Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel GSN variant outside the G2 calcium‐binding domain associated with Amyloidosis of the Finnish type

Gelsolin (GSN) variants have been implicated in amyloidosis of the Finnish type. This case series reports a novel GSN:c.1477T>C,p.(Trp493Arg) variant in a family with ocular and systemic features consistent with Finnish Amyloidosis. Exome sequencing performed on affected individuals from two families manifesting cutis laxa and polymorphic corneal stromal opacities demonstrated the classic GSN:c.654G>A,p.Asp214Asn variant in single affected individual from one family, and a previously undocumented GSN:c.1477T>C variant in three affected first‐degree relatives from a separate family. Immunohistochemical studies on corneal tissue from a proband with the c.1477T>C variant identified gelsolin protein within histologically defined corneal amyloid deposits. This study reports a novel association between the predicted pathogenic GSN:c.1477T>C variant and amyloidosis of the Finnish type, and is the first to provide functional evidence of a pathological GSN variant at a locus distant to the critical G2 calcium‐binding region, resulting in the phenotype of amyloidosis of the Finnish type.
Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap for Biomedical Informatics Research in 2021

Study Design: Narrative review. Objectives: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care. Methods: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice. Results: A variety of data assets are available for spine research, ranging from commonly used datasets, such as administrative billing data, to emerging resources, such as mobile health and biobanks. Both regression and machine learning techniques are valuable for analyzing these assets, and researchers should recognize the particular strengths and weaknesses of each approach. Few studies have focused on the implementation of HIT, and a variety of methods exist to help translate analytic tools into clinically useful interventions. Finally, a number of HIT-related challenges must be recognized and addressed, including stakeholder acceptance, regulatory oversight, and ethical considerations. Conclusions: Biomedical informatics has the potential to support the development of new HIT that can improve spine surgery quality and outcomes. By understanding the development life-cycle that includes identifying an appropriate data asset, selecting an analytic approach, and leveraging an effective implementation strategy, spine researchers can translate this potential into measurable advances in patient care.
Semiconductor nanowire arrays for optical sensing: a numerical insight on the impact of array periodicity and density

Recent advances in the nanofabrication and modeling of metasurfaces have shown the potential of these systems in providing unprecedented control over light–matter interactions at the nanoscale, enabling immediate and tangible improvement of features and specifications of photonic devices that are becoming always more crucial in enhancing everyday life quality. In this work, we theoretically demonstrate that metasurfaces made of periodic and non-periodic deterministic assemblies of vertically aligned semiconductor nanowires can be engineered to display a tailored effective optical response and provide a suitable route to realize advanced systems with controlled photonic properties particularly interesting for sensing applications. The metasurfaces investigated in this paper correspond to nanowire arrays that can be experimentally realized exploiting nanolithography and bottom-up nanowire growth methods: the combination of these techniques allow to finely control the position and the physical properties of each individual nanowire in complex arrays. By resorting to numerical simulations, we address the near- and far-field behavior of a nanowire ensemble and we show that the controlled design and arrangement of the nanowires on the substrate may introduce unprecedented oscillations of light reflectance, yielding a metasurface which displays an electromagnetic behavior with great potential for sensing. Finite-difference time-domain numerical simulations are carried out to tailor the nanostructure parameters and systematically engineer the optical response in the VIS-NIR spectral range. By exploiting our computational-methods we set-up a complete procedure to design and test metasurfaces able to behave as functional sensors. These results are especially encouraging in the perspective of developing arrays of epitaxially grown semiconductor nanowires, where the suggested design can be easily implemented during the nanostructure growth, opening the way to fully engineered nanowire-based optical metamaterials.
Trade-off between number and length of remote videos for rapid assessments of reef fish assemblages.

Remote underwater videos are widely employed to assess the structure and composition of reef fish assemblages but the sampling effort employed on each survey differs considerably, indicating that both the number of assessments and video length could be optimized. We searched for this optimal sampling effort in remote video samples to conduct rapid assessments of community composition and discussed the relation between number of replicates and video length, and how it impacts the method's efficiency to characterize species assemblages. We used remote video recordings from tropical reefs in Northeastern Brazil to investigate how fish species richness and composition builds across time and number of assays. Videos as short as 5 min successfully recorded richness, requiring about 5 repetitions to record most species that compose 80% of the total biomass. Recording species composition required even less time in these reefs, setting a minimum of 3 min with the same 5 videos. By comparing the detected richness per analyzed time unit, we found several shorter videos recorded more species than a few longer videos, indicating that increasing the sampling coverage in the reef area might be better than just extending video length for rapid assessments. This article is protected by copyright. All rights reserved.
Visual outcome after rhegmatogenous retinal detachment repair surgery in patients with multifocal vs monofocal intraocular lenses

