bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the role of Saliva in COVID 19: A global cross-sectional study on the knowledge, awareness and perception among dentists
Authors: Kritika Selvakumar , Mahalaxmi Sekar , Srinivasan N , Krithikadatta Jogikalmat 
Published: June 2023

Abstract
Objectives
The global pandemic outbreak of the coronavirus has instilled the quest amongst researchers on the expedited need for the early detection of viral load. Saliva is a complex oral biological fluid which not only causes the disease transmission but can be an effective alternative sample for detection of SARS-CoV2. This provides an ideal opportunity for dentists to be the frontline healthcare professionals who can collect the salivary samples; however the awareness of this amongst dentists is uncertain. Hence the aim of this survey was to evaluate the knowledge, perception and awareness of the role of saliva in detecting the SARS-CoV2 among dentists worldwide.

Methods
The online questionnaire comprising of 19 questions was shared to 1100 dentists worldwide and a total of 720 responses was collected. The data was tabulated, statistically analysed using the non- parametric Kruskal-Wallis test (p < 0.05). Based on the principal component analysis, 4 components (knowledge about virus transmission, perception about SARS-CoV2 virus, awareness on the sample collection and knowledge about prevention of the virus) were obtained which was compared with the 3 independent variables (years of clinical experience, occupation and region).

Results
A statistically significant difference was observed in the awareness quotient amongst the dentists with 0–5 years and greater than 20 years of clinical experience. In terms of the occupation, a significant difference was noted when comparing the postgraduate students to practitioners knowledge about the virus transmission. A highly significant difference was seen on comparing academicians and postgraduate students and also between academicians and practitioners. No significant difference was evidenced amongst the different regions, however the mean score was in the range of 3-3.44.

Conclusion
This survey highlights the deficiency in the knowledge, perception and awareness among dentists worldwide.
Therapeutic efficacy of sorafenib and plant-derived phytochemicals in human colorectal cancer cells
Authors: Bahman Abdulmajeed , Abaza Mohamed-Salah , Khoushaish Sarah , Al-Attiyah Rajaa J. 
Published: June 2023

Abstract
Background
The present study aimed to investigate the sequence-dependent anticancer effects of combined treatment with sorafenib (Sora), a Food and Drug Administration-approved multikinase inhibitor drug, and plant-derived phytochemicals (PPCs) on human colorectal cancer (CRC) cell growth, and proteins associated with the control of cell cycle and apoptosis.

Methods
The cytotoxic effects of 14 PPCs on CRL1554 fibroblast cells were determined using an MTT assay. Moreover, the cytotoxicity of Sora, PPCs, and a combination of both on CRC cells were also investigated. Cell cycle analysis was performed using flow cytometry, and cell apoptosis was investigated using DNA fragmentation, Annexin V/propidium iodide double staining, and mitochondrial membrane potential analyses. The cell cycle- and apoptosis-associated protein expression levels were analysed using western blotting.

Results
Based on their low levels of cytotoxicity in CRL1554 cells at ≤ 20%, curcumin, quercetin, kaempferol, and resveratrol were selected for use in subsequent experiments. The combined treatment of sora and PPCs caused levels of CRC cytotoxicity in a dose-, cell type-, and schedule-dependent manner. Moreover, the combined treatment of CRC cells arrested cell growth at the S and G2/M phases, induced apoptotic cell death, caused extensive mitochondrial membrane damage, and altered the expression of the cell cycle and apoptotic proteins.

Conclusions
Results of the present study highlighted a difference in the level of sora efficacy in CRC cells when combined with PPCs. Further in vivo and clinical studies using the combined treatment of sora and PPCs are required to determine their potential as a novel therapeutic strategy for CRCs.
Systematic review of economic evaluations of aromatase inhibitors in estrogen receptor-positive breast cancer: quality evaluation
Authors: Althuwaibi Maha F. , Fernandez-Garcia Cristina , Hayes Louise , McNally Richard , Coughlan Diarmuid 
Published: June 2023

Abstract
Background
Breast cancer (BC) is a leading cause of premature death in women and the most expensive malignancy to treat. Since the introduction of targeted therapies has resulted in changes to BC therapy practices, health economic evaluations have become more important in this area. Taking generic medications, Aromatase Inhibitors (AIs), as a case study, we conducted a systematic review of the recent economic evaluations of AIs for estrogen receptor-positive breast cancer patients and evaluated the quality of these health economic studies.

Objective
To systematically review and examine the quality of the available economic studies of AIs in estrogen receptor-positive breast cancer.

Methods
A literature search was performed using six relevant databases (MEDLINE, Embase, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, and SCOPUS) from January 2010 to July 2021. All economic studies were independently assessed by two reviewers using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist to evaluate the quality of the economic evaluations. This systematic review is registered in the PROSPERO database. To compare the different currencies used in these studies, all costs were converted to international dollars (2021).

