Miracle-dz/UniFAR-FTUs huggingface dataset:
Reproduction study using public data of: Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs

We have attempted to reproduce the results in Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs, published in JAMA 2016; 316(22), using publicly available data sets. We re-implemented the main method in the original study since the source code is not available. The original study used non-public fundus images from EyePACS and three hospitals in India for training. We used a different EyePACS data set from Kaggle. The original study used the benchmark data set Messidor-2 to evaluate the algorithm’s performance. We used another distribution of the Messidor-2 data set, since the original data set is no longer available. In the original study, ophthalmologists re-graded all images for diabetic retinopathy, macular edema, and image gradability. We have one diabetic retinopathy grade per image for our data sets, and we assessed image gradability ourselves. We were not able to reproduce the original study’s results with publicly available data. Our algorithm’s area under the receiver operating characteristic curve (AUC) of 0.951 (95% CI, 0.947-0.956) on the Kaggle EyePACS test set and 0.853 (95% CI, 0.835-0.871) on Messidor-2 did not come close to the reported AUC of 0.99 on both test sets in the original study. This may be caused by the use of a single grade per image, or different data. This study shows the challenges of reproducing deep learning method results, and the need for more replication and reproduction studies to validate deep learning methods, especially for medical image analysis. Our source code and instructions are available at: https://github.com/mikevoets/jama16-retina-replication.
A statistical state dynamics approach to wall turbulence

This paper reviews results obtained using statistical state dynamics (SSD) that demonstrate the benefits of adopting this perspective for understanding turbulence in wall-bounded shear flows. The SSD approach used in this work employs a second-order closure that retains only the interaction between the streamwise mean flow and the streamwise mean perturbation covariance. This closure restricts nonlinearity in the SSD to that explicitly retained in the streamwise constant mean flow together with nonlinear interactions between the mean flow and the perturbation covariance. This dynamical restriction, in which explicit perturbation–perturbation nonlinearity is removed from the perturbation equation, results in a simplified dynamics referred to as the restricted nonlinear (RNL) dynamics. RNL systems, in which a finite ensemble of realizations of the perturbation equation share the same mean flow, provide tractable approximations to the SSD, which is equivalent to an infinite ensemble RNL system. This infinite ensemble system, referred to as the stochastic structural stability theory system, introduces new analysis tools for studying turbulence. RNL systems provide computationally efficient means to approximate the SSD and produce self-sustaining turbulence exhibiting qualitative features similar to those observed in direct numerical simulations despite greatly simplified dynamics. The results presented show that RNL turbulence can be supported by as few as a single streamwise varying component interacting with the streamwise constant mean flow and that judicious selection of this truncated support or ‘band-limiting’ can be used to improve quantitative accuracy of RNL turbulence. These results suggest that the SSD approach provides new analytical and computational tools that allow new insights into wall turbulence. This article is part of the themed issue ‘Toward the development of high-fidelity models of wall turbulence at large Reynolds number’.
Expanding the Hygiene Hypothesis: Early Exposure to Infectious Agents Predicts Delayed-Type Hypersensitivity to Candida among Children in Kilimanjaro

Background Multiple lines of evidence suggest that infections in early life prevent the development of pathological immune responses to allergens and autoantigens (the hygiene hypothesis). Early infections may also affect later immune responses to pathogen antigen. Methods To evaluate an association between early infections and immune responses to pathogen antigen, delayed-type hypersensitivity (DTH) to Candida albicans was evaluated among 283 2- to 7-year-old children in Kilimanjaro, Tanzania. A questionnaire and physical examination were used to characterize variables reflecting early exposure to infectious agents (family size, house construction materials, BCG vaccination, hospitalization history). Logistic regression was used to evaluate the association between early exposure to infectious agents and DTH to C. albicans. Results Triceps skinfold thickness (OR: 1.11; 95% CI: 1.01, 1.22) and age (OR: 1.27; 95% CI: 1.04, 1.55) were positively associated with DTH to C. albicans. Adjusted for age and sex, large family size (OR: 2.81; 95% CI: 1.04, 7.61), BCG vaccination scar (OR: 3.10; 95% CI: 1.10, 8.71), and hospitalization during infancy with an infectious disease (OR: 4.67; 95% CI: 1.00, 21.74) were positively associated with DTH to C. albicans. Conclusions Early life infections were positively associated with later DTH to C. albicans. This result supports an expansion of the hygiene hypothesis to explain not only pathological immune responses to allergens, but also appropriate immune responses to pathogens. Immune system development may be responsive to early infections as an adaptive means to tailor reactivity to the local infectious disease ecology.
Toward an integrative molecular approach to wildlife disease

Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host–parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern.
Crystal structure of a SFPQ/PSPC1 heterodimer provides insights into preferential heterodimerization of human DBHS family proteins

Members of the Drosophila behavior human splicing (DBHS) protein family are nuclear proteins implicated in many layers of nuclear functions, including RNA biogenesis as well as DNA repair. Definitive of the DBHS protein family, the conserved DBHS domain provides a dimerization platform that is critical for the structural integrity and function of these proteins. The three human DBHS proteins, splicing factor proline- and glutamine-rich (SFPQ), paraspeckle component 1 (PSPC1), and non-POU domain–containing octamer-binding protein (NONO), form either homo- or heterodimers; however, the relative affinity and mechanistic details of preferential heterodimerization are yet to be deciphered. Here we report the crystal structure of a SFPQ/PSPC1 heterodimer to 2.3-Å resolution and analyzed the subtle structural differences between the SFPQ/PSPC1 heterodimer and the previously characterized SFPQ homodimer. Analytical ultracentrifugation to estimate the dimerization equilibrium of the SFPQ-containing dimers revealed that the SFPQ-containing dimers dissociate at low micromolar concentrations and that the heterodimers have higher affinities than the homodimer. Moreover, we observed that the apparent dissociation constant for the SFPQ/PSPC1 heterodimer was over 6-fold lower than that of the SFPQ/NONO heterodimer. We propose that these differences in dimerization affinity may represent a potential mechanism by which PSPC1 at a lower relative cellular abundance can outcompete NONO to heterodimerize with SFPQ.
Transoral endoscopic total thyroidectomy vestibular approach: A case series and literature review

Conventional open thyroidectomy is often associated with post-operative complications including nerve damage, voice disturbances, paraesthesias, adhesions and prominent scarring. Several endoscopic surgical techniques have been reported as alternatives to conventional thyroidectomy. Natural orifice transluminal endoscopic surgery is a promising approach which leaves no scar, produces few complications and affords faster discharge from care. Several studies have explored its utility in total thyroidectomy in patients with benign or malignant thyroid disease. Herein, we present a case series on the successful application of transoral endoscopic total thyroidectomy vestibular approach (TOETVA) in benign and malignant diseases of the thyroid. We performed TOETVA in 11 patients presenting with benign or malignant thyroid nodules in our hospital, between 1st January 2015 and 30th June 2016. The surgery was completed successfully in all patients with a pre-operative diagnosis of multinodular goitre. The surgery was performed under general anaesthesia and the mean operative time was 130 min. The mean blood loss was 2–3 cc. No incidence of recurrent laryngeal nerve injury, damage to mental nerve, parathyroid damage or peri-incisional adhesion occurred in the study participants. No visible scarring occurred in the patients following surgery. The patients had an uneventful recovery after the surgery and were discharged after 4 days. TOETVA is safe and effective in the surgical management of multinodular goitre and offers a scar-free alternative to conventional surgery.
The association between waterpipe smoking and gastroesophageal reflux disease.