One year after successful anatomical repair of pseudophakic rhegmatogenous retinal detachment, functional outcome of multifocal eyes is restored, and corrected distance visual acuity is comparable with monofocal eyes. Purpose: To evaluate functional outcome after retinal detachment (RD) repair surgery in eyes with a multifocal intraocular lens (mIOL). Setting: Ludwig-Maximilians-University, Munich, Germany. Design: Single-center case control study. Methods: 52 pseudophakic eyes with successful anatomical outcome after surgical RD repair were included. Retrospectively, 21 mIOL eyes were compared with a matched group of 21 monofocal eyes over 6 weeks. Prospectively, corrected distance visual acuity (CDVA) was evaluated over 12 months in these eyes. Furthermore, uncorrected distance, intermediate, and near visual acuity (UDVA, UIVA, and UNVA, respectively), defocus curves, and patient-reported outcomes were evaluated at 1 year in 24 mIOL eyes. Results: 52 eyes of 48 patients comprised the study. The mean CDVA (logMAR) improved significantly from 1.35 ± 1.38 to 0.29 ± 0.37 at 6 weeks and remained stable at 12 months postoperatively in monofocal eyes (P = .001) and from 1.16 ± 1.2 to 0.37 ± 0.29 (6 weeks) and 0.20 ± 0.36 (12 months) in mIOL eyes (P = .001). Univariate factorial analysis of variance showed no statistically significant differences in CDVA at 6 weeks or 12 months postoperatively for IOL type or for preoperative macular status (P > .05). In the prospective cohort of 24 mIOL eyes, a mean CDVA of 0.13 ± 0.33 logMAR, UDVA of 0.21 ± 0.34 logMAR, UIVA of 0.17 ± 0.28 logMAR, and UNVA of 0.23 ± 0.32 logMAR was achieved. Macular status did not affect final outcome significantly (P > .05). Most patients stated they usually did not need spectacles; no patient wanted mIOL replacement. Conclusions: 1 year after successful anatomical repair after 23-gauge vitrectomy with gas tamponade, functionality of mIOL was restored, and CDVA was comparable with that of patients with monofocal IOL.
Long-term comparison between index selection and optimal independent culling in plant breeding programs with genomic prediction

In the context of genomic selection, we evaluated and compared breeding programs using either index selection or independent culling for recurrent selection of parents. We simulated a clonally propagated crop breeding program for 20 cycles using either independent culling or an economic index with two unfavourably correlated traits under selection. Cycle time from crossing to selection of parents was kept the same for both strategies. Both methods led to increasingly unfavourable genetic correlations between traits and, compared to independent culling, index selection led to larger changes in the genetic correlation between the two traits. When linkage disequilibrium was not considered, the two methods had similar losses of genetic diversity. Two independent culling approaches were evaluated, one using optimal culling levels and one using the same selection intensity for both traits. Optimal culling levels outperformed the same selection intensity even when traits had the same economic importance. Therefore, accurately estimating optimal culling levels is essential for maximizing gains when independent culling is performed. Once optimal culling levels are achieved, independent culling and index selection lead to comparable genetic gains.
Endocrine disrupting chemicals: strategies to protect present and future generations

ABSTRACT Introduction: Endocrine-disrupting chemicals (EDCs) are chemicals that alter the actions of hormones. In the 21st Century, numerous expert groups of clinicians, scientists, and environmental activists have called for action to protect present and future generations from the harm induced by EDC exposures. These demands for regulatory responses come because of the strong weight of the evidence from epidemiology, wildlife, and controlled laboratory studies. Areas covered: In this review, we examine the conclusions drawn by experts from different scientific and medical disciplines. We also address several areas where recent findings or work has changed the landscape of EDC work including new approaches to identify and evaluate the evidence for EDCs using a key characteristics approach, the need to expand our understanding of vulnerable periods of development, and the increasing concern that traditional methods used to evaluate toxicity of environmental chemicals are insufficient for EDCs and how collaborative science could help to address these gaps. Expert opinion: The science is clear: there is more than enough evidence to demonstrate that EDCs affect the health of humans and wildlife. Waiting to act is a decision that puts the health of current and future generations at risk.
Feature-weighted ordinal classification for predicting drug response in multiple myeloma

