Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone Morophogenetic Protein Application as Grafting Materials for Bone Regeneration in Craniofacial Surgery: Current Application and Future Directions

Copyright © 2021 Mutaz B. Habal, MD. Unauthorized reproducti From the Department of Biomedical and Dental Sciences and Morphological and Functional Images, University of Messina, Messina, Italy. Received May 6, 2020. Accepted for publication June 22, 2020. Address correspondence and reprint requests to Prof. Marco Cicciù, DDS, PhD, Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98100 Messina, Italy; E-mail: acromarco@yahoo.it, mcicciu@unime.it The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jcraniofacialsurgery.com). Copyright # 2020 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000006937
Inflammatory markers and incident heart failure in older men: the role of NT-proBNP

Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01–1.98] and 1.71 [1.24–2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81–1.63] and 1.25 [0.89–1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF.
Modified Nasoseptal Rescue Flap Technique for Pituitary Adenoma Resection via Endoscopic Endonasal Approach

Supplemental Digital Content is available in the text Abstract Nasoseptal rescue flap (NSRF), which preserves the pedicle of the flap and is harvested as a nasoseptal flap (NSF) when intraoperative leakage of cerebrospinal fluid (CSF) occurs, is an alternative strategy for skull base reconstruction in patients with pituitary adenoma resection via an endoscopic endonasal approach. However, in practice, the original NSRF technique cannot meet the needs during operation. Therefore, the authors aimed to describe a modified NSRF technique for the resection of pituitary adenoma via endoscopic endonasal approach and to examine its utility and outcomes. The authors retrospectively analyzed the medical records of 87 consecutive patients with pituitary adenoma who underwent endoscopic endonasal surgery performed using NSRF technique from September 2019 to August 2020. Data on intraoperative CSF leakage, NSF conversion rate, and reconstruction-related complications were analyzed. The average age of patients was 50.1 years (men, 50.5%). Twenty-five cases of intraoperative CSF leakage were observed: 23 cases of low-flow CSF leakage and two cases of high-flow CSF leakage. NSRF was converted to NSF in 11 cases. Two patients experienced postoperative CSF leakage after reconstruction without NSF and required unplanned reoperation to rebuild the skull base with NSF. In conclusion, this modified NSRF utilized a minimally invasive way to provide sufficient surgical corridor without the need for pedicle retraction, and it can be effectively converted to an NSF for skull base reconstruction in patients with pituitary adenoma.
Therapeutic Assessment of Combination Therapy with a Neprilysin Inhibitor and Angiotensin Type 1 Receptor Antagonist on Angiotensin II–Induced Atherosclerosis, Abdominal Aortic Aneurysms, and Hypertension

Combined neprilysin (NEP) inhibition (sacubitril) and angiotensin type 1 receptor (AT1R) antagonism (valsartan) is used in the treatment of congestive heart failure and is gaining interest for other angiotensin II (AngII)-related cardiovascular diseases. In addition to heart failure, AngII promotes hypertension, atherosclerosis, and abdominal aortic aneurysms (AAAs). Similarly, NEP substrates or products have broad effects on the cardiovascular system. In this study, we examined NEP inhibition (with sacubitril) and AT1R antagonism (with valsartan) alone or in combination on AngII-induced hypertension, atherosclerosis, or AAAs in male low-density lipoprotein receptor–deficient mice. Preliminary studies assessed drug delivery via osmotic minipumps for simultaneous release of sacubitril and/or valsartan with AngII over 28 days. Mice were infused with AngII (1000 ng/kg per minute) in the absence (vehicle) or presence of sacubitril (1, 6, or 9 mg/kg per day), valsartan (0.3, 0.5, 1, 6, or 20 mg/kg per day), or the combination thereof (1 and 0.3, or 9 or 0.5 mg/kg per day of sacubitril and valsartan, respectively). Plasma AngII and renin concentrations increased 4-fold at higher valsartan doses, indicative of removal of AngII negative feedback on renin. Sacubitril doubled plasma AngII concentrations at lower doses (1 mg/kg per day). Valsartan dose-dependently decreased systolic blood pressure, aortic atherosclerosis, and AAAs of AngII-infused mice, whereas sacubitril had no effect on atherosclerosis or AAAs but reduced blood pressure of AngII-infused mice. Combination therapy with sacubitril and valsartan did not provide additive benefits. These results suggest limited effects of combination therapy with NEP inhibition and AT1R antagonism against AngII-induced hypertension, atherosclerosis, or AAAs. SIGNIFICANCE STATEMENT The combination of valsartan (angiotensin type 1 receptor antagonist) and sacubitril (neprilysin inhibitor) did not provide benefit above valsartan alone on AngII-induced hypertension, atherosclerosis, or abdominal aortic aneurysms in low-density lipoprotein receptor–deficient male mice. These results do not support this drug combination in therapy of these AngII-induced cardiovascular diseases.
Knockdown of Annexin-A1 Inhibits Growth, Migration and Invasion of Glioma Cells by Suppressing the PI3K/Akt Signaling Pathway

