Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering cross-species reactivity of LAMP-1 antibodies using deep mutational epitope mapping and AlphaFold

ABSTRACT Delineating the precise regions on an antigen that are targeted by antibodies has become a key step for the development of antibody therapeutics. X-ray crystallography and cryogenic electron microscopy are considered the gold standard for providing precise information about these binding sites at atomic resolution. However, they are labor-intensive and a successful outcome is not guaranteed. We used deep mutational scanning (DMS) of the human LAMP-1 antigen displayed on yeast surface and leveraged next-generation sequencing to observe the effect of individual mutants on the binding of two LAMP-1 antibodies and to determine their functional epitopes on LAMP-1. Fine-tuned epitope mapping by DMS approaches is augmented by knowledge of experimental antigen structure. As human LAMP-1 structure has not yet been solved, we used the AlphaFold predicted structure of the full-length protein to combine with DMS data and ultimately finely map antibody epitopes. The accuracy of this method was confirmed by comparing the results to the co-crystal structure of one of the two antibodies with a LAMP-1 luminal domain. Finally, we used AlphaFold models of non-human LAMP-1 to understand the lack of mAb cross-reactivity. While both epitopes in the murine form exhibit multiple mutations in comparison to human LAMP-1, only one and two mutations in the Macaca form suffice to hinder the recognition by mAb B and A, respectively. Altogether, this study promotes a new application of AlphaFold to speed up precision mapping of antibody–antigen interactions and consequently accelerate antibody engineering for optimization.
Thyroglossal duct diseases: presentation and outcomes

Objective The incidence of thyroglossal duct diseases in the general population is about 7%. We aimed to demonstrate the clinical presentations and management of thyroglossal duct diseases. Methods We conducted a retrospective review of all patients who underwent surgery for histopathologically confirmed thyroglossal duct cyst, sinus, or fistula at a single center. Results A total of 151 cases were included in this study. There were more female patients (87, 58%) than male patients (64, 42%). The patients’ ages ranged from 1 to 63 years old. The most prevalent complaint was painless upper midline neck swelling (93.3%). Most cases were diagnosed as thyroglossal duct cysts (137, 90.7%). Six cases (4%) were associated with carcinoma. All the cases were managed using the modified Sistrunk procedure. There were no procedure-related complications, and five cases of recurrence. Conclusions Although thyroglossal duct cyst is the most common neck anomaly in children, it may also present with various characteristics later in life. This condition can be managed successfully without complications and with a low recurrence rate.
Seismic modeling in viscoelastic media

Anelasticity is usually caused by a large number of physical mechanisms which can be modeled by different microstructural theories. A general way to take all these mechanisms into account is to use a phenomenologic model. Such a model which is consistent with the properties of anelastic media can be represented mechanically by a combination of springs and dash‐pots. A suitable system can be constructed by the parallel connection of several standard linear elements and is referred to as the general standard linear solid rheology. Two relaxation functions that describe the dilatational and shear dissipation mechanisms of the medium are needed. This model properly describes the short and long term behaviors of materials with memory and is the basis for describing viscoelastic wave propagation. This work presents two‐dimensional (2-D) and three‐dimensional (3-D) forward modeling in linear viscoelastic media. The theory implements Boltzmann’s superposition principle based on a spectrum of relaxation mechanisms.
How subjective well-being, patient-reported clinical improvement (PROMs) and experience of care (PREMs) relate in an acute psychiatric care setting?

