bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHRNB2 represses pancreatic cancer migration and invasion via inhibiting β-catenin pathway
Authors: Qin Cheng , Li Tianhao , Wang Yuanyang , Zhao Bangbo , Li Zeru , Li Tianyu , Yang Xiaoying , Zhao Yutong , Wang Weibin 
Published: November 2022

Abstract
Background
Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear.

Methods
Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and β-catenin pathway via Western Blot.

Results
High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated β-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2.

Conclusions
CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit β-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.
Achieving malaria testing and treatment targets for children under five in Mozambique: a cost-effectiveness analysis
Authors: Avanceña Anton L. V. , Miller Angie , Canana Neide , Dula Janeth , Saifodine Abuchahama , Cadrinho Baltazar , Maffioli Elisa M. 
Published: November 2022

Abstract
Background
The entire population of Mozambique is at risk for malaria, which remains one of the leading causes of death. The 2017–2022 National Malaria Strategic Plan focuses on reducing malaria morbidity and mortality in high- and low-transmission areas. This study aimed to estimate the costs and health benefits of six variations of the World Health Organization’s “test-and-treat” strategy among children under five.

Methods
A decision tree model was developed that estimates the costs and health outcomes for children under five. Data on probabilities, costs, weights for disability-adjusted life years (DALYs), and quality-adjusted life years (QALYs) were based on peer-reviewed, grey literature, and primary data analysis of the 2018 Malaria Indicator Survey. Six scenarios were compared to the status quo and calculated the incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, DALY averted, and life saved. Deterministic and probabilistic sensitivity analyses were conducted to understand the effect of parameter uncertainty on the findings.

Results
In the base case, reaching the target of 100% testing with rapid diagnostic tests (RDTs; Scenario 1) is more cost-effective than improving the testing rate alone by 10% (Scenario 2). Achieving a 100% (Scenario 3) or a 10% increase in treatment rate (Scenario 4) have ICERs that are lower than Scenarios 1 and 2. Both Scenarios 5 and 6, which represent combinations of Scenarios 1–4, have lower ICERs than their constituent strategies on their own, which suggests that improvements in treatment are more cost-effective than improvements in testing alone. These results held when DALYs averted or lives saved were used as health outcomes. Deterministic and probabilistic sensitivity analyses revealed that the cost-effectiveness of Scenarios 1–6 are subject sensitive to parameter uncertainty, though Scenarios 4 and 5 are the optimal choice when DALYs averted or QALYs gained were used as the measure of health outcomes across all cost-effectiveness thresholds.

Conclusions
Improving testing rates alone among children at risk for malaria has the potential to improve health but may not be the most efficient use of limited resources. Instead, small or large improvements in treatment, whether alone or in conjunction with improvements in testing, are the most cost-effective strategies for children under five in Mozambique.
Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes
Authors: Vargas-Soria Maria , Ramos-Rodriguez Juan Jose , del Marco Angel , Hierro-Bujalance Carmen , Carranza-Naval Maria Jose , Calvo-Rodriguez Maria , van Veluw Susanne J. , Stitt Alan W. , Simó Rafael , Bacskai Brian J. , Infante-Garcia Carmen , Garcia-Alloza Monica 
Published: November 2022

Abstract
Background
While aging is the main risk factor for Alzheimer´s disease (AD), emerging evidence suggests that metabolic alterations such as type 2 diabetes (T2D) are also major contributors. Indeed, several studies have described a close relationship between AD and T2D with clinical evidence showing that both diseases coexist. A hallmark pathological event in AD is amyloid-β (Aβ) deposition in the brain as either amyloid plaques or around leptomeningeal and cortical arterioles, thus constituting cerebral amyloid angiopathy (CAA). CAA is observed in 85–95% of autopsy cases with AD and it contributes to AD pathology by limiting perivascular drainage of Aβ.

