Miracle-dz/UniFAR-FTUs huggingface dataset:
Highly sensitive detection of antibody nonspecific interactions using flow cytometry

ABSTRACT The rapidly evolving nature of antibody drug development has resulted in technologies that generate vast numbers (hundreds to thousands) of lead antibody candidates during early discovery. These candidates must be rapidly pared down to identify the most drug-like candidates for in-depth analysis of their safety and efficacy, which can only be performed on a limited number of antibodies due to time and resource requirements. One key biophysical property of successful antibody therapeutics is high specificity, defined as low levels of nonspecific binding or polyspecificity. Although there has been some progress in developing assays for detecting antibody polyspecificity, most of these assays are limited by poor sensitivity or assay formats that require proprietary antibody surface display methods, and some of these assays use complex and poorly defined polyspecificity reagents. Here we report the PolySpecificity Particle (PSP) assay, a sensitive flow cytometry assay for evaluating antibody nonspecific interactions that overcomes previous limitations and can be used for evaluating diverse types of IgGs, multispecific antibodies and Fc-fusion proteins. Our approach uses micron-sized magnetic beads coated with Protein A to capture antibodies at extremely dilute concentrations (<0.02 mg/mL). Flow cytometry analysis of polyspecificity reagent binding to these conjugates results in sensitive detection of differences in nonspecific interactions for clinical-stage antibodies. Our PSP assay strongly discriminates between antibodies with different levels of polyspecificity using previously reported polyspecificity reagents that are either well-defined proteins or highly complex protein mixtures. Moreover, we also find that a unique reagent, namely ovalbumin, results in the best assay sensitivity and specificity. Importantly, our assay is much more sensitive than standard assays such as ELISAs. We expect that our simple, sensitive, and high-throughput PSP assay will accelerate the development of safe and effective antibody therapeutics.
An rfuABCD-Like Operon and Its Relationship to Riboflavin Utilization and Mammalian Infectivity by Borrelia burgdorferi

Riboflavin is an essential micronutrient, but its transport and utilization have remained largely understudied among pathogenic spirochetes. Here, we show that Borrelia burgdorferi, the zoonotic spirochete that causes Lyme disease, is able to import riboflavin via products of its rfuABCD-like operon as well as synthesize flavin mononucleotide and flavin adenine dinucleotide despite lacking canonical genes for their synthesis. ABSTRACT Riboflavin is an essential micronutrient, but its transport and utilization have remained largely understudied among pathogenic spirochetes. Here, we show that Borrelia burgdorferi, the zoonotic spirochete that causes Lyme disease, is able to import riboflavin via products of its rfuABCD-like operon as well as synthesize flavin mononucleotide and flavin adenine dinucleotide despite lacking canonical genes for their synthesis. Additionally, a mutant deficient in the rfuABCD-like operon is resistant to the antimicrobial effect of roseoflavin, a natural riboflavin analog, and is attenuated in a murine model of Lyme borreliosis. Our combined results indicate not only that are riboflavin and the maintenance of flavin pools essential for B. burgdorferi growth but also that flavin utilization and its downstream products (e.g., flavoproteins) may play a more prominent role in B. burgdorferi pathogenesis than previously appreciated.
Proton-Pump Inhibitors: Do Children Break a Leg by Using Them?

ABSTRACT The risk of bone fracture in children under proton-pump inhibitors (PPI) treatment has been the subject of recent publications and naturally raises concerns among prescribing doctors, patients and their parents. Currently, there is no consistency in those risk claims according to the available evidence and an update on it is beneficial to reduce anxiety on one hand, and prompt for well-planned studies addressing the issue on the other. Furthermore, common sense and well-founded prescriptions must be the general rule for this as for any other therapeutic drug.
Synthesis and Characterization of CuxS (x = 1–2) Nanocrystals Formed by the Langmuir–Blodgett Technique

Here, we present the results on the investigation of structural and vibrational properties of CuxS (x = 1–2) nanocrystals formed using the Langmuir–Blodgett technique. The synthesis requires deposition of high quality Langmuir–Blodgett films of copper behenates on a solid substrate (Si, Au, and Pt). The Langmuir–Blodgett film is then sulfidized, what results in the formation of the copper sulfide nanocrystals embedded in behenic acid matrix. Finally, free-standing CuxS nanocrystals are obtained after temperature annealing at 120–400 °C in an Ar atmosphere. Morphology (size, shape, and areal density) and the crystal structure of nanocrystals were determined by direct structural methods including scanning and transmission electron microscopies and high-energy electron diffraction. Surface-enhanced Raman scattering (SERS) by optical phonons in CuxS nanocrystals in the vicinity of metal nanoclusters provided a significant enhancement factor (about 25) and allowed the fine structure of their phonon spectrum to.
Exploring the experience of acute inpatient mental health care from the perspective of family and carers of people experiencing psychosis: A qualitative thematic analysis study conducted during the COVID‐19 pandemic