Results
A total of eight studies were included in the review; six (75%) were performed from the healthcare providers’ perspective. They were conducted in seven different countries, and all were model-based analyses using Markov models. Six (75%) considered both Quality Adjusted Life Years (QALYs) and Life Years (LY) outcomes, and all costs were derived from national databases. When compared to tamoxifen, AIs were generally cost-effective in postmenopausal women. Only half of the studies addressed the increased mortality following adverse events, and none mentioned medication adherence. For the quality assessment, six studies fulfilled 85% of the CHEERS checklist requirements and are deemed good quality.

Conclusion
AIs are generally considered cost-effective compared to tamoxifen in estrogen receptor-positive breast cancer. The overall quality of the included studies was between high and average but characterizing heterogeneity, and distributional effects should be considered in any future economic evaluation studies of AIs. Studies should include adherence and adverse effects profiles to provide evidence to facilitate decision-making among policymakers.
Multiple and diversified transposon lineages contribute to early and recent bivalve genome evolution
Authors: Martelossi Jacopo , Nicolini Filippo , Subacchi Simone , Pasquale Daniela , Ghiselli Fabrizio , Luchetti Andrea 
Published: June 2023

Abstract
Background
Transposable elements (TEs) can represent one of the major sources of genomic variation across eukaryotes, providing novel raw materials for species diversification and innovation. While considerable effort has been made to study their evolutionary dynamics across multiple animal clades, molluscs represent a substantially understudied phylum. Here, we take advantage of the recent increase in mollusc genomic resources and adopt an automated TE annotation pipeline combined with a phylogenetic tree-based classification, as well as extensive manual curation efforts, to characterize TE repertories across 27 bivalve genomes with a particular emphasis on DDE/D class II elements, long interspersed nuclear elements (LINEs), and their evolutionary dynamics.

Results
We found class I elements as highly dominant in bivalve genomes, with LINE elements, despite less represented in terms of copy number per genome, being the most common retroposon group covering up to 10% of their genome. We mined 86,488 reverse transcriptases (RVT) containing LINE coming from 12 clades distributed across all known superfamilies and 14,275 class II DDE/D-containing transposons coming from 16 distinct superfamilies. We uncovered a previously underestimated rich and diverse bivalve ancestral transposon complement that could be traced back to their most recent common ancestor that lived ~ 500 Mya. Moreover, we identified multiple instances of lineage-specific emergence and loss of different LINEs and DDE/D lineages with the interesting cases of CR1- Zenon, Proto2, RTE-X, and Academ elements that underwent a bivalve-specific amplification likely associated with their diversification. Finally, we found that this LINE diversity is maintained in extant species by an equally diverse set of long-living and potentially active elements, as suggested by their evolutionary history and transcription profiles in both male and female gonads.

Conclusions
We found that bivalves host an exceptional diversity of transposons compared to other molluscs. Their LINE complement could mainly follow a “stealth drivers” model of evolution where multiple and diversified families are able to survive and co-exist for a long period of time in the host genome, potentially shaping both recent and early phases of bivalve genome evolution and diversification. Overall, we provide not only the first comparative study of TE evolutionary dynamics in a large but understudied phylum such as Mollusca, but also a reference library for ORF-containing class II DDE/D and LINE elements, which represents an important genomic resource for their identification and characterization in novel genomes.
Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort
Authors: Bueno Junior Carlos Roberto , Bano Arjola , Tang Yaling , Sun Xiuqin , Abate Alex , Hall Elizabeth , Mitri Joanna , Morieri Mario Luca , Shah Hetal , Doria Alessandro 
Published: June 2023

Abstract
Background
Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors.

Methods
Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7–3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI).

Results
Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51–4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63–5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001).

Conclusions
In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.
Prognostic impacts of diabetes status and lipoprotein(a) levels in patients with ST-segment elevation myocardial infarction: a prospective cohort study
Authors: Li Nan , Zhou Jinying , Chen Runzhen , Zhao Xiaoxiao , Li Jiannan , Zhou Peng , Liu Chen , Chen Yi , Wang Ying , Song Li , Yan Shaodi , Zhao Hanjun , Yan Hongbing 
Published: June 2023

Abstract
Objects
This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups.

Methods
Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan–Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted.

Results
During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10–3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32–1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11–2.50, P = 0.013), 1.53-fold (95% CI 1.02–2.31, P = 0.041), and 2.08-fold (95% CI 1.33–3.26, P = 0.001), respectively.

Conclusions
In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM.
Trial registration: clinicaltrials.gov NCT: 03593928
Comparing field-collected versus remotely-sensed variables to model malaria risk in the highlands of western Uganda
Authors: Hollingsworth Brandon D. , Sandborn Hilary , Baguma Emmanuel , Ayebare Emmanuel , Ntaro Moses , Mulogo Edgar M. , Boyce Ross M. 
Published: June 2023

Abstract
Background
Malaria risk is not uniform across relatively small geographic areas, such as within a village. This heterogeneity in risk is associated with factors including demographic characteristics, individual behaviours, home construction, and environmental conditions, the importance of which varies by setting, making prediction difficult. This study attempted to compare the ability of statistical models to predict malaria risk at the household level using either (i) free easily-obtained remotely-sensed data or (ii) results from a resource-intensive household survey.

