bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
Authors: Obón-Santacana Mireia , Díez-Villanueva Anna , Alonso Maria Henar , Ibáñez-Sanz Gemma , Guinó Elisabet , López Ana , Rodríguez-Alonso Lorena , Mata Alfredo , García-Rodríguez Ana , Palomo Andrés García , Molina Antonio J. , Garcia Montse , Binefa Gemma , Martín Vicente , Moreno Victor 
Published: November 2021

Abstract
Background
Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study.

Methods
A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation.

Results
The overall PRS range was 110–156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22–3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53–0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48–0.57).

Conclusions
PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce.
SToRytelling to Improve Disease outcomes in Gout (STRIDE-GO): a multicenter, randomized controlled trial in African American veterans with gout
Authors: Singh Jasvinder A. , Joseph Amy , Baker Joshua , Richman Joshua S. , Shaneyfelt Terrence , Saag Kenneth G. , Eisen Seth 
Published: November 2021

AbstractBackgroundUrate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).MethodsIn a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.ResultsThe 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n= 152) or stress reduction video (n= 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p> 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p= 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p= 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p= 0.003), and 6 months, 29.5 vs. 34.5 (p= 0.03), respectively.ConclusionsA culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.Trial registrationRegistered atClinicalTrials.govNCT02741700
Predicted norovirus resurgence in 2021–2022 due to the relaxation of nonpharmaceutical interventions associated with COVID-19 restrictions in England: a mathematical modeling study
Authors: O’Reilly Kathleen M. , Sandman Frank , Allen David , Jarvis Christopher I. , Gimma Amy , Douglas Amy , Larkin Lesley , Wong Kerry L. M. , Baguelin Marc , Baric Ralph S. , Lindesmith Lisa C. , Goldstein Richard A. , Breuer Judith , Edmunds W. John 
Published: November 2021

Abstract
Background
To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions.

Methods
Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020–2021.

Results
We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages.

Conclusions
Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.
Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia
Authors: Sivkov Andrey , Chernus Natalya , Gorenkov Roman , Sivkov Sergey , Sivkova Svetlana , Savina Tamara 
Published: November 2021

Abstract
Background
To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia.

Methods
The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels.

Results
The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes.

Conclusions
The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.
The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection
Authors: Nabi-Afjadi Mohsen , Karami Hadis , Goudarzi Kaveh , Alipourfard Iraj , Bahreini Elham 
Published: November 2021

AbstractThe concern of today's communities is to find a way to prevent or treat COVID-19 and reduce its symptoms in the patients. However, the genetic mutations and more resistant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge; the designed vaccines and adjuvant therapies would potentially control the symptoms and severity of COVID-19. The most important complication of this viral infection is acute respiratory distress syndrome, which occurs due to the infiltration of leukocytes into the alveoli and the raised cytokine storm. Interferons, as a cytokine family in the host, play an important role in the immune-related antiviral defense and have been considered in the treatment protocols of COVID-19. In addition, it has been indicated that some nutrients, including vitamin D, magnesium and zinc are essential in the modulation of the immune system and interferon (IFN) signaling pathway. Several recent studies have investigated the treatment effect of vitamin D on COVID-19 and reported the association between optimal levels of this vitamin and reduced disease risk. In the present study, the synergistic action of vitamin D, magnesium and zinc in IFN signaling is discussed as a treatment option for COVID-19 involvement.
Thymol-loaded PLGA nanoparticles: an efficient approach for acne treatment
Authors: Folle Camila , Marqués Ana M. , Díaz-Garrido Natalia , Espina Marta , Sánchez-López Elena , Badia Josefa , Baldoma Laura , Calpena Ana Cristina , García Maria Luisa 
Published: November 2021

Abstract
Background
Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed.

Results
Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around − 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage.

Conclusion
TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment.