Abstract Family and carers play an important role in supporting service users who are in receipt of acute mental health inpatient care, but they can also be significantly emotionally and physically impacted. The aim of this study was to examine their needs and priorities during this time. Fourteen family and carers of inpatients experiencing psychosis completed semi‐structured interviews examining their experiences of inpatient care during the COVID‐19 pandemic. Thematic analysis was used to analyse data. Four key themes were identified: ‘A turbulent journey to hospital admission’, ‘I need information and support’, ‘Maintaining my relationship with my loved one’ and ‘Inpatient care is a mixed bag’. Each theme comprised four or five subthemes. The findings demonstrated that family and carers feel excluded from inpatient care and struggled to maintain contact with their loved ones, which was exacerbated by COVID‐19 related restrictions. Communication and being regularly informed about their loved one’s care, as well as visiting loved ones, was particularly problematic. Inpatient care needs to be more inclusive of family and carers and ensure they are kept in mind at every stage of the admission.
Defective interferon amplification and impaired host responses against influenza virus in obese mice

Obesity is a major risk factor that increases morbidity and mortality upon infection. Although type I and type III interferon (IFN)‐induced innate immune responses represent the first line of defense against viral infections, their functionality in the context of metabolic disorders remains largely obscure. This study aimed to investigate IFN responses upon respiratory viral infection in obese mice.
Individual versus Group Calibration of Machine Learning Models for Physical Activity Assessment Using Body-Worn Accelerometers

Supplemental digital content is available in the text. ABSTRACT Modeling approaches for translating accelerometer data into physical activity metrics are often developed using a group calibration approach. However, it is unknown if models developed for specific individuals will improve measurement accuracy. Purpose We sought to determine if individually calibrated machine learning models yielded higher accuracy than a group calibration approach for physical activity intensity assessment. Methods Participants (n = 48) wore accelerometers on the right hip and nondominant wrist while performing activities of daily living in a semistructured laboratory and/or free-living setting. Criterion measures of activity intensity (sedentary, light, moderate, vigorous) were determined using direct observation. Data were reintegrated into 30-s epochs, and eight random forest models were created to determine physical activity intensity by using all possible conditions of training data (individual vs group), protocol (laboratory vs free-living), and placement (hip vs wrist). A 2 × 2 × 2 repeated-measures analysis of variance was used to compare epoch-level accuracy statistics (% accuracy, kappa [κ]) of the models when used to determine activity intensity in an independent sample of free-living participants. Results Main effects were significant for the type of training data (group: accuracy = 80%, κ = 0.59; individual: accuracy = 74% [P = 0.02], κ = 0.50 [P = 0.01]) and protocol (free-living: accuracy = 81%, κ = 0.63; laboratory: accuracy = 74% [P = 0.04], κ = 0.47 [P < 0.01]). Main effects were not significant for placement (hip: accuracy = 79%, κ = 0.58; wrist: accuracy = 75% [P = 0.18]; κ = 0.52 [P = 0.18]). Point estimates for mean absolute error were generally lowest for the group training, free-living protocol, and hip placement. Conclusions Contrary to expectations, individually calibrated machine learning models yielded poorer accuracy than a traditional group approach. In addition, models should be developed in free-living settings when possible to optimize predictive accuracy.
Letter. Fivefold-coordinated aluminum in tectosilicate glasses observed by triple quantum MAS NMR

Abstract Eight glasses with molar Mg/2Al ≈ 1 in the system MgO-Al2O3-SiO2 have been studied by magic angle spinning (MAS) NMR spectroscopy. Using triple quantum (3Q) NMR techniques we find evidence for significant concentrations of Al coordinated to five O atoms in all glasses, the proportion increasing with decreasing Mg/Al and decreasing silica content. In glasses with Mg/2Al = 1, up to 6% of the Al is estimated to be coordinated to five rather than four O atoms. Calculations of the polymerization state of these liquids made assuming that all aluminum is in tetrahedral coordination charge balanced by magnesium are thus seriously in error. Such errors may be of even greater importance at the high temperatures and pressures relevant to the Earth and materials sciences.
Bioanalytical strategies in drug discovery and development

