarian cancer. While women with a history of GDM or with the delivery of LGA infant increased the risk of developing endometrial cancer but not ovarian cancer. The odds of women with a history of GDM or with the delivery of LGA infant developing endometrial cancer was 2.691 (95% CI: 1.548, 4.3635, p=0.0003), or 6.383 (95% CI: 2.812, 13.68, p&lt;0.0001) respectively, compared to the controls. The odds ratio of women who did not use IUDs developing ovarian cancer was 1.606 (95% CI: 1.057, 2.434), compared to the controls. There was no association of age at first birth and developing endometrial or ovarian cancer.ConclusionOur observational data suggested that GDM and delivery of an LGA infant are associated with an increased risk of endometrial cancer.
Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma
Authors: Ribbat-Idel Julika , Dressler Franz F. , Krupar Rosemarie , Watermann Christian , Paulsen Finn-Ole , Kuppler Patrick , Klapper Luise , Offermann Anne , Wollenberg Barbara , Rades Dirk , Laban Simon , Reischl Markus , Bruchhage Karl-Ludwig , Idel Christian , Perner Sven 
Published: April 2021

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far.Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering.Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies.Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones.
Retrieval of 30 Lymph Nodes Is Mandatory for Selected Stage II Gastric Cancer Patients
Authors: Chen Yong-He , Lu Jun , Nie Run-Cong , Liu Dan , Liu Ai-Hong , Deng Zi-Jian , Chen Xi-Jie , Xiang Jun , Chen Ying-Bo , Huang Chang-Ming , Chen Shi , Peng Jun-Sheng 
Published: April 2021

BackgroundAccording to the 8th edition AJCC staging manual, a least of 16 lymph nodes retrieval (LNRs) is the minimal requirement for lymph nodes (LNs) dissection of gastric cancer surgery. Previous studies have shown that increasing the number of LNRs (≥30) prolongs survival for selected patients. However, the necessity of retrieving 30 or more LN for stage II gastric cancer patients is still under debate.AimThis study aims to explore the impact of retrieving 30 or more lymph nodes on the survival of stage II cancer patients.MethodsA total of 1,177 patients diagnosed with stage II gastric cancer were enrolled in this study. The clinicopathological parameters and the impact of different LNRs (&lt;30 or ≥30) and positive lymph node ratio (NR) on overall survival (OS) were retrospectively analyzed.ResultsThe mean number of LNRs was 34 ± 15. A total of 44% (518/1,177) of patients had an LNRs &lt;30, while 56% (659/1,177) of patients had an LNRs ≥30. The 5-year survival rate was 81% for all patients, 76% for the LNRs &lt;30 group, and 86% for LNRs ≥30 group, respectively (P = 0.003). The survival benefit of retrieving 30 lymph nodes was significant in certain subgroups: age &gt;60 years/male/underwent total gastrectomy/stage IIB. For N+ patients, higher NR was significantly correlated with poor survival.ConclusionThe survival benefit of retrieving 30 LNs varies in different subgroups. An LNRs of 30 is mandatory for selected stage II gastric cancer patients.
Can Risk Stratification Based on Ultrasound Elastography of Background Liver Assist CEUS LI-RADS in the Diagnosis of HCC?
Authors: Li Jiawu , Ling Wenwu , Chen Shuang , Yang Lulu , Ma Lin , Lu Qiang , Luo Yan 
Published: April 2021

ObjectiveTo explore whether risk stratification based on ultrasound elastography of liver background assists contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) in diagnosing HCC.Materials and MethodsIn total, 304 patients with focal liver lesions (FLLs) confirmed by pathology underwent CEUS and ultrasound elastography were included in this retrospective study. Patients with chronic hepatitis B (CHB, n=193) and non-CHB (n=111) were stratified by four liver stiffness measurement (LSM) thresholds. A LI-RADS category was assigned to FLLs using CEUS LI-RADS v2017. The diagnostic performance was assessed with the AUC, sensitivity, specificity, PPV, and NPV.ResultsThe mean background liver stiffness of HCC patients with CHB, HCC patients without CHB and non-HCC patients without CHB were 9.72 kPa, 8.23 kPa and 4.97 kPa, respectively. The AUC, sensitivity, specificity and PPV of CEUS LI-RADS for HCC in CHB patients with LSM ≥ 5.8 kPa, ≥ 6.8 kPa, ≥ 9.1 kPa, and ≥ 10.3 kPa were high, with corresponding values of 0.745 to 0.880, 94.2% to 95.3%, 81.3% to 85.7%, and 98.1% to 98.8%, respectively. Higher AUC and specificity for HCC was observed in non-CHB patients with LSM ≥ 9.1 kPa and ≥ 10.3 kPa compared to non-CHB patients with LSM ≥ 5.8 kPa and ≥ 6.8 kPa, with corresponding values of0.964/1.000 vs 0.590/0.580, and 100%/100% vs 60%/70%, respectively.ConclusionCEUS LI-RADS has a good diagnostic performance in CHB patients regardless of the background liver stiffness. Furthermore, CEUS LI-RADS can be applied for non-CHB patients with a LSM ≥ 9.1 kPa.