Background Unlike cigarettes, there is little information about the association between other tobacco products and the risk of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma. Methods We used the baseline data from the Pars Cohort Study conducted in southern Iran. In 2012, 9264 local residents between 40 and 75 years old were enrolled, with detailed information about lifestyle, including duration and frequency of tobacco use. GERD was defined based on questions assessing heartburn and regurgitation in the past 12 months, frequency and severity. Associations were calculated by logistic regression models adjusted for age, sex, education, cigarettes and body mass index. Results In the study, 25.4% of the participants had severe GERD (interfering with participants' routines), 25.1% had frequent GERD (at least once a week) and 11.2% had both severe and frequent GERD, all more common among women (p < 0.001); 45.6% of women and 28.3% of men smoked waterpipes. Among people not using medications against reflux symptoms, there was an association between waterpipe smoking and severe [odds ratio (OR) = 1.18; 95% confidence interval (CI):1.04-1.35], frequent (OR = 1.16; 95% CI: 1.02-1.32) and severe and frequent reflux (OR = 1.30; 95% CI: 1.08-1.56). The associations increased with the duration of use, intensity and cumulative waterpipe-years, reaching an OR of 1.44 (95% CI: 1.12-1.86) for severe and frequent reflux in those who had smoked more than 48 waterpipe-years. There was effect modification by sex, and all the associations were only seen among women. Conclusion The increasing trend in the association between cumulative waterpipe use and reflux disease among women is particularly important given the growing waterpipe tobacco epidemic in many populations.
Meiofauna in the Gollum Channels and the Whittard Canyon, Celtic Margin—How Local Environmental Conditions Shape Nematode Structure and Function

The Gollum Channels and Whittard Canyon (NE Atlantic) are two areas that receive high input of organic matter and phytodetritus from euphotic layers, but they are typified by different trophic and hydrodynamic conditions. Sediment biogeochemistry was analysed in conjunction with structure and diversity of the nematode community and differences were tested between study areas, water depths (700 m vs 1000 m), stations, and sediment layers. The Gollum Channels and Whittard Canyon harboured high meiofauna abundances (1054–1426 ind. 10 cm−2) and high nematode diversity (total of 181 genera). Next to enhanced meiofauna abundance and nematode biomass, there were signs of high levels of organic matter deposition leading to reduced sedimentary conditions, which in turn structured the nematode community. Striking in this respect was the presence of large numbers of ‘chemosynthetic’ Astomonema nematodes (Astomonema southwardorum, Order Monhysterida, Family Siphonolaimidae). This genus lacks a mouth, buccal cavity and pharynx and possesses a rudimentary gut containing internal, symbiotic prokaryotes which have been recognised as sulphur-oxidising bacteria. Dominance of Astomonema may indicate the presence of reduced environments in the study areas, which is partially confirmed by the local biogeochemical environment. The nematode communities were mostly affected by sediment layer differences and concomitant trophic conditions rather than other spatial gradients related to study area, water depth or station differences, pointing to small-scale heterogeneity as the main source of variation in nematode structure and function. Furthermore, the positive relation between nematode standing stocks, and quantity and quality of the organic matter was stronger when hydrodynamic disturbance was greater. Analogically, this study also suggests that structural diversity can be positively correlated with trophic conditions and that this relation is tighter when hydrodynamic disturbance is greater.
Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea

Abstract Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.
Assessing Exposures to Magnetic Resonance Imaging’s Complex Mixture of Magnetic Fields for In Vivo, In Vitro, and Epidemiologic Studies of Health Effects for Staff and Patients

