Miracle-dz/UniFAR-FTUs huggingface dataset:
A Natural History of Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Microbiomes

Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains of Propionibacterium and Malassezia at higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains of Staphylococcus aureus were relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC. ABSTRACT Cutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in Australia. The majority of SCCs progress from premalignant actinic keratosis (AK) lesions that form on chronically sun-exposed skin. The role of skin microbiota in this progression is not well understood; therefore, we performed a longitudinal microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone immunocompetent men. The majority of variability in microbial profiles was attributable to subject, followed by time and lesion type. Propionibacterium and Malassezia organisms were relatively more abundant in nonlesional photodamaged skin than in AKs and SCCs. Staphylococcus was most commonly associated with lesional skin, in particular, sequences most closely related to Staphylococcus aureus. Of 11 S. aureus-like operational taxonomic units (OTUs), six were significantly associated with SCC lesions across seven subjects, suggesting their specific involvement with AK-to-SCC progression. If a causative link exists between certain S. aureus-like OTUs and SCC etiology, therapeutic approaches specifically targeting these bacteria could be used to reduce SCC. IMPORTANCE Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains of Propionibacterium and Malassezia at higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains of Staphylococcus aureus were relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.
Paradox of hypercholesterolaemia in highly trained, keto-adapted athletes

Objective A growing number of ultra-endurance athletes have switched to a very low-carbohydrate/high-fat eating pattern. We compared markers of cholesterol and the lipoprotein profile in a group of elite ultra-runners consuming a high-carbohydrate (HC) or low-carbohydrate (LC) diet. Methods Fasting blood was obtained from competitive male ultra-endurance runners habitually consuming a very low-carbohydrate (LC; n=10) or high-carbohydrate (HC; n=10) diet to determine blood cholesterol profile, lipoprotein particle distribution and sterol biomarkers of cholesterol balance. Results Plasma total cholesterol, low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) cholesterol were all significantly greater (p<0.000) in the LC group (65%, 83% and 60%, respectively). There were also significant differences in lipoprotein particle distribution as evidenced by a greater size and concentration of large HDL and LDL particles, and total LDL particle concentration was significantly greater in the LC group, but they had significantly fewer small LDL particles. Conclusion Ultra-endurance athletes habitually consuming a very low-carbohydrate/high-fat diet for over a year showed unique cholesterol profiles characterised by consistently higher plasma LDL-C and HDL-C, less small LDL particles, and lipoprotein profiles consistent with higher insulin sensitivity. There may be a functional purpose to the expansion of the circulating cholesterol pool to meet the heightened demand for lipid transport in highly trained, keto-adapted athletes.
Accuracy of advanced CT imaging in prediction of functional outcome after endovascular treatment in patients with large-vessel occlusion

Background and purpose Computed tomography perfusion (CTP) and multiphase CT angiography (mCTA) help selection for endovascular treatment (EVT) in anterior ischemic stroke (AIS). Our aim was to investigate the ability of perfusion maps and collateral score to predict functional outcome after EVT. Patients and methods Patients with M1-middle cerebral artery occlusion, evaluated by mCTA and CTP and treated with EVT within six hours of onset, were enrolled. Perfusion parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time to maximum of tissue residue function (Tmax) were generated; areas of altered perfusion were manually outlined to obtain volumes CBFv, CBVv, T max , v 16 - 25 s and T max , v 9 . 5 - 25 s . Diffusion-weighted imaging (DWI) at 24–36 hours was used to manually outline the ischemic core (volume: DWIv). Collateral vessels were assessed on mCTA considering extent and delay of maximal enhancement (six-point scale). Functional outcome was evaluated by modified Rankin Scale score at three months. Volumes in good and poor outcome groups were compared by Wilcoxon rank-sum test t, and their discriminative ability for outcome was determined by receiver operating characteristic analysis. A logistic regression model, including Tmax, CBF and collaterals, was used to differentiate good and poor outcome. Results Seventy-one patients (mean age 75 ± 11 years, range 45–99 years) were included. T max , v 16 - 25 s , T max , v 9 . 5 - 25 s , CBVv, CBFv and DWIv were statistically different between the two groups. CBF had the best discriminative value for good and poor outcome (area under the curve (AUC) 0.73; 64.5% sensitivity; 74.4% specificity); the logistic regression model might be promising (AUC 0.79, 64.5% sensitivity, 82.1% specificity). Conclusions In patients with AIS, the combined use of CTP and mCTA predicts functional outcome of EVT and might allow better selection.
Diffusion tensor imaging of white matter in patients with prediabetes by trace‐based spatial statistics

