bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors
Authors: Bjaanæs Maria Moksnes , Nilsen Gro , Halvorsen Ann Rita , Russnes Hege G. , Solberg Steinar , Jørgensen Lars , Brustugun Odd Terje , Lingjærde Ole Christian , Helland Åslaug 
Published: October 2021

Abstract
Background
Genetic alterations are common in non-small cell lung cancer (NSCLC), and DNA mutations and translocations are targets for therapy. Copy number aberrations occur frequently in NSCLC tumors and may influence gene expression and further alter signaling pathways. In this study we aimed to characterize the genomic architecture of NSCLC tumors and to identify genomic differences between tumors stratified by histology and mutation status. Furthermore, we sought to integrate DNA copy number data with mRNA expression to find genes with expression putatively regulated by copy number aberrations and the oncogenic pathways associated with these affected genes.

Methods
Copy number data were obtained from 190 resected early-stage NSCLC tumors and gene expression data were available from 113 of the adenocarcinomas. Clinical and histopathological data were known, and EGFR-, KRAS- and TP53 mutation status was determined. Allele-specific copy number profiles were calculated using ASCAT, and regional copy number aberration were subsequently obtained and analyzed jointly with the gene expression data.

Results
The NSCLC tumors tissue displayed overall complex DNA copy number profiles with numerous recurrent aberrations. Despite histological differences, tissue samples from squamous cell carcinomas and adenocarcinomas had remarkably similar copy number patterns. The TP53-mutated lung adenocarcinomas displayed a highly aberrant genome, with significantly altered copy number profiles including gains, losses and focal complex events. The EGFR-mutant lung adenocarcinomas had specific arm-wise aberrations particularly at chromosome7p and 9q. A large number of genes displayed correlation between copy number and expression level, and the PI(3)K-mTOR pathway was highly enriched for such genes.

Conclusions
The genomic architecture in NSCLC tumors is complex, and particularly TP53-mutated lung adenocarcinomas displayed highly aberrant copy number profiles. We suggest to always include TP53-mutation status when studying copy number aberrations in NSCLC tumors. Copy number may further impact gene expression and alter cellular signaling pathways.
Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line
Authors: Weiner F. , Schille J. T. , Koczan D. , Wu X.-F. , Beller M. , Junghanss C. , Hewicker-Trautwein M. , Murua Escobar H. , Nolte I. 
Published: October 2021

Abstract
Background
The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood.

Methods
In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets.

Results
Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression.

Conclusions
FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.
Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482
Authors: Skorodumova Liubov O. , Belodedova Alexandra V. , Sharova Elena I. , Zakharova Elena S. , Iulmetova Liliia N. , Bikbov Mukharram M. , Usubov Emin L. , Antonova Olga P. , Selezneva Oksana V. , Levchenko Anastasia , Fedorenko Olga Yu , Ivanova Svetlana A. , Gainetdinov Raul R. , Malyugin Boris E. 
Published: October 2021

Abstract
Background
Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482.

Methods
This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array.

Results
The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients.

Conclusion
rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.
Diffusion tensor imaging based multiparametric characterization of renal lesions in infants with urinary tract infections: an explorative study
Authors: Simrén Yvonne , Stokland Eira , Hansson Sverker , Hebelka Hanna , Svensson Par-Arne , Lagerstrand Kerstin M. 
Published: October 2021

Abstract
Background
Conventional diffusion weighted imaging (DWI) is a promising non-invasive tool in the evaluation of infants with symptomatic urinary tract infections (UTI). The use of multiparametric diffusion tensor imaging (DTI) provides further information on renal pathology by reflecting renal microstructure. However, its potential to characterize and distinguish between renal lesions, such as acute pyelonephritic lesions, permanent renal damages or dysplastic changes has not been shown. This study aimed to evaluate the potential of multiparametric DTI for characterization of renal lesions with purpose to distinguish acute pyelonephritis from other renal lesions in young infants with their first UTI.

Methods
Nine kidneys in seven infants, age 1.0–5.6 months, with renal lesions i.e. uptake reductions, on acute scintigraphy performed after their first UTI, were included. The DTI examinations were performed during free breathing without sedation. The signal in the lesions and in normal renal tissue was measured in the following images: b0, b700, apparent diffusion coefficient (ADC), and fractional anisotropy (FA). In addition, DTI tractographies were produced for visibility.