Methods
To further explore these alterations when AD and T2D coexist, we have used in vivo multiphoton microscopy to analyze over time the Aβ deposition in the form of plaques and CAA in a relevant model of AD (APPswe/PS1dE9) combined with T2D (db/db). We have simultaneously assessed the effects of high-fat diet-induced prediabetes in AD mice. Since both plaques and CAA are implicated in oxidative-stress mediated vascular damage in the brain, as well as in the activation of matrix metalloproteinases (MMP), we have also analyzed oxidative stress by Amplex Red oxidation, MMP activity by DQ™ Gelatin, and vascular functionality.

Results
We found that prediabetes accelerates amyloid plaque and CAA deposition, suggesting that initial metabolic alterations may directly affect AD pathology. T2D significantly affects vascular pathology and CAA deposition, which is increased in AD-T2D mice, suggesting that T2D favors vascular accumulation of Aβ. Moreover, T2D synergistically contributes to increase CAA mediated oxidative stress and MMP activation, affecting red blood cell velocity.

Conclusions
Our data support the cross-talk between metabolic disease and Aβ deposition that affects vascular integrity, ultimately contributing to AD pathology and related functional changes in the brain microvasculature.
Deep learning in CT image segmentation of cervical cancer: a systematic review and meta-analysis
Authors: Yang Chongze , Qin Lan-hui , Xie Yu-en , Liao Jin-yuan 
Published: November 2022

Abstract
Background
This paper attempts to conduct a systematic review and meta-analysis of deep learning (DLs) models for cervical cancer CT image segmentation.

Methods
Relevant studies were systematically searched in PubMed, Embase, The Cochrane Library, and Web of science. The literature on DLs for cervical cancer CT image segmentation were included, a meta-analysis was performed on the dice similarity coefficient (DSC) of the segmentation results of the included DLs models. We also did subgroup analyses according to the size of the sample, type of segmentation (i.e., two dimensions and three dimensions), and three organs at risk (i.e., bladder, rectum, and femur). This study was registered in PROSPERO prior to initiation (CRD42022307071).

Results
A total of 1893 articles were retrieved and 14 articles were included in the meta-analysis. The pooled effect of DSC score of clinical target volume (CTV), bladder, rectum, femoral head were 0.86(95%CI 0.84 to 0.87), 0.91(95%CI 0.89 to 0.93), 0.83(95%CI 0.79 to 0.88), and 0.92(95%CI 0.91to 0.94), respectively. For the performance of segmented CTV by two dimensions (2D) and three dimensions (3D) model, the DSC score value for 2D model was 0.87 (95%CI 0.85 to 0.90), while the DSC score for 3D model was 0.85 (95%CI 0.82 to 0.87). As for the effect of the capacity of sample on segmentation performance, no matter whether the sample size is divided into two groups: greater than 100 and less than 100, or greater than 150 and less than 150, the results show no difference (P > 0.05). Four papers reported the time for segmentation from 15 s to 2 min.

Conclusion
DLs have good accuracy in automatic segmentation of CT images of cervical cancer with a less time consuming and have good prospects for future radiotherapy applications, but still need public high-quality databases and large-scale research verification.
Mutation spectrum of chinese amyotrophic lateral sclerosis patients with frontotemporal dementia
Authors: Yang Xunzhe , Sun Xiaohai , Liu Qing , Liu Liyang , Li Jinyue , Cai Zhengyi , Zhang Kang , Liu Shuangwu , He Di , Shen Dongchao , Liu Mingsheng , Cui Liying , Zhang Xue 
Published: November 2022

Abstract
Background
Studies have reported that a noncoding hexanucleotide repeat in C9ORF72, is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasian population, nevertheless it is rare in Chinese population. Therefore, we aimed to investigate the mutation spectrum of Chinese ALS patients with FTD (ALS-FTD).

Methods
ALS patients with and without cognitive impairments were enrolled. Clinical features were collected including age, sex, disease duration, ALSFRS-r, family history and cognitive evaluation. Thirty-six ALS genes were screened by whole exome sequencing (WES) and repeat-primed polymerase chain reaction (PCR) were used for detection of and abnormal repeat expansions of C9ORF72.