A complex mixture of electromagnetic fields is used in magnetic resonance imaging (MRI): static, low-frequency, and radio frequency magnetic fields. Commonly, the static magnetic field ranges from one to three Tesla. The low-frequency field can reach several millitesla and with a time derivative of the order of some Tesla per second. The radiofrequency (RF) field has a magnitude in the microtesla range giving rise to specific absorption rate values of a few Watts per kilogram. Very little attention has been paid to the case where there is a combined exposure to several different fields at the same time. Some studies have shown genotoxic effects in cells after exposure to an MRI scan while others have not demonstrated any effects. A typical MRI exam includes muliple imaging sequences of varying length and intensity, to produce different types of images. Each sequence is designed with a particular purpose in mind, so one sequence can, for example, be optimized for clearly showing fat water contrast, while another is optimized for high-resolution detail. It is of the utmost importance that future experimental studies give a thorough description of the exposure they are using, and not just a statement such as “An ordinary MRI sequence was used. ” Even if the sequence is specified, it can differ substantially between manufacturers on, e.g., RF pulse height, width, and duty cycle. In the latest SCENIHR opinion, it is stated that there is very little information regarding the health effects of occupational exposure to MRI fields, and long-term prospective or retrospective cohort studies on workers are recommended as a high priority. They also state that MRI is increasingly used in pediatric diagnostic imaging, and a cohort study into the effects of MRI exposure on children is recommended as a high priority. For the exposure assessment in epidemiological studies, there is a clear difference between patients and staff and further work is needed on this. Studies that explore the possible differences between MRI scan sequences and compare them in terms of exposure level are warranted.
Suicide Attempt, Clinical Correlates, and BDNF Val66Met Polymorphism in Chronic Patients With Schizophrenia

Objective: Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. Method: This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. Results: There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. Conclusions: The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients.
Perceptions of Audio Computer-Assisted Self-Interviewing (ACASI) among Women in an HIV-Positive Prevention Program

Background Audio Computer-Assisted Self Interviewing (ACASI) has improved the reliability and accuracy of self-reported HIV health and risk behavior data, yet few studies account for how participants experience the data collection process. Methodology/Principal Findings This exploratory qualitative analysis aimed to better understand the experience and implications of using ACASI among HIV-positive women participating in sexual risk reduction interventions in Chicago (n = 12) and Philadelphia (n = 18). Strategies of Grounded Theory were used to explore participants' ACASI experiences. Conclusion/Significance Key themes we identified included themes that could be attributed to the ACASI and other methods of data collection (e.g., paper-based self-administered questionnaire or face-to-face interviews). The key themes were usability; privacy and honesty; socially desirable responses and avoiding judgment; and unintentional discomfort resulting from recalling risky behavior using the ACASI. Despite both positive and negative findings about the ACASI experience, we conclude that ACASI is in general an appropriate method for collecting sensitive data about HIV/AIDS risk behaviors among HIV-positive women because it seemed to ensure privacy in the study population allowing for more honest responses, minimize socially desirable responses, and help participants avoid actual or perceived judgment.
Exploring the Link Between Substance Use and Mental Health Status: What Can We Learn from the Self-medication Theory?

Abstract: The high rate of co-occurring mental health issues and substance-use disorders has been well documented. The primary objective of this research was to evaluate the association between use of alcohol, marijuana, and other illicit drugs, and unmet mental health need and service use. A secondary aim of this research was to determine if the observed patterns of alcohol, marijuana, and other illicit drugs use and unmet mental health need and mental health service use are consistent with a theory of self-medication theory. On the latter view, people use psychoactive substances as a self-regulation strategy to alleviate distress. Research was conducted through secondary analysis of 2014 National Survey on Drug Use and Health (NSDUH) data. Overall, study findings supported the established correlation between mental health issues and substance use as well as a theory of self-medication. This study focused on people 18–25 years of age.
Signal-Driven Computations in Speech Processing

Learning a language requires both statistical computations to identify words in speech and algebraic-like computations to discover higher level (grammatical) structure. Here we show that these computations can be influenced by subtle cues in the speech signal. After a short familiarization to a continuous speech stream, adult listeners are able to segment it using powerful statistics, but they fail to extract the structural regularities included in the stream even when the familiarization is greatly extended. With the introduction of subliminal segmentation cues, however, these regularities can be rapidly captured.