Miracle-dz/UniFAR-FTUs huggingface dataset:
US FDA-approved therapeutic antibodies with high-concentration formulation: summaries and perspectives

Abstract Thirty four (34) of the total US FDA approved 103 therapeutic antibody drugs, accounts for one third of the total approved mAbs, are formulated with high protein concentration (100 mg/mL or above) which are the focus of this article. The highest protein concentration of these approved mAbs is 200 mg/mL. The dominant administration route is subcutaneous (76%). Our analysis indicates that it may be rational to implement a platform formulation containing polysorbate, histidine and sucrose to accelerate high concentration formulation development for antibody drugs. Since 2015, the FDA approval numbers are significantly increased which account for 76% of the total approval numbers, i.e., 26 out of 34 highly concentrated antibodies. Thus, we believe that the high concentration formulations of antibody drugs will be the future trend of therapeutic antibody formulation development, regardless of the challenges of highly concentrated protein formulations.
A Model for the Production of Portable Stone Mortars and Bowls

Two incidental observations of portable mortars in the process of manufacture, one discovered by chance in the field, the other an artifact in a private collection, prompted research into the manner in which portable stone mortars or bowls were produced by the aboriginal peoples of California desert region and elsewhere. The production of steatite vessels in the California coastal regions and on the Channel Islands has been studied and well-documented; steatite, however, is a soft material, having the lowest rating (i.e., 1) on the Mohs Hardness Scale. It is easily carved to shape. The majority of the portable mortars or bowls found at archaeological sites in the deserts of Southern California are of much denser and harder lithic materials (usually 6 or 7 on the Mohs Hardness Scale). The energy expended in their production and the technology used were very different. The production model for stone mortars that we propose hypothesizes that the manipulation of granites, basalts, andesites, sandstones, metavolcanics, and metasedimentary materials was possible employing techniques of stoneworking that were widely used for a variety of purposes. We further hypothesize that the aboriginal stoneworkers attempted to be as efficient and energy-conserving as possible. By isolating a large segment of a mortar blank and then removing that portion by percussion, they were able to create a reasonably flat working surface that would ultimately become the rim of the mortar or bowl. A variation of this technique was often used to create the central concavity.
Allergic Diseases: A Comprehensive Review on Risk Factors, Immunological Mechanisms, Link with COVID-19, Potential Treatments, and Role of Allergen Bioinformatics

The prevalence of allergic diseases is regarded as one of the key challenges in health worldwide. Although the precise mechanisms underlying this rapid increase in prevalence are unknown, emerging evidence suggests that genetic and environmental factors play a significant role. The immune system, microbiota, viruses, and bacteria have all been linked to the onset of allergy disorders in recent years. Avoiding allergen exposure is the best treatment option; however, steroids, antihistamines, and other symptom-relieving drugs are also used. Allergen bioinformatics encompasses both computational tools/methods and allergen-related data resources for managing, archiving, and analyzing allergological data. This study highlights allergy-promoting mechanisms, algorithms, and concepts in allergen bioinformatics, as well as major areas for future research in the field of allergology.
Tilting Pad Journal Bearings: On Bridging the Hot Gap Between Experimental Results and Model Predictions

The accurate prediction of the forced performance of tilting pad journal bearings (TPJB) relies on coupling a fluid film model that includes thermal energy transport, and on occasion fluid inertia, to the structural stiffness of the pads’ pivots and the thermomechanical deformation of the pads’ surfaces. Often enough, the flexibility of both pads and pivots is ignored prior to the bearing actual operation; practice dictating that force coefficients, damping in particular, decrease dramatically due to pivot flexibility. Even in carefully conducted experiments, components’ flexibilities are invoked to explain dramatic differences between measurements and predictions. A multiple-year test program at TAMU has demonstrated the dynamic forced response of TPJBs can be modeled accurately with matrices of constant stiffness K, damping C, and added mass M coefficients. The K-C-M model, representing frequency independent force coefficients, is satisfactory for excitation frequencies less or equal to the shaft synchronous speed. However, as shown by the authors in Ref. [1], pivot flexibility reduces the applicability of the simple constant parameter model to much lower excitation frequencies. Presently, a fluid film flow model predicts the journal eccentricity and force coefficients of a five-pad rocker-back TPJB tested at TAMU under a load-between-pad (LBP) configuration. The predictions agree well with the test results provided the model uses actual hot bearing clearances and an empirical characterization of the pivot stiffness. A study follows to determine the effects of pad preload, Display Formular¯p = 0.0, 0.27 (test article) and 0.50, as well as the load orientation, LBP and load-on-pad (LOP), on bearing performance with an emphasis on ascertaining the configuration with most damping and stiffness, largest film thickness, and the least drag friction. In the study, a rigid pivot and two flexible pivots are considered throughout. Further examples present the effective contribution of the pads’ mass and mass moment of inertia and film fluid inertia on the bearing force coefficients. To advance results of general character, predictions are shown versus Sommerfeld number (S), a design parameter proportional to shaft speed and decreasing with applied load. Both LBP and LOP configurations show similar performance characteristics; the journal eccentricity increasing with pivot flexibility. For LBP and LOP bearings with 0.27 preload, pivot flexibility decreases dramatically the bearing damping coefficients, in particular at the low end of S, i.e., large loads. The model and predictions aid to better design TPJBs supporting large specific loads. © 2014 ASME
Verification of Iron Loss Calculation Method Using a High‐Precision Iron Loss Analyzer

