bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity, well-being, and priorities of older women during the COVID-19 pandemic: a survey of Women’s Health Initiative Strong and Healthy (WHISH) intervention participants
Authors: Wegner Lauren , Mendoza-Vasconez Andrea S , Mackey Sally , McGuire Valerie , To Cynthia , White Bailey , King Abby C , Stefanick Marcia L
Published: October 2021

Sheltering-in-place, social distancing, and other strategies to minimize COVID-19 transmission may impact physical activity (PA) and well-being in older adults. To assess self-reported PA changes, well-being, and priorities of older women across the USA early in the COVID-19 pandemic. In May 2020, a 10-question survey was emailed to 5,822 women, aged over 70 years, who had been assigned to the Women’s Health Initiative (WHI) Strong and Healthy (WHISH) trial PA intervention and had provided email addresses. The survey assessed general and physical well-being, current priorities, and PA levels before and during the COVID-19 pandemic. Demographic and physical function data were collected previously. Descriptive analyses characterized participants’ priorities and PA changes from before the pandemic to the time of data collection during the pandemic. Differences in PA change by age, physical function, and geographic region were assessed by Kruskal-Wallis and post hoc Dunn tests. Among 2,876 survey respondents, 89% perceived their general well-being as good, very good, or excellent, despite 90% reporting at least moderate (to extreme) concern about the pandemic, with 18.2% reporting increased PA levels, 27.1% reporting no changes, and 54.7% reporting decreased PA levels. Top priorities “in the midst of the COVID-19 outbreak” were staying in touch with family/friends (21%) and taking care of one’s body (20%). Among priorities related to physical well-being, staying active was selected most frequently (33%). Support for maintaining PA in older populations should be a priority during a pandemic and similarly disruptive events.
CoQ10 Promotes Resolution of Necrosis and Liver Regeneration After Acetaminophen-Induced Liver Injury
Authors: Chen Shen , Tang Yi , Fang Wanjun , He Taiping , Chen Xu , Zhang Peiwen
Published: October 2021

Coenzyme Q10 (CoQ10) which acts as an electron transporter in the mitochondrial respiratory chain has many beneficial effects on liver diseases. In our previous research, CoQ10 has been found to attenuate acetaminophen (APAP)-induced acute liver injury (ALI). However, whether CoQ10 administration is still effective at the late stage of APAP overdose is still unknown. In this study, we aimed to test CoQ10 efficacy at the late stage of APAP overdose. C57BL/6J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 16 h after APAP treatment. The results showed that while CoQ10 treatment at 16 h post-APAP overdose had no effects on the expression of ROS generated genes or scavenged genes, it still significantly decreased necrosis of hepatocytes following APAP-induced ALI. Moreover, CoQ10 increased MerTK+ macrophages accumulation in the APAP-overdose liver and inhibition of MerTK signaling partly abrogated the protective role of CoQ10 treatment on the hepatic necrosis. CoQ10 treatment also significantly enhanced hepatocytes proliferation as shown in the increased 5-bromodeoxyuridine incorporation in the APAP-intoxicated mice liver section. In addition, CoQ10 treatment increased hepatic Proliferating Cell Nuclear Antigen (PCNA) and Cyclin D1 expression and promoted activation of the β-catenin signaling in APAP-overdose mice. To conclude, these data provide evidence that CoQ10 treatment is still effective at the late stage of APAP-induced ALI and promotes resolution of necrosis and liver regeneration following ALI.
Endovascular Arteriovenous Fistula Creation
Authors: Tyagi Ravi , Karani Kunal , Ahmed Osman , Navuluri Rakesh
Published: October 2021

End-stage renal disease is increasingly prevalent and ultimately requires renal replacement therapy via renal transplant, peritoneal dialysis, or hemodialysis (HD). The ideal form of renal replacement therapy is renal transplantation; however, due to a shortage in organ availability, transplantation is least commonly utilized. Peritoneal dialysis is underutilized due to the requirement of significant patient training and occasional financial disincentive from funding agencies. HD remains the most common form of renal replacement therapy. Nearly half a million people in North America underwent HD in 2018.1
Blood and urine biomarkers in osteoarthritis – an update on cartilage associated type II collagen and aggrecan markers
Authors: Bay-Jensen Anne C. , Mobasheri Ali , Thudium Christian S. , Kraus Virginia B. , Karsdal Morten A.
Published: October 2021

Purpose of review

Osteoarthritis (OA) is a painful disease for which drug development has proven difficult. One major reason for this is the heterogeneity of the disease and the current lack of operationalized means to distinguish various disease endotypes (molecular subtypes). Biomarkers measured in blood or urine, reflecting joint tissue turnover, have been developed and tested during the last decades. In this narrative review, we provide highlights on biomarkers derived from the two most studied and abundant cartilage proteins – type II collagen and aggrecan.

