bluuebunny/crossref_metadata_2025_split huggingface dataset:
CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/β-catenin signaling pathway
Authors: Wang Qi , Xu Jiaju , Xiong Zhiyong , Xu Tianbo , Liu Jingchong , Liu Yuenan , Chen Jiaping , Shi Jian , Shou Yi , Yue Changjie , Liu Di , Liang Huageng , Yang Hongmei , Yang Xiong , Zhang Xiaoping 
Published: October 2021

AbstractClear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/β-catenin signaling pathway. The elevated β-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/β-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.
Integrative eQTL-weighted hierarchical Cox models for SNP-set based time-to-event association studies
Authors: Lu Haojie , Wei Yongyue , Jiang Zhou , Zhang Jinhui , Wang Ting , Huang Shuiping , Zeng Ping 
Published: October 2021

AbstractBackgroundIntegrating functional annotations into SNP-set association studies has been proven a powerful analysis strategy. Statistical methods for such integration have been developed for continuous and binary phenotypes; however, the SNP-set integrative approaches for time-to-event or survival outcomes are lacking.MethodsWe here propose IEHC, an integrative eQTL (expression quantitative trait loci) hierarchical Cox regression, for SNP-set based survival association analysis by modeling effect sizes of genetic variants as a function of eQTL via a hierarchical manner. Three p-values combination tests are developed to examine the joint effects of eQTL and genetic variants after a novel decorrelated modification of statistics for the two components. An omnibus test (IEHC-ACAT) is further adapted to aggregate the strengths of all available tests.ResultsSimulations demonstrated that the IEHC joint tests were more powerful if both eQTL and genetic variants contributed to association signal, while IEHC-ACAT was robust and often outperformed other approaches across various simulation scenarios. When applying IEHC to ten TCGA cancers by incorporating eQTL from relevant tissues of GTEx, we revealed that substantial correlations existed between the two types of effect sizes of genetic variants from TCGA and GTEx, and identified 21 (9 unique) cancer-associated genes which would otherwise be missed by approaches not incorporating eQTL.ConclusionIEHC represents a flexible, robust, and powerful approach to integrate functional omics information to enhance the power of identifying association signals for the survival risk of complex human cancers.
Inoculation of mother’s own milk could personalize pasteurized donor human milk used for feeding preterm infants
Authors: Mallardi D. , Tabasso C. , Piemontese P. , Morandi S. , Silvetti T. , Biscarini F. , Cremonesi P. , Castiglioni B. , Pica V. , Stuknyte M. , De Noni I. , Amato O. , Liotto N. , Mosca F. , Roggero P. 
Published: October 2021

AbstractBackgroundHuman milk is a vehicle for bioactive compounds and beneficial bacteria which promote the establishment of a healthy gut microbiome of newborns, especially of preterm infants. Pasteurized donor human milk (PDHM) is the second-best option when preterm mother’s own milk is unavailable. Since pasteurization affect the microbiological quality of donor milk, PDHM was inoculated with different preterm milk samples and then incubated, in order to evaluate the effect in terms of bacterial growth, human milk microbiome and proteolytic phenomena.MethodsIn an in-vitro study PDHM was inoculated at 10% v/v using ten preterm milk samples. Microbiological, metataxonomic and peptidomic analyses, on preterm milk samples at the baseline (T0), on PDHM and on inoculated milk (IM) samples at T0, after 2 h (T1) and 4 h (T2) of incubation at 37 °C, were conducted.ResultsIM samples at T2 showed a Total Bacterial Count not significantly different (p > 0.01) compared to preterm milk samples. At T2 lactic acid bacteria level was restored in all IM. After inoculation, metataxonomic analysis in IM samples showed that Proteobacteria remained the predominant phylum while Firmicutes moved from 3% at T1 to 9.4% at T2. Peptidomic profile of IM resembled that of PDHM, incubated for the same time, in terms of number and type of peptides.ConclusionThe study demonstrated that inoculation of PDHM with mother’s own milk could restore bacterial growth and personalize human milk microbiome in PDHM. This effect could be beneficial because of the presence of maternal probiotic bacteria which make PDHM more similar to mother’s own milk.
Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators
Authors: Zhang Shiyu , Holmes Andrew P. , Dick Alexej , Rashad Adel A. , Enríquez Rodríguez Lucía , Canziani Gabriela A. , Root Michael J. , Chaiken Irwin M. 
Published: October 2021

Abstract
Background
We previously developed drug-like peptide triazoles (PTs) that target HIV-1 Envelope (Env) gp120, potently inhibit viral entry, and irreversibly inactivate virions. Here, we investigated potential mechanisms of viral escape from this promising class of HIV-1 entry inhibitors.

