Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic Performance of Deep Learning Algorithms Applied to Three Common Diagnoses in Dermatopathology

Background: Artificial intelligence is advancing at an accelerated pace into clinical applications, providing opportunities for increased efficiency, improved accuracy, and cost savings through computer-aided diagnostics. Dermatopathology, with emphasis on pattern recognition, offers a unique opportunity for testing deep learning algorithms. Aims: This study aims to determine the accuracy of deep learning algorithms to diagnose three common dermatopathology diagnoses. Methods: Whole slide images (WSI) of previously diagnosed nodular basal cell carcinomas (BCCs), dermal nevi, and seborrheic keratoses were annotated for areas of distinct morphology. Unannotated WSIs, consisting of five distractor diagnoses of common neoplastic and inflammatory diagnoses, were included in each training set. A proprietary fully convolutional neural network was developed to train algorithms to classify test images as positive or negative relative to ground truth diagnosis. Results: Artificial intelligence system accurately classified 123/124 (99.45%) BCCs (nodular), 113/114 (99.4%) dermal nevi, and 123/123 (100%) seborrheic keratoses. Conclusions: Artificial intelligence using deep learning algorithms is a potential adjunct to diagnosis and may result in improved workflow efficiencies for dermatopathologists and laboratories.
Vitamin D supplementation to prevent vitamin D deficiency for children with epilepsy

Background : Vitamin D deficiency is highly prevalent among children with epilepsy. Lack of high-quality evidence led to variability among scientific societies recommendations. Therefore, we aim to determine the efficacy of different common doses used in the pediatric practice to maintain optimal 25-hydroxy vitamin D (25 [OH] vitamin D) level in children with epilepsy and normal baseline 25 (OH) vitamin D level over 6 months of supplementation. Methods : This is a protocol for phase IV pragmatic randomized superiority controlled open-label trial at King Saud University Medical City in Riyadh. Children with epilepsy and receiving chronic antiepliptic medication and normal baseline 25 (OH) vitamin D level will be randomly assigned to receive Cholecalciferol 400 IU/day versus 1000 IU/day for 6 months. Our primary outcome is the proportion of children with vitamin D insufficiency (25 (OH) vitamin D level < 75nmol/L) at 6 months. Secondary outcomes include seizure treatment failure, seizure frequency, parathyroid hormone (PTH) levels, bone mineral density, and safety. Discussion: Our trial is set out to evaluate the efficacy of common different vitamin D maintenance doses on 25 (OH) vitamin D level, seizure control, and bone health for children with epilepsy. The results of our study will possibly help in shaping current vitamin D guidelines for vitamin D supplementation in children with epilepsy and provide a link between 25 (OH) vitamin D level and seizure control.
AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer

Prostate cancer bone metastasis remains lethal and incurable, and often arises years after elimination of the primary tumor. It is unclear what underlies the decades-long clinical latency before recurrence, but evidence points to the existence of dormant residual tumor cells that disseminated before the primary tumor was eliminated. To design therapies to prevent progression of disseminated tumor cells (DTC) into lethal metastases, it is crucial to understand the mechanism(s) underlying this dormancy. The current study functionally validated our previous observation that implicated the GAS6/AXL axis in mediating DTC dormancy in the bone marrow. AXL-null and AXL-overexpressing prostate cancer cell lines were generated to determine if AXL was necessary and/or sufficient for dormancy. Characterization of these cells in vitro and using in vivo mouse models of DTC growth demonstrated that AXL was indeed sufficient to induce dormancy, but was unable to maintain it long-term and was not absolutely required for a dormancy period. Clinically, AXL expression correlated with longer survival in prostate cancer patients, and AXL was not expressed by cancer cells in primary or metastatic tissue. These data point to a tumor-suppressive role for AXL in prostate cancer, and future work is required to determine if AXL is expressed on human bone marrow DTCs. Implications: The ability of AXL to initiate but not maintain dormancy, coupled with its dispensability, suggests that targeting AXL alone will not prevent lethal metastatic outgrowth, and likely a cooperative network of factors exists to mediate long-term cellular dormancy.
Periwinkle climbing response to water- and airbone predator chemical cues may depend on home-marsh geography