Prediabetes is an intermediate state in which blood glucose is higher than normal but does not meet the diagnostic criteria for diabetes. Diffusion tensor imaging (DTI) is an MRI method that can sensitively detect microscopic lesions in the white matter of the brain, but most previous DTI studies only focused on patients with diabetes, and little is known about prediabetes.
The utility of a smartphone‐enabled ophthalmoscope in pre‐clinical fundoscopy training

Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA; Icahn School of Medicine at Mount Sinai, New York, New York, USA; Clinical Sciences Department, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; Department of Ophthalmology, Cedars Sinai Medical Center, Los Angeles, California, USA
Testing New Concepts for Crop Cultivation in Space: Effects of Rooting Volume and Nitrogen Availability

Long term human missions to the Moon and Mars, rely on life support systems for food production and regeneration of resources. In the EU H2020 TIME SCALE-project, an advanced life support system concept was developed to facilitate plant research and technology demonstration under different gravity conditions. Ground experiments assessed irrigation systems and effects of rooting- and nutrient solution volume. The maximal allowed volume for existing International Space Station research facilities (3.4 L) was able to support cultivation of two lettuce heads for at least 24 days. A smaller rooting volume (0.6 L) increased root biomass after 24 days, but induced a 5% reduction in total biomass at day 35. Regulating effects of nitrate supply on plant water fluxes in light and dark were also investigated. At low concentrations of nitrate in the nutrient solution, both transpiration and stomatal conductance increased rapidly with increasing nitrate concentration. During day-time this increase levelled off at high concentrations, while during nigh-time there was a distinct decline at supra optimal concentrations. Plants supplied with nitrate concentrations as low as 1.25 mM did not show visible signs of nutrient stress or growth reduction. These findings hold promise for both reducing the environmental impact of terrestrial horticulture and avoiding nutrient stress in small scale closed cultivation systems for space.
Gait biomechanics after combined HTO‐ACL reconstruction versus HTO alone: A matched cohort study

The purpose of the present study was to compare bilateral external knee moments during gait in patients with concomitant medial compartment knee OA, varus alignment and chronic anterior cruciate ligament (ACL) deficiency who underwent either medial opening‐wedge high tibial osteotomy alone (HTO) or simultaneous HTO and ACL reconstruction (HTO‐ACLR). Fifty‐two patients (26 matched pairs) completed 3D gait analysis preoperatively and at a minimum 5 years postoperatively. Patients were matched for preoperative age, sex, body mass index and magnitude of correction. Primary outcomes selected a priori were the peak knee adduction moment (KAM) and knee flexion (KFM) moment during stance. Moments were compared using mixed model repeated measures analysis of variance (ANOVA). For the peak KAM, there was a significant time by limb interaction. For both groups, there were similar reductions in the peak KAM 5 years postoperatively in the surgical limb only [−1.34 %BW × Ht (−1.71, −0.96) and −1.72 %BW × Ht (−1.99, −1.44) for HTO and HTO‐ACLR, respectively]. For the peak KFM, there was a significant time by group by limb interaction. There was a decrease in the peak KFM 5 years postoperatively in the HTO group [−0.88 %BW × Ht (−1.45, −0.31)] but not in the HTO‐ACLR group [0.03 %BW × Ht (−0.43, 0.48)]. These results suggest that individuals with medial knee OA, varus alignment and chronic ACL deficiency who undergo simultaneous medial opening‐wedge HTO and ACL reconstruction may not experience the same long‐term (5 year) changes in sagittal plane knee biomechanics observed in patients undergoing HTO alone. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Comparing Suicide Risk Factors Among Individuals with a History of Aborted, Interrupted, and Actual Suicide Attempts

Recent standardized nomenclature has suggested distinctions among aborted, interrupted, and actual suicide attempts. This study examined differences in self-reported symptoms among individuals with a history of aborted, interrupted, and actual suicide attempts. 167 young adults with a history of suicidality completed self-report measures of suicide attempt history and current symptoms, a clinical interview assessing past suicidal behavior, and a pain tolerance task. Only 78.8% of participants who initially reported a suicide attempt history were classified as suicide attempters following the clinical interview. Individuals who reported only aborted attempts during the clinical interview reported less severe clinical symptoms than those reporting a history of at least one actual attempt. Individuals with a history of actual suicide attempts may represent a more clinically severe group than those with a history of aborted attempts only.
Arginine in the FARM and SARM: A Role in Chain-Length Determination for Arginine in the Aspartate-Rich Motifs of Isoprenyl Diphosphate Synthases from Mycobacterium tuberculosis †