Results
There was a difference between lesions and normal tissue in b700 signal (197 ± 52 and 164 ± 53, p = 0.011), ADC (1.22 ± 0.11 and 1.45 ± 0.15 mm2/s, p = 0.008), and FA (0.18 ± 0.03 and 0.30 ± 0.10, p = 0.008) for all nine kidneys. Six kidneys had focal lesions with increased b700 signal, decreased ADC and FA indicating acute inflammation. In three patients, the multiparametric characteristics of the lesions were diverging.

Conclusion
Multiparametric DTI has the potential to further characterize and distinguish acute pyelonephritis from other renal lesions in infants with symptomatic UTI.
Cultural variation in factors associated with sudden infant death during sleep
Authors: Ahn Young Mee , Yang Kyung-moo , Ha Hong Il , Cho Jung Ae 
Published: October 2021

AbstractBackgroundDespite the significant reduction decades ago in sudden unexpected death in infancy (SUDI), decline of rates has slowed and stalled in some countries, including the USA. This led to an appreciation of ethnic variations in SUDI rates and the need to increase cultural sensitivity regarding sleep practices and circumstantial factors of SUDI. The study explored SUDI-related factors, in journal articles from two geo-cultural regions (Asian and Western countries), particularly for factors related to infant sleep practices.MethodsA systematic review was conducted to identify SUDI-related factors in articles from PubMed, Scopus, and the Korean Citation Index from January 1992 to April 2019. From each article, SUDI-related factors were retrieved and categorized through the identification, aggregation, and categorization of factors into the areas of the triple risk model (TRM) of SUDI by their meanings and commonality. Significant trends in the frequency of factors were analyzed across time and between the two geo-cultural regions (Asian and Western countries) of article.ResultsFrom a review of 218 articles (38 Asian and 180 Western articles), 84 SUDI-related factors were identified: 39 factors for TRM 1, 44 factors for TRM 2, and one factor for TRM 3. Four of the top-ranked 10 factors were found in both cultural zones: sleep position, male sex, bed-sharing, and genetics. Both cultural zones identified sleep position (44.0%), bed-sharing (22.0%), and rooming-in (16.5%) as the three most important sleep-related factors for SUDI. Variations between the cultural zones were observed in the place of SUDI occurrence, overheating, swaddling or bedding standards, and smoking.ConclusionsRegardless of the urgent need to identify SUDI-related factors in low-SUDI societies, Asian cultures showed a significant lack of articles on SUDI. Several sociocultural issues were recognized such as the meaning of bed-sharing and rooming-in, along with residential styles and traditional health beliefs on sleep-related SUDI factors. Particularly little attention towards smoking was found in Asian articles in terms of frequency, suggesting the need to enhance SUDI reduction strategies by incorporating gender-sensitive smoking cessation interventions. This review of SUDI factors requests child health professionals to be alert to sociocultural variations in sleep practices and SUDI factors.
LGBT+ inclusion and human rights in Thailand: a scoping review of the literature
Authors: Newman Peter A. , Reid Luke , Tepjan Suchon , Akkakanjanasupar Pakorn 
Published: October 2021

AbstractBackgroundGlobally, LGBT+ people continue to struggle to achieve full realization of their human rights. Amid reported health and mental health disparities, and economic insecurity, we conducted a scoping review to explore the breadth of the literature, map and summarize the evidence, and identify knowledge gaps on LGBT+ inclusion and human rights in Thailand.MethodsWe conducted a scoping review in accordance with the methodology developed by the Joanna Briggs Institute and PRISMA-ScR guidelines. We systematically searched 16 databases for peer-reviewed literature, and government and nongovernmental organization websites for grey literature, published in English or Thai from January 1, 2000–August 21, 2020. Two reviewers independently screened studies according to pre-set criteria. We abstracted and analyzed data on publication characteristics and focal populations, and synthesized findings in six domains of LGBT+ inclusion: political and civic participation, education, family, personal security and violence, economic well-being, and health.ResultsThe review captured 3327 results in total, which was scoped to 76 peer-reviewed articles and 39 grey literature sources, the majority published after 2010. Gay men and transgender women were the primary focal populations in the peer-reviewed literature, LGBT+ people as a whole in the grey literature. Health was the predominant domain across publications. Key findings include the absence of generalized antidiscrimination legislation for LGBT+ individuals and lack of recourse for transgender individuals to change their legal gender; multifaceted stigma and discrimination in the educational system; social isolation and exclusion in families; disproportionate prevalence of sexual violence and reluctance to report to police; discrimination and marginalization in employment; and LGBT+ disparities in health and mental health.ConclusionsFuture research and programmatic initiatives on LGBT+ inclusion in Thailand should aim to address: 1) understudied populations—lesbian and bisexual women, transmasculine persons; 2) underrepresented topics, including constraints to LGBT+ advocacy; 3) strategic policy initiatives around anti-discrimination laws and legal recognition of same-sex marriage and families; and 4) the need for consistent collection of disaggregated data on LGBT+ persons in education, family, economic, personal security/violence, and health domains in order to assess indicators of inclusion and progress in advancing human rights for LGBT+ people in Thailand.
Sub-regional disparities in the use of antenatal care service in Mauritania: findings from nationally representative demographic and health surveys (2011–2015)
Authors: Shibre Gebretsadik , Zegeye Betregiorgis , Ahinkorah Bright Opoku , Idriss-Wheeler Dina , Keetile Mpho , Yaya Sanni 
Published: October 2021