The salt marsh periwinkle, Littorina irrorata, exhibits a spatial refuge from predation by climbing the stems of Spartina alterniflora in order to avoid benthic predators. Salt marsh periwinkles have a broad geographic distribution, and for many species, responses to predators also varies with biogeography. This study sought to determine if the geographical location of the home marsh influenced the response of periwinkles (climbing height) to blue crab predator cues both via air and water. Snails from Louisiana (LA) climbed higher in general than those from North Carolina (NC), regardless of chemical cue. However, LA snails climbed 11 cm higher in the presence of waterborne predators than control snails with no cue, while NC snails only climbed five cm higher in the same comparisons. Airborne chemical cue tended to have snails climbing at intermediate heights. These responses were significantly enhanced when both populations of snails were housed together. Periwinkle response to predator cues was stronger in LA than NC, and so it is possible that the behavioral response of these snails to predators varies with biogeography of the home marsh. Also interestingly, the results of this study also suggest that cue delivery is probably occurring via mechanisms other than water, and potentially via airborne cues. Therefore, salt marsh periwinkles likely respond to numerous cues that initiate behavioral responses, including airborne cues, and these responses may vary by home-marsh geography.
Balloon remodeling-assisted Woven EndoBridge technique: description and feasibility for complex bifurcation aneurysms

Background Woven EndoBridge (WEB) deployment remains challenging in aneurysms with a complex shape or orientation. Objective To show that embolization of wide-neck bifurcation aneurysms using the WEB device balloon remodeling-assisted technique is a feasible and elegant endovascular solution compared with other techniques, such as balloon remodeling or stent-assisted coiling. Materials and methods 10 cases (10 aneurysms in 9 patients) of balloon remodeling-assisted WEB treatment of unruptured complex bifurcation aneurysms were treated in our institution and retrospectively analyzed. Details of clinical presentations, technical details, perioperative and postoperative complications, and outcomes were collected. Immediate and long-term angiographic results were also evaluated. Results Aneurysms included six middle cerebral artery aneurysms, one anterior communicating artery aneurysm, one posterior communicating artery aneurysm, one basilar artery aneurysm, and one T-shaped carotid aneurysm. Mean dome width was 6.55 mm, mean neck size 4.5 mm, mean height 4.79 mm, and mean dome-to-neck ratio was 1:1.46. Treatment was performed exclusively with the balloon remodeling-assisted WEB technique in all cases. The device was successfully deployed in every case. Periprocedural thromboembolic or hemorrhagic events did not occur. The modified Rankin Scale score at discharge was 0 for all patients. At mid-term or long-term angiographic follow-up, adequate occlusion was observed in 7 aneurysms from 8 controlled cases (87.5%), and one patient (2 aneurysms) did not have angiographic follow-up. Conclusion The balloon remodeling-assisted WEB technique seems to be a safe and effective solution for endovascular treatment of unruptured wide-neck bifurcation aneurysms with specific complex anatomy. However, further studies are needed to evaluate the rate of complications and long-term efficacy.
Clinical significance of the Kidney Donor Profile Index in deceased donors for prediction of post-transplant clinical outcomes: A multicenter cohort study