Isoprenyl chains are found in many important metabolites. These are derived from precursors of the appropriate length produced by isoprenyl diphosphate synthases (IDSs). The human pathogen Mycobacterium tuberculosis makes various isoprenoids/terpenoids, with important roles in their biosynthesis played by two closely related IDSs, encoded by grcC1 (Rv0562) and grcC2 (Rv0989c), with Rv0989c generating the 10-carbon precursor (E)-geranyl diphosphate (GPP), and Rv0562 the 20-carbon precursor (E,E,E)-geranylgeranyl diphosphate (GGPP). Intriguingly, while Rv0562 contains the prototypical trans-IDS first and second aspartate-rich (DDxxD) motifs (FARM and SARM, respectively), Rv0989c uniquely contains arginine in place of the second Asp in the FARM and first Asp in the SARM. Here site-directed mutagenesis of the corresponding residues in both Rv0562 and Rv0989c reveals that these play a role in determination of product chain length. Specifically, substitution of Asp for the Arg in the FARM and SARM of Rv0989c leads to increased production of the longer 15-carbon farnesyl diphosphate (FPP), while substitution of Arg for the corresponding Asp in Rv0562 leads to increased release of shorter products, both FPP and GPP. Accordingly, while the primary role of the FARM and SARM is known to be chelation of the divalent magnesium ion co-factors that assist substrate binding and catalysis, the Arg substitutions found in Rv0989c seem to provide a novel means by which product chain length is moderated, at least in these M. tuberculosis IDSs.
Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors

Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors. Materials and Methods: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels. Results: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes. Conclusion: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.
Glycolysis Paradigm Shift Dictates a Reevaluation of Glucose and Oxygen Metabolic Rates of Activated Neural Tissue

In 1988 two seminal studies were published, both instigating controversy. One concluded that “the energy needs of activated neural tissue are minimal, being fulfilled via the glycolytic pathway alone,” a conclusion based on the observation that neural activation increased glucose consumption, which was not accompanied by a corresponding increase in oxygen consumption (Fox et al., 1988). The second demonstrated that neural tissue function can be supported exclusively by lactate as the energy substrate (Schurr et al., 1988). While both studies continue to have their supporters and detractors, the present review attempts to clarify the issues responsible for the persistence of the controversies they have provoked and offer a possible rationalization. The concept that lactate rather than pyruvate, is the glycolytic end-product, both aerobically and anaerobically, and thus the real mitochondrial oxidative substrate, has gained a greater acceptance over the years. The idea of glycolysis as the sole ATP supplier for neural activation (glucose → lactate + 2ATP) continues to be controversial. Lactate oxidative utilization by activated neural tissue could explain the mismatch between glucose and oxygen consumption and resolve the existing disagreements among users of imaging methods to measure the metabolic rates of the two energy metabolic substrates. The postulate that the energy necessary for active neural tissue is supplied by glycolysis alone stems from the original aerobic glycolysis paradigm. Accordingly, glucose consumption is accompanied by oxygen consumption at 1–6 ratio. Since Fox et al. (1988) observed only a minimal if non-existent oxygen consumption compared to glucose consumption, their conclusion make sense. Nevertheless, considering (a) the shift in the paradigm of glycolysis (glucose → lactate; lactate + O2 + mitochondria → pyruvate → TCA cycle → CO2 + H2O + 17ATP); (b) that one mole of lactate oxidation requires only 50% of the amount of oxygen necessary for the oxidation of one mole of glucose; and (c) that lactate, as a mitochondrial substrate, is over eight times more efficient at ATP production than glucose as a glycolytic substrate, suggest that future studies of cerebral metabolic rates of activated neural tissue should include along with the measurements of CMRO2 and CMRglucose the measurement of CMRlactate.
The Formation of the Goldfish-Like Fish Derived From Hybridization of Female Koi Carp × Male Blunt Snout Bream