ANXA1, which can bind phospholipid in a calcium dependent manner, is reported to play a pivotal role in tumor progression. However, the role and mechanism of ANXA1 involved in the occurrence and development of malignant glioma are still not well studied. Therefore, we explored the effects of ANXA1 on normal astrocytes and glioma cell proliferation, apoptosis, migration and invasion and the underlying mechanisms. We found that ANXA1 was markedly up-regulated in glioma cell lines and glioma tissues. Down-regulation of ANXA1 inhibited normal astrocytes and glioma cell proliferation and induced the cell apoptosis, which suggested that the consequences of loss of Annexin 1 are not specific to the tumor cells. Furthermore, the siRNA-ANXA1 treatment significantly reduced tumor growth rate and tumor weight. Moreover, decreasing ANXA1 expression caused G2/M phase arrest by repressing expression levels of cdc25C, cdc2 and cyclin B1. Interestingly, ANXA1 did not affect the expressions of β-catenin, GSK-3β and NF-κB, the key signaling molecules associated with cancer progression. However, siRNA-ANXA1 was found to negatively regulate phosphorylation of AKT and the expression and activity of MMP2/-9. Finally, the decrease of cell proliferation and invasiveness induced by ANXA1 down-regulation was partially reversed by combined treatment with AKT agonist insulin-like growth factor-1 (IGF-1). Meanwhile, the inhibition of glioma cell proliferation and invasiveness induced by ANXA1 down-regulation was further enhanced by combined treatment with AKT inhibitor LY294002. In summary, these findings demonstrate that ANXA1 regulates proliferation, migration and invasion of glioma cells via PI3K/AKT signaling pathway.
Magnetic characteristics of R2Fe14B systems prepared with high purity rare earths (R=Ce, Pr, Dy, and Er)

Commercial rare earth metals contain several atomic % oxygen, and intermetallics synthesized using these ingredients deviate markedly from the intended compositions. In this work, high purity rare earths (<20 ppm oxygen by weight) were used. Results for R2Fe14B systems with R = Y, Nd, Sm, or Gd have been previously reported. The earlier work has now been extended to include systems containing Ce, Pr, Dy and Er. All were ordered magnetically at room temperature, with Curie temperatures ranging from 437 K (Ce) to 592 K (Dy). Results suggest that Ce in this system exists in the quadripositive state. Saturation magnetizations (77 K) are 29.4, 34.8, 12.1, and 14.7 μB/formula unit, respectively, for R = Ce, Pr, Dy, and Er. These may be contrasted with 30.4 μB/f.u. for Y2Fe14B, which is the Fe magnetization alone. These results imply ferromagnetic coupling for Pr2Fe14B and antiferromagnetic coupling for the Dy and Er compounds. Room temperature anisotropy fields ranged from 37 kOe (R = Ce) to 158 kOe (R = Dy). E.
Systematic Review of Treatments for Colorectal Metastases in Elderly Patients to Guide Surveillance Cessation Following Hepatic Resection for Colorectal Liver Metastases