Results
A total of 1208 patients, including 66 familial ALS (FALS) and 1142 sporadic ALS (SALS) patients were included. Twenty-three patients with sporadic ALS and one familial ALS index had concomitant FTD, which accounts for 1.99% (24/1208) of patients with ALS. In sporadic ALS-FTD, one case harboring C9ORF72 expansion variant, two cases harboring ANXA11 variants and one individual carrying CCNF variant were identified. A recurrent UBQLN2 variant was detected in a familial ALS-FTD patient. All of the ALS-FTD patients carrying variants in known causative genes manifested motor symptom onset (two bulbar onset and three limb onset) and developed cognitive impairment thereafter. It is not easy to draw a conclusion of the genotype-phenotype association in ALS-FTD with certain variants, limited by the small number of patients.

Conclusion
Our findings provide an overview of spectrum of genetic variants in Chinese ALS-FTD patients. Variants of uncertain significance in UBQLN2, ANXA11 and CCNF were identified and further studies are required for causal relations of these variants with ALS-FTD.
Global child and adolescent mental health perspectives: bringing change locally, while thinking globally
Authors: Kaku Sowmyashree Mayur , Sibeoni Jordan , Basheer Salah , Chang Jane Pei-Chen , Dahanayake Dulangi Maneksha Amerasinghe , Irarrazaval Matias , Lachman Jamie M , Mapayi Boladale Moyosore , Mejia Anilena , Orri Massimiliano , Jui-Goh Tze , Uddin Md Saleh , Vallance Inge 
Published: November 2022

AbstractChild and adolescent mental health (CAMH) are a global priority. Different countries across the globe face unique challenges in CAMH services that are specific to them. However, there are multiple issues that are also similar across countries. These issues have been presented in this commentary from the lens of early career CAMH professionals who are alumni of the Donald J Cohen Fellowship program of the IACAPAP. We also present recommendations that can be implemented locally, namely, how promoting mental health and development of children and adolescents can result in better awareness and interventions, the need to improve quality of care and access to care, use of technology to advance research and practices in CAMH, and how investing in research can secure and support CAMH professionals and benefit children and adolescents across the globe. As we continue to navigate significant uncertainty due to dynamic circumstances globally, bolstering collaborations by “bringing change locally, while thinking globally” are invaluable to advancing global CAMH research, clinical service provision, and advancement of the field.
A genome-wide association study of mammographic texture variation
Authors: Liu Yuxi , Chen Hongjie , Heine John , Lindstrom Sara , Turman Constance , Warner Erica T. , Winham Stacey J. , Vachon Celine M. , Tamimi Rulla M. , Kraft Peter , Jiang Xia 
Published: November 2022

Abstract
Background
Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited.

Methods
We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors.

Results
We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (rg = 0.79, P = 5.91 × 10−5), percent density (rg = 0.73, P = 1.00 × 10−4), and adult BMI (rg =  − 0.36, P = 3.88 × 10−7). Additional significant relationships were observed for non-dense area (z =  − 4.14, P = 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10−4), and childhood body fatness (z =  − 4.91, P = 9.05 × 10−7) from the SNP-set tests.

Conclusions
These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.
Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents
Authors: Elmorsy Mohamed R. , Mahmoud Samar E. , Fadda Ahmed A. , Abdel-Latif Ehab , Abdelmoaz Miral A. 
Published: November 2022

