bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Preoperative Breast Satisfaction among Patients Undergoing Mastectomy and Immediate Reconstruction: BREAST-Q Insights
Authors: Shamsunder Meghana G. , Polanco Thais O. , McCarthy Colleen M. , Allen Robert J. , Matros Evan , Coriddi Michelle , Mehrara Babak J. , Pusic Andrea , Nelson Jonas A. 
Published: November 2021

Background:
This study aims to present normative values for satisfaction with breasts among preoperative breast reconstruction patients as assessed using the BREAST-Q instrument and to delineate factors associated with preoperative breast satisfaction.

Methods:
A retrospective analysis of prospectively collected data was performed examining women undergoing postmastectomy breast reconstruction at a tertiary care center who preoperatively completed the BREAST-Q from 2010 to 2017. Because breast satisfaction scores were nonnormally distributed, scores were categorized into quartiles for analysis. Patient- and treatment-level variables were tested in a multivariable ordinal logistic regression model as predictors of breast satisfaction. Preoperative satisfaction was also tested for association with choice of reconstructive modality.

Results:
Among 1306 postmastectomy reconstruction patients included in the study, mean preoperative Satisfaction with Breasts score was 61.8 ± 21.5 and the median score was 58.0 (interquartile range, 48 to 70). Factors associated with significantly lower preoperative satisfaction included history of psychiatric diagnosis, preoperative radiotherapy, marital status (married), and higher body mass index. Factors associated with significantly higher scores were malignancy (localized tumor), medium bra size (B to C cup), and self-identification as black. Preoperative breast satisfaction was lower among patients who elected autologous reconstruction than among those with implant reconstruction (p < 0.001).

Conclusions:
Preoperative breast satisfaction is influenced by multiple factors. Understanding these factors may improve preoperative counseling and expectation management for patients who undergo postmastectomy breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
A Role for NRF2-Signaling in the Treatment and Prevention of Solar Lentigines
Authors: Kerns Michelle L. , Chien Anna L. , Kang Sewon 
Published: November 2021

Background:
Photoaging is premature skin aging resulting from oxidative stress generated by exposure to solar radiation. A key clinical feature is solar lentigines, areas of hyperpigmentation on sun-exposed skin. Skin pigmentation is determined by cross-talk between keratinocytes and melanocytes, which is exquisitely sensitive to oxidative stress. Toll-like receptor (TLR) signaling and NF-E2-related factor 2 (NRF2) signaling, an endogenous antioxidant system, serve as a bridge between the oxidative stress response and immune regulation. Moreover, TLR-mediated induction of IL-6 production has been shown to prevent ultraviolet (UV)-induced hyperpigmentation.

Methods:
Shave biopsies of solar lentigines were obtained from 14 individuals. An additional 7 subjects applied broccoli sprout extract (BSE) containing sulforaphane daily or vehicle on photodamaged skin. Immunofluorescence staining was used to determine total and phosphorylated NRF2 in the lentiginous skin. Dermoscopy and Fontana & Masson staining were used to assess the effect of topical BSE on UV-induced pigmentation. Similar topical treatments were performed in a mouse model of UVB-induced hyperpigmentation utilizing WT, Nrf2–/–
, or K14-Cre-ERT2IL-6Rαfl/fl C57BL/6 mice.

Results:
NRF2 expression is altered in solar lentigines, and UV-induced skin pigmentation in humans could be ameliorated with topical BSE. Corresponding mouse models replicated the authors’ clinical findings and identified a potential mechanistic link to IL-6Rα signaling in keratinocytes.

Conclusion:
The authors’ findings suggest that dysregulation of NRF2 signaling is involved in the pathogenesis of UV-induced skin pigmentation and pharmacological activation of NRF2 may represent a potential therapeutic target in photoaging.
Pharmacotherapy of cerebellar and vestibular disorders
Authors: Lemos João , Manto Mario 
Published: November 2021

Purpose of review
Major therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years.

Recent findings
Recently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-l-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12-week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Ménière's disease patients remains controversial.

