Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical Evaluation of an Engineered Single-Chain Fragment Variable-Fragment Crystallizable Targeting Human CD44

Glycoprotein CD44 and alternative splice variants are overexpressed in many cancers and cancer stem cells. Binding of hyaluronic acid to CD44 activates cell signaling pathways, inducing cell proliferation, cell survival, and invasion. As such, CD44 is regarded as an excellent target for cancer therapy when this interaction can be blocked. In this study, we developed a CD44-specific antibody fragment and evaluated it for imaging CD44-positive cancers using PET. Methods: A human single-chain fragment variable (scFv) was generated by phage display, using the extracellular domain of recombinant human CD44. The specificity and affinity of the scFv-CD44 were evaluated using recombinant and tumor cell–expressed CD44. Epitope mapping of the putative CD44 binding site was performed via overlapping peptide microarray. The scFv-CD44 was reformatted into a bivalent scFv-Fc-CD44, based on human IgG1–fragment crystallizable (Fc). The scFv-Fc-CD44 was radiolabeled with 64Cu and 89Zr. The purified reagents were injected into athymic nude mice bearing CD44-positive human tumors (MDA-MB-231, breast cancer, triple-negative). Biodistribution studies were performed at different times after injection of [64Cu]Cu-NOTA-scFv-Fc-CD44 or [89Zr]Zr-DFO-scFv-Fc-CD44. PET/CT imaging was conducted with [89Zr]Zr-DFO-scFv-Fc-CD44 on days 1 and 7 after injection and compared with a scFv-Fc control antibody construct targeting glycophorin A. Results: Epitope mapping of the scFv binding site revealed a linear epitope within the extracellular domain of human CD44, capable of blocking binding to native hyaluronic acid. Switching from a monovalent scFv to a bivalent scFv-Fc format improved its binding affinity toward native CD44 on human breast cancer cells by nearly 200-fold. In vivo biodistribution data showed the highest tumor uptake and tumor-to-blood ratios for [89Zr]Zr-DFO-scFv-Fc-CD44 between days 5 and 7. PET imaging confirmed excellent tumor specificity for [89Zr]Zr-DFO-scFv-Fc-CD44 when compared with the control scFv-Fc. Conclusion: We developed a CD44-specific scFv-Fc construct that binds with nanomolar affinity to human CD44. When radiolabeled with 64Cu or 89Zr, it demonstrated specific uptake in CD44-expressing MDA-MB-231 tumors. The high tumor uptake (∼56% injected dose/g) warrants clinical investigation of [89Zr]Zr-DFO-scFv-Fc-CD44 as a versatile PET imaging agent for patients with CD44-positive tumors.
Levels of Predation Modulate Antipredator Defense Behavior and Metamorphic Traits in the Toad Bufo melanostictus

Abstract The influence of the presence of nonlethal predators on antipredator defense behavior and metamorphic traits was studied in the toad Bufo melanostictus. Tadpoles reared with caged predaceous tadpoles of Hoplobatrachus tigerinus delayed metamorphosis and also emerged at a smaller size compared to those in a predator-free environment. Different predaceous cues (kairomones, alarm cues and dietary cues, derived after feeding the predator with conspecific prey) induced increase in stationary phase and swimming speed and decrease in swimming spurts and time used for feeding. The intensity of defense behaviors varied with the cue. They were more intense in response to cues of predators fed on conspecific prey item. The response to alarm cues or kairomones or predators fed on heterogeneric tadpole species was similar but lower in magnitude compared to that elicited in response to predators fed on conspecific prey item. Most intense defense behavior in response to the odors of the predator that consumed conspecific members is possibly caused by a combined effect of kairomones, alarm, and dietary cues. The findings suggest that B. melanostictus tadpoles are capable of assessing levels of predation risk and modulating the intensity of their defense behavior in accordance with the perceived threat. Interestingly, despite longer larval period, size at metamorphosis of the toadlets was smaller in the presence of caged predator.
High genetic diversity of spider species in a mosaic montane grassland landscape

