Miracle-dz/UniFAR-FTUs huggingface dataset:
Interventional hepatic apoC-III knockdown improves atherosclerotic plaque stability and remodeling by triglyceride lowering

Apolipoprotein C-III (apoC-III) is a critical regulator of triglyceride metabolism and correlates positively with hypertriglyceridemia and cardiovascular disease (CVD). It remains unclear if therapeutic apoC-III lowering reduces CVD risk and if the CVD correlation depends on the lipid-lowering or antiinflammatory properties. We determined the impact of interventional apoC-III lowering on atherogenesis using an apoC-III antisense oligonucleotide (ASO) in 2 hypertriglyceridemic mouse models where the intervention lowers plasma triglycerides and in a third lipid-refractory model. On a high-cholesterol Western diet apoC-III ASO treatment did not alter atherosclerotic lesion size but did attenuate advanced and unstable plaque development in the triglyceride-responsive mouse models. No lesion size or composition improvement was observed with apoC-III ASO in the lipid-refractory mice. To circumvent confounding effects of continuous high-cholesterol feeding, we tested the impact of interventional apoC-III lowering when switching to a cholesterol-poor diet after 12 weeks of Western diet. In this diet switch regimen, apoC-III ASO treatment significantly reduced plasma triglycerides, atherosclerotic lesion progression, and necrotic core area and increased fibrous cap thickness in lipid-responsive mice. Again, apoC-III ASO treatment did not alter triglyceride levels, lesion development, and lesion composition in lipid-refractory mice after the diet switch. Our findings suggest that interventional apoC-III lowering might be an effective strategy to reduce atherosclerosis lesion size and improve plaque stability when lipid lowering is achieved.
CORRELATION BETWEEN THE MORPHOMETRIC PARAMETERS OF MAXILLARY SINUSES AND NASAL APERTURES AS A FORENSIC IDENTIFICATION AID USING CONE BEAM CT: A PILOT STUDY

Objectives: Bone remodelling of the cranium determines the enlargement of the maxillary sinuses. The process involves the resorption of the internal walls of the maxillary sinus that slightly exceed the growth of the maxilla. During this process, bone deposition occurs at the medial border of the nasal cavity as does simultaneous resorption of the lateral wall of the nasal cavity. Very few studies have investigated the correlation between the growth of the maxillary sinuses with changes in the dimensions of the nasal aperture. Therefore, the present study aimed to determine, compare and correlate the three-dimensional morphometric parameters of the maxillary sinus and nasal apertures in a study population from the states of Karnataka and Kerala in India, to utilize the data for the purpose of individual identification, sexual dimorphism or any other application in the field of forensic facial reconstruction and/or human identification. Materials and Methods: This pilot study analysed the measurements of the morphometric landmarks of the maxillary sinus and the nasal aperture of 20 subjects, ranging in age from 18 to 30. Results: The Morphometric parameters of the maxillary sinus and the nasal aperture were seen to be statistically significant in a few of the groups, and these findings can be applied to evaluate sexual dimorphism. Conclusions: The maxillary sinuses remain intact even though the skull and other bones of the cranium may be severely disfigured in victims that are incinerated or that have experienced external trauma. Morphometric measurements, such as width, depth and height which were used to investigate the accuracy and reliability of the maxillary sinuses, can also be used for sex estimation. These dimensions can be correlated with the measurements of the nasal aperture, which will also provide an insight into the development of the cranium. Moreover, these measurements are important anthropometric parameters for classifying the race and sex of an individual whose identity is unknown.
“Investor sentiment measurement based on technical analysis indicators affecting stock returns: Empirical evidence on VN100”

ARTICLE INFO Lai Cao Mai Phuong and Vu Cam Nhung (2021). Investor sentiment measurement based on technical analysis indicators affecting stock returns: Empirical evidence on VN100. Investment Management and Financial Innovations, 18(4), 297-308. doi:10.21511/imfi.18(4). 2021.25 DOI http://dx.doi. org/10.21511/imfi.18(4). 2021.25 RELEASED ON Friday, 03 December 2021 RECEIVED ON Monday, 18 October 2021
Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters

An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.
Suicide crises among women and mothers during and around the time of pregnancy: Prevalence and timing of initial contact with first responders and health services