Methods
The results of a household malaria survey conducted in 3 villages in western Uganda were combined with remotely-sensed environmental data to develop predictive models of two outcomes of interest (1) a positive ultrasensitive rapid diagnostic test (uRDT) and (2) inpatient admission for malaria within the last year. Generalized additive models were fit to each result using factors from the remotely-sensed data, the household survey, or a combination of both. Using a cross-validation approach, each model’s ability to predict malaria risk for out-of-sample households (OOS) and villages (OOV) was evaluated.

Results
Models fit using only environmental variables provided a better fit and higher OOS predictive power for uRDT result (AIC = 362, AUC = 0.736) and inpatient admission (AIC = 623, AUC = 0.672) compared to models using household variables (uRDT AIC = 376, Admission AIC = 644, uRDT AUC = 0.667, Admission AUC = 0.653). Combining the datasets did not result in a better fit or higher OOS predictive power for uRDT results (AIC = 367, AUC = 0.671), but did for inpatient admission (AIC = 615, AUC = 0.683). Household factors performed best when predicting OOV uRDT results (AUC = 0.596) and inpatient admission (AUC = 0.553), but not much better than a random classifier.

Conclusions
These results suggest that residual malaria risk is driven more by the external environment than home construction within the study area, possibly due to transmission regularly occurring outside of the home. Additionally, they suggest that when predicting malaria risk the benefit may not outweigh the high costs of attaining detailed information on household predictors. Instead, using remotely-sensed data provides an equally effective, cost-efficient alternative.
Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration
Authors: Xiong Wenjun , Chen Yuehong , Zhang Chaoting , Li Jin , Huang Haipeng , Zhu Yu , Deng Guangxu , Cheng Junhong , Lin Yixiong , Shi Zhimin , Mou Tingyu 
Published: June 2023

Abstract
Background
Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion.

Methods
AOM/DSS model in Il11−/− and Apcmin/+/Il11−/− mice were used to detect tumor growth and CD8+ T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8+ T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital.

Results
IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8+ T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11−/− mice or Il11−/− mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth.

Conclusions
This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.
Implementation and scale-up of a single-visit, screen-and-treat approach with thermal ablation for sustainable cervical cancer prevention services: a protocol for a stepped-wedge cluster randomized trial in Kenya
Authors: Shin Michelle B. , Oluoch Lynda Myra , Barnabas Ruanne V. , Baynes Colin , Fridah Harriet , Heitner Jesse , Kerubo Mary Bernadette , Ngure Kenneth , Pinder Leeya F. , Thomas Katherine K. , Mugo Nelly Rwamba , Gimbel Sarah 
Published: June 2023

Abstract
Background
An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30–49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya.

Methods
The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy.

Discussion
Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy.

Trial registration
NCT05472311.
Validation of a QTL associated with resistance to Vibrio anguillarum in rainbow trout (Oncorhynchus mykiss)
Authors: Karami Asma Mohammad , Marana Moonika Haahr , Mathiessen Heidi , Dalsgaard Inger , Nielsen Torben Fejer , Kania Per Walter , Buchmann Kurt 
Published: June 2023

AbstractVibriosis is a bacterial disease in fish caused by the Gram negative bacterium Vibrio anguillarum with severe impact on rainbow trout (Oncorhynchus mykiss) farming. Sustainable control methods should be developed and we here show that marker assisted selective breeding of fish naturally resistant to the disease is feasible. We have validated the use of a single nucleotide polymorphism (SNP) marker SNP AX-89,945,921 (QTL on chromosome 21). The QTL was previously found associated with resistance to vibriosis and described following a genome wide association analysis (GWAS) of trout exposed to the bacterium. For this validation spawners were genotyped by use of the 57 K Axiom®Trout Microarray (Affymetrix) and homozygous male fish carrying the allele with the SNP AX-89,945,921 were then selected and used to fertilize eggs from outbred female trout resulting in fish all carrying the SNP (QTL-fish). Control fish (non-QTL fish) were produced by fertilizing the same batch of eggs by use of male parents negative for the SNP. The fish were exposed in freshwater to V. anguillarum (water bath infection) at 19 C°. A total of 900 fish were challenged in a common garden set-up in triplicate. A bacterial solution of V. anguillarum (serotype O1) was added to each of three freshwater fish tanks, each with 150 QTL and 150 non-QTL fish. Fish were tagged by tail fin cut (upper/lower) to discern the two groups, whereafter fish were monitored around the clock to detect disease signs and remove moribund fish. Clinical vibriosis developed within two days in non-QTL-fish (overall morbidity of 70%). QTL fish developed clinical signs later and the morbidity was significantly lower and did not reach 50%. Rainbow trout farming may benefit from using the QTL associated with higher resistance towards vibriosis. The effect may be optimized in the future by use of both male and female parents homozygous for the marker allele.