bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of multiparametric MRI-based nomogram for predicting occult metastasis risk in early tongue squamous cell carcinoma
Authors: Saenthaveesuk Pensiri , Yang Le , Zeng Bin , Xu Meng , Young Simon , Liao Guiqing , Liang Yujie 
Published: April 2021

AbstractBackgroundNomograms are currently used in predicting individualized outcomes in clinical oncology of several cancers. However, nomograms for evaluating occult nodal metastasis of patients with squamous cell carcinoma of lateral tongue (SCCLT) have not been widely investigated for their functionality. This retrospective cohort study was designed to address this question.MethodsThis study was divided into primary and validation cohorts. The primary cohort comprised 120 patients diagnosed between 2012 and 2017, whereas the validation cohort included 41 patients diagnosed thereafter. The diagnostic value of multiparametric MRI, including radiologic tumor thickness threshold (rTTT) in three-dimensions, paralingual distance, and sublingual distance were investigated. A nomogram was developed based on stepwise logistic regression of potential predictors associated with nodal metastasis in the primary cohort and then tested for predictive accuracy in the validation cohort using area under the curve (AUC) and goodness-of-fit tests.ResultsMultivariate analysis, tumor size (odd ratio [OR] 15.175, 95% confidence interval [CI] 1.436–160.329,P = 0.024), rTTT (OR 11.528, 95% CI 2.483–53.530,P = 0.002), paralingual distance (OR 11.976, 95% CI 1.981–72.413,P = 0.005), and tumor location (OR 6.311, 95% CI 1.514–26.304,P = 0.011) were included in the nomogram to predict the likelihood of having cervical metastasis. A nomogram cutoff value of 210 points (sensitivity 93.8%, specificity 87.5%) was significantly different to classify the patients metastasis risk group (P < 0.001). Nomogram showed predictive accuracy with AUC 0.881 (95% CI 0.779–0.983,P < 0.001) and good calibration after the validation.ConclusionsA preoperative nomogram incorporating multiparametric MRI demonstrated good prediction and performed adequately in our study. Three-dimensional assessment of occult metastasis risk value obtained from this nomogram can assist in preoperative decision making for individual patients with early-stage SCCLT. The probability of nodal metastasis tended to be greater than 20% in patients with high metastasis risk or nomogram total score > 210 points.
The Regeneración Urbana, Calidad de Vida y Salud - RUCAS project: a Chilean multi-methods study to evaluate the impact of urban regeneration on resident health and wellbeing
Authors: Baeza Fernando , Vives Vergara Alejandra , González Francisca , Orlando Laura , Valdebenito Roxana , Cortinez-O’Ryan Andrea , Slesinski Claire , Diez Roux Ana V. 
Published: April 2021

Abstract
Background
The available evidence of the health effects of urban regeneration is scarce In Latin America, and there are no studies focused on formal housing that longitudinally evaluate the impact of housing and neighborhood interventions on health. The “Regeneración Urbana, Calidad de Vida y Salud” (Urban Regeneration, Quality of Life, and Health) or RUCAS project is a longitudinal, multi-method study that will evaluate the impact of an intervention focused on dwellings, built environment and community on the health and wellbeing of the population in two social housing neighborhoods in Chile.

Methods
RUCAS consists of a longitudinal study where inhabitants exposed and unexposed to the intervention will be compared over time within the study neighborhoods (cohorts), capitalizing on interventions as a natural experiment. Researchers have developed a specific conceptual framework and identified potential causal mechanisms. Proximal and more distal intervention effects will be measured with five instruments, implemented pre- and post-interventions between 2018 and 2021: a household survey, an observation tool to evaluate dwelling conditions, hygrochrons for measuring temperature and humidity inside dwellings, systematic observation of recreational areas, and qualitative interviews. Survey baseline data (956 households, 3130 individuals) is presented to describe sociodemographics, housing and health characteristics of both cohorts, noting that neighborhoods studied show worse conditions than the Chilean population.