Graphical Abstract
Understanding socioeconomic differences in metabolic syndrome remission among adults: what is the mediating role of health behaviors?
Authors: Hoveling Liza A. , Liefbroer Aart C. , Bültmann Ute , Smidt Nynke 
Published: November 2021

Abstract
Background
Although the incidence of metabolic syndrome (MetS) strongly varies based on individuals’ socioeconomic position (SEP), as yet no studies have examined the SEP-MetS remission relationship. Our aim is to longitudinally assess the associations between SEP measures education, income and occupational prestige, and MetS remission, and whether these associations are mediated by health behaviors, including physical activity, smoking, alcohol intake and diet quality.

Methods
A subsample (n = 16,818) of the adult Lifelines Cohort Study with MetS at baseline was used. MetS remission was measured upon second assessment (median follow-up time 3.8 years), defined according to NCEP-ATPIII criteria. To estimate direct associations between SEP, health behaviors and MetS remission multivariable logistic regression analyses were used. To estimate the mediating percentages of health behaviors that explain the SEP-MetS remission relationship the Karlson-Holm-Breen method was used. Analyses were adjusted for age, sex, the other SEP measures and follow-up time.

Results
At the second assessment, 42.7% of the participants experienced MetS remission. Education and income were positively associated with MetS remission, but occupational prestige was not. The association between education and MetS remission could partly (11.9%) be explained by health behaviors, but not the association between income and MetS remission.

Conclusions
Individuals with higher education more often experienced remission from MetS, mainly because individuals with higher education were more likely to have healthier behaviors. However, individuals with higher income more often experienced MetS remissions, regardless of their health behaviors. The occupational prestige of individuals was not associated with MetS remission.
The effectiveness of digital interventions for increasing physical activity in individuals of low socioeconomic status: a systematic review and meta-analysis
Authors: Western Max J. , Armstrong Miranda E. G. , Islam Ishrat , Morgan Kelly , Jones Una F. , Kelson Mark J. 
Published: November 2021

Abstract
Background
Digital technologies such as wearables, websites and mobile applications are increasingly used in interventions targeting physical activity (PA). Increasing access to such technologies makes an attractive prospect for helping individuals of low socioeconomic status (SES) in becoming more active and healthier. However, little is known about their effectiveness in such populations. The aim of this systematic review was to explore whether digital interventions were effective in promoting PA in low SES populations, whether interventions are of equal benefit to higher SES individuals and whether the number or type of behaviour change techniques (BCTs) used in digital PA interventions was associated with intervention effects.

Methods
A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Web of Science, Scopus and The Cochrane Library, published between January 1990 and March 2020. Randomised controlled trials, using digital technology as the primary intervention tool, and a control group that did not receive any digital technology-based intervention were included, provided they had a measure of PA as an outcome. Lastly, studies that did not have any measure of SES were excluded from the review. Risk of Bias was assessed using the Cochrane Risk of Bias tool version 2.

Results
Of the 14,589 records initially identified, 19 studies were included in the final meta-analysis. Using random-effects models, in low SES there was a standardised mean difference (SMD (95%CI)) in PA between intervention and control groups of 0.06 (− 0.08,0.20). In high SES the SMD was 0.34 (0.22,0.45). Heterogeneity was modest in both low (I2 = 0.18) and high (I2 = 0) SES groups. The studies used a range of digital technologies and BCTs in their interventions, but the main findings were consistent across all of the sub-group analyses (digital interventions with a PA only focus, country, chronic disease, and duration of intervention) and there was no association with the number or type of BCTs.

Discussion
Digital interventions targeting PA do not show equivalent efficacy for people of low and high SES. For people of low SES, there is no evidence that digital PA interventions are effective, irrespective of the behaviour change techniques used. In contrast, the same interventions in high SES participants do indicate effectiveness. To reduce inequalities and improve effectiveness, future development of digital interventions aimed at improving PA must make more effort to meet the needs of low SES people within the target population.
The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis
Authors: Ismail Fatme Seval , Meuth Sven G. , Melzer Nico 
Published: November 2021