MOTIVATION Ordinal classification problems arise in a variety of real-world applications, in which samples need to be classified into categories with a natural ordering. An example of classifying high-dimensional ordinal data is to use gene expressions to predict the ordinal drug response, which has been increasingly studied in pharmacogenetics. Classical ordinal classification methods are typically not able to tackle high-dimensional data and standard high-dimensional classification methods discard the ordering information among the classes. Existing work of high-dimensional ordinal classification approaches usually assume a linear ordinality among the classes. We argue that manually-labeled ordinal classes may not be linearly arranged in the data space, especially in high-dimensional complex problems. RESULTS We propose a new approach that can project high-dimensional data into a lower discriminating subspace, where the innate ordinal structure of the classes is uncovered. The proposed method weights the features based on their rank correlations with the class labels and incorporates the weights into the framework of linear discriminant analysis. We apply the method to predict the response to two types of drugs for patients with Multiple Myeloma, respectively. A comparative analysis with both ordinal and nominal existing methods demonstrates that the proposed method can achieve a competitive predictive performance while honoring the intrinsic ordinal structure of the classes. We provide interpretations on the genes that are selected by the proposed approach to understand their drug-specific response mechanisms. AVAILABILITY AND IMPLEMENTATION The data underlying this article are available in the Gene Expression Omnibus Database at https://www.ncbi. nlm.nih. gov/geo/ and can be accessed with accession number GSE9782 and GSE68871. The source code for FWOC can be accessed at https://github.com/pisuduo/Feature-Weighted-Ordinal-Classification-FWOC.
Patient Experiences of Postinfectious Olfactory Dysfunction

Introduction: To highlight the importance of the need for new treatment modalities, this study aimed to characterise the experience of patients with postinfectious olfactory dysfunction (PIOD) in terms of the treatment they received. Methods: An online survey was hosted by the Norwich Clinical Trials Unit on the secure REDCap server. Members of the charity Fifth Sense (the UK charity that represents and supports people affected by smell and taste disorders) were invited to participate. Results: There were 149 respondents, of whom 127 had identified themselves as having (or had) PIOD. The age range of respondents to the survey was 28–85 years, with a mean of 58 ± 12 years, with the duration of their disorder <5 years in 63% of cases. Respondents reported experiencing variable treatment with oral and/or intranasal steroids given typically (28%), often with no benefit, but with 50% receiving no treatment whatsoever; only 3% reported undertaking olfactory training. Over two-thirds of patients experience parosmia and, up to 5 years from the onset of the problem, were still actively seeking a solution. Conclusion: There appears to be a need to encourage greater use of guidelines for olfactory disorders amongst medical practitioners and also to develop more effective treatments for patients with PIOD, where there is clearly an unmet need.
Ti-9Mn β-type alloy exhibits better osteogenicity than Ti-15Mn alloy in vitro.

Ti-9Mn and Ti-15Mn were prepared using an arc furnace in order to understand their osteogenic behavior as a biomedical implant. Ti-9Mn surface showed a significantly lower contact angle value (41%) as compared with the Ti-15Mn surface. The higher Ra and lower hydrophilicity values of Ti-9Mn alloy as compared with Ti-15Mn alloy indicates that Ti-9Mn can have better osteoconductive properties. ALP activity of the osteoblast cells on the Ti-9Mn alloy was elevated by 45% on day 7 and 20% on day 14 as compared to the Ti-15Mn alloy that reflects faster induction of osteoblast phenotypes of MG63 cells. Filopodia and lamellipodia structures were spread more on the Ti-9Mn specimens as compared to the Ti-15Mn alloy. Cell viability on Ti-9Mn alloy increased by 25% and 32%, respectively after 7 and 14 days of culture as compared to Ti-15Mn alloy. On day 14 of culture, the relative expression of RUNX2, COL1, and OC on Ti-9Mn alloy were elevated by 35%, 21%, and 30% respectively than the Ti-15Mn alloy. Ti-9Mn alloy also exhibited an inductive effect on the cell proliferation, and upregulation in the expression of ALP, RUNX2, and OC that is, the genes related to osteoblastic differentiation. Hence, the present in vitro results suggest that Ti-9Mn can be a preferred implant material than the Ti-15Mn alloy.
Expression of Concern: The Communication Factor EDF and the Toxin–Antitoxin Module mazEF Determine the Mode of Action of Antibiotics

