Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevention of Fab-arm exchange and antibody reduction via stabilization of the IgG4 hinge region

ABSTRACT IgG4s are dynamic molecules that undergo a process called Fab-arm exchange. Disulfide bonds between heavy chains are transiently reduced, resulting in half antibodies that reform intact antibodies with other IgG4 half antibodies. In vivo, therapeutic IgG4s can recombine with endogenous IgG4s, resulting in a heterogeneous mixture of bispecific antibodies. A related issue that can occur for any therapeutic protein during manufacturing is interchain disulfide bond reduction. For IgG4s, this primarily results in high levels of half-mAb that persist through purification processes. The S228P mutation has been used to prevent half-mAb formation. However, we demonstrated that IgG4s with the S228P mutation are subject to half-mAb formation and Fab-arm exchange in reducing environments. We identified two novel mutations that stabilize the heavy–heavy chain interaction via incorporation of additional disulfide bonds in the hinge region. Individually, these mutations increase stability toward reduction and lessen Fab-arm exchange. Combination of all three mutations, Y219C, G220C, and S228P, has an additive benefit resulting in an IgG4 with ˃7-fold increase in stability toward reduction while preventing Fab-arm exchange. Importantly, the mutations do not affect antigen binding or Fc effector function. These mutations hold great promise for solving mAb reduction during manufacturing and preventing Fab-arm exchange in vivo.
Risk, resilience, psychological distress, and anxiety at the beginning of the COVID‐19 pandemic in Germany

The current COVID‐19 pandemic comes with multiple psychological stressors due to health‐related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID‐19 pandemic and to analyze possible risk and protective factors.
Sympathetic nervous system activity and reactivity in women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is associated with vascular dysfunction. Sympathetic nervous system activity (SNA) is an important regulator of vascular function, and is influenced by glucose and insulin. The association between GDM and SNA (re)activity is unknown. We hypothesize that women with GDM would have increased SNA during baseline and during stress.
Risk of medication errors and nurses' quality of sleep: a national cross-sectional web survey study.

OBJECTIVE We aimed to evaluate quality of sleep and self-perception risk of medication errors, in a significantly-sized sample of nurses in Italy, using a web survey. SUBJECTS AND METHODS An anonymous questionnaire about self-perception of quality of sleep (Pittsburgh Sleep Quality Index - PSQI) and risk of medication errors (based on the 7 R-rule), was made up and delivered by social media, i.e., Facebook and Instagram. Risk of medication errors was intended as near misses, i.e., accidents that do not cause the patient harm. RESULTS A poor quality of sleep stated by PSQI score >5, was present in 87.9% of subjects and the risk of medication errors during the last shift was reported in 76% of them. However, more than half of nurses' sample (60.1%) reported a good or excellent self-perception quality of sleep. Risk of medication errors was associated with poor quality of sleep and it was independently associated with short resting time after night shift and bad self-perception quality of sleep (OR 3.165, 95% CI 1.468-6.827, p=0.003). CONCLUSIONS Absence of proper resting is crucial on performance even if nurses perceived a good quality sleep. The relationship between shift work, poor sleep quality, and risk of medication errors represents crucial point for all health professionals' community, and web-survey represents a valuable information in order to capture the risk of medication errors. Health care organizations should encourage such a type of research in order to show a more proactive approach towards patient safety.
Methodology to simulate unsaturated zone hydrology in Storm Water Management Model (SWMM) for green infrastructure design and evaluation

Hydrologic models such as the USEPA Stormwater Management Model (SWMM) are commonly used to assess the design and performance of green infrastructure (GI). To accurately represent GI performance models used in design need to be able to address both the hydrology/hydraulics of the catchment and the GI unsaturated (vadose) zone hydrology. While hydrologic models, such as SWMM, address the need for catchment hydrology/hydraulics, they often simplify the unsaturated zone hydrology. This paper presents a methodology utilizing existing components of SWMM to represent unsaturated zone hydrology in an accessible format that does not require adjustments to the SWMM source code. The methodology simulated the unsaturated soil water movement by considering flow caused by differences of soil matric head and flow caused by gravity between soil layers with finite depth/length. The flow flux related to the soil matric head is a function of soil water diffusivity (D) and the soil moisture gradient, where D can be represented by a pump curve in SWMM. The flow flux related to gravity was controlled by unsaturated hydraulic conductivity (K) only and was also simulated by a pump. The methodology was compared to another variably saturated model, HYDRUS, with theoretical soils (with single layers of sand, loam, silt, and clay, as well as dual-layer scenarios). Field data was used to compare the methodology to HYDRUS and the SWMM LID (Low Impact Development) module. In all comparisons the presented methodology and HYDRUS delivered similar results for the vadose zone response to a storm event, while the LID module of SWMM exhibited slower water movement. The results showed that under natural conditions, the approximation of the presented methodology yielded satisfactory results to simulate flow through the unsaturated vadose zone.
Descriptions of the Tadpoles of Aglyptodactylus laticeps and Aglyptodactylus securifer from Western Madagascar, with Notes on Life History and Ecology