Recent findings

Multiple biomarkers assessing type II collagen degradation and formation, and aggrecan turnover have been developed. Several markers, such as uCTX-II, have been validated for their association with disease severity and prognosis, as well as pharmacodynamically used to describe the mode of action and efficacy of drugs in development. There is a great need for biomarkers for subdividing patients (i.e., endotyping) and recent scientific advances have not yet come closer to achieving this goal.

There is strong support for using biomarkers for understanding OA, reflecting degradation and formation of the joint tissues, focused on type II collagen and aggrecan. There is still a lack of in vitro diagnostics, in all contexts of use.
Health Disparity, Natural Disaster, and COVID-19
Authors: Levarity Breanne R.
Published: October 2021

Trauma clusters are formed when 2 or more disasters occur simultaneously and/or consecutively. These disasters have the propensity to potentiate health disparities. The purpose of this article is to share thoughts about critical caring theory and how the theory can inform holistic nursing action when health disparity amplifies trauma clustering.
Impact of Expanding Screening Colonoscopy Interval on Providers Choice of Prescribing Colonoscopy for Colorectal Cancer Screening
Authors: Rex Douglas K. , Lahr Rachel E. , Handel Daniel A. , Gebke Kevin B. , Vemulapalli Krishna C.
Published: October 2021

Goals:

We investigated if increasing the colonoscopy screening interval from 10 to 15 years would increase provider preferences for colonoscopy as a screening test. We further examined whether having colonoscopy performed at a 15-year interval by an endoscopist with a high adenoma detection rate would influence preferences.

Background:

Colonoscopy is recommended every 10 years in average risk individuals without polyps for colorectal cancer (CRC) screening. The use of a 15-year interval offers substantial protection, increases cost-effectiveness, and might make colonoscopy more attractive to patients and health care providers who order CRC screening tests.

Study:

An anonymous online survey of health care providers across a health care system that serves a single US state and encompasses both academic and community physicians was conducted. Physicians and nurse practitioners in family medicine, obstetrics-gynecology, and internal medicine were included. Providers were asked to indicate their preference for CRC screening tests as a proportion of tests they prescribe among 5 common screening tools. Responses were compared for current colonoscopy screening intervals and if the screening intervals are increased to 15 years.

Results:

One hundred and twelve (34%) responded of 326 providers. Colonoscopy was the most frequently ordered test for CRC screening. Increasing screening interval from 10 to 15 years increased the choice of colonoscopy from 75.2% to 78.6% (P=0.003).

Conclusions:

Expanding colonoscopy screening interval to 15 years could produce an increase in physicians and nurse practitioners choice of using colonoscopy for CRC screening, but the clinical impact appears minor. Additional surveys of patients and providers are needed.
Early-Onset Frontotemporal Dementia-Related Semantic Variant of Primary Progressive Aphasia
Authors: Tsiouris Spyridon , Bougias Charalampos , Konitsiotis Spyridon , Papadopoulos Athanasios , Fotopoulos Andreas
Published: October 2021

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by cortical and subcortical atrophies, with early involvement of the hippocampus and amygdala. A 58-year-old man with clinical presentation of primary progressive aphasia—particularly its svPPA (semantic variant)—and bilateral asymmetric (left-predominant) anterior temporal lobe atrophy on MRI was referred for brain perfusion SPECT. This revealed bilateral hypoperfusion of the anterior temporal lobe (sustained by software-fused SPECT/MRI), pointing toward FTD rather than Alzheimer disease. Furthermore, voxel-based MRI volumetric analysis confirmed bilateral atrophy affecting the hippocampus and amygdala. Combining SPECT with MRI was supportive of the early-onset FTD-related svPPA diagnosis.
Cardiopulmonary Resuscitation Training for Healthcare Professionals
Authors: Lauridsen Kasper Glerup , Løfgren Bo , Brogaard Lise , Paltved Charlotte , Hvidman Lone , Krogh Kristian
Published: October 2021

Summary Statement

The optimal strategy for training cardiopulmonary resuscitation (CPR) for healthcare professionals remains to be determined. This scoping review aimed to describe the emerging evidence for CPR training for healthcare professionals.

We screened 7605 abstracts and included 110 studies in this scoping review on CPR training for healthcare professionals. We assessed the included articles for evidence for the following topics: training duration, retraining intervals, e-learning, virtual reality/augmented reality/gamified learning, instructor-learner ratio, equipment and manikins, other aspects of contextual learning content, feedback devices, and feedback/debriefing. We found emerging evidence supporting the use of low-dose, high-frequency training with e-learning to achieve knowledge, feedback devices to perform high-quality chest compressions, and in situ team simulations with debriefings to improve the performance of provider teams.
Using Self-Rated Examinations to Ensure Competence in Laparoscopy
Authors: Thinggaard Ebbe , Fjørtoft Karn , Gögenur Ismail , Konge Lars
Published: October 2021

Introduction

Asking participants to rate their own performance during unsupervised training in laparoscopy is reliable and may be cost-effective. The objective of the study was to explore the reliability of self-rated examinations where participants rate their own performance and decide themselves when they have passed tasks in basic laparoscopic skills.