Summary
Although the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.
The relationship between ethnicity and stone composition in a large multi-ethnic London NHS Trust
Authors: Vaggers S , Warner R , Forster L , Ali Z , Pal P , Graham S 
Published: November 2021

AbstractPurposeFew studies have examined kidney stone composition of an ethnically diverse group living in the same location, we aimed to study this in an ethnically diverse NHS trust.MethodsWe reviewed all patients (n=312) with laboratory stone analysis and compared their ethnicity with their stone composition.ResultsUsing a Chi Squared analysis there was no significant difference between stone composition in different ethnic groups (p=0.07). Uric acid stones were more common in the White-other group at 22.0% compared to 10.3% for White British, 5.2% for Asian and 9.52% for Black patients. Calcium oxalate stone were more common in the Asian population with 71.9% and Black population at 76.1%, compared with 56.7% in the White British population and 52.6% in the White-other population. Calcium phosphate stones were found commonly in the White British population (26.8%) compared to 18.6% for White-other, 16.7% for Asian and 9.5% for Black patients. Cystine and Struvite stones were found at low levels of between 0-3.4% in each group. Repeat stone formers with calcium oxalate, uric acid or cystine stones formed the same stone again 100.0% of the time. The odds for the Black population having a stone analysed (OR 0.62, CI 0.39-0.97, p=0.04) was significantly lower than the local population, and for the Asian population this was significantly higher (OR 1.31, CI1.05-1.62, p=0.01),ConclusionUric acid stones are found more frequently in the White-other population and calcium oxalate stones are found more frequently in the Asian and black population. However, these results were not statistically significant. The odds ratio of having a stone was significantly higher in the Asian population and lower in the Black population.
Exploring the relationships between autozygosity, educational attainment, and cognitive ability in a contemporary, trans-ancestral American sample
Authors: Colbert Sarah MC , Keller Matthew C , Agrawal Arpana , Johnson Emma C 
Published: November 2021

AbstractPrevious studies have found significant associations between estimated autozygosity - the proportion of an individual’s genome contained in homozygous segments due to distant inbreeding - and multiple traits, including educational attainment (EA) and cognitive ability. In one study, estimated autozygosity showed a stronger association with parental EA than the subject’s own EA. This was likely driven by parental EA’s association with mobility: more educated parents tended to migrate further from their hometown, therefore choosing more genetically diverse partners. We examined the associations between estimated autozygosity, cognitive ability, and parental EA in a contemporary sub-sample of adolescents from the Adolescent Brain and Cognitive Development StudySM (ABCD Study®) (analytic N=6,504). We found a negative association between autozygosity and child cognitive ability consistent with previous studies, while the associations between autozygosity and parental EA were in the expected direction of effect (with greater levels of autozygosity being associated with lower EA) but the effect sizes were significantly weaker than those estimated in previous work. We also found a lower mean level of autozygosity in the ABCD sample compared to previous autozygosity studies, which may reflect overall decreasing levels of autozygosity over generations. Variation in migration and mobility patterns in the ABCD study compared to other studies may explain the pattern of associations between estimated autozygosity, EA, and cognitive ability in the current study.
Uncoupling differential water usage from drought resistance in a dwarf Arabidopsis mutant
Authors: Ginzburg Daniel N. , Bossi Flavia , Rhee Seung Y. 
Published: November 2021

AbstractUnderstanding the molecular and physiological mechanisms of how plants respond to drought is paramount to breeding more drought resistant crops. Certain mutations or allelic variations result in plants with altered water-use requirements. To correctly identify genetic differences which confer a drought phenotype, plants with different genotypes must be subjected to equal levels of drought stress. Many reports of advantageous mutations conferring drought resistance do not control for soil water content variations across genotypes and may therefore need to be re-examined. Here, we reassessed the drought phenotype of the Arabidopsis thaliana dwarf mutant, chiquita1-1 (also called costl), by growing mutant seedlings together with the wild type to ensure uniform soil water availability across genotypes. Our results demonstrate that the dwarf phenotype conferred by loss of CHIQ1 function results in constitutively lower water usage, but not increased drought resistance.
Genomic insights into the recent population history of Mapuche Native Americans
Authors: Vicuña Lucas , Mikhailova Anastasia , Norambuena Tomás , Ilina Anna , Klimenkova Olga , Shchur Vladimir , Eyheramendy Susana 
Published: November 2021