Gene flow and genetic variation were examined within and among populations of five of the most common spider species in shrublands of the mountainous Golden Gate Highlands National Park (GGHNP), South Africa. These species included three active hunters, Dendryphantes purcelli Peckham & Peckham, 1903 (Salticidae), Pherecydes tuberculatus O.P.-Cambridge, 1883 (Thomisidae) and Philodromus browningi Lawrence, 1952 (Philodromidae), and two web-builders, Neoscona subfusca (C.L. Koch, 1837) (Araneidae) and a Theridion Walckenaer, 1802 species (Theridiidae). A total of 249 spiders (57 D. purcelli, 69 N. subfusca, 34 P. browningi, 56 P. tuberculatus and 33 Theridion sp.) were collected and analysed from six shrubland localities in the park. Analyses of sequence variation of the mitochondrial cytochrome oxidase c subunit I (COI) gene for each species revealed relatively low nucleotide diversity (π < 0.0420) but high genetic diversity (Hd > 0.6500) within populations for all species, except P. tuberculatus. Genetic differentiation was also noted to differ between species, with only P. tuberculatus indicating very large divergence (Fst > 0.2500). These results were reflected by gene flow, with D. purcelli, N. subfusca and the Theridion sp. estimated as experiencing more than one disperser per generation. Overall, highest gene flow was found in the two web-building species, indicating possible high dispersal ability of these spiders in the GGHNP. Additionally, constructed phylogenies indicated possible cryptic speciation occurring in the majority of the investigated species. Our current results indicate that the five investigated spider species were able to maintain gene flow between shrubland populations within the GGHNP to some degree, despite the mountainous landscape. However, further analyses incorporating additional molecular markers are needed to properly determine the extent of genetic diversity and gene flow of these species within the GGHNP.
Development of the Hearing Rehabilitation for Older Adults (HeRO) Healthcare Mobile Application and Its Likely Utility for Elderly Users

The present study aimed to develop a healthcare application for the elderly who suspect or know they have a hearing loss, namely, the Hearing Rehabilitation for Older Adults (HeRO), which is available in a mobile device, and then to confirm its probability of acceptance among elderly users. Under a web server system, HeRO which had four types of tailored training for the aged auditory system (i.e., syllable, sentence, discourse, working memory) and a self-reported questionnaire to screen amount of the hearing loss was completed for the elderly. To verify whether the HeRO contents and functions were user-friendly to the elderly users, the technology acceptance model (TAM) was used. Forty-four older adults were asked to use the developed application for 10 days and then respond to a TAM questionnaire with 25 items. The Cronbach’s α coefficient of each subcategory was very high. The construct validity of all subcategories showed high eigenvalues using principal component analysis. Furthermore, our regression model statistically supported a persuasive intention to use the healthcare application because the elderly readily accept it and find it easy to manipulate. We expect the current technology to be applied to the general public as well as the elderly who want to explore digital health.
The Effect of Temperature On Development and Survival of Heterodera Schachtii Schm

The sugar-beet nematode, Heterodera schachtii Schm. , produced five generations in one growing season in the Imperial Valley of California where sugar-beets are planted in the fall, grown through the winter, and harvested the following April, May or June. Encysted eggs survived 3 months' summer fallow in surface soils in which temperatures as high as 52° C were recorded. In a controlled temperature test maximum reproduction of H. schachtii occurred at 27.5 ° C. Reproduction at 27.5° C was twice that at 25° C. Only a few females formed at 30° C and no development occurred at 32.5° C. A population of H. schachtii from the winter beet area (Imperial Valley) and one from a summer beet area (Orange County) did not differ in their response to soil temperature.
High Frequency of Intravenous Injection of Human Adipose Stem Cell Conditioned Medium Improved Embryo Development of Mice in Advanced Maternal Age through Antioxidant Effects

Simple Summary In this study, we examined the anti-oxidative effect of human adipose stem cell conditioned medium (ASC-CM) on the ovary and uterus of mice in advanced maternal age (AMA) and the optimal conditions of intravenous injection for ASC-CM administration. Human ASC-CM upregulated expression of antioxidant genes, restored the quality of oocytes derived from aged ovaries and resulted in improved in vitro and in vivo embryo development. The anti-oxidative effect human ASC-CM was optimized with high frequency of administration. Comprehensively, our study successfully introduced the potential of ASC-CM as an antioxidant intervention against age-related infertility in AMA. Abstract Advanced maternal age (AMA) has become prevalent globally. With aging, weakened antioxidant defense causes loss of normal function in the ovary and uterus due to oxidative stress. Here, we aimed to improve embryo development in AMA mice by intravenous injection (IV) of human adipose stem cell conditioned medium (ASC-CM) at various frequencies and intervals as an antioxidant intervention. Four- and six-month-old female ICR (Institute of Cancer Research) mice were randomly divided into groups IV treated with human ASC-CM under different conditions, and in vitro and in vivo embryo development were evaluated. Consequently, compared to the control group, blastocyst formation rate of parthenotes was significantly promoted in 4-month-old mice and the mean number of implanted fetuses after natural mating was significantly increased by approximately two-fold in 6-month-old mice. Through gene analysis, the anti-apoptotic and anti-oxidative effects of human ASC-CMs were confirmed in the ovaries and uterus of pregnant mice at both ages. In particular, ovarian expression of gpx1 and catalase drastically increased in 6-month-old mice. Furthermore, the levels of gpx1 and catalase were further increased, with a high frequency of injection regardless of age. Thus, we demonstrated for the first time the anti-oxidative effect of human ASC-CM administration against ovarian aging and the optimal injection condition.
Rapid Assessment of Glutenin and Gliadin in Wheat by UV Spectrophotometer