Because of the improved performance of power devices, the volume of the ac filter inductors used in high‐frequency PWM inverters has been reduced. However, the temperature rise in the filter inductor due to this miniaturization has become more pronounced. Therefore, we have proposed an iron loss calculation method for the ac filter inductor. However, the accuracy of the value calculated via the loss map method cannot be verified, because the iron loss arising during each switching period cannot be measured with conventional power measuring instruments. In order to resolve this problem, we developed an inductor loss analyzer (ILA), which allows precise measurement of the iron loss in the inductor during each switching period. The accuracy of the calculation of iron loss in the filter inductor by the loss map method was verified with the ILA. We found that the value calculated by the loss map method differed slightly from the value measured with the ILA. However, these differences can be reduced if we take into account the accurate flux density calculation and the effect of the duty ratio of PWM pulses on the loss. Finally, we verified that the loss map method can provide accurate iron loss calculations.
An anomalous device degradation of SOI narrow width devices caused by STI edge influence

The effects of shallow trench isolation (STI) on silicon-on-insulator (SOI) devices are investigated for various device sizes with three different gate shapes. Both NMOSFETs and PMOSFETs with the channel region butted to the STI show a reduction in mobility (NMOSFETs and PMOSFETs) and an increase of low-frequency noise as the channel width is reduced. In comparison, the devices without the STI-butted channel region show much less variation in mobility for various channel widths. The degradation of MOSFET yield in SOI MOSFETs with the STI is found to be dependent on the device width since the contribution of the interface roughness (or damage) between the STI and the channel formed during the dry etch process becomes significant with the decrease of channel width and the increase of channel length. From the charge-pumping results, the interface state (N/sub it/) generated by the STI process was identified as the cause of the anomalous degradation.
Diet Quality of Australian Children and Adolescents on Weekdays versus Weekend Days: A Secondary Analysis of the National Nutrition and Physical Activity Survey 2011–2012

Daily routines may influence children and adolescents’ eating patterns, however the influence of days of the week on dietary intake has rarely been explored. This study aimed to examine discretionary choices intake in the context of diet quality on weekdays versus weekends. A secondary analysis was conducted using the Australian National Nutrition and Physical Activity Survey 2011–2012. Differences in discretionary choices intake and diet quality on weekdays versus weekends, were examined using ANCOVA analyses. Associations between child and parent-proxy characteristics and weekday/weekend discretionary choices intake were examined using multivariable regression models. Primary analyses included 2584 Australian 2–17-year-olds. There were small differences in discretionary choices intake and diet quality between weekdays and weekends in all age subgroups. Compared to weekdays, intakes on weekends were characterized by a higher intake of discretionary choices, and lower total Dietary Guidelines Index for Children and Adolescents (DGI-CA) scores across the age subgroups (all p < 0.01). Parent-proxy discretionary choices intake and child age were predictors of weekday and weekend discretionary choices intake. Parent-proxy obesity weight status compared with healthy weight status was a predictor of weekend intake, while parent-proxy education level was a predictor of weekday discretionary choices intake. Future intervention strategies should target discretionary choices intake on both weekdays and weekends.
Academic Research Consortium High Bleeding Risk Criteria associated with 2-year bleeding events and mortality after transcatheter aortic valve replacement discharge: a Japanese Multicentre Prospective OCEAN-TAVI Registry Study

