Miracle-dz/UniFAR-FTUs huggingface dataset:
A Homozygous Missense Mutation in FANCA Gene in a 46,XY Female with Gonadal Dysgenesis

Fanconi anemia (FA) is a pleiotropic condition with 2 characteristic phenotypic markers of hematological and cytogenetic changes. The phenotype of patients with FA is very heterogeneous, associated with an array of congenital malformations affecting the skeletal, renal, genital, and/or central nervous systems. Here, we report on a 46,XY female who presented with gonadal dysgenesis and microcephaly. Exome sequencing showed that she was homozygous for a rare variant in the FANCA gene (c.4232C>T, p.P1411L, rs201494304). Both parents were heterozygous for the mutation. The FA mutation was associated with an atypical clinical presentation, and thus exome sequencing provided essential data that otherwise would have been overlooked in the diagnosis of this patient.
Associations of Overweight, Obesity, and Underweight With High Serum Total Cholesterol Level Over 30 Years Among the Japanese Elderly: NIPPON DATA 80, 90, and 2010

Background The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. Methods Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220 mg/dL and above. For participants aged ≥50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. Results A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83–3.24 and 0.92; 95% CI, 0.66–1.27 among men and 1.43; 95% CI, 1.18–1.72 and 1.08; 95% CI, 0.81–1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12–0.60 and 0.37; 95% CI, 0.10–1.28 among men and 0.39; 95% CI, 0.26–0.57 and 0.96; 95% CI, 0.58–1.57 among women, respectively). Conclusions These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.
Quercetin‐3‐methyl ether inhibits esophageal carcinogenesis by targeting the AKT/mTOR/p70S6K and MAPK pathways

Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia, especially in China. Research findings indicate that nitrosamines, malnutrition, unhealthy living habits, and genetics contribute to esophageal carcinogenesis. Currently, the 5‐year survival rate for ESCC patients remains low, owing in part to a lack of a clear understanding of mechanisms involved. Chemoprevention using natural or synthesized compounds might be a promising strategy to reduce esophageal cancer incidence. The epidermal growth factor receptor (EGFR) can activate downstream pathways including the phosphatidylinositol 3‐kinase (PI3K) pathway and the Ras/mitogen‐activated protein kinase (MAPK) pathways. Among the important players, AKT and ERKs have an important relationship with cancer initiation and progression. Here, we found that phosphorylated (p)‐AKT and p‐ERKs were highly expressed in esophageal cancer cell lines and in esophageal cancer patients. Human phospho‐kinase array and pull‐down assay results showed that quercetin‐3‐methyl ether (Q3ME) is a natural flavonoid compound that interacted with AKT and ERKs and inhibited their kinase activities. At the cellular level, Q3ME attenuated esophageal cancer cell proliferation and anchorage‐independent growth. Western blot analysis showed that this compound suppressed the activation of AKT and ERKs downstream signaling pathways, subsequently inhibiting activating protein‐1 (AP‐1) activity. Importantly, Q3ME inhibited the formation of esophageal preneoplastic lesions induced by N‐nitrosomethylbenzylamine (NMBA). The inhibition by Q3ME was associated with decreased inflammation and esophageal cancer cell proliferation in vivo. Collectively, our data suggest that Q3ME is a promising chemopreventive agent against esophageal carcinogenesis by targeting AKT and ERKs.
Spatial and Temporal Trends of Number of Deaths Attributable to Ambient PM2.5 in the Korea