Discussion
RUCAS’ design allows for a comprehensive evaluation of the effects that the intervention could have on various dimensions of health and health determinants. RUCAS will face some challenges, like changes in the intervention process due to adjustments of the master plan, exogenous factors –including COVID-19 pandemic and associated lockdowns– and lost to follow-up. Given the stepped wedge design, that the study capitalizes on within household changes over time, the possibility of adjusting data collection process and complementarity of methods, RUCAS has the flexibility to adapt to these circumstances. Also, RUCAS’ outreach and retention strategy has led to high retention rates. RUCAS will provide evidence to inform regeneration processes, highlighting the need to consider potential health effects of regeneration in designing such interventions and, more broadly, health as a key priority in urban and housing policies.
Are people aware of the link between alcohol and different types of Cancer?
Authors: Calvert Collin M. , Toomey Traci , Jones-Webb Rhonda 
Published: April 2021

Abstract
Background
Alcohol consumption is causally linked to several different types of cancer, including breast, liver, and colorectal cancer. While prior studies have found low awareness of the overall alcohol-cancer link, few have examined how awareness differs for each type of cancer. Greater awareness of risks associated with alcohol use may be a key factor in reducing alcohol-related cancer incidence.

Methods
We surveyed 1759 people of legal drinking age at the 2019 Minnesota State Fair. We used multivariable generalized linear models and linear regression models with robust standard errors to investigate factors associated with alcohol-cancer risk awareness. Models were fit examining predictors of overall awareness of alcohol as a risk factor for cancer, and prevalence of awareness of alcohol as a risk factor for specific types of cancer.

Results
Prevalence of awareness varied by cancer type, with awareness of alcohol causing liver cancer having the highest prevalence (92%) and awareness of alcohol causing breast cancer having the lowest prevalence (38%). Factors associated with awareness of alcohol-cancer risk differed by type of cancer.

Conclusions
In general, awareness of the risk of alcohol for certain types of cancer was low to moderate, reflecting a need to inform people not only that alcohol increases risk of cancer, but which types of cancer are most highly associated alcohol.
A novel variant in the PDE4D gene is the cause of Acrodysostosis type 2 in a Lithuanian patient: a case report
Authors: Petraitytė Gunda , Šiaurytė Kamilė , Mikštienė Violeta , Cimbalistienė Loreta , Kriaučiūnienė Dovilė , Matulevičienė Aušra , Utkus Algirdas , Preikšaitienė Eglė 
Published: April 2021

Abstract
Background
Acrodysostosis is a rare hereditary disorder described as a primary bone dysplasia with or without hormonal resistance. Pathogenic variants in the PRKAR1A and PDE4D genes are known genetic causes of this condition. The latter gene variants are more frequently identified in patients with midfacial and nasal hypoplasia and neurological involvement. The aim of our study was to analyse and confirm a genetic cause of acrodysostosis in a male patient.

Case presentation
We report on a 29-year-old Lithuanian man diagnosed with acrodysostosis type 2. The characteristic phenotype includes specific skeletal abnormalities, facial dysostosis, mild intellectual disability and metabolic syndrome. Using patient’s DNA extracted from peripheral blood sample, the novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G > C was identified in the gene PDE4D via Sanger sequencing. This variant causes amino acid change (NP_001098101.1:p.(Arg194Pro)) in the functionally relevant upstream conserved region 1 domain of PDE4D.

Conclusions
This report further expands the knowledge of the consequences of missense variants in PDE4D that affect the upstream conserved region 1 regulatory domain and indicates that pathogenic variants of the gene PDE4D play an important role in the pathogenesis mechanism of acrodysostosis type 2 without significant hormonal resistance.
Chronic temperature stress inhibits reproduction and disrupts endocytosis via chaperone titration in Caenorhabditis elegans
Authors: Plagens Rosemary N. , Mossiah Isiah , Kim Guisbert Karen S. , Guisbert Eric 
Published: April 2021

