Miracle-dz/UniFAR-FTUs huggingface dataset:
NR2F1 regulates a Schwann cell precursor‐vs‐melanocyte cell fate switch in a mouse model of Waardenburg syndrome type IV

Waardenburg syndrome type 4 (WS4) combines abnormal development of neural crest cell (NCC)‐derived melanocytes (causing depigmentation and inner ear dysfunction) and enteric nervous system (causing aganglionic megacolon). The full spectrum of WS4 phenotype is present in Spot mice, in which an insertional mutation close to a silencer element leads to NCC‐specific upregulation of the transcription factor‐coding gene Nr2f1. These mice were previously found to develop aganglionic megacolon because of NR2F1‐induced premature differentiation of enteric neural progenitors into enteric glia. Intriguingly, this prior work also showed that inner ear dysfunction in Spot mutants specifically affects balance but not hearing, consistent with the absence of melanocytes in the vestibule only. Here, we report an analysis of the effect of Nr2f1 upregulation on the development of both inner ear and skin melanocytes, also taking in consideration their origin relative to the dorsolateral and ventral NCC migration pathways. In the trunk, we found that NR2F1 overabundance in Spot NCCs forces dorso‐laterally migrating melanoblasts to abnormally adopt a Schwann cell precursor (SCP) fate and conversely prevents ventrally migrating SCPs to normally adopt a melanoblast fate. In the head, Nr2f1 upregulation appears not to be uniform, which might explain why SCP‐derived melanocytes do colonize the cochlea while non‐SCP‐derived melanocytes cannot reach the vestibule. Collectively, these data point to a key role for NR2F1 in the control of SCP‐vs‐melanocyte fate choice and unveil a new pathogenic mechanism for WS4. Moreover, our data argue against the proposed existence of a transit‐amplifying compartment of melanocyte precursors in hair follicles.
Guidance Through Surrogate: Toward a Generic Diagnostic Attack

Adversarial training (AT) is an effective approach to making deep neural networks robust against adversarial attacks. Recently, different AT defenses are proposed that not only maintain a high clean accuracy but also show significant robustness against popular and well-studied adversarial attacks, such as projected gradient descent (PGD). High adversarial robustness can also arise if an attack fails to find adversarial gradient directions, a phenomenon known as “gradient masking. ” In this work, we analyze the effect of label smoothing on AT as one of the potential causes of gradient masking. We then develop a guided mechanism to avoid local minima during attack optimization, leading to a novel attack dubbed guided projected gradient attack (G-PGA). Our attack approach is based on a “match and deceive” loss that finds optimal adversarial directions through guidance from a surrogate model. Our modified attack does not require random restarts a large number of attack iterations or a search for optimal step size. Furthermore, our proposed G-PGA is generic, thus it can be combined with an ensemble attack strategy as we demonstrate in the case of auto-attack, leading to efficiency and convergence speed improvements. More than an effective attack, G-PGA can be used as a diagnostic tool to reveal elusive robustness due to gradient masking in adversarial defenses.
Blood biomarkers for canine cancer, from human to veterinary oncology

Abstract In recent decades, interest in circulating tumour biomarkers is increasing both in human and veterinary oncology. An ideal tumour biomarker would allow early diagnosis of neoplasia, identify it specifically, accurately, establish a prognosis and predict its behaviour, especially regarding different therapeutic solutions. It would also allow to monitor its evolution over time and all this in a non‐invasive and inexpensive way. Actually, no biomarkers meeting all of these criteria have been identified in veterinary medicine, particularly due to a lack of specificity of the main protein tumour biomarkers studied to date. However, great hope is currently placed in biomarkers grouped under the name of liquid biopsy, which could prove to be effective tools for common clinical use in the near future. This review gives an update on blood cancer biomarkers studied in dogs, such as ions, proteins, nucleic acids and also circulating cells, of which some might become more prominent in the coming years to help improve the management of animal care.
Contrast Media Volume to Creatinine Clearance Ratio in Predicting Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