Background We aimed to evaluate the spatial and temporal trends of the health burden attributable to particulate matter less than 2.5 µm in diameter (PM2.5) in the metropolitan cities and provinces of the Korea. Methods We used modeled PM2.5 concentration data for the basic administrative levels, comprising the cities and the provinces of Korea, the corresponding annual population census data for each level, and the age and cause specific mortality data. We applied cause-specific integrated exposure-response functions to calculate the premature mortality attributable to ambient PM2.5 for four disease end points (ischemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], lung cancer [LC], and cerebrovascular disease [stroke]) for the year 2015. Moreover, the temporal trends of the health burden from 2006 to 2015 were assessed. Results The annual average PM2.5 concentration for Korea was 24.4 μg/m3, and 11,924 premature deaths were attributable to PM2.5 exposure in 2015. By simulating the reduction in the annual mean values of PM2.5 to 10 µg/m3, about 8,539 premature deaths were preventable. There was spatial variation in mortality burden attributable to PM2.5 across the sub-national regions of Korea. In particular, the high burden was concentrated at Seoul and Gyeonggi province due to the high population density. However, decreasing trends were noted for most of the metropolitan cities and provinces of Korea since 2006. Conclusion Our findings show that further actions to improve air quality in Korea would substantially improve the health burden due to particulate matter.
Reason for optimism: How a shifting focus on neural population codes is moving cognitive neuroscience beyond phrenology

Abstract Multivariate pattern analysis can address many of the challenges for cognitive neuroscience highlighted in After Phrenology (Anderson 2014) by illuminating the information content of brain regions and by providing insight into whether functional overlap reflects the recruitment of common or distinct computational mechanisms. Further, failing to consider submaximal but reliable population responses can lead to an overly modular account of brain function.
Occurrence and dietary exposure assessment of multiple mycotoxins in corn-based food products from Shandong, China

ABSTRACT This study was designed to investigate the occurrence and exposure assessment of multiple mycotoxins in corn-based food products from Shandong Province, China. Results demonstrated that the mean level of total mycotoxins in test samples was 197.2 µg/kg. The most frequently found mycotoxins were deoxynivalenol (96.7%) and fumonisin B1 (94.4%), with mean contamination levels of 65.24 and 128.2, respectively. Among these corn-based food products, thin corn pancake had the highest mean contamination (886.7 µg/kg), followed by wotou (143.7 µg/kg), corn cake (135.4 µg/kg) and mantou (63.73 µg/kg). The average exposure values to total fumonisins and deoxynivalenol were 0.05 and 0.02 µg/kg bw/day, which were lower than the provisional maximum tolerable daily intake values of 2 and 1 µg/kg bw/day, respectively, as established by the Joint FAO/WHO Expert Committee on Food Additives. In the future strict control and systematic monitoring are needed to secure food safety and human health.
Phylogeny of Mental Glands, Revisited

Mental glands and their associated delivery behaviors during courtship are unique to the plethodontid salamanders. Because previous interpretations of the evolution of these features were conducted using older phylogenetic hypotheses, we reanalyzed these traits with newer courtship descriptions and contemporary phylogenetic methods. Using Bayesian ancestral state reconstruction methods that have been developed since the first phylogenetic analyses were conducted in the mid-1990s, we reconstructed mental gland and courtship behavior evolution on a Bayesian phylogeny of the nuclear gene Rag1. The most probable ancestral condition for plethodontids was resolved as presence of a mental gland. Loss of a mental gland occurred in each subfamily and was recovered as the most probable ancestral condition for the Spelerpinae. In contrast, parsimony reconstruction recovered the presence of a mental gland in the ancestor to Spelerpinae with multiple secondary losses. We hypothesize that that absence of a mental gland is possibly ancestral in some clades (i.e., Spelerpinae) and secondary in others (e.g., paedomorphic Eurycea). The most probable ancestral form of the mental gland is likely to be the large pad-type distributed extensively in Plethodontinae and Bolitoglossinae. Desmognathans have the most unique mental glands, occurring in an anterior protrusion or bifurcated form (in Desmognathus wrighti). Fan-shaped mental glands evolved independently in Eurycea and Oedipina. Small pads arose independently in Bolitoglossinae, Plethodontinae, and Spelerpinae. Head-rubbing behavior for mental gland delivery mode was recovered as the most probable and parsimonious ancestral state for the Plethodontidae, with independent losses of this behavior in Plethodontinae and Spelerpinae. Because head-rubbing was observed in outgroups, we hypothesize that head-rubbing behavior predated mental gland evolution. Pulling, snapping, slapping, and biting behaviors evolved independently in the Plethodontinae and Spelerpinae and are not homologous with head-rubbing. All hypotheses of mental gland and courtship evolution invoke homoplasy.
Holmium laser versus thulium laser enucleation of the prostate: a matched-pair analysis from two centers