Abstract
Background
Skilled antenatal care (ANC) has been identified as a proven intervention to reducing maternal deaths. Despite improvements in maternal health outcomes globally, some countries are signaling increased disparities in ANC services among disadvantaged sub-groups. Mauritania is one of sub-Saharan countries in Africa with a high maternal mortality ratio. Little is known about the inequalities in the country’s antenatal care services. This study examined both the magnitude and change from 2011 to 2015 in socioeconomic and geographic-related disparities in the utilization of at least four antenatal care visits in Mauritania.

Methods
Using the World Health Organization’s Health Equity Assessment Toolkit (HEAT) software, data from the 2011 and 2015 Mauritania Multiple Indicator Cluster Surveys (MICS) were analyzed. The inequality analysis consisted of disaggregated rates of antenatal care utilization using four equity stratifiers (economic status, education, residence, and region) and four summary measures (Difference, Population attributable risk, Ratio and Population attributable fraction). A 95% Uncertainty Interval was constructed around point estimates to measure statistical significance.

Results
Substantial absolute and relative socioeconomic and geographic related disparities in attending four or more ANC visits (ANC4+ utilization) were observed favoring women who were richest/rich (PAR = 19.5, 95% UI; 16.53, 22.43), educated (PAF = 7.3 95% UI; 3.34, 11.26), urban residents (D = 19, 95% UI; 14.50, 23.51) and those living in regions such as Nouakchott (R = 2.1, 95% UI; 1.59, 2.56). While education-related disparities decreased, wealth-driven and regional disparities remained constant over the 4 years of the study period. Urban-rural inequalities were constant except with the PAR measure, which showed an increasing pattern.

Conclusion
A disproportionately lower ANC4+ utilization was observed among women who were poor, uneducated, living in rural areas and regions such as Guidimagha. As a result, policymakers need to design interventions that will enable disadvantaged subpopulations to benefit from ANC4+ utilization to meet the Sustainable Development Goal (SDG) of reducing the maternal mortality ratio (MMR) to 140/100, 000 live births by 2030.
Physical activity and sleep differences between osteoarthritis, rheumatoid arthritis and non-arthritic people in China: objective versus self report comparisons
Authors: Xu Ting , Jia Xiaojun , Chen Shuanghong , Xie Yingying , Tong K. K. , Iezzi Tony , Jackson Todd 
Published: October 2021

Abstract
Background
Objectively measured differences in physical activity (PA) and sleep have been documented among people with osteoarthritis (OA) and rheumatoid arthritis (RA) compared to non-arthritic controls. However, it is not clear whether OA and RA subgroups also differ on these indexes or the extent to which distinct arthritis subgroups versus controls can be accurately identified on the basis of objective PA and sleep indexes compared to self-report responses on questionnaires. This study addressed these gaps.

Methods
This case-control study comprised Chinese adults with OA (N = 40) or RA (N = 40) diagnoses based on physician assessments as well as a control group of adults without chronic pain (N = 40). All participants wore a Sensewear Armband (SWA) for consecutive 7 days and completed the International Physical Activity Questionnaire Short Form-Chinese as well as Pittsburgh Sleep Diary to obtain objective and subjective PA and sleep data, respectively.

Results
There were no differences between the three groups on any self-report indexes of PA or sleep. Conversely, OA and RA subgroups displayed significantly lower PA levels and more sleep problems than controls did on a majority of SWA indexes, though arthritis subgroups were not differentiated from one another on these measures. Logistic regression analyses indicated four non-multicollinear SWA indexes (i.e., steps, active energy expenditure, vigorous activity, time awake after sleep onset) correctly identified the subgroup membership of 75.0–82.5% of participants with RA or OA while classification accuracy results were attenuated for controls.