Abstract The three members of the Malagasy genus Aglyptodactylus (Aglyptodactylus madagascariensis, Aglyptodactylus laticeps, Aglyptodactylus securifer) form, together with Laliostoma labrosum, the subfamily Laliostominae within the Mantellidae (Ranoidea: Anura). In this paper, the morphology, life history, and ecology of sympatric tadpoles of A. laticeps and A. securifer are described and compared to those of A. madagascariensis and L. labrosum. Tadpoles of all Aglyptodactylus species are morphologically more similar to each other than to L. labrosum. However, all species differ with respect to habitat, feeding habits, and life history.
Anti-Hepatocellular-Cancer Activity Exerted by β-Sitosterol and β-Sitosterol-Glucoside from Indigofera zollingeriana Miq

Indigofera zollingeriana Miq (I. zollingeriana) is a widely grown tree in Vietnam. It is used to cure various illnesses. The purpose of this study was to investigate the chemical constituents of an I. zollingeriana extract and test its anticancer activity on hepatocellular cells (Huh7 and HepG2). The experimental results of the analysis of the bioactive compounds revealed that β-sitosterol (β-S) and β-sitosterol-glucoside (β-SG) were the main ingredients of the I. zollingeriana extract. Regarding anticancer activity, the β-S and β-SG of I. zollingeriana were found to exhibit cytotoxic effects against HepG2 and Huh7 cells, but not against normal human primary fibroblasts. The β-S was able to inhibit the proliferation of HepG2 and Huh7 cells in a dose-dependent manner with half-maximal inhibitory concentration (IC50) values of 6.85 ± 0.61 µg/mL and 8.71 ± 0.21 µg/mL, respectively (p < 0.01), whereas the β-SG IC50 values were 4.64 ± 0.48 µg/mL for HepG2 and 5.25 ± 0.14 µg/mL for Huh7 cells (p < 0.01). Remarkably, our study also indicated that β-S and β-SG exhibited cytotoxic activities via inducing apoptosis and activating caspase-3 and -9 in these cells. These findings demonstrated that β-S and β-SG from I. zollingeriana could potentially be developed into promising therapeutic agents to treat liver cancer.
Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30–69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11–1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.
Development of a Tailored, Complex Intervention for Clinical Reflection and Communication about Suspected Urinary Tract Infections in Nursing Home Residents

Background: Inappropriate antibiotic treatments for urinary tract infections (UTIs) in nursing homes cause the development of resistant bacteria. Nonspecific symptoms and asymptomatic bacteriuria are drivers of overtreatment. Nursing home staff provide general practice with information about ailing residents; therefore, their knowledge and communication skills influence prescribing. This paper describes the development of a tailored, complex intervention for a cluster-randomised trial that targets the knowledge of UTI and communication skills in nursing home staff to reduce antibiotic prescriptions. Methods: A dialogue tool was drafted, drawing on participatory observations in nursing homes, interviews with stakeholders, and a survey in general practice. The tool was tailored through a five-phase process that included stakeholders. Finally, the tool and a case-based educational session were tested in a pilot study. Results: The main barriers were that complex patients were evaluated by healthcare staff with limited knowledge about disease and clinical reasoning; findings reported to general practice were insignificant and included vague descriptions; there was evidence of previous opinion bias; nonspecific symptoms were interpreted as UTI; intuitive reasoning led to the inappropriate suspicion of UTI. Conclusion: Sustainable change in antibiotic-prescribing behaviour in nursing homes requires a change in nursing home staff’s beliefs about and management of UTIs.
Introduction to the Scaling of Aquatic Animal Locomotion

