bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Late Pleistocene Wetland Setting in the Arid Jurf ed Darawish Region in Central Jordan
Authors: Mischke Steffen , Lai Zhongping , Faershtein Galina , Porat Naomi , Röhl Matthias , Braun Paul , Kalbe Johannes , Ginat Hanan 
Published: September 2021

Current conditions in the southern Levant are hyperarid, and local communities rely on fossil subsurface water resources. The timing of more favourable wetter periods and also their spatial characteristics are not yet well constrained. To improve our understanding of past climate and environmental conditions in the deserts of the southern Levant, sedimentary sections including artefact-bearing beds from Jurf ed Darawish on the Central Jordanian Plateau were investigated using sedimentological and micropalaeontological analyses and OSL dating. Grain-size analysis and structures of the clayey-silty sediments show that they mainly represent reworked loess deposits. The OSL ages suggest that these fine-grained sediments were accumulated during Marine Isotope Stages (MIS) 5-3. Recorded ostracod valves (mostly Potamocypris, Ilyocypris and Pseudocandona), remains of aquatic and terrestrial gastropod shells, and charophyte gyrogonites and stem encrustations indicate that an in-stream wetland existed at the location of Jurf ed Darawish during MIS 5-4 which was replaced by a vegetated alluvial plain in MIS 3. The prevailing aggradational setting was replaced by an erosional setting sometime after 30 ka. Abundant artefacts, distributed over a vertical range of up to 40 cm in a bed covered by a sedimentary sequence of 12-m thickness, provide evidence for the presence of humans in the region during a relatively long period from ca. 85 to 65 ka. The reconstruction of an in-stream wetland at Jurf ed Darawish, and the presence of humans at the site and in other desert regions of the Jordanian Plateau, the Wadi Arava/Araba, and the Negev and the Nefud deserts, show that the regional climate in the late MIS 5 and MIS 4 was significantly wetter than today and provided favourable conditions for humans in the Southern Levant and the northwestern Arabian Peninsula.
Educating for Biocultural Diversity and Sustainable Development in First Years of Schooling: An Analysis of Documents From the Portuguese Educational System
Authors: Batista Bruna Fonseca , Andrade Ana Isabel 
Published: September 2021

Educating for sustainable development can encompass different perspectives and possibilities that enable the achievement of the goals of (more) sustainable development, as predicted by the United Nations for 2030. This type of education also involves a humanist and citizenship education, which can prepare children, youth, and adults to face current and future challenges, local and global, as actors in building a better future. We believe, however, that for education to bear fruit, it is important that children, from the first years of schooling (primary education), can be in contact with different perspectives, people, ways of learning, and worldviews, locally contextualized and relevant, with strong links to the natural and social environment involving their communities, such as education must value linguistic and cultural diversity, without forgetting biodiversity and the influences they exert on the education of individuals. Thus, looking at an education that encompasses the relationships among linguistic, cultural (stories, celebrations, heritage, artefacts, relationships, and behaviors between people, etc.), and biological diversity, the present study aimed to understand how biocultural diversity is present in the main normative-legal documents that govern education for the first years of schooling in the Portuguese educational system and, above all, if its existence is considered in education for sustainable development. For this study, seven guiding documents of the Portuguese educational system, and primary education in particular (education that includes the interval from the 1st to the 4th year and the average age-groups of 5–10 years of age), were analyzed, and the results show a gap regarding the presence of biocultural diversity, which points to an incomplete perspective of education for sustainable development, forgetting languages, cultures, and individuals.
Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort
Authors: Long Wei , Guo Fang , Yao Ruen , Wang Ying , Wang Huaiyan , Yu Bin , Xue Peng 
Published: September 2021