The studies investigated the predictive value of the contrast media volume to creatinine clearance ratio (V/CrCl) for contrast-induced nephropathy (CIN) after a percutaneous coronary intervention (PCI) showed conflicting results and different cut-off values. The objective is to evaluate V/CrCl in the prediction of CIN after PCI. PubMed, Embase, and the Cochrane library were searched for eligible studies published from inception to November 2020. The optimal cut-off points of V/CrCl for predicting CIN were examined using odds ratios (ORs) and 95% confidence intervals (CIs). The random-effect model was used for analyses. Six studies (8 datasets, 16 899 patients) were included. V/CrCl was associated with CIN (OR = 2.67, 95% CI: 1.88–3.78, P < .001; I2 = 79.3%, Pheterogeneity < .001). V/CrCl was associated with CIN in Asians (OR = 2.13, 95% CI: 1.52–2.98, P = .022; I2 = 68.8%, Pheterogeneity < .001) and Europeans (OR = 3.87, 95% CI: 1.77–8.45, P < .001; I2 = 85.1%, Pheterogeneity = .001). The association between V/CrCl and CIN was observed in the prospective cohort studies (OR = 2.16, 95% CI: 1.42–3.29, P = .009; I2 = 78.9%, Pheterogeneity < .001) and retrospective cohort studies (OR = 3.31, 95% CI: 1.82–6.02, P < .001; I2 = 80.6%, Pheterogeneity < .001). The sensitivity analysis showed the results were robust. V/CrCl is independently associated with an increased risk of CIN. V/CrCl could be considered a reliable predictor for the development of CIN in patients undergoing PCI.
Understanding ocular comfort differences between 0.7% olopatadine and 0.3% pheniramine maleate/0.025% naphazoline hydrochloride eye drops

ABSTRACT Clinical Relevance This study found 0.7% olopatadine (Pataday Once Daily Relief Extra Strength) eye drops to provide better initial comfort than 0.3% pheniramine maleate/0.025% naphazoline hydrochloride (VISINE® Allergy Eye Relief Multi-Action Antihistamine and Redness Reliever) eye drops suggesting that patients may comply better with the Pataday than VISINE. Background To compare the ocular comfort at instillation of Pataday and VISINE allergy eye drops. Methods Minimally symptomatic participants were recruited based upon Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores (≤3 units); they also had minimal between-eye inter-ocular comfort differences as judged by visual analogue scale scores (VAS; ≤7 units). Baseline comfort was evaluated by eye with a VAS. One drop of Pataday or VISINE was then applied to the right eye with the alternative drop being applied to the left eye. The same VAS evaluated comfort by eye at drop instillation, and then at 30 seconds, 1 minute, and 2 minutes post-instillation. Drop experience was also evaluated with Likert questions. LogMAR visual acuities and bulbar conjunctival redness were evaluated pre- and post-drop instillation. Results A total of 159 participants were recruited (mean ± SD age = 26.2 ± 7.5). The VAS found that eyes treated with Pataday were significantly more comfortable at instillation than eyes treated with VISINE. Likert questions indicated that participants significantly preferred Pataday drops compared to the VISINE drops at instillation with regards to overall eye comfort, eye stinging, eye burning, and foreign body sensation. There were no between drop differences in visual acuity, though eyes treated with VISINE were less red than eyes treated with Pataday. Conclusions Topically applied Pataday drops were more comfortable than VISINE drops.
Xpert MTB/RIF Ultra versus Xpert MTB/RIF for diagnosis of tuberculous pleural effusion: A systematic review and comparative meta-analysis