Methods

This prospective observational study was conducted at the Copenhagen Academy for Medical Education and Simulation where simulation-based laparoscopic skill training is offered. Here, participants taking part in a basic laparoscopic skills course were asked to rate their own performance and decide when they had passed the Training and Assessment of Basic Laparoscopic Techniques test. To explore reliability, all examinations were video recorded and rated by a blinded rater after the end of the course.

Results

Thirty-two surgical trainees participated in the course, and 28 completed the study. We found a high reliability when comparing self-rated scores and blinded ratings with an intraclass correlation coefficient of 0.89 (P < 0.001); self-rated scores compared with blinded ratings were not significantly different (mean = 451 vs. 455, P = 0.28), and the participants did not underestimate nor overestimate their performance.

Conclusions

Ratings from self-rated examinations in a basic laparoscopic skills course are reliable, and participants neither underestimate nor overestimate their performance. Self-rated examinations may also be beneficial because they also can offer a cost-effective approach to assessment of surgical trainees.
Admixture dynamics in colonial Mexico and the genetic legacy of the Manila Galleon
Authors: Rodríguez-Rodríguez Juan Esteban , Ioannidis Alexander G. , Landa-Chavarría Erika , Blanco-Portillo Javier , Quinto-Cortés Consuelo D. , Peñaloza-Espinosa Rosenda I. , Sandoval Karla , Moreno-Estrada Andrés
Published: October 2021

Mexico has considerable population substructure due to pre-Columbian diversity and subsequent variation in admixture levels from trans-oceanic migrations, primarily from Europe and Africa, but also, to a lesser extent, from Asia. Detailed analyses exploring sub-continental structure remain limited and post-Columbian demographic dynamics within Mexico have not been inferred with genomic data. We analyze the distribution of ancestry tracts to infer the timing and number of pulses of admixture in ten regions across Mexico, observing older admixture timings in the first colonial cities and more recent timings moving outward into southern and southeastern Mexico. We characterize the specific origin of the heterogeneous Native American ancestry in Mexico: a widespread western-central Native Mesoamerican component in northern Aridoamerican states and a central-eastern Nahua contribution in Guerrero (southern Mexico) and Veracruz to its north. Yucatan shows lowland Mayan ancestry, while Sonora exhibits a unique northwestern native Mexican ancestry matching no sampled reference, each consistent with localized indigenous cultures. Finally, in Acapulco, Guerrero a notable proportion of East Asian ancestry was observed, an understudied heritage in Mexico. We identified the source of this ancestry within Southeast Asia—specifically western Indonesian and non-Negrito Filipino—and dated its arrival to approximately thirteen generations ago (1620 CE). This points to a genetic legacy from the 17thcentury Manila Galleon trade between the colonial Spanish Philippines and the Pacific port of Acapulco in Spanish Mexico. Although this piece of the colonial Spanish trade route from China to Europe appears in historical records, it has been largely ignored as a source of genetic ancestry in Mexico, neglected due to slavery, assimilation as “Indios” and incomplete historical records.
A review of the effectiveness and experiences of welfare advice services co-located in health settings: a critical narrative systematic review
Authors: Reece Sian , Sheldon Trevor A , Dickerson Josie , Pickett Kate E
Published: October 2021

The links between financial insecurity and poor health and wellbeing are well established. Individuals experiencing financial insecurity are also more likely to face challenges in accessing the support services they need. There is evidence of unequal uptake of welfare support and benefits, particularly in some ethnic minority groups. The COVID-19 pandemic has further exacerbated financial insecurity for the most vulnerable and action is needed to improve the support provided for those affected during the recovery from the pandemic.

One approach to improving uptake of benefits has been to deliver welfare services within health settings. This has the potential to increase income and possibly improve health. We conducted systematic review with a critical narrative synthesis to assess the health, social and financial impacts of welfare advice services co-located in health settings and explore the facilitators and barriers to successful implementation of these services, in order to guide future policy and practice.

The review identified 14 studies published in the UK from 2010. The services provided generated on average £27 of social, economic and environmental return on investment per £1 invested. Individuals on average benefitted from an additional £2,757 household income per annum and cost savings for the NHS were demonstrated. The review demonstrated that improvements to health were made by addressing key social determinants of health, thereby reducing health inequalities. Co-located welfare services actively incorporated elements of proportionate universalism and targeted those, who due to predominately health needs, were most in need of this support. The nature of the welfare advice service, how it operates within a health setting, and how visible and accessible this service is to participants and professionals referring into the service, were seen as important facilitators. Co-production during service development and ongoing enhanced multi-disciplinary collaboration were also considered vital to the success of co-located services.
Visual space curves before eye movements
Authors: Adeyefa-Olasupo Ifedayo-EmmanuEL , Xiao Zixuan
Published: October 2021