Background We investigated whether the Kidney Donor Profile Index (KDPI) system is useful in predicting clinical outcomes in deceased donor kidney transplantation (DDKT). Methods Four hundred sixty-nine kidney transplant recipients (KTRs) receiving kidneys from 359 deceased donors were included in this study, which involved three transplant centers. KTRs were divided into high and low KDPI KTR groups based on the median KDPI score of 67%. We compared clinical outcomes between the high KDPI and low KDPI groups. Results There were no significant differences in the incidence of delayed graft function and acute rejection between high and low KDPI KTR groups. In comparison with histologic findings in allograft tissues obtained within three months from KT, the proportion of glomerulosclerosis was significantly higher in the high KDPI KTR group than in the low KDPI KTR group. With Kaplan-Meier analysis, the graft survival rate was significantly lower in the high KDPI KTR group than in the low KDPI KTR group (Log rank, P = 0.017), and multivariate analysis also demonstrated that a high KDPI score was a significant risk factor for death censored allograft failure (HR 2.62, 95% CI, 1.29–5.33, P = 0.008). Conclusion The KDPI scoring system is useful in predicting allograft outcomes in a Korean DDKT cohort.
Normal pregnancy induced glucose metabolic stress in a longitudinal cohort of healthy women

Abstract During normal pregnancy, mothers face a unique physiological challenge in the adaptation of glucose metabolism in preparation for the metabolic stress presented by fetal development. However, the responsible mechanism remains elusive. The purpose of this study is to investigate the mechanism of the metabolic stress of glucose metabolism in pregnant women using metabolomics method. A Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometer-based untargeted metabolomics study was performed to investigate the dynamic urinary signature of the intermediates of glucose metabolism in a longitudinal cohort of 232 healthy pregnant women in their first, second, and third trimesters. Twelve glucose metabolic intermediates were screened out from hundreds of candidate metabolites using partial least squares discriminant analysis models. These 12 markers were mainly involved in the metabolic pathways of insulin resistance, glycolysis/gluconeogenesis, tricarboxylic acid cycle, nonabsorbable carbohydrate metabolism, and N-glycan biosynthesis. In particular, L-acetylcarnitine, a metabolite that is beneficial for the amelioration of insulin resistance, decreased in a time-dependent manner during normal pregnancy. Moreover, thiamine pyrophosphate, an intermediate product of glycolysis/gluconeogenesis, significantly increased in the second trimester, and argininosuccinic acid and oxalosuccinic acid, intermediates involved in the tricarboxylic acid cycle, significantly decreased in the third trimester, suggesting an increased glucose demand in the maternal body during fetal development. These findings provide novel insight into the normal pregnancy-induced elevation of insulin resistance and glycolysis/gluconeogenesis, as well as the observed reduction in the aerobic oxidation of glucose.
Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression

Collaboration among writers-readers-erasers of m6A regulates the stability of tumor-specific genes. The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m6A levels by silencing either N6-adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m6A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor–β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in m6A modifications, as altered m6A status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the m6A status of target genes by controlling each other’s expression and by inhibiting m6A reader YTHDF3 (YTH N6-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased m6A and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for m6A in cancer and shows that the collaboration among writers-erasers-readers sets up the m6A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that m6A threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.
Low‐Calorie Sweeteners: Exploring Underutilized Database Resources to Understand Dietary Patterns and Obesity

The use and impact of low‐calorie sweeteners (LCS) in relation to the national challenges of overweight and obesity are complex and controversial. Most research on LCS have focused on the prevalence of consumption of LCS in beverages. The 2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health rather than a focus on specific nutrients or foods. The committee took this approach to shift the national emphasis onto the context of total rather than individual nutrient consumption. A broader research paradigm is needed to elucidate the actual exposure to LCS and how they are consumed within dietary patterns in the US population. National‐level databases exist that can be used to broaden scientific understanding of the effects of LCS and health outcomes. These databases are underutilized, and they provide potential tools for grasping a fuller picture of LCS in the US diet.
Maternal obesity impairs fetal cardiomyocyte contractile function in sheep