AbstractBackgroundTemperature influences biology at all levels, from altering rates of biochemical reactions to determining sustainability of entire ecosystems. Although extended exposure to elevated temperatures influences organismal phenotypes important for human health, agriculture, and ecology, the molecular mechanisms that drive these responses remain largely unexplored. Prolonged, mild temperature stress (48 h at 28 °C) has been shown to inhibit reproduction inCaenorhabditis eleganswithout significantly impacting motility or viability.ResultsAnalysis of molecular responses to chronic stress using RNA-seq uncovers dramatic effects on the transcriptome that are fundamentally distinct from the well-characterized, acute heat shock response (HSR). While a large portion of the genome is differentially expressed ≥ 4-fold after 48 h at 28 °C, the only major class of oogenesis-associated genes affected is the vitellogenin gene family that encodes for yolk proteins (YPs). Whereas YP mRNAs decrease, the proteins accumulate and mislocalize in the pseudocoelomic space as early as 6 h, well before reproduction declines. A trafficking defect in a second, unrelated fluorescent reporter and a decrease in pre-synaptic neuronal signaling indicate that the YP mislocalization is caused by a generalized defect in endocytosis. Molecular chaperones are involved in both endocytosis and refolding damaged proteins. Decreasing levels of the major HSP70 chaperone, HSP-1, causes similar YP trafficking defects in the absence of stress. Conversely, increasing chaperone levels through overexpression of the transcription factor HSF-1 rescues YP trafficking and restores neuronal signaling.ConclusionsThese data implicate chaperone titration during chronic stress as a molecular mechanism contributing to endocytic defects that influence multiple aspects of organismal physiology. Notably, HSF-1 overexpression improves recovery of viable offspring after exposure to stress. These findings provide important molecular insights into understanding organismal responses to temperature stress as well as phenotypes associated with chronic protein misfolding.
Do clinicians in areas of declining malaria transmission adhere to malaria diagnosis guidelines? A cross-sectional study from Kampala, Uganda
Authors: Atukunda Angella , Deogratius Mwaka Amos , Arinaitwe Emmanuel , Orishaba Philip , Kamya Moses R. , Nankabirwa Joaniter I. 
Published: April 2021

Abstract
Background
Uganda's clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever (history of fever or an axillary temperature ≥ 37.5 °C), and only those with a positive test receive anti-malarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. This study assessed the clinicians’ diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda.

Methods
Between January and March 2020, 383 participants aged ≥ 12 years and presenting to Kisenyi Health Centre IV in Kampala district with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading.

Results
Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02–1.13, p = 0.011), being married (aPR = 1.07, 95% CI 1.01–1.13, p = 0.022), and having tertiary education (aPR = 1.09 95% CI 1.01–1.17, p = 0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear.

Conclusion
Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic settings even when the transmission has significantly declined.
Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight
Authors: Jamshaid Humzah , Din Fakhar ud , Khan Gul Majid 
Published: April 2021

AbstractAs a neglected tropical disease, Leishmaniasis is significantly instigating morbidity and mortality across the globe. Its clinical spectrum varies from ulcerative cutaneous lesions to systemic immersion causing hyperthermic hepato-splenomegaly. Curbing leishmanial parasite is toughly attributable to the myriad obstacles in existing chemotherapy and immunization. Since the 1990s, extensive research has been conducted for ameliorating disease prognosis, by resolving certain obstacles of conventional therapeutics viz. poor efficacy, systemic toxicity, inadequate drug accumulation inside the macrophage, scarce antigenic presentation to body’s immune cells, protracted length and cost of the treatment. Mentioned hurdles can be restricted by designing nano-drug delivery system (nano-DDS) of extant anti-leishmanials, phyto-nano-DDS, surface modified—mannosylated and thiolated nano-DDS. Likewise, antigen delivery with co-transportation of suitable adjuvants would be achievable through nano-vaccines. In the past decade, researchers have engineered nano-DDS to improve the safety profile of existing drugs by restricting their release parameters. Polymerically-derived nano-DDS were found as a suitable option for oral delivery as well as SLNs due to pharmacokinetic re-modeling of drugs. Mannosylated nano-DDS have upgraded macrophage internalizing of nanosystem and the entrapped drug, provided with minimal toxicity. Cutaneous Leishmaniasis (CL) was tackling by the utilization of nano-DDS designed for topical delivery including niosomes, liposomes, and transfersomes. Transfersomes, however, appears to be superior for this purpose. The nanotechnology-based solution to prevent parasitic resistance is the use of Thiolated drug-loaded and multiple drugs loaded nano-DDS. These surfaces amended nano-DDS possess augmented IC50 values in comparison to conventional drugs and un-modified nano-DDS. Phyto-nano-DDS, another obscure horizon, have also been evaluated for their anti-leishmanial response, however, more intense assessment is a prerequisite. Impoverished Cytotoxic T-cells response followed by Leishmanial antigen proteins delivery have also been vanquished using nano-adjuvants. The eminence of nano-DDS for curtailment of anti-leishmanial chemotherapy and immunization associated challenges are extensively summed up in this review. This expedited approach is ameliorating the Leishmaniasis management successfully. Alongside, total to partial eradication of this disease can be sought along with associated co-morbidities.
Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair
Authors: Zhang Xiaobing , Hu Jiajia , Becker Kaelyn V. , Engle Jonathan W. , Ni Dalong , Cai Weibo , Wu Dong , Qu Shuping 
Published: April 2021