Abstract Aims To investigate the ability of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and ARC-HBR score to predict 2-year bleeding and mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Methods and results We enrolled 2514 patients who underwent successful TAVR during 2013–17. In this study, we used the ARC-HBR score for further HBR-risk stratification, and the ARC-HBR score was calculated as follows: each major criterion was 2 points and each minor criterion was 1 point. The impact of the ARC-HBR criteria and increasing ARC-HBR score on the incidence of moderate/severe bleeding events, mortality, and ischaemic stroke in the first 2 years were evaluated. We used survival classification and regression tree (CART) analysis for 2-year moderate or severe bleeding events, and patients were statistically classified into HBR low- (ARC-HBR score ≤1), intermediate- (ARC-HBR score = 2–4), or high-risk (ARC-HBR score ≥5) groups, and 91.4% were at HBR (ARC-HBR score ≥2). The rates of 2-year moderate/severe bleeding events and all-cause mortality were higher in the ARC-HBR group and highest in the HBR high-risk group. An increased HBR score was significantly associated with moderate/severe bleeding events [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.07–1.31; P = 0.001] and all-cause mortality (adjusted HR 1.24, 95% CI 1.17–1.32; P < 0.001). Conclusions The ARC-HBR criteria identify patients at HBR after TAVR; an increased ARC-HBR score is associated with 2-year moderate/severe bleeding events and mortality.
Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.
Understanding the Role of Metakaolin towards Mitigating the Shrinkage Behavior of Alkali-Activated Slag

This research investigates the mechanism of metakaolin for mitigating the autogenous and drying shrinkages of alkali-activated slag with regard to the activator parameters, including concentration and modulus. The results indicate that the incorporation of metakaolin can decrease the initial viscosity and setting time. Increasing activator concentration can promote the reaction process and shorten the setting time. An increase in the metakaolin content induces a decrease in compressive strength due to reduced formation of reaction products. However, increasing activator dosage and modulus can improve the compressive strength of alkali-activated slag containing 30% metakaolin. The inclusion of metakaolin can mitigate the autogenous and drying shrinkage of alkali-activated slag by coarsening the pore structure. On the other hand, increases in activator concentration and modulus result in an increase in magnitude of the autogenous and drying shrinkage of alkali-activated slag containing metakaolin. The influence of the activator modulus on the shrinkage behavior of alkali-activated slag-metakaolin binary system should be further investigated.
How many people will be awakened by nighttime aircraft noise

Increasing demand for air travel has prompted plans by several airports around the U.S. to increase their capacity, primarily by adding new runways or by extending existing ones. These capacity-increase plans usually raise public concerns about increased noise. One common concern is increased sleep disturbance. In response to this public concern, some of the associated environmental documents attempt to address sleep disturbance. The relevant environmental regulations do not prescribe specific criteria, metrics, or computation methods for determining sleep disturbance.
Prevention of Low Back Pain in Adults with a Back School-Based Intervention

Background: Low back pain is highly prevalent and has a major socio-economic impact worldwide. Among the rehabilitation options is the Back School, which consists of programmes that include exercise and educational interventions to treat and prevent back pain. The effects of this type of programme are usually evaluated in patients with low back pain. The aim of this study was to evaluate the effects on low back functionality and the prevention of medical visits due to low back pain during one year of follow-up in a healthy adult population. Methods: A quasi-experimental study was conducted with 56 healthy participants who were divided into an experimental group (n = 30), who underwent the programme consisting of a total of 16 sessions, and a control group (n = 26), who did not undergo the intervention. All participants were administered the Partial Curl-up Test, Biering Sorense Test, Modified Schöber Test, and Toe Touch Test, and they completed the Short Form 36 Health Survey before and after the intervention. In addition, a telephone call was made to ask whether they attended a doctor for low back pain in the following year post-intervention. Results: In the experimental group, statistically significant improvements were observed in trunk muscle strength, spinal flexion joint range of motion, and hamstring flexibility, and they had fewer visits to the doctor for low back pain in the following year. Conclusions: The theoretical–practical programme based on the Back School seems to have beneficial effects on low back functionality by increasing its strength and flexibility in an adult population. In addition, this programme reduced the number of medical visits due to low back pain during the following year after the intervention.
Off-Site Construction in Saudi Arabia: The Way Forward