AbstractAutoimmune encephalitis (AE) is an inflammatory brain disease which is frequently associated with antibodies (Abs) against cell-surface, synaptic or intracellular neuronal proteins. There is increasing evidence that dendritic cells (DCs) are implicated as key modulators in keeping the balance between immune response and tolerance in the CNS. Migratory features of DCs to and from the brain are linked to initiating and maintaining of neuroinflammation. Genetic polymorphisms together with other triggers such as systemic or cerebral viral infection, or systemic malignancies could contribute to the dysbalance of “regulatory” and “encephalitogenic” DCs with subsequent dysregulated T and B cell reactions in AE. Novel in vivo models with implantation of mature DCs containing neuronal antigens could help to study the pathogenesis and perhaps to understand the origin of AE. Investigations of DCs in human blood, lymphoid tissues, CSF, and brain parenchyma of patients with AE are necessary to deepen our knowledge about the complex interactions between DCs, T and B cells during neuroinflammation in AE. This can support developing new therapy strategies.
Anti-viral and pro-inflammatory functions of Toll-like receptors during gamma-herpesvirus infections
Authors: Gaglia Marta Maria 
Published: November 2021

AbstractToll-like receptors (TLRs) control anti-viral responses both directly in infected cells and in responding cells of the immune systems. Therefore, they are crucial for responses against the oncogenic γ-herpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus and the related murine virus MHV68, which directly infect immune system cells. However, since these viruses also cause lifelong persistent infections, TLRs may also be involved in modulation of inflammation during latent infection and contribute to virus-driven tumorigenesis. This review summarizes work on both of these aspects of TLR/γ-herpesvirus interactions, as well as results showing that TLR activity can drive these viruses’ re-entry into the replicative lytic cycle.
Exploring the roles of HPV16 variants in head and neck squamous cell carcinoma: current challenges and opportunities
Authors: Cochicho Daniela , Gil da Costa Rui , Felix Ana 
Published: November 2021

AbstractThe incidence of squamous cell carcinomas of the head and neck (HNSCC) is consistently increasing, in association with human papillomavirus (HPV) infection, especially HPV16. HPV variants show heterogeneity in the pathogenicity of cervical cancer, but little has been established about their relevance on HNSCC. This review addresses the distribution of HPV16 variants in HNSCC and their potential contribution to clinical practice. A search was performed in PubMed using the keywords HNSCC HPV16 variants. Sixty articles were identified between 2000 and 2020 and 9 articles were selected for a systematic analysis. Clinical cohorts comprised 4 to 253 patients aged between 17 and 91 years with confirmed HPV16-positive HNSCC. Samples were collected from fresh biopsies of the tumour, oral rinse or formol fixed/paraffin embedded tissue, from the oral cavity, oropharynx, hypopharynx, larynx and Waldeyer's tonsillar ring. HPV16 variants were identified using Sanger sequencing techniques. Seven studies addressed the HPV16 E6 gene, one studied E6 and E7, another studied L1 and one focused on the long control region. European variants represent 25–95%, Asian-American 5–57% and African 2–4% of the total isolates, suggesting a marked predominance of European strains. No correlations could be drawn with patient prognosis, partly because many studies relied on small patient cohorts. Additional studies are needed, particularly those employing next generation sequencing techniques (NGS), which will allow faster and accurate analysis of large numbers of samples.
A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
Authors: McAllister James P. , Talcott Michael R. , Isaacs Albert M. , Zwick Sarah H. , Garcia-Bonilla Maria , Castaneyra-Ruiz Leandro , Hartman Alexis L. , Dilger Ryan N. , Fleming Stephen A. , Golden Rebecca K. , Morales Diego M. , Harris Carolyn A. , Limbrick David D. 
Published: November 2021

AbstractBackgroundMany animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods.MethodsAcquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed.ResultsBilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3for 6 sham controls aged 45–55 days, (p < 0.001). Past the post-induction recovery period, untreated pigs were asymptomatic despite exhibiting mild-moderate ventriculomegaly. Three out of 4 shunted animals showed a reduction in ventricular volume after 20–30 days of treatment, however some developed ataxia and lethargy, from putative shunt malfunction.ConclusionsKaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.