Conclusions
Where possible, objective measures should be used to assess PA and sleep of adults with OA and RA while particular self-report PA questionnaires should be used sparingly.
Non Hodgkin lymphoma in Lebanon: a retrospective epidemiological study between 1984 and 2019
Authors: Touma Elsie , Antoun Leony , Hallit Souheil , Nasr Fadi , Massoud Marcel , El Othman Radwan , Chahine Georges 
Published: October 2021

Abstract
Background
Lymphomas are ranked as the fifth most common cancer in Lebanon. There is concern about the need of information regarding the prevalence of lymphoid neoplasm particularly Non-Hodgkin lymphoma (NHL) subtypes in the Lebanese population. This study intended to establish a descriptive status of NHL histological subtypes distribution in Lebanon thus identifying the most common types, knowing that the literature is poor regarding the distribution of lymphoid malignancies particularly NHLs in Lebanon.

Methods
A bicenter retrospective descriptive study was performed. Patients aged above 18, diagnosed with NHL between January 1984 and March 2019 and registered in two Lebanese Medical centers were included in this study; 699 medical files were reviewed and the baseline characteristics of the disease were collected. Histological classification was based on the Working Formulation (WF) and World Health Organization (WHO) classification systems, whereas staging was based on the Ann Arbor system. Disease status was monitored with imaging studies.

Results
The mean age at diagnosis was 53.52 ± 17.46 years in the studied population, with 380 (54.4%) males and 319 (45.6%) females. B-cell lymphoma (BCL) accounted for 86.3% while T-cell neoplasms accounted for 13.7%. The most common subtype was diffuse large B-cell lymphoma (DLBCL) (54%) followed by follicular lymphoma (FL) (17.2%). Mantle cell lymphoma (MCL) represented 3% of all BCL and small lymphocytic lymphoma (SLL) comprised less than 2%. Mucosa-associated lymphoid tissue (MALT) and Burkitt’s lymphomas represented 3 and 1.7% respectively. 36.5% of the patients had extranodal disease at diagnosis. High-grade tumor represented 80.1% with 33.1% stage IV disease.

Conclusion
These observations indicate that the epidemiological patterns of NHLs in Lebanon were comparable to Western countries. Aggressive lymphomas account for the majority of NHLs in Lebanon.
“Y no quedó nada, nada de la casa, todo salió volando” (And there was nothing left, nothing of the house, everything flew away): a critical medical ecological perspective on the lived experience of hurricane María in Puerto Rico
Authors: Vega Ocasio D. , Pérez Ramos J. G. , Dye T. D. V. 
Published: October 2021

Abstract
Background
Ecological disasters create dramatic changes as man-made and natural ecosystems adapt to their effects. In 2017, Hurricanes Irma and María devastated Puerto Rico. Public focus after such traumatic ecological events often neglects pre-existing community dynamics, heterogeneity of lived experience, and complexity of decision-making in the disaster context. We intended to better understand the lived experience of this ecological trauma in communities across ecosystems in Puerto Rico and among those displaced to Florida.

Method
We used the Critical Medical Ecological (CME) framework to assess the relative contribution of ecological dimensions on lived experience across community levels and time. We used qualitative methods with emic coding and etic mapping of salient constructs to the ecological model. In total, 96 people participated in 23 discussion encounters. Two people coded interviews in Spanish using Dedoose. We identified common themes in sequential order mapped to elements of the CME to approximate the participants’ temporal experience.

Results
Codes applied to the period of the hurricane’s landfall, traverse, and exit were markedly distinct from the other two periods (before and after) examined in this study: the experience of the hurricane’s strike was highly personal and, at this level, reflected a mix of sociocultural, biological, and abiotic factors. After the hurricanes, social and community factors re-emerged while new risks and conditions arose that were biological (e.g., leptospirosis, no food or water) or abiotic (e.g., unusable roads/bridges, structures destroyed), but created ongoing stressors and social needs for communities. As we found, the dynamics of the social and household landscape sometimes involved the decision to leave Puerto Rico altogether, or forced people to continually face and adapt to the ongoing collapse in basic services that were only slowly and differentially restored.

Conclusion
Lived experience across each stage of the hurricanes differed substantially from one another. Communities disrupted by ecological disaster are also frequently entangled within global economic and political histories and dependencies that could preclude recovery. Island nations are especially vulnerable to both climate-induced ecological change and political-economic exploitation. The ongoing health effect of the hurricane remains palpable in many communities of Puerto Rico and among the diaspora in Florida.