Goldfish (Carassius auratus var., GF; 2n = 100) is the most popular ornamental fish in the world. It is assumed that GF evolved from red crucian carp (C. auratus red var., RCC; 2n = 100). However, this hypothesis lacks direct evidence. Furthermore, our knowledge of the role of hybridization in the formation of new species is sparse. In this study, goldfish-like fish with twin tails (GF-L; 2n = 100) was produced by self-mating red crucian carp-like fish (RCC-L; 2n = 100) derived from the distant crossing of koi carp (Cyprinus carpio haematopterus, KOC; 2n = 100; ♀) with blunt snout bream (Megalobrama amblycephala, BSB; 2n = 48; ♂). The phenotypes and genotypes of GF-L and RCC-L were very similar to those of GF and RCC, respectively. Microsatellite DNA and 5S rDNA analyses revealed that GF-L and RCC-L were closely related to GF and RCC, respectively. The presence of a twin tail of GF-L was related to a base mutation in chordinA from G in RCC-L to T in GF-L, indicating that the lineage of RCC-L and GF-L can be used to study gene variation and function. The sequences of 5S rDNA in GF-L and RCC-L were mapped to the genomes of CC and BSB, which revealed that the average similarities of both GF-L and RCC-L to CC were obviously higher than those to BSB, supporting that the genomes of both RCC-L and GF-L were mainly inherited from KOC. GF-L and RCC-L were homodiploids that were mainly derived from the genome of KOC with some DNA fragments from BSB. The reproductive traits of GF-L and RCC-L were quite different from those of their parents, but were the same as those of GF and RCC. RCC-L easily diversified into GF-L, suggesting that RCC and GF evolved within the same period in their evolutionary pathway. This study provided direct evidence of the KOC–RCC–GF evolutionary pathway that was triggered by distant hybridization, which had important significance in evolutionary biology and genetic breeding.
Cubic Regularization with Momentum for Nonconvex Optimization

Momentum is a popular technique to accelerate the convergence in practical training, and its impact on convergence guarantee has been well-studied for first-order algorithms. However, such a successful acceleration technique has not yet been proposed for second-order algorithms in nonconvex optimization.In this paper, we apply the momentum scheme to cubic regularized (CR) Newton's method and explore the potential for acceleration. Our numerical experiments on various nonconvex optimization problems demonstrate that the momentum scheme can substantially facilitate the convergence of cubic regularization, and perform even better than the Nesterov's acceleration scheme for CR. Theoretically, we prove that CR under momentum achieves the best possible convergence rate to a second-order stationary point for nonconvex optimization. Moreover, we study the proposed algorithm for solving problems satisfying an error bound condition and establish a local quadratic convergence rate. Then, particularly for finite-sum problems, we show that the proposed algorithm can allow computational inexactness that reduces the overall sample complexity without degrading the convergence rate.
Improved diabetes medication convenience and satisfaction in persons with type 2 diabetes after switching to insulin glargine 300 U/mL: results of the observational OPTIN-D study

Objective Insulin glargine 300 (Gla-300) provides less hypoglycemia risk and more flexibility in injection time. The extent to which these effects translate into improved patient-reported outcomes (PROs) is unknown, and is the subject of this observational study. Research design and methods Adults with type 2 diabetes treated with basal insulin for at least 6 months initiating Gla-300 were included. Data were collected at baseline (start Gla-300) and at 3-month and 6-month follow-up. Patients and physicians gave reasons for switching to Gla-300 at baseline and the extent to which Gla-300 fulfilled their expectations at 6 months. Mixed model analyses examined PRO changes over time, with emotional well-being (WHO-5 Well-Being Index) as the primary outcome. The secondary outcomes were hypoglycemia incidence, hemoglobin A1c (HbA1c), hypoglycemia worries (worry subscale of the Hypoglycemia Fear Survey), diabetes distress (short form of the Dutch version of the Problem Areas In Diabetes Scale), diabetes medication convenience (Diabetes Medication System Rating Questionnaire (DMSRQ)), sleep quality and duration (Pittsburgh Sleep Quality Index), and adherence (Summary of Diabetes Self-Care Activities). Results 162 patients participated: 53.70% were men, the mean age was 65.54 years (9.05), baseline mean HbA1c was 7.87% (1.15) (62.48 mmol/mol (12.61)), and mean diabetes duration was 15.14 years (6.65). Mean WHO-5 Well-Being Index scores improved non-significantly from 61.94 (19.52) at baseline (T0) to 63.83 (19.67) at 6 months (T2). Mean DMSRQ scores improved significantly from 32.96 (9.02) (T0) to 36.70 (8.85) (T2) (p<0.001). Dose (less volume) was a switching reason in 69.60% of patients and 63% of physicians, and flexibility in 33.30% and 24.70%, respectively. Gla-300 fulfilled the expectations or even better than expected in 92.30% of patients and 88.90% of physicians. Conclusion In a relatively well-controlled sample of adults with type 2 diabetes, switching to Gla-300 improves diabetes medication convenience.