Background: Although included in surveillance programmes for colorectal cancer (CRC) metastases, elderly patients are susceptible to declines in health and quality of life that may render them unsuitable for further surveillance. Deciding when to cease surveillance is challenging. Methods: There are no publications focused on surveillance of elderly patients for CRC metastases. A systematic review of studies reporting treatment outcomes for CRC metastases in elderly patients was performed to assess the risk-benefit balance of the key objectives of surveillance; detecting and treating CRC metastases. Results: Sixty-eight eligible studies reported outcomes for surgery and chemotherapy in the elderly. Liver resections and use of chemotherapy, including biologics, are more conservative and have poorer outcomes in the elderly compared with younger patients. Selected studies demonstrated poorer quality-of-life (QoL) following surgery and chemotherapy. Studies of ablation in elderly patients are limited. Discussion: The survival benefit of treating CRC metastases with surgery or chemotherapy decreases with advancing age and QoL may decline in the elderly. The relatively lower efficacy and detrimental QoL impact of multimodal therapy options for detected CRC metastases in the elderly questions the benefit of surveillance in some elderly patients. Care of elderly patients should thus be customized based on their preference, formal geriatric assessment, natural life-expectancy, and the perceived risk-benefit balance of treating recurrent CRC metastases. Clinicians may consider surveillance cessation in patients aged 75 years and above if geriatric assessment is unsatisfactory, patients decline surveillance, or patient fitness deteriorates catastrophically.
Functional differences and similarities in activated peripheral blood mononuclear cells by lipopolysaccharide or phytohemagglutinin stimulation between human and cynomolgus monkeys

Background The monkey is a primary species used in toxicological research. However, the failures of preclinical studies to predict a life-threatening “cytokine storm”, which, for instance, rapidly occurred in six healthy volunteers with the CD28 superagonist monoclonal antibody (mAb) TGN1412 in the first-in-human phase I clinical trial, have emphasized a need to clarify the differences between human and monkey immune systems. Methods In the present study, we analyzed and compared the lymphocyte proliferation, cytokine secretion, and gene expression profiles after phytohemagglutinin (PHA) and lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMCs) from three healthy humans and cynomolgus monkeys (Macaca fascicularis). Results The results derived from comparison with the corresponding control groups showed that PHA in humans induced a stronger proliferation and wider range of cytokine secretion, along with a greater number of differently expressed genes (DEGs), than when PHA was applied in cynomolgus monkeys. The significant upregulation of genes involved in the mitotic cell cycle, including cyclin B2, TOP2A, TYMS, and CEP55, was observed in human PBMCs with PHA stimulation, while only infrequent or slight upregulation occurred in cynomolgus monkey PBMCs, which may be one of the reasons for a stronger response to PHA in humans. In contrast to PHA, LPS in both species induced a similar proliferation ratio, cytokine profile, and DEG count, suggesting that human and cynomolgus monkeys have a similar response intensity for innate immune responses. Furthermore, 38 and 20 overlapped genes under PHA and LPS stimulation, respectively, were found in both species. These overlapped DEGs were associated with the same biological functions, including DNA replication, mitosis, immune response, chemotaxis, and inflammatory response. Thus, these results might reflect the highly conserved signatures of immune responses to PHA/LPS stimulation across the primates. Moreover, there were some differences in antigen processing and presentation, and the interferon gamma (INF-γ)–mediated signaling pathway in these species detected by gene expression profile study. Conclusions In conclusion, this is the first study to compare data on the responses of PBMCs to PHA and LPS in humans versus cynomolgus monkeys, and these findings may provide crucial insights into translating non-human primate (NHP) studies into human trials.
Development of the VISAGE enhanced tool and statistical models for epigenetic age estimation in blood, buccal cells and bones

DNA methylation is known as a biomarker for age with applications in forensics. Here we describe the VISAGE (VISible Attributes through GEnomics) Consortium’s enhanced tool for epigenetic age estimation in somatic tissues. The tool is based on eight DNA methylation markers (44 CpGs), bisulfite multiplex PCR followed by sequencing on the MiSeq FGx platform, and three statistical prediction models for blood, buccal cells and bones. The model for blood is based on six CpGs from ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59 and PDE4C, and predicts age with a mean absolute error (MAE) of 3.2 years, while the model for buccal cells includes five CpGs from PDE4C, MIR29B2CHG, ELOVL2, KLF14 and EDARADD and predicts age with MAE of 3.7 years, and the model for bones has six CpGs from ELOVL2, KLF14, PDE4C and ASPA and predicts age with MAE of 3.4 years. The VISAGE enhanced tool for age estimation in somatic tissues enables reliable collection of DNA methylation data from small amounts of DNA using a sensitive multiplex MPS assay that provides accurate estimation of age in blood, buccal swabs, and bones using the statistical model tailored to each tissue.
Methane and carbon dioxide hydrate formation in water droplets: Spatially resolved measurements from magnetic resonance microimaging