Traditional breeding of common wheat (Triticum aestivum L.) concentrates largely on the improvement of protein quality because of the importance of protein in end-product functionality, nutritional value, and economic impact. New, rapid, and inexpensive protein quality tests are required to identify premium quality families from large and diverse early-generation breeding populations. In this study, a simple method was designed using organic solvents to divide wheat proteins into monomeric-rich (single-chain, mostly gliadin), polymeric-rich (multichain, mostly low- and high-molecular weight glutenin), and total soluble protein (monomeric and polymeric protein). Monomeric-rich and total soluble protein fractions were quantified at 280 nm with an ultraviolet (UV) spectrophotometer. Protein fractions were expressed in terms of absolute concentration and as a proportion of total soluble protein. A strong linear relationship between the protein concentration in the fractions and the absorbance reading indicated that the method could accommodate a large range of protein fraction concentrations. The specific relationships between quantity and proportion of monomeric/polymeric protein fractions and dough quality tests allowed for the design of an algorithm eliminating poor quality lines from further breeding assessment. Simplicity, reliability, low cost, and a potential for automation could make this UV-spectrophotometric method suitable for routine use in wheat breeding programs.
Testosterone levels and cause-specific mortality in the older French men without metabolic syndrome

OBJECTIVES Previous studies have reported controversial findings regarding the association of testosterone with mortality in older men. This heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, as well as differential associations according to causes of death. METHODS We used data from a random subsample of the Three-City study, in which hormone levels were measured in 338 men ≥65 years without metabolic syndrome who were followed-up for 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate the hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (CIs). RESULTS Over the follow-up period, 130 men died (30 from cardiovascular disease, 45 from cancer, 55 from other causes). The association of testosterone with mortality showed significant heterogeneity across causes of death (p=0.027 and p=0.022 for total and bioavailable testosterone, respectively). Higher testosterone levels were associated with increased cardiovascular mortality (HR for 1-standard deviation increase, 1.86; 95% CI, 1.28 to 2.71 and 1.50; 95% CI, 1.04 to 2.17 for total and bioavailable testosterone, respectively). By contrast, there were no significant associations of testosterone with mortality from cancer and other causes. CONCLUSIONS Our data suggest that the association of testosterone with mortality in men without metabolic syndrome might be differential according to the cause of death. These findings may partially explain the heterogeneity across studies on the relationship between testosterone levels and mortality.
Average symptom severity and related predictors of prolonged recovery in pediatric patients with concussion

Abstract The purpose of this study is to compare the predictive utility of total number of individual symptoms endorsed, total symptom severity, and average symptom severity on prolonged recovery among children/adolescents with a concussion. Patients (n = 115) completed the Post-Concussion Symptom Scale (PCSS) at their initial clinical visit (7.9 ± 6.6 days) days post-injury. PCSS outcomes were total symptom severity (i.e., total PCSS score), number of symptoms endorsed (i.e., number out of 22-items on the PCSS with a symptom score >0) and average symptom severity (i.e., mean of scores for each of the 22-items on the PCSS, not just endorsed symptoms). Logistic regression was performed with all symptom measures and recovery time >30 days as the binary outcome. Logistic regression indicated that average symptom severity (OR = 1.9; p = 0.01) and later time to first clinical visit (OR = 5.0; p < 0.001) were the only significant predictors of recovery time. Average symptom severity at initial clinic visit and earlier clinical visit may be a better predictor of recovery time than total number of symptoms endorsed or total symptom severity among children and adolescents.
Development of Norway spruce dominated stands after single-tree selection and low thinning

The study included 23 stands (at least 2 ha each in size) distributed from southern to northern Finland. These Norway spruce (Picea abies (L.) Karst. ) dominated stands grew on fertile (OxalisMyrtillus and Myrtillus site types) mineral soils. Each stand contained two substands randomly treated with single-tree selection or low thinning. The harvested volumes (trees > 9 cm) varied greatly but averaged 94 m3·ha1 in the former consisting of mainly medium-sized and larger (>15 cm) trees and 68 m3·ha1 in the latter of mainly medium-sized and smaller ( 9 cm) increased 38% in single-tree selection and 27% in low thinning. The respective current annual volume an.
Effect of Preinjury Oral Anticoagulants on Outcomes Following Traumatic Brain Injury from Falls in Older Adults

Warfarin has been the oral anticoagulant of choice for the treatment of thromboembolic disease. However, upward of 50% of all new anticoagulant prescriptions are now for direct oral anticoagulants (DOAC). Despite this, outcome data evaluating preinjury anticoagulants remain scarce following traumatic brain injury (TBI). Our study objective is to determine the effects of preinjury anticoagulation on outcomes in older adults with TBI.
Thermal stability of some flavonoids and phenolic acids in sheep tallow olein