Objectives: Suicide is a leading cause of maternal mortality. Suicidality during and around the time of pregnancy can have detrimental impacts on a child’s development and outcomes. This paper examines prevalence, demographic characteristics, and timing of initial contact with first responders and health services for a cohort of women who experienced suicidality during and around the time of pregnancy. Methods: Findings are drawn from the Partners in Prevention (PiP) study, a population-wide linked data set of suicide-related attendances by police or paramedics in Queensland, Australia. A sub-cohort of women was identified, who were between 6 months preconception and 2 years postpartum at the time of a suicide-related contact with police or paramedics (PiP-Maternal). Findings are compared to other girls and women who had a suicide-related contact with police or paramedics (PiP-Female). Prevalence, demographic characteristics, timing of contact with first responders and health services, re-presentations, and mortality are reported. Results: The PiP-Maternal cohort comprised 3020 individuals and 3400 births. Women in the PiP-Maternal cohort were younger, more likely to be of Aboriginal and/or Torres Strait Islander descent and live outside of a major city than the PiP-Female cohort. There were high rates of out-of-hours calls to police and ambulance, and similar perceived seriousness of the call between women in the PiP-Maternal and PiP-Female cohorts. Women in the PiP-Maternal cohort were less likely to be admitted to an emergency department within 24 hours, even after matching on covariates. Prevalence of suicidality for women who were pregnant and up to 2 years postpartum was 1.32% (95% CI = [1.27, 1.37]). Conclusion: Vulnerabilities and high rates of contact with police or paramedics, coupled with lower levels of follow-up, highlight the critical need to improve service responses for women with mental health needs during these phases of life.
Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by Yersinia pestis depends on the U.S. Food and Drug Administration Animal Rule testing pathway, as testing in humans is not feasible. Here, preclinical studies were conducted in the African green monkey (AGM) inhalational model of pneumonic plague to test the efficacy of gepotidacin. AGMs infected with Y. pestis were dosed intravenously with gepotidacin (48, 36, or 28 milligrams/kilogram per day) for 10 days to provide a plasma concentration that would support a rationale for a 1000 mg twice or thrice daily intravenous dose in humans or saline as a control. The primary end point was AGM survival with predefined euthanasia criteria. Secondary end points included survival duration and bacterial clearance. Gepotidacin showed activity in vitro against diverse Y. pestis isolates including antibiotic-resistant strains. All control animals in the inhalational plague studies succumbed to plague and were blood culture and organ culture positive for Y. pestis. Gepotidacin provided a 75 to 100% survival benefit with all dose regimens. All surviving animals were blood culture and organ culture negative for Y. pestis. Our randomized, controlled efficacy trials in the AGM pneumonic plague nonhuman primate model together with the in vitro Y. pestis susceptibility data support the use of gepotidacin as a treatment for pneumonic plague caused by Y. pestis. Description Gepotidacin, a first-in-class triazaacenaphthylene antibacterial agent, shows efficacy in nonhuman primates for treating pneumonic plague. A new antibiotic for treating pneumonic plague Mortality rates from infection with Yersinia pestis are nearly 100% without treatment. Jakielaszek et al. now show that the triazaacenaphthylene antibacterial compound gepotidacin is active against a variety of Y. pestis strains in vitro, including strains resistant to other antibacterial agents. The authors demonstrate that gepotidacin is efficacious in a well-characterized, inhalational model of pneumonic plague in nonhuman primates at gepotidacin exposures that have been achieved in humans.
Positive Selection of Mutations in the Helicobacter pylori katA 5′ Untranslated Region in a Mongolian Gerbil Model of Gastric Disease

To evaluate potential effects of gastric inflammation on Helicobacter pylori diversification and evolution within the stomach, we experimentally infected Mongolian gerbils with an H. pylori strain in which Cag type IV secretion system (T4SS) activity is controlled by a TetR/tetO system. Gerbils infected with H. pylori under conditions in which Cag T4SS activity was derepressed had significantly higher levels of gastric inflammation than gerbils infected under conditions with repressed Cag T4SS activity. ABSTRACT To evaluate potential effects of gastric inflammation on Helicobacter pylori diversification and evolution within the stomach, we experimentally infected Mongolian gerbils with an H. pylori strain in which Cag type IV secretion system (T4SS) activity is controlled by a TetR/tetO system. Gerbils infected with H. pylori under conditions in which Cag T4SS activity was derepressed had significantly higher levels of gastric inflammation than gerbils infected under conditions with repressed Cag T4SS activity. Mutations in the 5′ untranslated region (UTR) of katA (encoding catalase) were detected in strains cultured from 8 of the 17 gerbils infected with Cag T4SS-active H. pylori and none of the strains from 17 gerbils infected with Cag T4SS-inactive H. pylori. Catalase enzymatic activity, steady-state katA transcript levels, and katA transcript stability were increased in strains with these single nucleotide polymorphisms (SNPs) compared to strains in which these SNPs were absent. Moreover, strains harboring these SNPs exhibited increased resistance to bactericidal effects of hydrogen peroxide, compared to control strains. Experimental introduction of the SNPs into the wild-type katA 5′ UTR resulted in increased katA transcript stability, increased katA steady-state levels, and increased catalase enzymatic activity. Based on site-directed mutagenesis and modeling of RNA structure, increased katA transcript levels were correlated with higher predicted thermal stability of the katA 5′ UTR secondary structure. These data suggest that high levels of gastric inflammation positively select for H. pylori strains producing increased levels of catalase, which may confer survival advantages to the bacteria in an inflammatory gastric environment.
Risk Factor Assessment for Survival of Removable Partial Dentures and Their Abutment Teeth: A Retrospective Analysis.