Background: The aim of our study was to compare perioperative and functional outcomes of two different prostatic laser enucleation techniques performed in two high-volume centers: 100 W holmium laser enucleation of the prostate (HoLEP) (Lyon, France) and 110 W thulium laser enucleation of the prostate (ThuLEP) (Varese, Italy). Materials and Methods: A nonrandomized, observational, retrospective and matched-pair analysis was performed on two homogeneous groups of 117 patients that underwent prostate laser enucleation in the HoLEP or ThuLEP centers between January 2015 and April 2017, following the classical ‘three lobes’ enucleation technique. The American Society of Anesthesiologists (ASA) score and prostate volume were the main parameters considered for matching the patients between the two groups. Patients on anticoagulant therapy, with documented detrusor hypoactivity or hyperactivity or with the finding of concurrent prostate cancer were excluded from the study. Follow up was assessed at 3, 6 and 12 months after surgery. Results: Median enucleation and morcellation time was 75.5 and 11.5 min, respectively, in the HoLEP group versus 70.5 and 12 min, respectively, in the ThuLEP group (p = 0.001 and 0.49, respectively). Enucleated adenoma weight was comparable (44 g versus 45.6 g, p = 0.60). Energy index (3884.63 versus 4137.35 J/g, p = 0.30) and enucleation index (0.57 versus 0.6 g/min, p = 0.81) were similar in the two groups. Catheterization time was comparable (1 versus 1 day; p = 0.14). The International Prostate Symptom Score and Quality of Life score significantly decreased, as well as maximal urinary flow rate. Median prostate-specific antigen (PSA) drop 1 year after surgery was 2.1 ng/ml in the HoLEP group (−52.83%) versus 1.75 ng/ml in the ThuLEP group (−47.85%) (p = 0.013). Conclusion: Both HoLEP (100 W) and ThuLEP (110 W) relieve lower urinary tract symptoms in a comparable way with high efficacy and safety, with negligible clinical differences.
Naturalistic Assessment of Task Interruption in Individuals With Mild Cognitive Impairment

Objective: Interruptions are ubiquitous in everyday life, and recovering from interruptions requires several cognitive processes working in tandem. In this study, we assessed the effects of an interruption on the performance of older individuals with and without mild cognitive impairment (MCI) completing everyday tasks in a naturalistic apartment setting. Method: Thirty-two persons with MCI and 64 cognitively healthy older adults (HOA) completed two different sets of everyday activities, of which one received an interruption. Participants also completed tests assessing cognitive constructs thought to be important in interruption recovery including retrospective memory, prospective memory, planning, working memory, and executive function. Results: As a consequence of an interruption, participants with MCI took longer to complete primary task demands and made more substitution errors, but did not make more omission errors. In contrast, an interruption led HOAs to make more omission errors, but their time on task was not affected. Results from a hierarchical linear regression suggest that the ecologically valid interruption task time was more predictive of everyday functional status than the traditional neuropsychological measures. Conclusions: Results suggest that a brief task interruption taxed cognitive resources of both MCI and HOA groups, but was more detrimental to MCI in terms of time on task and total errors committed. Participant groups appeared to use a speed–accuracy trade-off to mitigate negative effects, where HOAs emphasized speed and MCI participants focused on accuracy. Amount of cognitive engagement/disengagement was also theorized to have played a role, where MCI may have maintained information online throughout the interruption, and HOAs disengaged and reengaged resulting in worse reactivation of goals. Although MCI held onto task goals, their execution of details was imperfect over the interruption delay resulting in substitution errors likely due to further taxed executive abilities.
Biology of TH17 Cells and Their Role in Inflammatory Diseases

1. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Department of Immunology, school of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Departmentof Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 4. Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Linking Neuroimaging with Functional Linguistic Analysis to Understand Processes of Successful Communication

Functional linguistic models posit a systematic link between language FORM and the FUNCTIONS for which language is used. This is a systematic (and therefore quantifiable) relationship. Yet many open questions remain about the mechanisms that link form, function and communication relevant outcomes. Neuroimaging methods can provide insight into such processes that are not apparent from other methods. We argue that the combination of neural and linguistic measures will allow insight into both individual and population-level communication processes that would not be possible using either method in isolation. We present examples illustrating this methodological integration and notes regarding the most amenable linguistic tools. We summarize a framework in which language presented to and produced by participants undergoing neuroimaging is correlated with the resulting neural data and other proximal communication outcomes allowing the triangulation of individual experimental with population level outcomes, thereby linking between micro and macro levels of analysis.
Poly-l-lysine-coated superparamagnetic nanoparticles: a novel method for the transfection of pro-BDNF into neural stem cells

Abstract Poly-l-lysine-coated superparamagnetic iron oxide nanoparticles (SPIONs-PLL) were prepared and used as a novel-carrier for the transfer of brain-derived neurotrophic factor (BDNF) into neural stem cells (NSCs) under the beneficial influence of an external magnetic field. Pro-BDNF, a gene from human brain cDNA libraries, was obtained by polymerase chain reaction and constructed in a mammalian expression vector (PSecTag2/HygroB). The nanoparticles (NPs) were examined using Fourier transform infrared spectroscopy, zeta potential, and Transmission electron microscopy. From the results, the levels of BDNF among the transfected and untransfected cells were 30.326 ± 5.9 and 5.85 ± 3.11 pg/mL, respectively, as detected by an ELISA method. Moreover, the enhanced green fluorescent protein vector was used to evaluate the gene expression efficiency for SPIONs-PLL as a non-viral carrier in NSCs. This was performed under the influence of a magnetic field and the transfection reagents (such as Lipofectamine 2000), which served as a positive control. The histological analysis revealed that the concentration of intracellular NPs was significantly higher than intercellular NPs. These results suggest that SPIONs-PLL can serve as a novel alternative for the transfection of BDNF-NSCs and could be used in gene therapy.
Uptake of HIV self‐testing and linkage to treatment among men who have sex with men (MSM) in Nigeria: A pilot programme using key opinion leaders to reach MSM

HIV self‐testing (HIVST) offers an alternative to facility‐based HIV testing services, particularly for populations such as men who have sex with men (MSM) who may fear accessing testing due to stigma, discrimination and criminalization. Innovative HIV testing approaches are needed to meet the goal of 90% of people living with HIV being diagnosed. This study piloted an intervention to distribute oral HIVST kits to MSM through key opinion leaders (KOLs) in Lagos, Nigeria and assessed the feasibility, acceptability, uptake of HIVST and linkage to HIV treatment.
Lack of research reproducibility, the rise of open science and the need for continuing education in research methods

Abstract In this opinion piece, we discuss the issue of lack of reproducibility in medical research and the different approaches that are being taken to address this problem. One general approach involves much greater transparency including the pre-publication of a study protocol, analysis plan and analysis code as well as the ultimate sharing of data, doing away with the concept of the ‘single wrap-up publication’. The other change required is to support the training and mentorship of young researchers and ensure that they are not working in isolation.
Chronic Illness with Complexity