Objective We compared diagnostic accuracy of pleural fluid Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) assays for diagnosing tuberculous pleural effusion (TPE), through systematic review and comparative meta-analysis. Methods We searched PubMed and Embase databases for publications reporting diagnostic accuracy of Xpert or Ultra for TPE. We used bivariate random-effects modeling to summarize diagnostic accuracy information from individual studies using either mycobacterial culture or composite criteria as reference standard. We performed meta-regression through hierarchical summary receiver operating characteristic (HSROC) modeling to evaluate comparative performance of the two tests from studies reporting diagnostic accuracy of both in the same study population. Results We retrieved 1097 publications, and included 74 for review. Summary estimates for sensitivity and specificity for Xpert were 0.52 (95% CI 0.43–0.60, I2 82.1%) and 0.99 (95% CI 0.97–0.99, I2 85.1%), respectively, using culture-based reference standard; and 0.21 (95% CI 0.17–0.26, I2 81.5%) and 1.00 (95% CI 0.99–1.00, I2 37.6%), respectively, using composite reference standard. Summary estimates for sensitivity and specificity for Ultra were 0.68 (95% CI 0.55–0.79, I2 80.0%) and 0.97 (95% CI 0.97–0.99, I2 92.1%), respectively, using culture-based reference standard; and 0.47 (95% CI 0.40–0.55, I2 64.1%) and 0.98 (95% CI 0.95–0.99, I2 54.8%), respectively, using composite reference standard. HSROC meta-regression yielded relative diagnostic odds ratio of 1.28 (95% CI 0.65–2.50) and 1.80 (95% CI 0.41–7.84) respectively in favor of Ultra, using culture and composite criteria as reference standard. Conclusion Ultra provides superior diagnostic accuracy over Xpert for diagnosing TPE, mainly because of its higher sensitivity.
Surgical treatment of spinal tuberculosis by anterior approach

OBJETIVO: Avaliar a correcao da deformidade cifotica, a estabilidade e a fusao promovida por implantes de titânio (Synex - Ventrofix de Synthes) na tuberculose da coluna vertebral. METODOS: Entre janeiro de 2010 e agosto de 2012, oito pacientes com diagnostico de tuberculose de coluna foram submetidos a intervencao cirurgica por acesso anterior, com acompanhamento de 18 meses. O procedimento consistiu em desbridamento amplo do corpo afetado, seguido por instrumentacao com implantes de titânio (Synex - Ventrofix de Synthes) e autoenxerto de costela. A indicacao cirurgica foi deficit neurologico e cifose do segmento. Previamente, os pacientes receberam tratamento para tuberculose por tres semanas. Os estudos por imagem antes e depois da cirurgia, como radiografia frontal e lateral, avaliaram a cifose. A fusao foi avaliada por tomografia simples pos-operatoria. A ressonância magnetica foi realizada no pre-operatorio. Alem dos exames de imagem, foram feitos os seguintes testes: hemograma completo, velocidade de sedimentacao globular (VSG), proteina C reativa (PCR) e exames microbiologicos de baciloscopia na urina e no catarro, cultura da expectoracao ou de urina. RESULTADOS: Oito pacientes foram operados por acesso anterior, sendo cinco homens com media de idade de 37,2 anos e tres mulheres media de idade de 56,3 anos. Todos os pacientes tinham deficit neurologico. Seis deles com lesoes incompletas tiveram melhora de algum grau neurologico. Dois paraplegicos nao recuperaram a funcao neurologica. A media da cifose pre-operatoria foi 14,38 graus e pos-operatoria, 6,8 graus. Nao houve perda significativa de correcao nem recorrencia da doenca. CONCLUSAO: O acesso anterior com instrumentacao e um metodo eficaz para tratar tuberculose vertebral, ao mesmo tempo em que evita a progressao da cifose ou a corrige.
Women Supporting Women: The Use of Art With Anxious/Depressed, Urban, Impoverished, Ethnically Diverse Women

BACKGROUND: Depression and anxiety disproportionately affect urban, ethnically diverse, impoverished women—particularly when access to culturally sensitive care is limited. Using community-based participatory research in the context of long-term, academic/community partnerships, women supporting women, a supportive/educative group intervention piloting an art project, was offered. AIMS: The purpose of this study was to examine the impact of an artist book-making project on diverse women struggling with anxiety and depression. METHODS: A descriptive qualitative approach was used within this mixed-method study. Thirty-one participants, aged 18 to 86 years, were asked: (1) How does this book tell your story? (2) How did creating this book impact you personally? (3) How would you describe the experience of creating your book alongside women from our group? (4) How did this project help you with anxiety and depression? (5) What did you do with the book that you made? The framework method for analysis of qualitative data in multidisciplinary health research was used. RESULTS: Four themes, with corresponding subthemes, were identified: (1) personal story entailed expression of past, present, and future journey and mediums to depict the story; (2) method of coping included relaxation, diversion, and self-care; (3) creative impact encompassed affirmation of identity, empowerment, healing, pride in work, and a vehicle to connect; and (4) creating in community incorporated inspiration, sharing, and solidarity. CONCLUSIONS: These results suggest that an art project provides a culturally sensitive, clinically relevant, and cost-effective self-care intervention for vulnerable women struggling with anxiety and depression.
Transmembranous and enchondral osteogenesis in transplants of rat limb buds cultivated in serum‐ and protein‐free culture medium