We have used 1H magnetic resonance microimaging to probe both methane and carbon dioxide hydrate formation processes inside dispersed water droplets. When bulk techniques such as gas uptake measurements are used for determining the kinetics of hydrate formation, these show a gradual conversion to hydrate, suggesting a relatively homogeneous process that might be modeled using a set of intrinsic kinetic parameters. The spatially resolved microimaging measurements show that in fact the conversion to hydrate is quite inhomogeneous, some drops converting quickly, others requiring hours or days. This indicates that the observation of gradual conversion in bulk samples only arises as a result of averaging over many local environments. Quantitative measurements of kinetic processes in subvolumes of a larger sample suggests that the smaller the volume observed, the more inhomogeneous the process appears to be. When hydrate-coated water droplets in 3,5,5-trimethylpentane are converted to hydrate, there is evidence.
The Third Man: DNA sensing as espionage in pulmonary vascular health and disease

For as long as nucleic acids have been utilized to vertically and horizontally transfer genetic material, living organisms have had to develop methods of recognizing cytosolic DNA as either pathogenic (microbial invasion) or physiologic (mitosis and cellular proliferation). Derangement in key signaling molecules involved in these pathways of DNA sensing result in a family of diseases labeled interferonopathies. An interferonopathy, characterized by constitutive expression of type I interferons, ultimately manifests as severe autoimmune disease at a young age. Afflicted patients present with a constellation of immune-mediated conditions, including primary lung manifestations such as pulmonary fibrosis and pulmonary hypertension. The latter condition is especially interesting in light of the known role that DNA damage plays in a variety of types of inherited and induced pulmonary hypertension, with free DNA detection elevated in the circulation of affected individuals. While little is known regarding the role of cytosolic DNA sensing in development of pulmonary vascular disease, exciting new research in the related fields of immunology and oncology potentially sheds light on future areas of fruitful exploration. As such, the goal of this review is to summarize the state of the field of nucleic acid sensing, extrapolating common shared pathways that parallel our knowledge of pulmonary hypertension, in a molecular and cell-specific manner. Principles of DNA sensing related to known pulmonary injury inducing stimuli are also evaluated, in addition to potential therapeutic targets. Finally, future directions in pulmonary hypertension research and treatments will be briefly discussed.
People use both heterogeneity and minority representation to evaluate diversity

Americans think of racial diversity in terms of heterogeneity; Blacks, Latinos, and Asians also weigh minority presence. The term “diversity,” although widely used, can mean different things. Diversity can refer to heterogeneity, i.e., the distribution of people across groups, or to the representation of specific minority groups. We use a conjoint experiment with a race-balanced, national sample to uncover which properties, heterogeneity or minority representation, Americans use to evaluate the extent of racial diversity a neighborhood and whether this assessment varies by participants’ race. We show that perceived diversity is strongly associated with heterogeneity. This association is stronger for Whites than for Blacks, Latinos, or Asians. In addition, Blacks, Latinos, and Asians view neighborhoods where their own group is largest as more diverse. Whites vary in their tendency to associate diversity with representation, and Whites who report conservative stances on diversity-related policy issues view predominately White neighborhoods as more diverse than predominately Black neighborhoods. People can agree that diversity is desirable while disagreeing on what makes a community diverse.
Enigmatic “love bites” and an indirect mating plug: revision of Thunberga Jäger, 2020 with description of new species (Araneae: Sparassidae: Heteropodinae)