Obesity is a major public health problem worldwide. In the United States, one‐third of women of reproductive age are obese. Human studies show that maternal obesity (MO) predisposes offspring to cardiovascular disease. However, the underlying mechanisms remain unclear. Given the similarities between pregnancy in sheep and humans, we studied sheep to examine the impact of MO on fetal cardiomyocyte contractility at term. We observed that MO impaired cardiomyocyte contractility by reducing peak shortening and shortening/relengthening velocity, prolonging time to relengthening. MO disrupted Ca2+ homeostasis in fetal cardiomyocytes, increasing intracellular Ca2+ and inducing cellular Ca2+ insensitivity. The Ca2+‐release channel was impaired, but Ca2+ uptake was unaffected by MO. The upstream kinases that phosphorylate the Ca2+‐release channel — ryanodine receptor‐2, PKA, and calmodulin‐dependent protein kinase II—were activated in MO fetuses. Contractile dysfunction was associated with an increased ratio of myosin heavy chain (MHC)‐β to MHC‐α and upregulated cardiac troponin (cTn)‐T and tropomyosin, as well as cTn‐I phosphorylation. In summary, this is the first characterization of the effects of MO on fetal cardiomyocyte contractility. Our findings indicate that MO impairs fetal cardiomyocyte contractility through altered intracellular Ca2+ handling, overloading fetal cardiomyocyte intracellular Ca2+ and aberrant myofilament protein composition. These mechanisms may contribute to developmental programming by MO of offspring cardiac function and predisposition to later life cardiovascular disease in the offspring. —Wang, Q. , Zhu, C. , Sun, M. , Maimaiti, R. , Ford, S. P., Nathanielsz, P. W. , Ren, J., Guo, W. Maternal obesity impairs fetal cardiomyocyte contractile function in sheep. FASEB J. 33, 2587–2598 (2019). www.fasebj. org
Expected changes in obesity after reformulation to reduce added sugars in beverages: A modeling study

Background Several strategies have been proposed to reduce the intake of added sugars in the population. In Mexico, a 10% sugar-sweetened beverages (SSBs) tax was implemented in 2014, and the implementation of other nutritional policies, such as product reformulation to reduce added sugars, is under discussion. WHO recommends that all individuals consume less than 10% of their total energy intake (TEI) from added sugars. We propose gradually reducing added sugars in SSBs to achieve an average 10% consumption of added sugars in the Mexican population over 10 years and to estimate the expected impact of reformulation in adult body weight and obesity. Methods and findings Baseline consumption for added sugars and SSBs, sex, age, socioeconomic status (SES), height, and weight for Mexican adults were obtained from the 2012 Mexico National Health and Nutrition Survey (ENSANUT). On average, 12.6% of the TEI was contributed by added sugars; we defined a 50% reduction in added sugars in SSBs over 10 years as a reformulation target. Using a dynamic weight change model, sugar reductions were translated into individual expected changes in body weight assuming a 43% caloric compensation and a 2-year lag for the full effect of reformulation to occur. Results were stratified by sex, age, and SES. Twelve years after reformulation, the TEI from added sugars is expected to decrease to 10%, assuming no compensation from added sugars; 44% of the population would still be above WHO recommendations, requiring further sugar reductions to food. Body weight could be reduced by 1.3 kg (95% CI −1.4 to −1.2) in the adult population, and obesity could decrease 3.9 percentage points (pp; −12.5% relative to baseline). Our sensitivity analyses suggest that the impact of the intervention could vary from 0.12 kg after 6 months to 1.52 kg in the long term. Conclusions Reformulation to reduce added sugars in SSBs could produce large reductions in sugar consumption and obesity in the Mexican adult population. This study is limited by the use of a single dietary recall and by data collected in all seasons except summer; still, these limitations should lead to conservative estimates of the reformulation effect. Reformulation success could depend on government enforcement and industry and consumer response, for which further research and evidence are needed.
Discovery of Two Chrysosporium Species with Keratinolytic Activity from Field Soil in Korea