Cartilage differentiates in rat limb buds cultivated in a chemically defined protein‐free medium in the same manner as in the richer serum‐supplemented medium. We aimed to investigate the remaining differentiation potential of pre‐cultivated limb buds by subsequent transplantation in vivo. Rat front (FLBs) and hind‐limb buds (HLBs) were isolated from Fischer rat dams at the 14th gestation day (GD 14) and cultivated at the air‐liquid interface in Eagle's Minimum Essential Medium (MEM) alone; with 5 μM of 5‐azacytidine (5azaC) or with rat serum (1:1). Overall growth was measured seven times during the culture by an ocular micrometre. After 14 days, explants were transplanted under the kidney capsule of adult males. Growth of limb buds was significantly lower in all limb buds cultivated in MEM than in those cultivated with serum. In MEM with 5azaC, growth of LBs was significantly lower only on day 3 of culture. Afterwards, it was higher throughout the culture period, although a statistically significant difference was assessed only for HLBs. In transplants, mixed structures developed with the differentiated transmembranous bone, cartilage with enchondral ossification, bone‐marrow, sebaceous gland, and hair that have never been found in vitro. Nerves differentiated only in transplants precultivated in the serum‐supplemented medium. We conclude that pre‐cultivation of LBs in a chemically defined protein‐free medium does not restrict osteogenesis and formation of epidermal appendages but is restrictive for neural tissue. These results are important for understanding limb development and regenerative medicine strategies.
Social class and the risk of dementia: A systematic review and meta-analysis of the prospective longitudinal studies

Background: The association between belonging to a disadvantaged socio-economic status or social class and health outcomes has been consistently documented during recent decades. However, a meta-analysis quantifying the association between belonging to a lower social class and the risk of dementia has yet to be performed. In the present work, we sought to summarise the results of prospective, longitudinal studies on this topic. Methods: We conducted a systematic review and meta-analysis of prospective, longitudinal studies measuring the association between indicators of social class and the risk of all-cause/Alzheimer’s dementia. The search was conducted in four databases (Medline, Embase, Web of Science and PsychInfo). Inclusion criteria for this systematic review and meta-analysis were: (a) longitudinal prospective study, (b) aged ⩾60 years at baseline, (c) issued from the general population, (d) no dementia at baseline and (e) mention of social class as exposure. Exclusion criteria were: (a) study of rare dementia types (e.g. frontotemporal dementia), (b) abstract-only papers and (c) articles without full text available. The Newcastle–Ottawa scale was used to assess the risk of bias in individual studies. We calculated the overall pooled relative risk of dementia for different social class indicators, both crude and adjusted for sex, age and the year of the cohort start. Results: Out of 4548 screened abstracts, 15 were included in the final analysis (76,561 participants, mean follow-up 6.7 years (2.4–25 years), mean age at baseline 75.1 years (70.6–82.1 years), mean percentage of women 58%). Social class was operationalised as levels of education, occupational class, income level, neighbourhood disadvantage and wealth. Education (relative risk (RR)=2.48; confidence interval (CI) 1.71–3.59) and occupational class (RR=2.09; CI 1.18–3.69) but not income (RR=1.28; CI 0.81–2.04) were significantly associated with the risk of dementia in the adjusted model. Some of the limitations of this study are the inclusion of studies predominantly conducted in high-income countries and the exclusion of social mobility in our analysis. Conclusions: We conclude that there is a significant association between belonging to a social class and the risk of dementia, with education and occupation being the most relevant indicators of social class regarding this risk. Studying the relationship between belonging to a disadvantaged social class and dementia risk might be a fruitful path to diminishing the incidence of dementia over time. However, a narrow operationalisation of social class that only includes education, occupation and income may reduce the potential for such studies to inform social policies.
Monitoring the transition to open access through its mode of implementation: A principal component analysis of two surveys