1. The same WT results appear to be reported in Figure 2A-B and Figure S4A-B. The figure legends report the same treatment conditions for Figure 2A and S4A, and the authors noted that these panels were intended to report distinct technical replicates of the same experiment. Image data provided to the journal indicated that for Figure 2A, either mutant data were not obtained on the same blot as the WT data shown, or the wrong data were shown in the mutant panel. Nevertheless, the data provided support the results shown in Figures 2A and S4A.
Pupil size in the evaluation of static and dynamic stimuli in peripheral vision

It has been evidenced that in attention-window tasks, the participants fixate on the center of a screen while inspecting two stimuli that appear at the same time in parafoveal vision. Such tasks have successfully been used to estimate a person’s breadth of attention under various conditions. While behavioral investigations of visual attention have often made use of response accuracy, recent research has shown that the pupil size can also be used to track shifts of attention to the periphery. The main finding of previous studies is that the harder the evaluation of the stimuli becomes, e.g., because they appear farther away from the central fixation point, the stronger the pupils dilate. In this paper, we present experimental data suggesting that in an attention-window task, the pupil size can also be used to assess whether the participants attend to static, non-moving, or dynamic, moving stimuli. That is, regression models containing information on presentation mode (static vs. dynamic) and the visual angle between spatially separated stimuli better predict accuracy of perception and pupil dilation than model without these sources of information. This finding is useful for researchers who aim at understanding the human attentional system, including potential differences in its sensitivity to static and dynamic objects.
Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.
When loneliness dimensions drift apart: Emotional, social and physical loneliness during the COVID‐19 lockdown and its associations with age, personality, stress and well‐being

Previous research differentiated between emotional loneliness (perceived lack of emotional connection with others) and social loneliness (perceived lack of a broader social network). We argue that physical loneliness (perceived lack of physical contact) constitutes a third dimension of loneliness that is particularly relevant in times of physical distancing. We conducted a longitudinal experience sampling study (N = 578) during the first 8 weeks of the COVID‐19 lockdown in Germany to test this claim. The results indicate that loneliness has a three‐dimensional structure encompassing emotional, social and physical loneliness. Each loneliness dimension explained a unique variance in perceived stress and psychological well‐being. However, the three loneliness dimensions differed in their prevalence during the contact restrictions and their associations with age and personality. Physical loneliness was higher during the contact restrictions whereas emotional and social loneliness remained on a normal level. Age was positively associated with social loneliness but negatively associated with physical loneliness. Extraversion was negatively associated with emotional and social loneliness but positively associated with physical loneliness. These findings expand loneliness models, enhance loneliness assessment and improve the prediction of vulnerability to loneliness.
Patient, hospital and country-level risk factors of all-cause mortality among patients with chronic heart failure: Prospective international cohort study

Background Although many studies have described patient-level risk factors for outcomes in heart failure (HF), health care structural determinants remain largely unexplored. This research reports patient-, hospital- and country-level characteristics associated with 1-year all-cause mortality among patients with chronic HF, and investigates geographic and hospital variation in mortality. Methods and findings We included 9,277 patients with chronic HF enrolled between May 2011 and November 2017 in the prospective cohort study European Society of Cardiology Heart Failure Long Term registry across 142 hospitals, located in 22 countries. Mean age of the selected outpatients was 65 years (sd 13.2) and 28% were female. The all-cause 1-year mortality rate per 100 person-years was 7.1 (95% confidence interval (CI) 6.6–7.7), and varied between countries (median 6.8, IQR 5.6–11.2) and hospitals (median 7.8, IQR 5.2–12.4). Mortality was associated with age (incidence rate ratio 1.03, 95% CI 1.02–1.04), diabetes mellitus (1.37, 1.15–1.63), peripheral artery disease (1.56, 1.27–1.92), New York Heart Association class III/IV (1.91, 1.60–2.30), treatment with angiotensin-converting enzyme inhibitor and angiotensin receptor antagonists (0.71, 0.57–0.87) and HF clinic (0.64, 0.46–0.89). No other hospital-level characteristics, and no country-level healthcare characteristics were associated with 1-year mortality, with case-mix standardised variance between countries being very low (1.83e-06) and higher for hospitals (0.372). Conclusions All-cause mortality at 1 year among outpatients with chronic HF varies between countries and hospitals, and is associated with patient characteristics and the availability of hospital HF clinics. After full adjustment for clinical, hospital and country variables, between-country variance was negligible while between-hospital variance was evident.