In most experiments within the field of cognitive and systems neuroscience, fixation is often required prior to the onset of an experimental trial. However, the term “fixation” is rather misleading since our eyes are constantly moving. One type of transient miniature movement ubiquitously observed during fixation is commonly referred to as fixational eye movements or microsaccades. Perimicrosaccadic compression of visual space — the ability of retinotopic cells to transiently exhibit predictive spatiotemporal retinotopic compressive shifts toward the target of an impending microsaccade — is known to dramatically alter visual perception. However, whether perimicrosaccadic compressive shifts can become spatially asymmetric, that is, continuously directed toward a specific foveal region over another (e.g., an upper over a lower region in the fovea) and for what purpose, remains poorly understood. Assuming that these transient shifts are indeed asymmetric under certain conditions, the perceptual and oculomotor consequences such asymmetricity might accompany across visual space is poorly understood. Equally unaccounted for is a mechanistic account of the neural computation and architecture that could support these transient asymmetric shifts while the visual system actively maintains retinotopic organization. Here, we systematically measured visual sensitivity in human subjects to faint probes presented during fixation and around the time of saccadic eye movement at geometrically symmetric retinotopic locations in the foveal, parafoveal, and peripheral regions of visual space. Remarkably, we observed transient local asymmetric visual sensitivity differences between these symmetric retinotopic locations where none should be observed. Equally surprising, we observed the trajectories of saccadic eye movements, which are expected to travel along a linear path, routinely deviate along a curved path toward orthogonal eccentric locations. To provide a mechanistic account of the neural computation and architecture that may explain our results, we proposed a novel neurobiologically inspired phenomenological force field model in which underlying attentional and oculomotor signals are modulated by transient eccentric error signals that manifest as temporally overlapping predictive forces and impinge on the retinotopic visual cortex. These forces, which transiently bias putative population sensitivity toward an orthogonal retinotopic foveal region and, around the time of a saccadic eye movement, along an axis orthogonal to the saccade direction toward a mislocalized peripheral region, succinctly capture the essence of our empirical observations.
Exome sequencing as a first-tier test for copy number variant detection : retrospective evaluation and prospective screening in 2418 cases
Authors: Testard Quentin , Vanhoye Xavier , Yauy Kevin , Naud Marie-Emmanuelle , Vieville Gaelle , Rousseau Francis , Dauriat Benjamin , Marquet Valentine , Bourthoumieu Sylvie , Genevieve David , Gatinois Vincent , Wells Constance , Willems Marjolaine , Coubes Christine , Pinson Lucile , Dard Rodolphe , Tessier Aude , Hervé Bérénice , Vialard François , Harzallah Ines , Touraine Renaud , Cogné Benjamin , Deb Wallid , Besnard Thomas , Pichon OIivier , Laudier Béatrice , Mesnard Laurent , Doreille Alice , Busa Tiffany , Missirian Chantal , Satre Véronique , Coutton Charles , Celse Tristan , Harbuz Radu , Raymond Laure , Taly Jean-François , Thevenon Julien
Published: October 2021

Purpose

Despite exome (ES) or genome sequencing (GS) availability, chromosomal microarray (CMA) remains the first-line diagnostic tests in most rare disorders diagnostic work-up, looking for Copy-number variations (CNV), with a diagnostic yield of 10-20%. The question of the equivalence of CMA and ES in CNV calling is an organisational and economic question, especially when ordering a GS after a negative CMA and/or ES.

Methods

This work measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNV on a retrospective cohort of 615 unrelated individuals. A prospective detection of ES CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.

Results

On the retrospective validation cohort every CNV was accurately detected (64/64 events). In the prospective cohort, 32 diagnostics were performed among the 2418 individuals with CNVs ranging from 704bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.

Conclusions

Combining SNV and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare mendelian disorders. Before considering the prescription of a GS after a negative ES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.
Microbiological Assessment of Health-Care Providers in Africa: Systematic Review and Meta-Analysis
Authors: Idris Abeer B. , Idris Alaa B. , Hasabo Elfatih A. , Badawi Marwan M. , Beirag Nazar
Published: October 2021

Background

Healthcare workers (HCWs) are the safeguards that help prevent illnesses and eliminate them when they occur. This study aimed to scan the related literature and provide pooled data about the level of knowledge/attitude toward infections, vaccination status and infection prevalence among African HCWs to provide better evidence toward specific detailed determination of gaps to strengthen. A total of 11,038 published articles were identified from the search strategy. Among them, 163 articles met our inclusion criteria and passed the quality assessment procedure.