The present study examines how different chronic illnesses and mental illness comorbidity (chronic illness with complexity [CIC]) associate with components of advance care planning (ACP). We also explore the role self-perceived burden plays in the relationship between illness and ACP. Data were gathered from a cross-sectional survey of 305 elderly participants from the New Jersey End-of-Life study. Participants with diabetes and those with cardiovascular disease (CVD) are less likely, while participants with CIC are more likely, to plan for the end-of-life. Participants with diabetes are less likely to make formal plans, whereas those with CVD are less likely to hold informal discussions. CIC is associated with increased odds of having an advance directive, but no other form of ACP. Self-perceived burden did not appear to be the gateway by which illness groups differentially engaged in ACP. Future research should investigate what aspects of illnesses drive ACP.
Sustainability Assessment for Indirect Potable Reuse: A Case Study from Reno, Nevada

A triple bottom line (TBL) approach was used to examine the trade‐offs between potential reclaimed water management strategies in a closed basin. The goals of the water management strategy included minimizing water source shortages, ensuring safe and resilient future water supplies, and protecting inland ecosystems through adequate surface flows. The TBL approach consisted of quantitative and qualitative impact assessments of social, environmental, and economic criteria. This research examined how potable reuse of reclaimed water addresses water needs in a closed basin such as maintaining water quality, managing reclaimed water disposal, meeting growing water demand, balancing groundwater extraction rates with inflows, preserving inland ecosystems, and ensuring a locally controlled safe drinking water source. The TBL assessment first evaluated water stress based on water demand and supply under status quo conditions. The results were compared with the potable reuse scenario, which provides more environmental and social benefits than the status quo scenario.
How to Detect Life on Icy Moons

Abstract The icy moons of the outer Solar System present the possibility of subsurface water, habitable conditions, and potential abodes for life. Access to evidence that reveals the presence of life on the icy moons can be facilitated by plumes that eject material from the subsurface out into space. One instrument capable of performing life-search investigations at the icy moons is the MAss SPectrometer for Planetary EXploration/Europa (MASPEX), which constitutes a high-resolution, high-sensitivity multibounce time-of-flight mass spectrometer capable of measuring trace amounts (ppb) of organic compounds. MASPEX has been selected for the NASA Europa Clipper mission and will sample any plumes and the surface-sputtered atmosphere to assess any evidence for habitability and life. MASPEX is capable of similar investigations targeted at other icy moons. Data may be forthcoming from direct sampling but also impact dissociation because of the high speed of some analytes. Impact dissociation is analogous to the dissociation provided by modern analytical pyrolysis methods. Radiolytic dissociation on the europan surface before or during the sputtering process can also induce fragmentation similar to pyrolysis. In this study, we have compiled pyrolysis mass spectrometry data from a variety of biological and nonbiological materials to demonstrate the ability of MASPEX to recognize habitability and detect life in any plumes and atmospheres of icy moons.
Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells

BRCA proteins are essential for Homologous Recombination DNA repair, and their germline or somatic inactivation is frequently observed in human tumors. Understanding the molecular mechanisms underlying the response to chemotherapy of BRCA-deficient tumors is paramount for developing improved personalized cancer therapies. While PARP inhibitors have been recently approved for treatment of BRCA-mutant breast and ovarian cancers, resistance to these novel drugs remains a major clinical problem. Several mechanisms of chemoresistance in BRCA2-deficient cells have been identified. Rather than restoring normal recombination, these mechanisms result in stabilization of stalled replication forks, which normally are subjected to degradation in BRCA2-mutated cells. Here, we show that the transcriptional repressor E2F7 controls chemoresistance in BRCA2-deficient cells. We found that E2F7 depletion restores PARP inhibitor and cisplatin resistance in BRCA2-depleted cells. Moreover, we show that the mechanism underlying this activity involves increased expression of RAD51, a target for E2F7-mediated transcriptional repression, which enhances both Homologous Recombination DNA repair, and replication fork stability in BRCA2-deficient cells. Our work describes a new mechanism of chemotherapy resistance in BRCA2-deficient cells, and identifies E2F7 as a novel biomarker for tumor response to PARP inhibitor therapy.