AbstractThe last few years have witnessed an explosive generation of genomic data from ancient and modern Native American populations. These data shed light on key demographic shifts that occurred in geographically diverse territories of South America, such as the Andean highlands, Southern Patagonia and the Amazon basin. We used genomic data to study the recent population history of the Mapuche, who are the major Native population from the Southern Cone (Chile and Argentina). We found evidence of specific shared genetic ancestry between the Mapuche and ancient populations from Southern Patagonia, Central Chile and the Argentine Pampas. Despite previous evidence of cultural influence of Inca and Tiwanaku polities over the Mapuche, we did not find evidence of specific shared ancestry between them, nor with Amazonian groups. We estimated the effective population size dynamics of the Mapuche ancestral population during the last millennia, identifying a population bottle-neck around 1650 AD, coinciding with a period of Spaniards’ invasions into the territory inhabited by the Mapuche. Finally, we show that admixed Chileans underwent post-admixture adaptation in their Mapuche subancestry component in genes related with lipid metabolism, suggesting adaptation to scarce food availability.
The GA4GH Phenopacket schema: A computable representation of clinical data for precision medicine
Authors: Jacobsen Julius O. B. , Baudis Michael , Baynam Gareth S. , Beckmann Jacques S. , Beltran Sergi , Callahan Tiffany J. , Chute Christopher G. , Courtot Mélanie , Danis Daniel , Elemento Olivier , Freimuth Robert R. , Gargano Michael A. , Groza Tudor , Hamosh Ada , Harris Nomi L. , Kaliyaperumal Rajaram , Khalifa Aly , Krawitz Peter M. , Köhler Sebastian , Laraway Brian J. , Lehväslaiho Heikki , Lloyd Kent C. , Matalonga Leslie , McMurry Julie A. , Metke-Jimenez Alejandro , Mungall Christopher J. , Munoz-Torres Monica C. , Ogishima Soichi , Papakonstantinou Anastasios , Piscia Davide , Pontikos Nikolas , Queralt-Rosinach Núria , Roos Marco , Schofield Paul N. , Siapos Anastasios , Smedley Damian , Smith Lindsay D. , Steinhaus Robin , Sundaramurthi Jagadish Chandrabose , Swietlik Emilia M. , Thun Sylvia , Vasilevsky Nicole A. , Wagner Alex H. , Warner Jeremy L. , Weiland Claus , Haendel Melissa A. , Robinson Peter N. 
Published: November 2021

AbstractDespite great strides in the development and wide acceptance of standards for exchanging structured information about genomic variants, there is no corresponding standard for exchanging phenotypic data, and this has impeded the sharing of phenotypic information for computational analysis. Here, we introduce the Global Alliance for Genomics and Health (GA4GH) Phenopacket schema, which supports exchange of computable longitudinal case-level phenotypic information for diagnosis and research of all types of disease including Mendelian and complex genetic diseases, cancer, and infectious diseases. To support translational research, diagnostics, and personalized healthcare, phenopackets are designed to be used across a comprehensive landscape of applications including biobanks, databases and registries, clinical information systems such as Electronic Health Records, genomic matchmaking, diagnostic laboratories, and computational tools. The Phenopacket schema is a freely available, community-driven standard that streamlines exchange and systematic use of phenotypic data and will facilitate sophisticated computational analysis of both clinical and genomic information to help improve our understanding of diseases and our ability to manage them.
Comparing Optimization Criteria in Antibiotic Allocation Protocols
Authors: Jamieson-Lane Alastair , Friedrich Alexander , Blasius Bernd 
Published: November 2021

AbstractClinicians prescribing antibiotics in a hospital context follow one of several possible “treatment protocols” -heuristic rules designed to balance the immediate needs of patients against the long term threat posed by the evolution of antibiotic resistance and multi-resistant bacteria. Several criteria have been proposed for assessing these protocols, unfortunately these criteria frequently conflict with one another, each providing a different recommendation as to which treatment protocol is best. Here we review and compare these optimization criteria. We are able to demonstrate that criteria focused primarily on slowing evolution of resistance are directly antagonistic to patient health both in the short and long term. We provide a new optimization criteria of our own, intended to more meaningfully balance the needs of the future and present. Asymptotic methods allow us to evaluate this criteria and provide insights not readily available through the numerical methods used previously in the literature. When cycling antibiotics, we find an antibiotic switching time which proves close to optimal across a wide range of modelling assumptions.
Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332)
Authors: Ullrich Sven , Ekanayake Kasuni B. , Otting Gottfried , Nitsche Christoph 
Published: November 2021

AbstractThe COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic nirmatrelvir (PF-07321332). We expressed Mpro of six SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, B.1.1.529 Omicron, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, P132H, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that nirmatrelvir has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of the specific Mpro inhibitor nirmatrelvir is not compromised in current COVID-19 variants.Graphical abstract
Rate discrimination training may partially restore temporal processing abilities from age-related deficits
Authors: Anderson Samira , DeVries Lindsay , Smith Edward , Goupell Matthew J. , Gordon-Salant Sandra 
Published: November 2021