Abstract In an ongoing survey of Korean indigenous fungi, two fungal strains (KNU16-74 and KNU16-99) belonging to the genus Chrysosporium were isolated from field soil in Gyeongnam, Korea. Morphological characterization and phylogenetic analysis using sequence of the internal transcribed spacer regions were carried out to confirm its precise identification. These strains were identified as Chrysosporium indicum (KNU16-74) and Chrysosporium fluviale (KNU16-99). To examine the keratin degradation efficiency of these two fungal species, human hair strands were incubated with fungus culture. Results revealed that these two fungal species have the ability to degrade keratin substrate. This is the first report of these two species in Korea.
Association of Monocarboxylate Transporter-1 (MCT1) A1470T Polymorphism (rs1049434) with Forward Football Player Status.

Abstract The aim of this study was to investigate the association between the MCT1 (monocarboxylate transporter 1) A1470T polymorphism and positional roles in a large cohort of professional football players from five different countries. We compared genotype distributions of the MCT1 A1470T polymorphism between football players (n=694) and non-athlete controls (n=781) from Italy, Poland, Lithuania, Ukraine and Malta, and we analyzed the MCT1 genotype distributions with respect to the players’ positions in the field (e. g. forwards, midfielders, defenders and goalkeepers). Genomic DNA was extracted from either buccal epithelium or peripheral blood using a standard protocol. In the pooled cohort of Italian, Polish, Lithuanian and Ukrainian football players, forwards (n=148) were more likely than controls (n=781) to possess the A allele (χ2=7.067, p=0.029, FDR q value 0.116), with a greater likelihood of having the AA genotype compared with the TT genotype (OR=1.97; C.I.=1.07-3.64; p=0.021, FDR q value 0.086). The MCT1 AA genotype was significantly more frequent in forwards then in controls. Further studies are needed to confirm these findings in other professional football player cohorts.
Impact of parallel fiber to Purkinje cell long-term depression is unmasked in absence of inhibitory input

Simultaneous impairment of Purkinje cell inhibitory input and parallel fiber LTD severely affects cerebellar learning. Pavlovian eyeblink conditioning has been used extensively to study the neural mechanisms underlying associative and motor learning. During this simple learning task, memory formation takes place at Purkinje cells in defined areas of the cerebellar cortex, which acquire a strong temporary suppression of their activity during conditioning. Yet, it is unknown which neuronal plasticity mechanisms mediate this suppression. Two potential mechanisms include long-term depression of parallel fiber to Purkinje cell synapses and feed-forward inhibition by molecular layer interneurons. We show, using a triple transgenic approach, that only concurrent disruption of both these suppression mechanisms can severely impair conditioning, highlighting that both processes can compensate for each other’s deficits.
Acupotomy therapy for lumbar disc herniation

Background: Lumbar disc herniation (LDH) is a clinically common degenerative spinal disease that adversely affects patients’ quality of life and work ability. Although several articles have reported that acupotomy can improve the clinical symptoms of LDH, the efficiency of acupotomy has not been scientifically or methodically evaluated. The primary objective of this study is to evaluate and synthesize evidence on the effectiveness and safety of acupotomy therapy in patients with LDH. Method: We plan to search eight English and Chinese electronic databases, including the Web of Science, Cochrane Library, PubMed, EMBASE, SinoMed, Wanfang, China Science and Technology Journal (VIP), and China National Knowledge Infrastructure (CNKI) databases, for potentially eligible studies. Randomized controlled trials (RCTs) on acupotomy treatment in LDH patients will be searched for independently by 2 reviewers in the databases from their inception to August 2018. We will combine data from clinically homogenous studies in a fixed effect meta-analysis using RevManV.5. 3.5, and the evidence level will be assessed by using the method for Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: This systematic review and meta-analysis will use high-quality evidence-based medicine to assess the efficacy and safety of acupotomy therapy in LDH. Conclusion: This study protocol will provide strong evidence to determine whether acupotomy therapy is an effective and safe intervention for patients with LDH.