Abstract : This introductory lecture attempts to discuss the scaling problems related to the locomotion of aquatic animals in two major categories characterized by low and high Reynolds numbers of swimming motion. In the low-Reynolds-number flow regime it first gives a brief survey of flagellar and ciliary locomotion in order to ascertain the different key parameters that play a role. The hydromechanical and physiological performance of a group of micro-organisms, of different sizes but otherwise similar in their organization from the scaling point of view, is examined. In the high-Reynolds-number category, discussions of the scaling problems include the carangiform and lunate-tail locomotion of different groups of fishes and cetaceans, with consideration of hydromechanical efficiency and physiological function. The discussion is based on the data of both comparative zoology and dynamical similarity. (Author)
Semantic and Sentiment Dissonant Framing Effects on Online News Sharing

Information artifacts incorporate cognitive elements in their design to inform users about and entice them to consume relevant content. Sparse research has examined how to design cognitive elements in information artifacts in the digital news platforms context. This study investigates how information artifacts’ semantic and sentiment elements convey meaning and emotion to elicit users to share online news. We propose a dissonant framework and hypothesize that three dissonance dimensions (namely, semantic dissonance, textual sentiment dissonance, and visual sentiment dissonance) influence news sharing. We tested the hypotheses using real-world data from 2013 to 2015 from Mashable—a popular digital news platform. We used novel machine-learning techniques to extract topics and sentiments from text and photos in news articles. Findings from our econometric analysis support that textual sentiment and visual sentiment dissonance positively affect news sharing.
Effect of measurement duration in respiration chambers on methane traits of beef cattle

Records on 1043 young Angus heifer and bull progeny from 73 sires, measured for methane production in respiration chambers, were used to evaluate the accuracy of a 1-day measurement relative to 2-day measurement duration. The traits assessed were dry matter intake (DMI, kg/day), methane-production rate (MPR, g/day), methane yield (MY, MPR per unit DMI) and four residual methane (RMP, g/day) traits. The RMP traits were computed as actual MPR minus expected MPR, where the expected MPR were calculated from three widely used equations. The expected MPR for the fourth RMP trait was computed by regressing MPR on DMI, using the data from the study. Variance components, heritability, phenotypic and genetic correlations, and the efficiency of selection using 1-day compared with 2-day measurement were used as assessment criteria. The environmental variance for the 2-day measurement was slightly lower than that of the 1-day measurement for all the traits studied, indicating that the addition of an extra day of data was effective in reducing the amount of unexplained variation in each trait. However, these minor reductions did not have a major impact on accuracy; hence, very high phenotypic (rp of 0.91–0.99) and genetic (rg of 0.99 for each trait) correlations were obtained between the two measurement durations. The very high genetic correlation between the two durations of measurement indicated that, at the genetic level, the 1-day duration is measuring the same trait as the 2-day measurement duration. Any enteric-methane emission-abatement strategy that seeks to reduce MPR per se, may have a detrimental impact on ruminant productivity through a correlated reduction in feed intake; hence, MY and the RMP traits are likely to be the traits of interest for genetic improvement. Efficiency of selection for MY and the RMP traits ranged from 0.96 to 0.99, which implies that there would be less than 5% loss in efficiency by adopting a 1-day relative to a 2-day methane-measurement duration. While the throughput of the respiration-chamber facility can be increased by adopting a 1-day measurement duration, additional resources, such as holding pens, would be required to take advantage of the extra day.
Thalassemia mutations in Gaziantep, Turkey

Ninety-eight postnatal and six prenatal cases of thalassemia were studied by the reverse dot-blot hybridization technique in the city of Gaziantep, Turkey. We found the following mutations: IVS 1.110 (G>A) in 29.1%, IVS 2.1 (G>A) in 12.3%, IVS 1.1 (G>A) in 7.7%, Codon 8 (-AA) in 5.6%, -30 (T>A) in 4.6%, IVS 1.6 (T>C) in 4.6%, Codon 39 (C>T) in 3.6%, Codon 44 (-C) in 3.1%, IVS 2.745 (C>G) in 1.5%, Codon 8/9 (+G) in 2.1%, Codon 36/37 (-T) in 2.1%, IVS 1.5 (G>C) in 2.1%, Codon 22 (7pb del) in 0.5%, Codon 5 (-CT) in 0.5% while 20.9% were undetermined. 54 of the thalassemia patients were homozygotes, 12 were compound heterozygous and 31 were heterozygotes. In one allele of 5 thalassemia patients, - thalassemia mutation (3.7 single gene deletions in 1 patient, anti-3.7 gene triplication in 4 patients) was determined at the same time. Finally, this is the first comprehensive study in this region and percentage of  and - globin genes mutation is 2.6 and 79.4%, respectively.
Violent Scene Detection based on Multiple Instance Learning and 3D Histogram of Oriented Gradients