Results
HIV-1 resistance to cyclic (AAR029b) and linear (KR13) PTs was obtained by dose escalation in viral passaging experiments. High-level resistance for both inhibitors developed slowly (relative to escape from gp41-targeted C-peptide inhibitor C37) by acquiring mutations in gp120 both within (Val255) and distant to (Ser143) the putative PT binding site. The similarity in the resistance profiles for AAR029b and KR13 suggests that the shared IXW pharmacophore provided the primary pressure for HIV-1 escape. In single-round infectivity studies employing recombinant virus, V255I/S143N double escape mutants reduced PT antiviral potency by 150- to 3900-fold. Curiously, the combined mutations had a much smaller impact on PT binding affinity for monomeric gp120 (four to ninefold). This binding disruption was entirely due to the V255I mutation, which generated few steric clashes with PT in molecular docking. However, this minor effect on PT affinity belied large, offsetting changes to association enthalpy and entropy. The escape mutations had negligible effect on CD4 binding and utilization during entry, but significantly altered both binding thermodynamics and inhibitory potency of the conformationally-specific, anti-CD4i antibody 17b. Moreover, the escape mutations substantially decreased gp120 shedding induced by either soluble CD4 or AAR029b.

Conclusions
Together, the data suggest that the escape mutations significantly modified the energetic landscape of Env’s prefusogenic state, altering conformational dynamics to hinder PT-induced irreversible inactivation of Env. This work therein reveals a unique mode of virus escape for HIV-1, namely, resistance by altering the intrinsic conformational dynamics of the Env trimer.
Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil
Authors: Kops Natália Luiza , Caierão Juliana , Bessel Marina , Horvath Jaqueline Driemeyer Correia , Domingues Carla Magda , Benzaken Adele Schwartz , Villa Luisa Lina , de Souza Flávia Moreno Alves , Pereira Gerson Fernando Mendes , Wendland Eliana Marcia 
Published: October 2021

Abstract
Objectives
To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines.

Methods
This was a cross-sectional, multicenter study with sexually active unvaccinated women (16–25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array.

Results
Of the 5268 women, 33.00% (95% CI 31.07–34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections.

Conclusions
In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.
Analysis of the levels of hope and influencing factors in infertile women with first-time and repeated IVF-ET cycles
Authors: Ni Ying , Huang Limin , Tong Chenye , Qian Wen , Fang Qiong 
Published: October 2021

Abstract
Purpose
To explore the hope levels and influencing factors in infertile women undergoing first-time and repeated in vitro fertilization-embryo transfer (IVF-ET) cycles.

Methods
This study was a cross-sectional and convenient sampling study conducted among patients undergoing IVF-ET from January to June 2019. Patients were divided into first-time and repeated groups by the number of IVF-ET cycles, and then a questionnaire survey was administered. The questionnaire included demographic information, Herth hope index (HHI) scale, Locke-Wallace short marital-adjustment test scale and social support rating scale. Multiple linear regression was used to analyse the influencing factors associated with hope levels.

Results
A total of 298 IVF-ET patients were recruited for the study, including 150 (50.3%) in the first-time cycle group and 148 (49.7%) in the repeated cycle group. The HHI score of the repeated cycle group was significantly lower than that of the first-time cycle group (34.4 ± 3.5 vs. 37.5 ± 3.7, P < 0.001). Multiple linear regression analysis indicated that repeated IVF-ET and age were independently negatively correlated with HHI, with standardized coefficient β values of − 0.895 and − 0.223, respectively (both P < 0.001). High education level (P = 0.002), high monthly income (P = 0.020), high degree of short marital-adjustment test (P < 0.001) and social support rating (P < 0.001) were independently positively correlated with HHI.

Conclusion
Infertile women undergoing repeated IVF-ET have low hope levels. Maintaining a good marriage adjustment and establishing a good social support and relationship network could effectively improve their hope levels.
Determinants of viral suppression among adolescents on antiretroviral treatment in Ehlanzeni district, South Africa: a cross-sectional analysis
Authors: Okonji Emeka F. , van Wyk Brian , Mukumbang Ferdinand C. , Hughes Gail D. 
Published: October 2021

Abstract
Background
Achieving undetectable viral load is crucial for the reduction of HIV transmissions, AIDS-related illnesses and death. Adolescents (10 to19 years) living with HIV (ALHIV) on antiretroviral treatment (ART) have worse treatment adherence and lower viral suppression rates compared to adults. We report on the clinical factors associated with viral suppression among ALHIV in the Ehlanzeni district, Mpumalanga in South Africa.