Abstract A reliable, rapid, and effective bioanalytical method is essential for the determination of the pharmacokinetic, pharmacodynamic, and toxicokinetic parameters that inform the safety and efficacy profile of investigational drugs. The overall goal of bioanalytical method development is to elucidate the procedure and operating conditions under which a method can sufficiently extract, qualify, and/or quantify the analyte(s) of interest and/or their metabolites for the intended purpose. Given the difference in the physicochemical properties of small and large molecule drugs, different strategies need to be adopted for the development of an effective and efficient bioanalytical method. Herein, we provide an overview of different sample preparation strategies, analytical platforms, as well as procedures for achieving high throughput for bioanalysis of small and large molecule drugs.
Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity

Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion. ABSTRACT Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolized via different pathways in A. fumigatus and that acetate utilization is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilization is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, antifungal drugs, and human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilization in A. fumigatus, and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of antifungal strategies. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion. This work shows that A. fumigatus metabolizes acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus in vivo virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterizes acetate utilization in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.
Trauma-Informed Care in Child Health Systems

Recent progress in understanding the lifelong effects of early childhood adversities has clarified the need for an organized strategy to identify and intervene with children, adolescents, and families who may be at risk for maladaptive responses. Trauma-informed care (TIC) in child health care operationalizes the biological evidence of toxic stress with the insights of attachment and resilience to enhance health care delivery to mitigate the effects of trauma. The resulting pediatric health care delivery strategy promotes and restores resilience in children and adolescents, partners with families to support relational health, and reduces secondary trauma among pediatric health care clinicians. This policy statement summarizes what policy makers, legislators, and health care organizations need to consider in terms of infrastructure, resources, and financial support to facilitate the integration of TIC principles into all pediatric points of care. The accompanying clinical report describes the elements of TIC in the direct care of children, adolescents, and families and covers the spectrum from prevention to treatment. The recommendations in this statement and the clinical report build on other American Academy of Pediatrics policies that address the needs of special populations (such as children and adolescents in foster or kinship care, in immigrant and refugee families, or in poor or homeless families) and are congruent with American Academy of Pediatrics policies and technical reports concerning the role of pediatric clinicians in the promotion of lifelong health.
Disentangled Feature Learning Network and a Comprehensive Benchmark for Vehicle Re-Identification

Vehicle Re-Identification (ReID) is of great significance for public security and intelligent transportation. Large and comprehensive datasets are crucial for the development of vehicle ReID in model training and evaluation. However, existing datasets in this field have limitations in many aspects, including the constrained capture conditions, limited variation of vehicle appearances, and small scale of training and test set, etc. Hence, a new, large, and challenging benchmark for vehicle ReID is urgently needed. In this paper, we propose a large vehicle ReID dataset, called VERI-Wild 2.0, containing 825,042 images. It is captured using a city-scale surveillance camera system, consisting of 274 cameras covering a very large area over 200 <inline-formula><tex-math notation="LaTeX">$km^2$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>k</mml:mi><mml:msup><mml:mi>m</mml:mi><mml:mn>2</mml:mn></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="duan-ieq1-3099253.gif"/></alternatives></inline-formula>. Specifically, the samples in our dataset present very rich appearance diversities thanks to the long time span collecting settings, unconstrained capturing viewpoints, various illumination conditions, diversified background environments, and different weather conditions. Furthermore, to facilitate more practical benchmarking, we define a challenging and large test set containing about 400K vehicle images that do not have any camera overlap with the training set. VERI-Wild 2.0 is expected to be able to facilitate the design, adaptation, development, and evaluation of different types of learning models for vehicle ReID. Besides, we also design a new method for vehicle ReID. We observe that orientation is a crucial factor for feature matching in vehicle ReID. To match vehicle pairs captured from similar orientations, the learned features are expected to capture specific detailed differential information for discriminating the visually similar yet different vehicles. In contrast, features are desired to capture the orientation invariant common information when matching samples captured from different orientations. Thus a novel disentangled feature learning network (DFNet) is proposed. It explicitly considers the orientation information for vehicle ReID, and concurrently learns the orientation specific and orientation common features that thus can be adaptively exploited via an adaptive matching scheme when dealing with matching pairs from similar or different orientations. The comprehensive experimental results show the effectiveness of our proposed method.
The association between maternal complications and small for gestational age in twin pregnancies using singleton and twin birth weight references