BackgroundThe molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear.MethodsWe performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the number of affected genes, or divided into a monoallelic group, a biallelic group, and an oligogenic group according to the pattern of the detected variants. The clinical characteristics were compared between groups.ResultsThyroid dysgenesis (TD) was observed in 10 patients and goiter in 5 patients, whereas 27 patients had normal-sized gland-in-situ (GIS). We identified 58 variants in five genes in 29 patients. The genes with the most frequent variants were DUOX2 (70.7%), followed by TSHR (12.1%), DUOXA2 (10.3%), and TPO (5.2%). Variants in the genes causing dyshormonogenesis (DH) were more common than those in the genes causing TD (87.9% versus 12.1%). Among the patients with detected variants, 26 (89.7%) were harboring a single gene variant (single-gene group), which include 22 patients harboring biallelic variants (biallelic group) and four patients harboring monoallelic variants (monoallelic group). Three (10.3%) patients harbored variants in two or three genes (multi-gene group or oligogenic group). Compared with the single-gene group, the levothyroxine (L-T4) dose at 1 year of age was higher in the multi-gene group (p = 0.018). A controllable reduction in the L-T4 dose was observed in 25% of patients in the monoallelic group and 59.1% of patients in the biallelic group; however, no patients with such reduction in the L-T4 dose were observed in the oligogenic group.ConclusionsPatients with normal-sized GIS accounted for the majority of our cohort. Genetic defects in the genes causing DH were more common than those in the genes causing TD, with biallelic variants in DUOX2 being dominant. DH might be the leading pathophysiology of CH in Chinese individuals.
Seasonal Changes of Thyroid Function Parameters in Women of Reproductive Age Between 2012 and 2018: A Retrospective, Observational, Single-Center Study
Authors: Fu Jinrong , Zhang Guofeng , Xu Pei , Guo Rui , Li Jiarong , Guan Haixia , Li Yushu 
Published: September 2021

BackgroundThyroid function can be influenced by external stimuli such as light and temperature. However, it is currently unknown whether there is seasonal variation of thyroid function in women of reproductive age. Adequate thyroid function in reproductive-aged women is necessary for optimal fetal–maternal outcomes. Therefore, this study aims to evaluate the seasonal changes in levels of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and TSH index (TSHI) in women of reproductive age.MethodsA large retrospective study was conducted that included women aged 20–49 years who visited our outpatient or checkup center between 2012 and 2018. Thyroid function was measured using the automated immunochemiluminescent assay kit. Subjects with overt thyroid dysfunction, pregnancy, thyroid disease, cancer, and severe infectious or psychological disease were excluded. Seasonal differences of thyroid function were analyzed using the Kruskal–Wallis test or the analysis of means with transformed ranks. Spearman’s correlation was performed to evaluate the association between thyroid function parameters and age. A subset of 181 subjects was included in the longitudinal analyses. Differences in thyroid function between summer and winter were analyzed using the Wilcoxon signed-rank test.ResultsA total of 48,990 women with a median age of 39 years were included. The prevalence of subclinical hypothyroidism was lower in summer but higher in winter (5.6% vs. 7.0%, p &lt; 0.05). The TSH, FT3, and FT4 levels and TSHI reached a peak in winter, while they declined to trough in summer. The TSH concentrations (r = 0.044, p &lt; 0.001) and TSHI (r = 0.025, p &lt; 0.001) were positively correlated with age, whereas FT3 (r = -0.073, p &lt; 0.001) and FT4 (r = -0.059, p &lt; 0.001) were negatively correlated with age. The associations of thyroid parameters with age were similar between subjects with positive thyroid peroxidase antibody (TPOAb) and those with negative TPOAb. In the matched longitudinal analysis of 181 subjects, no differences were detected in the thyroid parameters between summer and winter.ConclusionsThis retrospective single-center study showed that thyroid hormone levels and central sensitivity to thyroid hormones are influenced by age and seasonal fluctuations among women of reproductive age, while their impact on reproductive health remains to be elucidated in future studies.
An Optimized Pathway for the Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome Based on Low-Dose Dexamethasone Suppression Test
Authors: Chen Kang , Chen Shi , Lu Lin , Zhu Huijuan , Zhang Xiaobo , Tong Anli , Pan Hui , Wang Renzhi , Lu Zhaolin 
Published: September 2021

ContextTraditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing’s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.ObjectivesTo develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.Design and SettingSingle-center retrospective study (2011–2019).PatientsTwo hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.ResultsFor the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p &lt; 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of &lt;26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma &lt;6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.ConclusionLDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.
Benefits and Risks Associated With Aspirin Use in Patients With Diabetes for the Primary Prevention of Cardiovascular Events and Mortality: A Meta-Analysis
Authors: Ma Hua , Gu Qing , Niu Huining , Li Xiaohua , Wang Rong 
Published: September 2021