Methods
A cross-sectional analysis was conducted with 9386 ALHIV, aged 10 to 19 years, who were enrolled in 136 ART clinics in the Ehlanzeni district. Clinical and immunological data were obtained from electronic medical records (Tier.net). ALHIV were categorised as having achieved viral suppression if their latest viral load count was < 1000 ribonucleic acid (RNA) copies/mL. Using a backward stepwise approach, a multivariate logistic regression analysis was performed to identify factors independently associated with viral suppression.

Results
The mean age of the participants was 14.75 years (SD = 2.9), and 55.43% were female. Mean duration on ART was 72.26 (SD = 42.3) months. Of the 9386 adolescents with viral load results recorded, 74% had achieved viral suppression. After adjusting for other covariates, the likelihood of achieving viral suppression remained significantly higher among ALHIV who were: female (AOR = 1.21, 95% CI 1.05–1.39), and had most recent CD4 count > 200 (AOR = 2.53, 95% CI 2.06–3.11). Furthermore, the likelihood of having viral suppression was lower among adolescents with CD4 count > 200 at baseline (AOR = 0.73, 95% CI 0.61–0.87), and who were switched to second line regimen (AOR = 0.41, 95% CI 0.34–0.49).

Conclusions
Viral suppression amongst ALHIV at 74% is considerably lower than the WHO target of 95%. Of particular concern for intervention is the lower rates of viral suppression amongst male ALHIV. Greater emphasis should be placed to early enrolment of ALHIV on ART and keeping them engaged in care (beyond 6 months). Furthermore, improved and regular viral load monitoring will help to adequately identify and manage ALHIV with unsuppressed viral load and subsequently switching to second line treatment.
Acute fibrinous and organizing pneumonia: two case reports and literature review
Authors: Chen Haihong , Kuang Yukun , Huang Xinyan , Ye Ziyin , Liu Yangli , Xie Canmao , Tang Ke-Jing 
Published: October 2021

Abstract
Background
Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet.

Case presentation
We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone.

Conclusions
We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.
Secretory breast carcinoma in a female adult with liver metastsis: a case report and literature review
Authors: Lian Jing , Wang Li-Xia , Guo Jiang-hong , Bu Peng , Xi Yan-feng , Yun Ke-ming 
Published: October 2021

AbstractBackgroundSecretory breast carcinoma is an uncommon subset of breast cancer that usually has a favorable outcome. Although initially described in children, it also occurs in adults where it may metastasize, possibly resulting in death. To date, only 20 cases of secretory breast carcinoma with distant metastases have been described.Case presentationA 42-year-old female presented with liver metastasis after modified radical mastectomy of the left breast in 2008 at 34 years of age. The liver metastasis was morphologically similar to the primary tumor. Pan-TRK and Fluorescence in situ hybridization showed a rearrangement in the ETV6 gene. She subsequently underwent adjuvant chemotherapy with a fatal outcome.ConclusionsAlthough secretory breast carcinoma is usually associated with favorable outcomes, our study and reviews provide a novel insight into the genetic spectrum and treatment of secretory breast carcinoma showing reduced expression of hormone receptors, abnormal genomic profiles, and possible poor prognosis. Targeted therapy may curb clinically aggressive cases. Additional molecular investigations are needed to determine the links between specific mutations and poor prognosis.
Preserving for the future the — once widespread but now vanishing — knowledge on traditional pig grazing in forests and marshes (Sava-Bosut floodplain, Serbia)
Authors: Molnár Zsolt , Szabados Klára , Kiš Alen , Marinkov Jelena , Demeter László , Biró Marianna , Öllerer Kinga , Katona Krisztián , Đapić Marko , Perić Ranko , Ulicsni Viktor , Babai Dániel 
Published: October 2021