Abstract Introduction In singleton pregnancies, maternal complications, such as preeclampsia and thyroid dysfunction are associated with small for gestational age (SGA). However, data on the association between SGA and maternal complications in twin pregnancies are limited and conflicting. Small sample size and the application of singleton birth weight reference (SBWR) to define SGA in twins may be reasons for the inconsistent conclusions. Purpose of this study was to define SGA in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies using both SBWR and twin birth weight reference (TBWR) and to determine whether certain maternal complications are associated with SGA in twin pregnancies. Materials and methods This retrospective cohort study included all twins delivered in a single tertiary center between 2013 and 2018. SGA was defined as a twin with birth weight <10th centile for gestational age using either SBWR or TBWR. The association between SGA and maternal complications was analyzed separately for DCDA and MCDA twin pregnancies, expressed as odds ratio (OR) and adjusted odds ratio (aOR) with 95% confidence interval (95%-CI). Results A total of 2005 DCDA and 467 MCDA twin pregnancies were enrolled. In DCDA pregnancies, SGA was significantly associated with PE according to TBWR (22.73 vs. 14.56%, aOR 1.823, 95%-CI 1.137–2.922). This association was even more pronounced between SGA and severe PE (9.09 vs. 4.54%, aOR 2.234, 95%-CI 1.115–4.479). In turn, PE was associated with higher risk of SGA defined according to TBWR (8.31 vs. 4.99%, aOR 1.825, 95%-CI 1.139–2.925). No association was detected between SGA and other maternal complications. Using SBWR, no association was found between preeclampsia and SGA. In MCDA pregnancies, according to TBWR, SGA was associated only with severe PE (12.5 vs. 4.06%, aOR 3.470, 95%-CI 1.256–9.587) and lower risk of PROM (aOR 0.067, 95%-CI 0.014–0.322). Conclusion PE was associated with SGA in DCDA pregnancies only when TBWR was used, suggesting that DCDA pregnancies complicated with PE should be closely monitored for signs of SGA and vice versa. In MCDA pregnancies, SGA defined according to TBWR was associated with only severe PE (but not with all PE) and lower risk of PROM. More basic experiments are needed to investigate the mechanisms underlying PE and SGA in DCDA and MCDA twin pregnancies respectively.
A Temporal-Spectral-Based Squeeze-and- Excitation Feature Fusion Network for Motor Imagery EEG Decoding

Motor imagery (MI) electroencephalography (EEG) decoding plays an important role in brain-computer interface (BCI), which enables motor-disabled patients to communicate with the outside world via external devices. Recent deep learning methods, which fail to fully explore both deep-temporal characterizations in EEGs itself and multi-spectral information in different rhythms, generally ignore the temporal or spectral dependencies in MI-EEG. Also, the lack of effective feature fusion probably leads to redundant or irrelative information and thus fails to achieve the most discriminative features, resulting in the limited MI-EEG decoding performance. To address these issues, in this paper, a MI-EEG decoding framework is proposed, which uses a novel temporal-spectral-based squeeze-and-excitation feature fusion network (TS-SEFFNet). First, the deep-temporal convolution block (DT-Conv block) implements convolutions in a cascade architecture, which extracts high-dimension temporal representations from raw EEG signals. Second, the multi-spectral convolution block (MS-Conv block) is then conducted in parallel using multi-level wavelet convolutions to capture discriminative spectral features from corresponding clinical subbands. Finally, the proposed squeeze-and-excitation feature fusion block (SE-Feature-Fusion block) maps the deep-temporal and multi-spectral features into comprehensive fused feature maps, which highlights channel-wise feature responses by constructing interdependencies among different domain features. Competitive experimental results on two public datasets demonstrate that our method is able to achieve promising decoding performance compared with the state-of-the-art methods.
Interprofessional clinical training based in a federally qualified health center: a short report

ABSTRACT A.T. Still University and HealthPoint, a federally qualified health center, worked together to develop novel interprofessional educational clinical experiences for dental and medical students. This short report is focused on evaluating outcomes related to student and patient experiences. Dental and medical faculty designed the program to be as hands on as possible while minimizing disruption to clinic flow. Second-year medical and fourth-year dental students worked together to assess the physical and oral health of the patients. One hundred forty-eight students participated. Of 429 total patients assessed, 83 were referred from the medical clinic to the dental clinic. Caries was present in 24.9% of patients. Overwhelmingly, the patients enjoyed having teams of students care for them. These types of clinical interprofessional experiences give students valuable opportunities to learn with, from, and about each other while providing hands-on care to patients.