Abstract The huntsman spider genus Thunberga Jäger, 2020 is revised. Twenty-five species are described for the first time: Thunberga aliena spec. nov. (♂), T. befotaka spec. nov. (♂), T. boyanslat spec. nov. (♀), T. cala spec. nov. (♀), T. conductor spec. nov. (♂, ♀), T. daraina spec. nov. (♂, ♀), T. elongata spec. nov. (♀), T. gosura spec. nov. (♀), T. jaervii spec. nov. (♀), T. jyoti spec. nov. (♀), T. mafira spec. nov. (♂, ♀), T. malala spec. nov. (♂, ♀), T. mama spec. nov. (♂, ♀), T. matoma spec. nov. (♀), T. milloti spec. nov. (♂), T. paulyi spec. nov. (♂, ♀), T. panusilem spec. nov. (♀), T. platnicki spec. nov. (♂, ♀), T. rothorum spec. nov. (♂), T. rugosa spec. nov. (♀), T. samsagala spec. nov. (♂), T. soruag spec. nov. (♀), T. v-insignita spec. nov. (♀), T. wasserthali spec. nov. (♀), T. woodae spec. nov. (♂, ♀). The male of T. greta is described for the first time. One species is transferred to Thunberga: T. laterifusca (Strand, 1908) comb. nov. (from Eusparassus), it is considered a nomen dubium. The distribution range of the genus includes now Madagascar with adjacent islands and Mayotte. Photos of living spiders are shown for the first time revealing a possible new diagnostic character: a small white patch in front of the fovea. Another new diagnostic character is a distal V- to U-shaped field of bristles situated ventrally on metatarsus IV, the metatarsus III exhibits ventro-distally a short to very stout bristle embedded in a scopula. Metatarsi I and II possess only scopula without bristles distally. In the female genitalia, plugs were observed not only at the copulatory openings, but in few cases also at the unpaired anterior pocket, the first known case within the Entelegynae that structures other than the copulatory openings are plugged. Externally recognisable mating plugs to various degrees were found in twelve out of twenty-three species known from females. Sixteen of these exhibited paired scars at the dorsal prosoma. It is hypothesized that males grab the females with their chelicerae and cause small punctuations in the cuticle (so-called “love bites”). Morphological and possible behavioural characters of Thunberga species are discussed.
An extension to the universal time scale for vortex ring formation

Abstract The formation of vortex rings emanating from orifices with different orifice-to-tube diameter ratios $D_0/D_p$ is studied using time-resolved particle image velocimetry. The invariants of the motion in their non-dimensional form are computed and presented in the non-dimensional time space $t^*=U_0 t/D_0$, where the subscript 0 refers to the exhaust quantities. The classic slug-flow model is revisited and extended to account for the contraction of the flow when fluid is being pushed out through the orifice. Accordingly, a new time scale in terms of the contracted quantities (subscript $\star$) is defined as $T^*=U_\star t/D_\star$. Results show that the modified slug-flow model unifies the formation number of orifices and straight nozzles with a value of approximately 4.
Momentum and energy transfer in open-channel flow over streamwise ridges

Abstract Stereoscopic particle image velocimetry measurements of open-channel flows over streamwise-orientated triangular-shaped ridges were used to explore interactions between ridge-induced secondary currents (SCs) and turbulence. Terms in the double-averaged (in space and in time) momentum and energy conservation equations were analysed for a range of ridge spacings ($s$) between 0.4 and 4.0 flow depths ($H$). The double-averaged equations neatly partition momentum and energy fluxes into turbulence and SC contributions, making them well suited to this study. The obtained data indicate that for a range of $s/H$ between 0.4 and 2.0, the normalised momentum and energy fluxes due to SCs approximately collapse when plotted as functions of $(z-d)/s$, where $z$ is the vertical coordinate and $d$ a constant that aligns the elevations of SC cell centres. The SCs controlled the shape of the mean velocity distribution with the vertical gradient of the double-averaged streamwise velocity found to be inversely proportional to $s$ near the elevations of SC cell centres. Partitioning the total kinetic energy into double-mean (DMKE), dispersive (DKE) and turbulent (SATKE) components and considering the balance equation for each component indicated that at the elevation of SC cell centres the production rate of SATKE via exchange with DMKE was comparable in magnitude to the production rate via exchange with DKE (due to SCs). For all ridge spacings, SATKE was reduced compared to a no-ridge benchmark case due to suppression of very-large-scale turbulent motions by the SCs. Finally, it is demonstrated that energy is supplied to SCs by turbulence.