Results

The prevalence of HBV was tested for 6,599 African HCWs;6.00% [95% Cl; 3.66, 8.33] were positive. The question Are you fully vaccinated against HBV?” was answered by 12,036 HCWs; 43.22% [95% Cl; 31.22, 55.21] answered yes. The most crucial local factor identified among respondents for the spread of antimicrobial resistance (AMR) was self-antibiotic prescription 42.00 % [18.79, 65.20]. The question “Does the infection prevention and control (IPC) guidelines available in your workplace?” was asked to 1,582 HCWs; 50.95% [95% Cl; 40.22, 61.67] answered yes.

Conclusion

This study determined many weaknesses to be addressed for the sake of improving health in Africa. The current pooled data are critically significant to be implemented in planning governmental or NGOs strategies.
Sex steroid hormones and risk of breast cancer incidence and survival: A two-sample Mendelian randomization study
Authors: Nounu Aayah , Kar Siddhartha P , Relton Caroline L , Richmond Rebecca C
Published: October 2021

Background

Breast cancer (BC) is the cancer with the highest incidence and mortality in women worldwide. Observational epidemiological studies suggest a positive association between testosterone, estradiol, dehydroepiandrosterone sulphate (DHEAS) and both pre- and post-menopausal BC. Since previous studies may be prone to bias and confounding, we used a two-sample Mendelian randomization (MR) analysis to investigate this association.

Methods

Genetic instruments for nine sex steroid hormones and sex hormone binding globulin (SHBG) were obtained from genome-wide association studies (GWAS) conducted in the UK Biobank (total testosterone (TT) N:230,454, bioavailable testosterone (BT) N: 188,507 and SHBG N: 189,473), The United Kingdom Household Longitudinal Study (DHEAS N: 9,722), the LIFE-Adult and LIFE-Heart cohorts (estradiol N: 2,607), the LIFE-Heart cohort only (androstenedione N: 711, aldosterone N: 685, progesterone N: 1,259 and 17-hydroxyprogesterone N: 711) and the CORtisol NETwork (CORNET) consortium (cortisol N: 25,314). GWAS summary statistics were also obtained from the Breast Cancer Association Consortium (BCAC) for overall BC risk (N: 122,977 cases and 105,974 controls) and BC mortality (96,661 BC cases and 7,697 BC-specific deaths). Subtype specific analysis were carried out for incidence of estrogen receptor (ER)+ BC, ER- BC, luminal A-like BC, luminal B-like BC, luminal B/HER2-negative-like BC, HER2-enriched-like BC, triple negative BC (TNBC) and BRCA1 mutated TNBC.

Results

Using an inverse-variance weighted (IVW) approach, we found that a standard deviation (SD) increase in TT, BT and estradiol increased the risk of overall BC (OR: 1.14, 95% CI: 1.09-1.21, OR: 1.19, 95% CI: 1.07-1.33 and OR: 1.03, 95% CI: 1.01-1.06, respectively) and ER+ BC (OR: 1.19, 95% CI: 1.12-1.27, OR: 1.25, 95% CI: 1.11-1.40 and OR: 1.06, 95% CI: 1.03-1.09, respectively). A SD increase in DHEAS also increased ER+ BC risk (OR: 1.09, 95% CI: 1.03-1.09). Subtype specific analyses showed similar associations with ER+ expressing subtypes: luminal A-like BC, luminal B-like BC and luminal B/HER2-negative-like BC. A SD increase in cortisol was associated with poor survival after a diagnosis of ER-BC (HR: 2.35, 95% CI: 1.00-5.49).

Discussion/Conclusion

TT, BT, DHEAS and estradiol increase the risk of ER+ type BCs similar to observational studies, but none of these hormone measures are associated with BC survival. We found some evidence that cortisol reduced ER- BC survival. Stronger genetic instruments are required before definitive conclusions can be made about the role of other sex-steroid hormones in breast cancer. Understanding the role of sex steroid hormones in BC risk, particularly subtype-specific risks, highlights the potential importance of attempts to modify and/or monitor hormone levels in order to prevent BC.
Head and Neck Cancer Primary Tumor Auto Segmentation using Model Ensembling of Deep Learning in PET-CT Images
Authors: Naser Mohamed A. , Wahid Kareem A. , van Dijk Lisanne V. , He Renjie , Ab-delaal Moamen Abobakr , Dede Cem , Mohamed Abdallah S.R. , Fuller Clifton D.
Published: October 2021

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that are able to demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient (DSC) up to 0.771 and median 95% Hausdorff distance (95% HD) as low as 2.919 mm. We employ label fusion ensemble approaches, including Simultaneous Truth and Performance Level Estimation (STAPLE) and a voxel-level threshold approach based on majority voting (AVERAGE), to generate consensus segmentations on the test data by combining the segmentations produced through different trained cross-validation models. We demonstrate that our best performing ensembling approach (256 channels AVERAGE) achieves a mean DSC of 0.770 and median 95% HD of 3.143 mm through independent external validation on the test set. Concordance of internal and external validation results suggests our models are robust and can generalize well to unseen PET/CT data. We advocate that ResUNet models coupled to label fusion ensembling approaches are promising candidates for PET/CT oropharyngeal primary tumors auto-segmentation, with future investigations targeting the ideal combination of channel combinations and label fusion strategies to maximize segmentation performance.
Metabolic disorders and the risk of head and neck cancer: a protocol for a systematic review and meta-analysis
Authors: Gormley Alexander , Richards Charlotte , Spiga Francesca , Gray Emily , Hooper Joanna , Main Barry G , Vincent Emma E , Richmond Rebecca C , Higgins Julian PT , Gormley Mark
Published: October 2021