PurposeA meta-analysis was conducted to assess the benefits and risks of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in adults with diabetes.MethodsAn extensive and systematic search was conducted in MEDLINE (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. Random-effects meta-analysis was used to calculate the pooled odds ratio for outcomes of cardiovascular events, death, and adverse events.FindingsA total of 8 studies were included with 32,024 patients with diabetes; 16,001 allocated to aspirin, and 16,023 allocated to the control group. There was no difference between aspirin and control groups with respect to all-cause mortality, cardiovascular mortality, or bleeding events. However, MACE was significantly lower in the aspirin group.ImplicationsAlthough aspirin has no significant risk on primary endpoints of cardiovascular events and bleeding outcomes in patients with diabetes compared to control, major adverse cardiovascular events (MACE) were significantly lower in the aspirin group. Further research on the use of aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research. Systematic Review Registrationidentifier [XU#/IRB/2020/1005].
Microplastics Occurrence in Surface Waters and Sediments in Five River Mouths of Manila Bay
Authors: Osorio Ezra D. , Tanchuling Maria Antonia N. , Diola Ma. Brida Lea D. 
Published: September 2021

Microplastics have been increasingly documented globally in numerous environmental compartments. However, little information exists in the Philippines despite the fact that the country is considered to be one of the largest contributors of plastics in oceans. This study, considered as one of the pioneering microplastic research, evaluated the abundance, distribution, and composition of microplastic pollution in the mouths of five rivers, namely Cañas, Meycauayan, Parañaque, Pasig and Tullahan, draining to Manila Bay. Surface water and sediments samples were collected, then passed through a stack of sieves with sizes from 2.36 mm at the top to 0.075 mm at the bottom. These samples were digested to remove organic matter, and salt solutions were added to allow the microplastics to float. Extracted particles were examined under a stereo microscope, and quantified and categorized into shape, size, color, and type. Results show that microplastics were present ubiquitously at all river mouths but with concentrations varying from 1,580 to 57,665 particles/m3 (surface water) and 386 to 1,357 particles/kg (dry sediment). Fragment was the most abundant shape, while white, blue, and transparent were the most prevalent colors. Fourier Transform Infrared Spectroscopy (FTIR) analysis revealed that polypropylene (PP), high and low-density polyethylene (high-density polyethylene and low-density polyethylene) and polystyrene were the main types of microplastics present in the river mouths.
Clinical Application of Whole Exome Sequencing for Monogenic Disorders in PICU of China
Authors: Liu Yingchao , Hao Chanjuan , Li Kechun , Hu Xuyun , Gao Hengmiao , Zeng Jiansheng , Guo Ruolan , Liu Jun , Guo Jun , Li Zheng , Qi Zhan , Jia Xinlei , Li Wei , Qian Suyun 
Published: September 2021

ObjectivesWhole exome sequencing (WES) has been widely used to detect genetic disorders in critically ill children. Relevant data are lacking in pediatric intensive care units (PICUs) of China. This study aimed to investigate the spectrum of monogenic disorders, the diagnostic yield and clinical utility of WES from a PICU in a large children’s hospital of China.MethodsFrom July 2017 to February 2020, WES was performed in 169 critically ill children with suspected monogenic diseases in the PICU of Beijing Children’s Hospital. The clinical features, human phenotype ontology (HPO) terms, and assessment of clinical impact were analyzed.ResultsThe media age of the enrolled children was 10.5 months (range, 1 month to 14.8 years). After WES, a total of 43 patients (25%) were diagnosed with monogenic disorders. The most common categories of diseases were metabolic disease (33%), neuromuscular disease (19%), and multiple deformities (14%). The diagnosis yield of children with “metabolism/homeostasis disorder” and “growth delay” or “ocular anomalies” was higher than that of children without these features. In addition, the diagnosis rate increased when more features were observed in children. The results of WES had an impact on the treatment for 30 cases (70%): (1) change of treatment (n= 11), (2) disease monitoring initiation (n= 18), (3) other systemic evaluation (n= 3), (4) family intervention (n= 2), and (5) rehabilitation and redirection of care toward palliative care (n= 12).ConclusionWES can be used as an effective diagnostic tool in the PICU of China and has an important impact on the treatment of patients with suspected monogenic conditions.
Characterization of the Potential Role of NTPCR in Epithelial Ovarian Cancer by Integrating Transcriptomic and Metabolomic Analysis
Authors: Shang Hongkai , Zhang Huizhi , Ren Ziyao , Zhao Hongjiang , Zhang Zhifen , Tong Jinyi 
Published: September 2021