Off-site construction, which gained prominence in the last quarter of the previous century, is the form of construction in which the intent is to move some of the effort that goes into construction from the construction site into the controlled environment of a manufacturing facility (Arif and Egbu 2010). Gibb (2001) traced the history of off-site construction as far back as 1851; however, Arif (2009) actually goes one step further and argues that the use of big boulders instead of smaller bricks in pyramids is no different from using prefabricated wall panels. Humanity has always looked for better ways of building faster, and the use of precut rocks and boulders leveraged the opportunity to fill large volumes of pyramid structures more quickly (Arif and Egbu 2010). The benefits of off-site construction have been well-documented in the literature. Gibb and Isack (2003) classified the benefits into five major categories: time, quality, cost, productivity, and people. Arif and Egbu (2010) identified off-site as a construction paradigm that can address the housing shortage in the future. However, there are some major challenges associated with the implementation of off-site construction. Pan et al. (2007) documented the barriers to the implementation of off-site construction. The most important five barriers identified by Pan et al. (2007) are higher capital cost, difficulties in achieving economies of scale, complexity of interfacing between systems, inability to freeze the design early on, and the nature of the planning system. Saudi Arabia, the world’s largest oil producer, has seen an economic boom in the previous five years, owing to high oil prices. Oil and gas exports have increased from 70.7 billion USD in 2001 to 205 billion USD in 2007 (Tabata 2009). This economic growth has resulted in significant economic activities being undertaken in the kingdom. However, the construction projects being performed are fraught with delays and inefficiencies (Alkharashi and Skitmore 2009). One documented benefit of off-site construction is productivity, leading to a higher speed of construction. To assess the issues with the implementation of off-site construction in Saudi Arabia, a workshop was organized in Jeddah in November 2010. There were 20 attendees in the workshop; all were project managers, either in government organizations or private construction companies. The objectives of the workshop were 1. To introduce the benefits and challenges associated with offsite construction to the audience. 2. To document the perceptions associated with off-site construction in the construction industry in Saudi Arabia. 3. To identify the major barriers to the implementation of off-site construction in Saudi Arabia. 4. To propose a way forward in implementing off-site construction in Saudi Arabia. Workshop Execution
Indole-3-Propionic Acid, a Functional Metabolite of Clostridium sporogenes, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation

Clostridium sporogenes (C. sporogenes), as a potential probiotic, metabolizes tryptophan and produces an anti-inflammatory metabolite, indole-3-propionic acid (IPA). Herein, we studied the effects of C. sporogenes and its bioactive metabolite, IPA, on skeletal muscle development and chronic inflammation in mice. In the in vivo study, the muscle tissues and serum samples of mice with C. sporogenes supplementation were used to analyze the effects of C. sporogenes on muscle metabolism; the IPA content was determined by metabonomics and ELISA. In an in vitro study, C2C12 cells were exposed to lipopolysaccharide (LPS) alone or LPS + IPA to verify the effect of IPA on muscle cell inflammation by transcriptome, and the involved mechanism was revealed by different functional assays. We observed that C. sporogenes colonization significantly increased the body weight and muscle weight gain, as well as the myogenic regulatory factors’ (MRFs) expression. In addition, C. sporogenes significantly improved host IPA content and decreased pro-inflammatory cytokine levels in the muscle tissue of mice. Subsequently, we confirmed that IPA promoted C2C12 cells’ proliferation by activating MRF signaling. IPA also effectively protected against LPS-induced C2C12 cells inflammation by activating Pregnane X Receptor and restoring the inhibited miR-26a-2-3p expression. miR-26a-2-3p serves as a novel muscle inflammation regulatory factor that could directly bind to the 3′-UTR of IL-1β, a key initiator factor in inflammation. The results suggested that C. sporogenes with its functional metabolite IPA not only helps muscle growth development, but also protects against inflammation, partly by the IPA/ miR-26a-2-3p /IL-1β cascade.
Insulin Topical Application for Wound Healing in Nondiabetic Patients

Background Low-cost and safe strategies to improve wound healing will be of great social and economic value. The goal of this pilot clinical trial is aimed at analyzing how effective insulin therapy is at healing wounds in nondiabetic people. Methods In this protocol research, 346 individuals were included. Patients were divided as 2 groups at random: experimental patients were given a ten-unit answer. For each 10 cm2 of wound, insulin was injected in solution with 1 mL 0.9 percent saline, whereas the control group got a standard dressing with normal saline. Results During the therapy period, no adverse effects were reported. After insulin therapy, no substantial insulin-related side effects were reduced. After 10 days of therapy, the experimental group's granulation tissue coverage rate and thickness were considerably improved as compared to control. Furthermore, a momentous difference in the occurrence of wound bleeding and suppurative wounds between the two groups (P = 0.05). Conclusion The results of this pilot research suggest that insulin injections could harmless and effective alternative therapy for wound healing in nondiabetic individuals and that larger, placebo-controlled trials are needed to evaluate effectiveness and safety of insulin treatment in wound healing patients.