Abstract
Background
Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair.

Results
To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited.

Conclusions
The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.

Graphic abstract
Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements
Authors: Stolt Emma , Olsen Thomas , Elshorbagy Amany , Kožich Viktor , van Greevenbroek Marleen , Øvrebø Bente , Thoresen Magne , Refsum Helga , Retterstøl Kjetil , Vinknes Kathrine J. 
Published: April 2021

Abstract
Background
Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health.

Method/design
Men and women (calculated sample size = 60), aged 18–45 years, with body mass index of 27–35 kg/m2 will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAAhigh, total diet SAA ~ 50–60 mg/kg body weight/day; SAAlow, total diet SAA ~ 15–25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation.

Discussion
The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders.
Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021
“Our Choice” improves use of safer conception methods among HIV serodiscordant couples in Uganda: a cluster randomized controlled trial evaluating two implementation approaches
Authors: Wagner Glenn J. , Wanyenze Rhoda K. , Beyeza-Kashesya Jolly , Gwokyalya Violet , Hurley Emily , Mindry Deborah , Finocchario-Kessler Sarah , Nanfuka Mastula , Tebeka Mahlet G. , Saya Uzaib , Booth Marika , Ghosh-Dastidar Bonnie , Linnemayr Sebastian , Staggs Vincent S. , Goggin Kathy 
Published: April 2021

Abstract
Background
Safer conception counseling (SCC) to promote the use of safer conception methods (SCM) is not yet part of routine family planning or HIV care. Guidelines for the use of SCM have been published, but to date there are no published controlled evaluations of SCC. Furthermore, it is unknown whether standard methods commonly used in resource constrained settings to integrate new services would be sufficient, or if enhanced training and supervision would result in a more efficacious approach to implementing SCC.

Methods
In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach (differentiated by amount of training and supervision), or existing family planning services (usual care). Three hundred eighty-nine HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy.

Results
The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]. The arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2.

Conclusions
More intensive provider training and more frequent supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard low intensity implementation approach.

Trial registration
Clinicaltrials.gov, NCT03167879; date registered May 23, 2017.
Behçet’s disease: successful aortic root reconstruction in severely dilated aortoventricular junction after aortic valve replacement with novel surgical method – case report
Authors: Pólos Miklós , Koppányi Ádám , Benke Kálmán , Daróczi László , Oláh Attila , Heltai Krisztina , Kiss Emese , Fintha Attila , Nagy Beáta , Hartyánszky István , Lakatos Bálint , Kovács Attila , Merkely Béla , Szabolcs Zoltán 
Published: April 2021

Abstract
Background
Behçet’s disease is an auto-inflammatory disorder categorized as a primer systemic vasculitis of unknown aetiology. Genetic factors, infectious agents and the irregularity of T-cell homeostasis are presumed to be responsible for the emergence of Behçet’s disease. Characteristic symptoms are multisystemic. Although cardiovascular involvement is rare, it should be noted due to the difficulty of surgical treatment options.

Case presentation
Our 44-year-old male patient underwent aortic valve replacement due to aortic regurgitation. At the 15-month follow-up, echocardiography showed detachment of the prosthetic valve and in the aortic root, multiple pseudo-aneurysms were identified. We performed an aortic root reconstruction with a Bentall procedure using a special „skirted” conduit to reduce strain in the suture line between the conduit and the extremely dilated left ventricular outflow tract.

Conclusions
The surgical treatment of cardiovascular manifestations of Behçet’s disease remains challenging. This new technique may be beneficial in well-selected cases where the annulus of the aorta is extremely dilated or annular tissue disorder is present.