Open access (OA) is transforming scholarly communication. Various modes of OA implementation have emerged, which reflect the complexity surrounding OA development. This study aimed to examine this development from the perspective of how OA is implemented. The sample comprised 2,368 randomly selected articles published in 2013 and 2,999 published in 2018 indexed in the Web of Science. We also conducted searches in Google and Google Scholar in 2015 for articles published in 2013 and in 2020 for articles published in 2018. Selected articles were categorized as either an “OA article,” “electronic subscription journal article,” or “not available online. ” OA articles were classified into 10 implementation modes: Gold, Hybrid, Delayed, Bronze, Subject Repositories, Institutional Repositories, Personal/Institutional Websites, Academic Social Networks (ASNs), Others, and Web Aggregator. Overall, 56.5% of all sampled articles in 2013 were available for free on at least one website in 2015, while 61.7% of all sampled articles in 2018 were freely available on at least one website in 2020. Concerning implementation mode, ASNs had the highest frequency (44.4% in 2015 and 56.0% in 2020), followed by Subject Repositories (35.0% in 2015 and 39.6% in 2020) and Gold (24.1% in 2015 and 37.4% in 2020). To obtain an overview of OA implementation, we conducted principal component analysis with OA implementation mode as the variable for both 2015 and 2020. The first principal component was the axis indicating the number of overlapping OA implementations for each article in 2015 and 2020, while the second principal component was the axis orthogonal to the first, which was difficult to interpret. We identified three groups of OA implementation in each plot of the principal component scores for articles in 2015 and 2020; however, the OA implementation of each group differed in 2015 and 2020. This diversity reflects the respective positions of various stakeholders regarding OA.
Examination performance of dentistry students during the COVID-19 pandemic

Abstract Objective The global COVID-19 pandemic has led to an increase in remote teaching and online assessment in higher education. The examination performance of undergraduate students of dentistry was evaluated to assess any possible association between the altered learning environment and learners’ performance. Materials and methods Using administrative data from the University of Helsinki, the examination performance during the years 2018 and 2019 was compared with that of 2020. Results In 16 out of 22 courses (73%) taught remotely during the pandemic, a statistically significant difference (p < .05) between the awarded grades was observed, as compared to the two previous years. Annual variation in examination grades was common even before the onset of remote teaching, but more so after it. The grade variation during the pandemic was nearly as prevalent towards falling grades (26%) as towards rising grades (36%), implying a multifactorial cause possibly unrelated to remote teaching. Conclusions Our results imply that online teaching did not systematically improve or worsen the examination performance of undergraduate students of dentistry. Our findings have important policy implications for educational practices in the future. The observed annual grade variation might reflect the effectiveness of remote teaching, changes in students’ performance, or non-systematic grading.
An improved pairing-free certificateless aggregate signature scheme for healthcare wireless medical sensor networks

In healthcare wireless medical sensor networks (HWMSNs), the medical sensor nodes are employed to collect medical data which is transmitted to doctors for diagnosis and treatment. In HWMSNs, medical data is vulnerable to various attacks through public channels. In addition, leakage of patients’ information happens frequently. Hence, secure communication and privacy preservation are major concerns in HWMSNs. To solve the above issues, Zhan et al. put forward a pairing-free certificateless aggregate signature (PF-CLAS) scheme. However, according to our cryptanalysis, the malicious medical sensor node (MSNi) can generate the forged signature by replacing the public key in the PF-CLAS scheme. Hence, to address this security flaw, we design the improved PF-CLAS scheme that can achieve unforgeability, anonymity, and traceability. Since we have changed the construction of the partial private key, the improved PF-CLAS scheme can resist Type I and Type II attacks under the Elliptic Curve Discrete Logarithm assumption. In terms of the performance evaluation, the proposed scheme outperforms related CLAS schemes, which is more suitable for HWMSNs environments.