BackgroundEpithelial ovarian carcinoma (EOC) is a malignant tumor with high motility in women. Our previous study found that dysregulated nucleoside-triphosphatase cancer-related (NTPCR) was associated with the prognosis of EOC patients, and thus, this present study attempted to explore the potential roles of NTPCR in disease progression.MethodsExpressed level of NTPCR was investigated in EOC tissues by RT-qPCR and Western blot analysis. NTPCR shRNA and overexpression vector were generated and transfected into OVCAR-3 or SKOV3 cells to detect the effect of NTPCR on cell proliferation, cell cycle, cell migration, and invasion. Transcriptomic sequencing and metabolite profiling analysis were performed in shNTPCR groups to identify transcriptome or metabolite alteration that might contribute to EOC. Finally, we searched the overlapped signaling pathways correlated with differential metabolites and differentially expressed genes (DEGs) by integrating analysis.ResultsComparing para-cancerous tissues, we found that NTPCR is highly expressed in cancer tissues (p &lt; 0.05). Overexpression of NTPCR inhibited cell proliferation, migration, and invasion and reduced the proportion of S- and G2/M-phase cells, while downregulation of NTPCR showed the opposite results. RNA sequencing analysis demonstrated cohorts of DEGs were identified in shNTPCR samples. Protein–protein interaction networks were constructed for DEGs. STAT1 (degree = 43) and OAS2 (degree = 36) were identified as hub genes in the network. Several miRNAs together with target genes were predicted to be crucial genes related to disease progression, including hsa-miR-124-3p, hsa-miR-30a-5p, hsa-miR-146a-5, EP300, GATA2, and STAT3. We also screened the differential metabolites from shNTPCR samples, including 22 upregulated and 22 downregulated metabolites. By integrating transcriptomics and metabolomics analysis, eight overlapped pathways were correlated with these DEGs and differential metabolites, such as primary bile acid biosynthesis, protein digestion, and absorption, pentose, and glucuronate interconversions.ConclusionNTPCR might serve as a tumor suppressor in EOC progression. Our results demonstrated that DEGs and differential metabolites were mainly related to several signaling pathways, which might be a crucial role in the progression of NTPCR regulation of EOC.
Intratumor Epigenetic Heterogeneity—A Panel Gene Methylation Study in Thyroid Cancer
Authors: Zhu Chaofan , Zhang Meiying , Wang Qian , Jen Jin , Liu Baoguo , Guo Mingzhou 
Published: September 2021

BackgroundThyroid cancer (TC) is the most common endocrine malignancy, and the incidence is increasing very fast. Surgical resection and radioactive iodine ablation are major therapeutic methods, however, around 10% of differentiated thyroid cancer and all anaplastic thyroid carcinoma (ATC) are failed. Comprehensive understanding the molecular mechanisms may provide new therapeutic strategies for thyroid cancer. Even though genetic heterogeneity is rigorously studied in various cancers, epigenetic heterogeneity in human cancer remains unclear.MethodsA total of 405 surgical resected thyroid cancer samples were employed (three spatially isolated specimens were obtained from different regions of the same tumor). Twenty-four genes were selected for methylation screening, and frequently methylated genes in thyroid cancer were used for further validation. Methylation specific PCR (MSP) approach was employed to detect the gene promoter region methylation.ResultsFive genes (AP2, CDH1, DACT2, HIN1, and RASSF1A) are found frequently methylated (&gt;30%) in thyroid cancer. The five genes panel is used for further epigenetic heterogeneity analysis. AP2 methylation is associated with gender (P &lt; 0.05), DACT2 methylation is associated with age, gender and tumor size (all P &lt; 0.05), HIN1 methylation is associated to tumor size (P &lt; 0.05) and extra-thyroidal extension (P &lt; 0.01). RASSF1A methylation is associated with lymph node metastasis (P &lt; 0.01). For heterogeneity analysis, AP2 methylation heterogeneity is associated with tumor size (P &lt; 0.01), CDH1 methylation heterogeneity is associated with lymph node metastasis (P &lt; 0.05), DACT2 methylation heterogeneity is associated with tumor size (P &lt; 0.01), HIN1 methylation heterogeneity is associated with tumor size and extra-thyroidal extension (all P &lt; 0.01). The multivariable analysis suggested that the risk of lymph node metastasis is 2.5 times in CDH1 heterogeneous methylation group (OR = 2.512, 95% CI 1.135, 5.557, P = 0.023). The risk of extra-thyroidal extension is almost 3 times in HIN1 heterogeneous methylation group (OR = 2.607, 95% CI 1.138, 5.971, P = 0.023).ConclusionFive of twenty-four genes were found frequently methylated in human thyroid cancer. Based on 5 genes panel analysis, epigenetic heterogeneity is an universal event. Epigenetic heterogeneity is associated with cancer development and progression.