PURPOSE To investigate the risk factors related to failure of removable partial dentures (RPDs) and to compare the survival of RPDs when abutment teeth have good vs reduced bone support. MATERIALS AND METHODS In this longitudinal patient record-based cohort study with a mean follow-up of 44.9 months, Cox regression models were used to evaluate the associations between clinical covariates and abutment tooth failure, as well as prosthesis failure. RESULTS A total of 142 patients and 172 RPDs were included. Of the 172 prostheses, 64 (nearly 40%) failed after a mean time of about 4 years. Loss of abutment teeth was the main reason leading to RPD failure, followed closely by poor fit and adaptation. No factor was shown to be statistically significant at the prosthesis level. Women (Hazard Ratio [HR] = 0.542), endodontic treatment (HR = 3.460), presence of post and core (HR = 0.302), presence of a prosthetic crown (HR = 3.403), and abutment tooth type (in relation to incisor: canine HR = 0.196, premolar HR = 0.449) were the risk factors statistically significantly associated with the loss of abutment teeth. The pre-prosthesis amount of bone support of the teeth did not affect their prognosis as abutments for RPDs. CONCLUSION RPD treatment modality presented a high failure rate after a mean follow-up of 4 years. Vital abutment teeth had a better survival rate than the ones treated endodontically (whether restored with or without a post and core); nevertheless, the amount of bone support did not affect their survival.
Cardiac inducing colonies halt fibroblast activation and induce cardiac/endothelial cells to move and expand via paracrine signaling

Myocardial fibrosis (MF), a common event that develops after myocardial infarction, initially is a reparative process but eventually leads to heart failure and sudden cardiac arrest. In MF, the infarct area is replaced by a collagenous-based scar induced by “excessive” collagen deposition from activated cardiac fibroblasts. The scar prevents ventricular wall thinning; however, over time it expands to noninfarcted myocardium. Therapies to prevent fibrosis include reperfusion, anti-fibrotic agents, and ACE inhibitors. Paracrine factor (PF)/stem cell research has recently gained significance as a therapy. We consistently find that cardiac inducing colonies (CiCs) (derived from human germline pluripotent stem cells) secrete PFs at physiologically relevant concentrations that suppress cardiac fibroblast activation and excessive extracellular matrix protein secretion. These factors also affect human cardiomyocytes and endothelial cells by inducing migration/proliferation of both populations into a myocardial wound model. Finally, CiC factors modulate matrix turnover and proinflammation. Taking the results together, we show that CiCs could help tip the balance from fibrosis toward repair.
A New Model for Estimating Vibrations Generated in the Defective Rolling Element Bearings of the vibration response due to defects on rolling element bearings requires

having an accurate representative vibration model. In this paper, a new model for vibration generation in the rolling element bearings has been introduced. The proposed model assumes a stochastic source of vibration excitation, which is produced as a result of metallic contact between bearing elements during rolling. This model explains high frequency vibration in the acceleration spectrum clearly. When a defect grows in the bearing, the roughness of the contacting surfaces increases locally and stochastic excitation becomes stronger in the defective area. The increased vibration level at the defective area is a good indicator of bearing faults. A numerical simulation of the proposed model was validated with experimental results. DOI: 10.1115/1.4003595
Nonfermented Dairy Intake, but Not Fermented Dairy Intake, Associated with a Higher Risk of Depression in Middle-Age and Older Finnish Men