In this study, the thermal stability of some phenolic antioxidants including flavonoids (quercetin and catechin) and phenolic acids (gallic acid, tannic acid, ellagic acid and caffeic acid) in tallow olein was investigated. Tallow olein fractionated from sheep tallow fat was used as a medium to study the antioxidant activity at 120, 140, 160 and 180°C. In order to extract tallow olein, a three-stage fractionation method was performed on sheep tallow fat at the constant temperatures of 25, 15 and 5°C using acetone as a solvent. The results suggested that quercetin and ellagic acid had the highest thermal stability amongst others, while gallic acid and caffeic acid exhibited the least thermal stability. Practical applications: The sheep tallow fat has been primarily used in soap manufacturing and its application as an edible fat has been limited due to its high content of saturated fatty acids. Extraction of the liquid phase of tallow fat (tallow olein) by fractionation reduces its long-chain saturated fatty acid content to an acceptable level for edible consumption. The fractionation process, as negatively affects the stability to autoxidation, should be followed by stabilisation with antioxidants. The recent interest in natural antioxidants encouraged the authors to investigate the thermal stability of phenolic antioxidants in tallow olein. It is necessary to determine the thermal stability of antioxidants to predict their appropriateness to be used in high-temperature applications such as deep frying. Fractionation and stabilisation with appropriate antioxidants are the important steps to utilise tallow olein as an edible oil for different applications in salad formulations, cooking and frying.
A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics

Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs.
Interventions to promote work ability by increasing physical activity among workers with physically strenuous jobs: A scoping review

Aims: The potential benefits of workplace physical activity (PA) interventions are in improving both health and important workplace outcomes. Despite the differences in PA level between physically strenuous and inactive work, the literature reporting the effectiveness of the interventions does not usually differentiate physically active and inactive jobs. The aim of the current study was therefore to collect and synthesise research evidence on workplace PA interventions to promote work ability specifically among workers in physically strenuous jobs by means of a scoping review. Methods: The databases Medline, Cochrane Central and Scopus were used to identify interventions to promote work ability by increasing PA among workers in physically strenuous jobs. An iterative method was used to obtain an overview of the study elements and to extract details on the study design, sample, intervention, outcomes and effectiveness. Results: A total of 47 studies evaluating eight categories of interventions were found. Out of these, 18 reported significant effects on work ability. Positive results came from a range of different interventions, including aerobic exercise, strength training, combined aerobic exercise and strength training, stretching, yoga, consultation and tailored physical exercise programmes. Conclusions: Few interventions were effective in promoting work ability by increasing PA among workers in physically strenuous jobs. In particular, trials based on the demands of work, multimodal interventions and applying wearable technology are needed.
Biomimicry of the Hawk Moth, Manduca sexta (L.), Produces an Improved Flapping-Wing Mechanism

Flapping-wing micro air vehicles (FWMAVs) that mimic the flight capabilities of insects have been sought for decades. Core to the vehicle’s flight capabilities is the mechanism that drives the wings to produce thrust and lift. This article describes a newly designed flapping-wing mechanism (FWM) inspired by the North American hawk moth, Manduca sexta. Moreover, the hardware, software, and experimental testing methods developed to measure the efficiency of insect-scale flapping-wing systems (i.e., the lift produced per unit of input power) are detailed. The new FWM weighs 1.2 grams without an actuator and wings attached, and its maximum dimensions are 21 × 24 × 11 mm. This FWM requires 402 mW of power to operate, amounting to a 48% power reduction when compared to a previous version. In addition, it generates 1.3 gram-force of lift at a flapping frequency of 21.6 Hz. Results show progress, but they have not yet met the power efficiency of the naturally occurring Manduca sexta. Plans to improve the technique for measuring efficiency are discussed as well as strategies to more closely mimic the efficiency of the Manduca sexta-inspired FWM.
A Review of Pharmacological Presbyopia Treatment

Abstract Presbyopia reduces an individual's ability to perform visual tasks at near distances. It is a global problem, affecting over a billion people worldwide. Contact lenses, glasses, refractive surgery, and intraocular lens surgery are the main modalities in presbyopia treatment, although they all have some disadvantages. Thus, there is an increasing need for effective, easy-to-use, and noninvasive approaches for treating presbyopia while not limiting patients’ daily activities. Pharmacological presbyopia treatment as an alternative method has been under investigation in recent years. We reviewed all relevant articles using the keywords “presbyopia,” “presbyopia treatment,” “pharmacological presbyopia treatment,” and “presbyopic corrections” from 2010 to February 9, 2020, and summarized the main results of clinical trials, investigating the drops used for presbyopia treatment.