Introduction

Head and neck cancer squamous cell carcinoma (HNSCC) is the 6th most common cancer internationally. Established risk factors include smoking, alcohol and presence of human papillomavirus (HPV). The incidence rate of new disease continues to rise, despite falls in alcohol consumption and a reduction in smoking, the rising rates are unlikely to be solely attributed to HPV status alone. Obesity and its associated conditions such as type 2 diabetes (T2D) are implicated in the risk and progression of a variety of cancers but there is paucity of evidence regarding its role in HNSCC.

Methods and analysis

A systematic review of cohort studies, reporting a risk of incident head and neck squamous cell carcinoma will be included. A systematic search strategy has been developed, multiple databases will be searched from January 1966, including Cochrane Library, OVID SP versions of Medline and EMBASE. The primary outcome will be incident HNSCC based on exposures of type 2 diabetes, obesity, dyslipidemia and hypertension as defined by the World Health Organisation (WHO). A combined risk effect across studies will be calculated using meta-analysis, although depending on the heterogeneity in study design, exposure and outcome reporting this may not be possible.

Ethics and dissemination

No ethical approval is required for this systematic review. The review will be published in a revelant peer-review journal and findings will be presented at scientific meetings in both poster and oral presentation form.

Registration details

This study has been registered with the international prospective register of systematic reviews (PROSPERO) with study registration number CRD42021250520. This protocol has been developed in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidance statement.

Article Summary

Strengths and limitations of this study

This systematic review will be the first to comprehensively review the literature and provide a meta-analysis of the effect of metabolic disorders and the risk of incident HNSCC.

The publication of this protocol provides a clear representation of the methods used in this review for transparency and to prevent future duplication.

This systematic review will be one of the first to pilot the The ROBINS-E tool (Risk Of Bias In Non-randomised Studies - of Exposures).

Despite the metabolic disorders being described as separate entities, the authors recognise the potential for disease processes to be related.

Among cohort studies there is significant variability in terms of length of follow-up for the outcome of interest, HNSCC.
Reduced locus coeruleus integrity linked to response inhibition deficits in parkinsonian disorders
Authors: Ye Rong , Hezemans Frank H. , O’Callaghan Claire , Tsvetanov Kamen A. , Rua Catarina , Jones P. Simon , Holland Negin , Malpetti Maura , Murley Alexander G. , Barker Roger A. , Williams-Gray Caroline H. , Robbins Trevor W. , Passamonti Luca , Rowe James B.
Published: October 2021

Parkinson’s disease and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals, and have been linked with worse prognosis and lack of improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus noradrenergic system. Here we test the hypothesis that loss of structural integrity of the locus coeruleus explains response inhibition deficits in progressive supranuclear palsy and Parkinson’s disease. This cross-sectional observational study recruited 24 people with idiopathic Parkinson’s disease, 14 with PSP-Richardson’s syndrome, and 24 age- and sex-matched controls. All participants undertook a stop-signal task and ultrahigh field 7T-magnetic transfer weighted imaging of the locus coeruleus. Hierarchical Bayesian estimation of the parameters of ‘race models’ of go-versus stop-decisions was used to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between locus coeruleus integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. Progressive supranuclear palsy caused a distinct pattern of abnormalities in inhibitory control, relative to Parkinson’s disease and healthy controls, with a paradoxically reduced threshold for go responses, but longer non-decision times, and more lapses of attention. The variation in response inhibition correlated with variation in the integrity of the locus coeruleus, across participants in both clinical groups. Structural imaging of the locus coeruleus, coupled with behavioural modelling in parkinsonian disorders, confirms that locus coeruleus integrity is associated with response inhibition and its degeneration contributes to neurobehavioural changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimisation of noradrenergic treatment is likely to benefit from stratification according to locus coeruleus integrity.
Genetic associations of protein-coding variants in human disease
Authors: Sun Benjamin B. , Kurki Mitja I. , Foley Christopher N. , Mechakra Asma , Chen Chia-Yen , Marshall Eric , Wilk Jemma B. ,   Biogen Biobank Team, Chahine Mohamed , Chevalier Philippe , Christé Georges , FinnGen  , Palotie Aarno , Daly Mark J. , Runz Heiko
Published: October 2021