ABSTRACT Background Despite the putative health benefits of fermented dairy products, evidence on the association between fermented dairy and nonfermented dairy intake, and depression incidence is limited. Objectives This study examined cross-sectional and prospective associations between total dairy, fermented dairy, and nonfermented dairy intake with 1) the presence of elevated depressive symptoms and 2) the risk of a future hospital discharge or outpatient diagnosis of depression. Methods Data from 2603 Finnish men (aged 42–60 y), recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study, were included. Multivariable logistic regression models were used to examine ORs and 95% CIs for elevated depressive symptoms (Human Population Laboratory scale ≥5 points) at baseline. Cox proportional hazards regression models were used to estimate HRs and 95% CIs between dairy categories and risk of depression diagnoses. Results In cross-sectional analyses, fermented dairy intake in the highest (compared with lowest) tertile was associated with lower odds of having elevated depressive symptoms (adjusted OR: 0.70; 95% CI: 0.52, 0.96). Each 100-g increase in nonfermented dairy intake was associated with higher odds of having elevated depressive symptoms (adjusted OR: 1.06; 95% CI: 1.01, 1.10). During a mean follow-up time of 24 y, 113 males received a diagnosis of depression. After excluding cheese intake, higher fermented dairy intake was associated with a lower risk of depression diagnosis (adjusted HR: 0.62; 95% CI: 0.38, 1.03), which was strengthened after excluding those with elevated depressive symptoms at baseline (adjusted HR: 0.55; 95% CI: 0.31, 0.99), whereas nonfermented dairy intake in the highest tertile was associated with a 2-fold higher risk of depression (adjusted HR: 2.02; 95% CI: 1.20, 3.42). Conclusions Fermented dairy and nonfermented dairy intake were differentially associated with depression outcomes when examined cross-sectionally and over a mean period of 24 y. These findings suggest that dairy fermentation status may influence the association between dairy intake and depression in Finnish men. The KIHD study was registered at clinicaltrials.gov as NCT03221127.
Molecular determinants of inhibition of the human proton channel hHv1 by the designer peptide C6 and a bivalent derivative

Significance We designed C6 peptide to address the absence of specific inhibitors of human voltage-gated proton channels (hHv1). Two C6 bind to the two hHv1 voltage sensors at the resting state, inhibiting activation on depolarization. Here, we identify the C6–hHv1 binding interface using tethered-toxin variants and channel mutants, unveil an important role for negatively charged lipids, and present a model of the C6–hHv1 complex. Inspired by nature, we create a peptide with two C6 epitopes (C62) that binds to both channel subunits simultaneously, yielding picomolar affinity and significantly improved inhibition at high potentials. C6 and C62 are peptides designed to regulate hHv1, a channel involved in innate immune-system inflammatory pathophysiology, sperm capacitation, cancer-cell proliferation, and tissue damage in ischemic stroke.
Human skeletal muscle acetylcholine receptor gene expression in elderly males performing heavy resistance exercise.

Muscle fiber denervation is a major contributor to the decline in muscle mass and function during aging. Heavy resistance exercise is an effective tool for increasing muscle mass and strength, but whether it can rescue denervated muscle fibers remains unclear. Therefore, the purpose of this study was to investigate the potential of heavy resistance exercise to modify indices of denervation in healthy elderly individuals. 38 healthy elderly men (72±5 years) underwent 16 weeks of heavy resistance exercise while 20 healthy elderly men (72±6 years) served as non-exercising sedentary controls. Muscle biopsies were obtained pre and post training, and midway at eight weeks. Biopsies were analysed by immunofluorescence for the prevalence of myofibers expressing embryonic myosin (MyHCe), neonatal myosin (MyHCn), nestin, and neural cell adhesion molecule (NCAM), and by RT-qPCR for gene expression levels of acetylcholine receptor (AChR) subunits, MyHCn, MyHCe, p16 and Ki67. In addition to increases in strength and type II fiber hypertrophy, heavy resistance exercise training led to a decrease in AChR α1 and ε subunit mRNA (at eight weeks). Changes in gene expression levels of the α1 and ε AChR subunits with eight weeks of heavy resistance exercise supports the role of this type of exercise in targeting stability of the neuromuscular junction. The number of fibers positive for NCAM, nestin, and MyHCn was not affected, suggesting that a longer timeframe is needed for adaptations to manifest at the protein level.
Tibial component rotation alters soft tissue balance in a cruciate retaining total knee arthroplasty

Abstract Our aim was to understand whether using different landmarks for tibial component rotation influenced articular contact pressures in a balanced total knee arthroplasty (TKA). Twelve patients underwent TKA (Triathlon CR, Stryker Inc., Mahwah, NJ) and contact pressures were assessed using a wireless sensor. Robotic arm assisted TKA using a functional alignment technique was performed, with balanced gaps between medial and lateral compartments. Compartment pressures were measured with the trial tibial component rotated to Akagi's line and to Insall's axis respectively. Rotating the tibial component to Akagi's line resulted in a significantly greater proportion of knees being balanced and lower contact pressures than when the tibial component was rotated to Insall's axis at 10°, 45° and 90° of flexion (p < 0.05). Medial compartment pressures were significantly increased in 10° of flexion, as were lateral compartment pressures in all positions when the tibial component was aligned to Insall's axis (p < 0.05). The mean difference in rotation observed with the two landmarks was 6.9° (range 4.1–9.1°). Rotational alignment of the tibial component using Akagi's line reduced contact pressures, improved balance and reduced the need for soft tissue release when compared with Insall's axis in robotic arm assisted TKA.