AbstractBackgroundTraditional knowledge is key for sustainability, but it is rapidly disappearing. Pig keeping in forests and marshes is an ancient, once widespread, now vanishing practice, with a major economic and ecological potential. The knowledge of pig keepers and the foraging activity of pigs are hardly documented.MethodsWe studied the knowledge of traditional pig keepers (svinjars) on wild plants and pig foraging on the Sava-Bosut forest-marsh complex in Serbia. We conducted picture-based interviews about 234 locally common and/or salient plant species, and participatory fieldwork (11 days) and visual observation (21 days) on pig foraging.Results181 wild plant species were known bysvinjars and 106 taxa were consumed by pigs.Svinjars knew well and could name most regularly foraged species. 98 species were reported bysvinjars as foraged and 56 as not eaten. 28 species were observed by the authors as eaten regularly, while 21 were nibbled and 17 avoided. Contradictory information on foraging was rare both amongsvinjars (8 species) and betweensvinjars and researchers (7 species); several of these species were rare. Leaves of 92, fruits or seeds of 21 and ‘roots’ of 20 species were reported or observed as eaten, usually with high seasonality.Svinjars were overall observant, but knew little about some less salient species (e.g.Veronica,Circaea). The most common forages (reported and/or observed) were fruits (Quercus, fleshy fruits), grasses (Agrostis,Glyceria), herbs (Ranunculus ficaria,Circaea), nutritious ‘roots’ (Carexspp.,Iris), young shrub leaves (Crataegus,Carpinus) and ‘tame’ plants growing in the sun (Persicaria dubia,Erigeron annuus). Traditional, now extinct pig breeds were reported as less selective and more ‘knowledgeable’ about plants, as they received less additional fodder.Svinjars learnt their knowledge since childhood, from community members, but long-term personal observations and everyday encounters with pigs were also important sources of knowledge.ConclusionsA deeper understanding of pig foraging could contribute to using pigs in nature conservation management, resource management and organic farming, and to a better understanding of wild boar foraging. The knowledge ofsvinjars is a disappearing intangible cultural heritage of European importance. Knowledge holders deserve recognition, and legal and financial support to continue this tradition.
Validation and refinement of the Stakeholder-driven Community Diffusion Survey for childhood obesity prevention
Authors: Korn Ariella R. , Appel Julia , Hammond Ross A. , Hennessy Erin , Mâsse Louise C. , Must Aviva , Economos Christina D. 
Published: October 2021

Abstract
Background
Whole-of-community interventions hold promise in addressing childhood obesity. The COMPACT Stakeholder-driven Community Diffusion theory posits that stakeholders’ knowledge of childhood obesity prevention efforts and engagement with the issue contribute to successful intervention implementation. Building on completed formative research and pilot testing, we describe the validation and refinement of knowledge and engagement measures.

Methods
We assessed content validity using a modified Delphi process with science (n=18) and practice-based (n=16) experts. Next, we refined the survey based on input from science- and practice-based experts, cognitive response testing, and item analysis of extant survey data. Field testing of the refined survey involved community stakeholders in Greenville County, South Carolina (n=50), East Boston, Massachusetts (n=30), and Tucson, Arizona (n=84) between 2019 and 2020. Construct validity was assessed with confirmatory factor analysis (CFA). Two-week test-retest reliability was assessed among a subsample of 14 paired respondents in South Carolina.

Results
Experts rated existing knowledge domains (intervention factors, roles, sustainability, problem, resources) and engagement domains (dialogue/mutual learning, flexibility, influence/power, leadership/stewardship, trust) highly for their importance in addressing childhood obesity. Expert input resulted in 11 new knowledge items and 7 new engagement items that mapped onto existing domains. Correspondingly, two domain names were modified: implementation/sustainability and trust/trustworthiness. We also eliminated 8 extant items (4 knowledge and 4 engagement) and adapted item language for comprehension and consistency. Further modifications based on CFA results and item analyses resulted in 23 knowledge items across four domains (roles and resources merged) and 23 engagement items across five domains. Modified knowledge and engagement scales had adequate fit and strong item factor loadings (most >0.7 and all >0.5). Knowledge (α=0.86–0.87) and engagement (α=0.75–0.90) subscales had high internal scale consistency. Knowledge intraclass correlation coefficients (ICCs) for test-retest agreement of subscale scores ranged from 0.50 for intervention factors to 0.86 for roles/resources. For engagement subscale scores, ICCs ranged from 0.70 for trust/trustworthiness to 0.96 for leadership/stewardship.

Conclusions
Findings from this multi-method survey development process increase our confidence of the knowledge and engagement measures’ content validity, construct validity, and reliability.