Genome-wide association studies (GWAS) have identified thousands of genetic variants linked to the risk of human disease. However, GWAS have thus far remained largely underpowered to identify associations in the rare and low frequency allelic spectrum and have lacked the resolution to trace causal mechanisms to underlying genes. Here, we combined whole exome sequencing in 392,814 UK Biobank participants with imputed genotypes from 260,405 FinnGen participants (653,219 total individuals) to conduct association meta-analyses for 744 disease endpoints across the protein-coding allelic frequency spectrum, bridging the gap between common and rare variant studies. We identified 975 associations, with more than one-third of our findings not reported previously. We demonstrate population-level relevance for mutations previously ascribed to causing single-gene disorders, map GWAS associations to likely causal genes, explain disease mechanisms, and systematically relate disease associations to levels of 117 biomarkers and clinical-stage drug targets. Combining sequencing and genotyping in two population biobanks allowed us to benefit from increased power to detect and explain disease associations, validate findings through replication and propose medical actionability for rare genetic variants. Our study provides a compendium of protein-coding variant associations for future insights into disease biology and drug discovery.
Shell shape as an indicator of phenotypic stocks of Tehuelche scallop (Aequipecten tehuelchus) in Northern Patagonia, Argentina
Authors: Getino Mamet Leandro Nicolás , Soria Gaspar , Schejter Laura , Márquez Federico
Published: October 2021

Tehuelche scallop, Aequipecten tehuelchus, is a commercially exploited species in Northern Patagonia, Argentina. Without genetic differentiation at the species level, A. tehuelchus presents three morphotypes: tehuelchus, madrynensis, and a non-common variant felipponei. The main goal of this study was to analyze the shell shape variation of Tehuelche scallop to differentiate and identify the phenotypic stocks. The shape differences between and within the two main morphotypes (tehuelchus and madrynensis) were assessed using geometric morphometrics in nine localities. The shell shape presented variability at geographic scale, with the morphologic traits that maximized the differentiation among localities between the tehuelchus and madrynensis morphotypes. Scallops from madrynensis morphotype presented higher and circular shell discs with smaller auricles than those from tehuelchus morphotype. Morphometric differentiation was also detected among localities of each morphotype, wherein most of the variability was related to the disc circularity and the symmetry of the auricles. The presence of morphologic variation in San Matías and San José gulfs, wherein a single genetic pool is shared, evidenced the plastic nature of the species. Given the distribution of this resource in distinct provincial jurisdictions, the differentiation of phenotypic stocks has relevance in the context of fishery management, especially if zoning and rotational strategies are implemented.
Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice
Authors: Zheng Xiaoyi , Higdon Lauren , Gaudet Alexandre , Shah Manav , Balistieri Angela , Li Catherine , Nadai Patricia , Palaniappan Latha , Yang Xiaoping , Santo Briana , Ginley Brandon , Wang Xiaoxin X. , Myakala Komuraiah , Nallagatla Pratima , Levi Moshe , Sarder Pinaki , Rosenberg Avi , Maltzman Jonathan S. , de Freitas Caires Nathalie , Bhalla Vivek
Published: October 2021

Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. In this study, we show that lower circulating Esm-1 predicts progressive stages of albuminuria in patients with diabetes. In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. Using hydrodynamic tail-vein injection, we show that over-expression of either mouse or human Esm-1 reduces diabetes-induced albuminuria relative to saline-injected controls independent of leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice increases the degree of diabetes-induced albuminuria versus wild-type controls. Mechanistically, over-expression of Esm-1 attenuates diabetes-induced podocyte injury. By glomerular RNAseq, we identify that Esm-1 attenuates diabetes-induced up-regulation of interferon-stimulated genes, and Esm-1 inhibits expression of kidney disease-promoting and interferon-related genes, includingAckr2andCxcl11. In conclusion, we demonstrate that Esm-1 protects against diabetes-induced albuminuria, and podocytopathy, possibly through select interferon signaling.
EEG-based clusters differentiate psychological distress, sleep quality and cognitive function in adolescents
Authors: Forbes Owen , Schwenn Paul E. , Wu Paul Pao-Yen , Santos-Fernandez Edgar , Xie Hong-Bo , Lagopoulos Jim , McLoughlin Larisa T. , Sacks Dashiell D. , Mengersen Kerrie , Hermens Daniel F.
Published: October 2021

1

Introduction

To better understand the relationships between brain activity, cognitive function and mental health risk in adolescence there is value in identifying data-driven subgroups based on measurements of brain activity and function, and then comparing cognition and mental health symptoms between such subgroups.

Methods

Here we implement a multi-stage analysis pipeline to identify data-driven clusters of 12-year-olds (M = 12.64, SD = 0.32) based on frequency characteristics calculated from resting state, eyes-closed electroencephalography (EEG) recordings. EEG data was collected from 59 individuals as part of their baseline assessment in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Applying multiple unsupervised clustering algorithms to these EEG features, we identified well-separated subgroups of individuals. To study patterns of difference in cognitive function and mental health symptoms between core clusters, we applied Bayesian regression models to probabilistically identify differences in these measures between clusters.