AbstractThe ability to understand speech in complex environments depends on the brain’s ability to preserve the precise timing characteristics of the speech signal. Age-related declines in temporal processing may contribute to the older adult’s experience of communication difficulty in challenging listening conditions. This study’s purpose was to evaluate the effects of rate discrimination training on auditory temporal processing. A double-blind, randomized control design assigned 77 young normal-hearing, older normal-hearing, and older hearing-impaired listeners to one of two treatment groups: experimental (rate discrimination for 100-Hz and 300-Hz pulse trains) and active control (tone detection in noise). All listeners were evaluated during pre-and post-training sessions using perceptual rate discrimination of 100-, 200-, 300-, and 400-Hz band-limited pulse trains and auditory steady-state responses (ASSRs) to the same stimuli. Training generalization was evaluated using several temporal processing measures and sentence recognition tests that included time-compressed and reverberant speech stimuli. Results demonstrated a session × training group interaction for perceptual and ASSR testing to the trained frequencies (100 and 300 Hz), driven by greater improvements in the training group than in the active control group. Further, post-test rate discrimination of the older listeners reached levels that were equivalent to those of the younger listeners at pre-test. The training-specific gains generalized to untrained frequencies (200 and 400 Hz), but not to other temporal processing or sentence recognition measures. Further, non-auditory inhibition/attention performance predicted training-related improvement in rate discrimination. Overall, the results demonstrate the potential for auditory training to partially restore temporal processing in older listeners and highlight the role of cognitive function in these gains.
COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme
Authors: Fasching Clare L. , Servellita Venice , McKay Bridget , Nagesh Vaishnavi , Broughton James P. , Sotomayor-Gonzalez Alicia , Wang Baolin , Brazer Noah , Reyes Kevin , Streithorst Jessica , Deraney Rachel N. , Stanfield Emma , Hendriks Carley G. , Miller Steve , Ching Jesus , Chen Janice S. , Chiu Charles Y. 
Published: November 2021

AbstractLaboratory tests for the accurate and rapid identification of SARS-CoV-2 variants can potentially guide the treatment of COVID-19 patients and inform infection control and public health surveillance efforts. Here we present the development and validation of a rapid COVID-19 variant DETECTR®assay incorporating loop-mediated isothermal amplification (LAMP) followed by CRISPR-Cas12 based identification of single nucleotide polymorphism (SNP) mutations in the SARS-CoV-2 spike (S) gene. This assay targets the L452R, E484K/Q/A, and N501Y mutations that are associated with nearly all circulating viral lineages and identifies the two circulating variants of concern, Delta and Omicron. In a comparison of three different Cas12 enzymes, only the newly identified enzyme CasDx1 was able to accurately identify all targeted SNP mutations. An analysis pipeline for CRISPR-based SNP identification from 139 clinical samples yielded an overall SNP concordance of 98% and agreement with SARS-CoV-2 lineage classification of 138/139 compared to viral whole-genome sequencing. We also showed that detection of the single E484A mutation was necessary and sufficient to accurately identify Omicron from other major circulating variants in patient samples. These findings demonstrate the utility of CRISPR-based DETECTR®as a faster and simpler diagnostic than sequencing for SARS-CoV-2 variant identification in clinical and public health laboratories.
Mutation-related apparent myelin, not axon density, drives white matter differences in premanifest Huntington’s disease: Evidence from in vivo ultra-strong gradient MRI
Authors: Casella Chiara , Chamberland Maxime , Laguna Pedro Luque , Parker Greg D. , Rosser Anne E. , Coulthard Elizabeth , Rickards Hugh , Berry Samuel C. , Jones Derek K. , Metzler-Baddeley Claudia 
Published: November 2021

AbstractWhite matter (WM) alterations have been observed early in Huntington’s disease (HD) progression but their role in the disease-pathophysiology remains unknown. We exploited ultra-strong-gradient MRI to tease apart contributions of myelin (with the magnetization transfer ratio), and axon density (with the restricted volume fraction from the Composite Hindered and Restricted Model of Diffusion) to WM differences between premanifest HD patients and age- and sex-matched controls. Diffusion tensor MRI (DT-MRI) measures were also assessed. We used tractometry to investigate region-specific changes across callosal segments with well-characterized early- and late-myelinating axonal populations, while brain-wise alterations were explored with tract-based cluster analysis (TBCA). Behavioural measures were included to explore disease-associated brain-function relationships. We detected lower myelin in the rostrum of patients (tractometry: p = 0.0343; TBCA: p = 0.030), but higher myelin in their splenium (p = 0.016). Importantly, patients’ myelin and mutation size were positively associated (all p-values < 0.01), indicating that increased myelination might be a direct result of the mutation. Finally, myelin was higher than controls in younger patients but lower in older patients (p = 0.003), suggesting detrimental effects of increased myelination later in the course of the disease. Higher FR in patients’ left cortico-spinal tract (CST) (p = 0.03) was detected, and was found to be positively associated with MTR in the posterior callosum (p = 0.033), possibly suggesting compensation to myelin alterations. This comprehensive, ultra-strong gradient MRI investigation provides novel evidence of CAG-driven myelin alterations in premanifest HD which may reflect neurodevelopmental, rather than neurodegenerative disease-associated changes.