AbstractA new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d. The structural elucidation of the products was proven by the collections of spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Their anti-cancer activity was examined against two cell lines, MDA-MB-231 (mammary carcinomas) and A-549 (lung cancer). Compared with cisplatin as a reference standard drug, 6-amino-4-(4-(diphenylamino)phenyl)-2-oxo-1-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b) and 6-amino-4-(4-(diphenylamino)phenyl)-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4e) exhibited better efficiency against the A-549 cell line, with IC50 = 0.00803 and 0.0095 μM, respectively. Also, these compounds 4b and 4e showed the most potency among the examined compounds against MDA-MB-231 with IC50 = 0.0103 and 0.0147 μM, respectively. The newly synthesized compounds were docked inside the active sites of the selected proteins and were found to demonstrate proper binding. 2-Cyano-2-(4,4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-N-(p-tolyl)acetamide (6c) offered the highest binding affinity (− 8.1868 kcal/mol) when docked into (PDB ID:2ITO), in addition to 2-cyano-N-(4-(diethylamino)phenyl)-2-(4-(4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (6a) gave the highest energy score (− 9.3507 kcal/mol) with (PDB ID:2A4L).
Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study
Authors: Rodríguez-Fernández Blanca , Vilor-Tejedor Natalia , Arenaza-Urquijo Eider M. , Sánchez-Benavides Gonzalo , Suárez-Calvet Marc , Operto Grégory , Minguillón Carolina , Fauria Karine , Kollmorgen Gwendlyn , Suridjan Ivonne , de Moura Manuel Castro , Piñeyro David , Esteller Manel , Blennow Kaj , Zetterberg Henrik , De Vivo Immaculata , Molinuevo José Luis , Navarro Arcadi , Gispert Juan Domingo , Sala-Vila Aleix , Crous-Bou Marta ,   for the ALFA study, Akinci Müge , Beteta Annabella , Brugulat-Serrat Anna , Cacciaglia Raffaele , Cañas Alba , Cumplido Irene , Deulofeu Carme , Dominguez Ruth , Emilio Maria , Falcon Carles , Fuentes Sherezade , Grau-Rivera Oriol , González-de-Echávarri José M. , Hernandez Laura , Genius Patricia , Huesa Gema , Huguet Jordi , Palacios Eva M. , Marne Paula , Menchón Tania , Milà-Alomà Marta , Peña-Gomez Cleofé , Polo Albina , Pradas Sandra , Salvadó Gemma , Shekari Mahnaz , Soteras Anna , Stankeviciute Laura , Vilanova Marc 
Published: November 2022

AbstractTelomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance,N= 2233; brain age and AD-related signatures,N= 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration,N= 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses byAPOE-ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only inAPOE-ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations.Graphical Abstract
Effectiveness of Bacille Calmette-Guerin vaccination policies in reducing infection and mortality of COVID-19: a systematic review
Authors: Obnial Joseph Christian , Suzuki Mystie , Escuadra Catherine Joy , Austria Janine Trixia , Ponce Ma. Jamaica Monique , Cunanan Elaine 
Published: November 2022

Abstract
Background
COVID-19 vaccination has been advocated as the most effective way to curb the pandemic. But with its inequitable distribution and slow rollout, especially in low- to middle- income countries, it will still take a long time before herd immunity is achieved. Alternative measures must therefore be explored to bolster current COVID-19 vaccination efforts. In particular, the Bacille Calmette-Guerin vaccine has been studied extensively as to its proposed conferment of non-specific immunity against different infections, including COVID-19. The aim of this study, therefore, is to evaluate the current evidence on the effectiveness of national BCG vaccination policies in reducing infection and mortality of COVID-19.

Methods
A systematic review was conducted between April to August 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA-P) guidelines. Literature was retrieved from PubMed, Cochrane, HERDIN, Web of Science, EBSCO, and Western Pacific Region Index Medicus (WPRIM). Studies conducted from January 2020 to August 2021 that fell within Level 1A to 2C of the Oxford Center for Evidence-Based Medicine were included in the review. Quality assessment was performed using the appropriate Joanna Briggs Institute critical appraisal tool and a quality assessment checklist for ecological studies adapted from Betran et al.

Results
A total of 13 studies were included in this review. Nine studies reported significant association between BCG vaccination policies and COVID-19 outcomes, even when controlling for confounding variables. In addition, among other mandated vaccines, such as pneumococcal, influenza, diphtheria-tetanus-pertussis, and measles, only BCG vaccination showed significant association with decreased COVID-19 adverse outcomes. However, other factors also showed positive association with COVID-19 outcomes, particularly markers of high economic status of countries, higher median age, and greater population densities.

Conclusion
The lower incidence and mortality of COVID-19 in countries with mandated BCG vaccination may not solely be attributable to BCG vaccination policies, but there is still some evidence that demonstrates a possible protective effect. Clinical trials must be continued before recommendations of BCG vaccinations are to be used as an alternative or booster vaccine against COVID-19.