Results

We identified 5 core clusters which were associated with distinct subtypes of resting state EEG frequency content. EEG features that were influential in differentiating clusters included Individual Alpha Frequency, relative power in 4 Hz bands up to 16 Hz, and 95% Spectral Edge Frequency. Bayesian models demonstrated substantial differences in psychological distress, sleep quality and cognitive function between these clusters. By examining associations between neurophysiology and health measures across clusters, we have identified preliminary risk and protective profiles linked to EEG characteristics.

Conclusion

In this work we have developed a flexible and scaleable pipeline to identify subgroups of individuals in early adolescence on the basis of resting state EEG activity. These findings provide new clues about neurophysiological subgroups of adolescents in the general population, and associated patterns of health and cognition that are not observed at the whole group level. This approach offers potential utility in clinical risk prediction for mental and cognitive health outcomes throughout adolescent development.
An Optimal Policy Model for Concurrent Uncertainty Estimation During Decision Making
Authors: Li Xiaodong , Su Ruixin , Chen Yilin , Yang Tianming
Published: October 2021

We often postpone or even avoid making decisions when we feel uncertain. Uncertainty estimation is not an afterthought of decision making but a dynamic process that accompanies decision making in parallel and affects decision making. To study concurrent uncertainty estimation during decision making, we adapted the classic random-dots motion direction discrimination task to allow a reaction-time measure of uncertainty responses. Subjects were asked to judge whether a patch of random dots was moving left or right. In addition, they could seek assistance by choosing to look at a second stimulus that had the same direction but high coherence any time during the task. The task allows us to measure the reaction time of both the perceptual decisions and the uncertainty responses. The subjects were more likely to choose the uncertainty response when the motion coherence was low, while their reaction times of the uncertainty responses showed individual variations. To account for the subjects’ behavior, we created an optimal policy decision model in which decisions are based on the value functions computed from the accumulated evidence using a drift-diffusion process. Model simulations captured key features of the subjects’ choices, reaction times, and proportions of uncertainty responses. Varying model parameters explained individual variations in the subjects and the correlations between decision accuracy, proportions of uncertainty responses, and reaction times at the individual level. Our model links perceptual decisions and value-based decisions and indicates that concurrent uncertainty estimation may be based on comparisons between values of uncertainty responses and perceptual decisions, both of which may be derived from the same evidence accumulation process during decision making. It provides a theoretical framework for future investigations, including the ones that aim at the underlying neural mechanism.
Coral niche construction: coral recruitment increases along a coral-built structural complexity gradient
Authors: Brambilla Viviana , Baird Andrew H. , Barbosa Miguel , Dehnert Inga , Madin Joshua T. , Peddie Clare , Dornelas Maria A.
Published: October 2021

Niche construction is the process through which organisms modify environmental states in ways favourable to their own fitness. Here, we test experimentally whether scleractinian corals can be considered niche constructors. In particular, we demonstrate a positive feedback involved in corals building structures which facilitate recruitment. Coral larval recruitment is a key process for coral reef persistence. Larvae require low flow conditions to settle from the plankton, and hence the presence of colony structures that can break the flow is expected to facilitate coral recruitment. Here, we show an increase in settler presence on artificial tiles deployed in the field along a gradient of coral-built structural complexity. Structural complexity had a positive effect on settlement, with an increase of 15,71% of settler presence probability along the range of structural complexity considered. This result provides evidence that coral built structural complexity creates conditions that facilitate coral settlement, while demonstrating that corals meet the criteria for ecological niche construction.
Short-term plasticity in the visual thalamus
Authors: Kurzawski Jan W. , Lunghi Claudia , Biagi Laura , Tosetti Michela , Morrone Maria Concetta , Binda Paola
Published: October 2021

While there is evidence that the visual cortex retains a potential for plasticity in adulthood, less is known about the subcortical stages of visual processing. Here we asked whether short-term ocular dominance plasticity affects the visual thalamus. We addressed this question in normally sighted adult humans, using ultra-high field (7T) magnetic resonance imaging combined with the paradigm of short-term monocular deprivation. With this approach, we previously demonstrated transient shifts of perceptual eye dominance and ocular dominance in visual cortex (Binda et al., 2018). Here we report evidence for short-term plasticity in the ventral division of the pulvinar (vPulv), where the deprived eye representation was enhanced over the non-deprived eye. This pulvinar plasticity effect was similar as previously seen in visual cortex and it was correlated with the ocular dominance shift measured behaviorally. In contrast, there was no short-term plasticity effect in Lateral Geniculate Nucleus (LGN), where results were reliably different from vPulv, despite their spatial proximity. We conclude that the visual thalamus retains potential for short-term plasticity in adulthood; the plasticity effect differs across thalamic subregions, possibly reflecting differences in their cortical connectivity.