In order to take advantage of the logical structure of video sequences and improve the recognition accuracy of the violence videos, a novel violent scene detection method based on 3D Histogram of Oriented Gradients (HOG3D) and Multi-Instance Learning (MIL) is proposed. Firstly, HOG3D was extracted from video clips. Then, K-means clustering algorithm was implemented to generate visual words vocabulary, and Bag of Visual Words (BoVW) model was used to construct the ﬁnal feature for video frame sequence. Next, the violent scene detection issue was formulated as a MIL problem, and an instance clean method was proposed to remove noise in sample data. With experimental evaluations on the well-known Hockey and Movies benchmarks, the results demonstrate that Citation-kNN is more suitable than the other two tested MIL methods named Axis-Parallel hyper Rectangle (APR) and mi-SVM for violent scene detection. And the proposed scheme obtains very competitive results: 92.7% on Hockey and 98.8% on Movies respectively in terms of mean average precision. And it outperforms the state-of-the-art on Hockey dataset and matches the best known accuracy on Movies, achieving the best balanced accuracy compared with all other methods.
The Primary Sclerosing Cholangitis (PSC) Wellbeing Study: Understanding psychological distress in those living with PSC and those who support them

Introduction The impact of living with Primary Sclerosing Cholangitis (PSC) on psychological wellbeing is not well-known. A recent scoping review by the authors found that both depression and anxiety frequently featured in the accounts of those living with the illness. However, less clear were the factors that led to such psychological distress, the impact that the illness had on families and how to best support those living or supporting someone living with the illness. In light of this, the aim of this study was to explore how the illness impacted the lives of both those diagnosed with the illness and those supporting them. Method and results This study adopted a phenomenological approach to understand the subjective experiences of individual participants. A total of 30 individuals took part in Asynchronous Virtual Focus Groups hosted on a Virtual Learning Environment for a four-week period. Chronological narratives of individuals’ lived experiences from diagnosis to post-transplant are presented below. These narratives centred upon individuals’ and families’ experiences of receiving a diagnosis, and adjusting to life post-diagnosis, particularly in regard to their relationships with health professionals and other family members, and in preparing for the possibility of transplant. Discussion The present article provides an in-depth look at how PSC can impact psychological wellbeing, how psychological distress arises and includes advice tailored to individuals, families and health professionals on how to best support each other.
Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.
Non-Autogenous Innovative Reconstruction Method Following Mandibulectomy

Plexiform ameloblastoma is a locally aggressive odontogenic tumor, rare in the anterior mandible. The treatment of choice is resection with 1–3 cm free margins. In most of reported cases, the affected mandible is reconstructed by autogenic bone graft or osseocutaneous microvascular free flap in order to return function and esthetics. Case description: A 2 cm diameter exophytic ameloblastoma, located in the anterior mandible of a 50-year-old male was resected and reconstructed in a unique manner—allogenic bone block, recombinant human bone morphogenetic protein (rhBMP) and xenograft particles via transcutaneous submental approach. After bone maturation, dental implants were placed and restored by fixed prosthetics. Practical implications: Mandible reconstruction modalities have a crucial influence on patient quality of life, function and esthetics. Allogenic bone block combined with rhBMP and xenograft particles can replace the traditional autogenous bone in certain circumstances. A submental transcutaneous “tent pole” approach can improve the success rate of the reconstruction procedure.
Effects of assistive technology-based occupational therapy on community-dwelling people recovering from stroke

ABSTRACT Purpose The purpose of this study was to investigate the effect of assistive technology-based occupational therapy on occupational performance, satisfaction, and psychosocial impacts of community-dwelling people recovering from stroke. Methods A total of eleven community-dwelling people recovering from stroke participated in an occupational therapy intervention based on the core concepts of the Human Activity Assistive Technology (HAAT) model. The intervention involved the adoption of assistive technology devices (ATDs) to perform individual goal activities in the daily lives of people recovering from stroke. The intervention was conducted weekly as a 30-min session for a total of 4 weeks, in the home where each participant actually resided. Results All participants in the intervention showed statistically significant improvements in occupational performance, satisfaction, and goal attainment level with regard to the individually meaningful activities, between pretest, posttest, and follow-up. User satisfaction with the ATDs and associated services was generally ‘satisfactory,’ and the mean score significantly increased from post-intervention to follow-up. The psychosocial impact of assistive technologies significantly improved from post-intervention to follow-up evaluation. Conclusion Interventions involving concepts, processes, and strategies based on the HAAT model should be continuously performed to select and adopt appropriate interventions involving assistive technologies.