Abstract Background Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are increasingly acknowledged as critical tools for enhancing patient-centred, value-based care. However, research is lacking on the impact of using standardized patient-reported indicators in acute psychiatric care. The aim of this study was to explore whether subjective well-being indicators (generic PROMs) are relevant for evaluating the quality of hospital care, distinct from measures of symptom improvement (disease-specific PROMs) and from PREMs. Methods Two hundred and forty-eight inpatients admitted to a psychiatric university hospital were included in the study between January and June 2021. Subjective well-being was assessed using standardized generic PROMs on well-being, symptom improvement was assessed using standardized disease-specific PROMs, and experience of care using PREMs. PROMs were completed at admission and discharge, PREMs were completed at discharge. Clinicians rated their experience of providing treatment using adapted PREMs items. Results Change in subjective well-being (PROMs) at discharge was significantly (p < 0.001), but moderately (r 2 = 28.5%), correlated to improvement in symptom outcomes, and weakly correlated to experience of care (PREMs) (r 2 = 11.0%), the latter being weakly explained by symptom changes (r 2 = 6.9%). Patients and clinicians assessed the experience of care differently. Conclusions This study supports the case for routinely measuring patients’ subjective well-being to better capture the unmet needs of patients undergoing psychiatric hospital treatment, and the use of standardized patient-reported measures as key indicators of high quality of care across mental health services.
Modelling of the correlation between velocity and reactive scalar gradients in turbulent premixed flames based on DNS data

The interaction between turbulence and reactive scalar fields is discussed for the wrinkled flamelets regime of turbulent premixed combustion. Emphasis is placed on the effects associated with the turbulent straining term. In the regime of turbulent combustion under consideration, which corresponds to Karlovitz and Damköhler numbers such that Ka < 1 and Da > 1, a clear and simple formulation is proposed to explain and to model the influence of the correlation between velocity and reactive scalar gradients. This formulation is based on the conservative variables budget across one-dimensional premixed laminar flamelets. The analysis firmly confirms the dependence on both the Damköhler number and the expansion factor, a feature already foreseen in recent studies. Nevertheless, in contrast with previous work, (i) the scaling arguments used in the present contribution are different from those used in other recent proposals, and (ii) the proposed closures are not only deduced from dimensional arguments but also from the consideration of conservative variable budgets across laminar flamelets. The resulting functional dependence on the expansion factor is found to be influenced by the underlying one-dimensional flamelet representation and two possible closures are put forward to take this dependence into account. (iii) The two closures do not exhibit a proportionality to the mean scalar dissipation rate as suggested in previous studies but to the square of this quantity. This results in the presence of a second contribution proportional to in the modelled transport equation for the mean scalar dissipation rate, in addition to the modelled molecular dissipation term. (iv) Since previous Direct Numerical Simulation (DNS) studies have been essentially devoted to the influence of the Damköhler number, the present DNS validation step is focused on the effects of the expansion rate. To this purpose, the proposed models are validated against three available DNS databases obtained for turbulent premixed flames with different values of the density ratio between unburned and fully burned gases.
Oral lesions associated with daily use of snus, a moist smokeless tobacco product. A cross-sectional study among Norwegian adolescents

Abstract Objective Use of snus, a moist, smokeless tobacco product, may lead to local changes in the oral mucous membrane in the area where the snus is placed. It can also cause irreversible gingival retraction. This cross-sectional study aimed to investigate the relationship between use of snus, oral mucosal lesions (snus induced lesions) and gingival retractions among adolescents in Norway. Material and Methods All 18–20 years olds visiting public dental health clinics in the south-eastern region of Norway between October 2015 and December 2016 were invited to participate. All participants (n = 1363) filled in an electronic questionnaire before a clinical examination. Of these, 216 used snus daily. Results Snus induced lesions were observed in 79.2% of daily snus using participants. In adjusted regression analyses, the odds of having a more severe lesion as opposed to a less severe lesion were 1.12 times greater for each additional box of snus used in a month (p < .01). Women were 46% less likely to have a severe lesion than men (p = .03). Gingival retractions were observed in 18.4% of the participants. The odds for dental retraction were significantly higher by 34% for each year of snus use. Conclusions Most of the adolescents using snus had snus induced lesions, whereas approximately one-fifth had gingival retractions. The severity of the lesion and gingival retraction increased with the amount of snus boxes used and the duration of the snus use, respectively.
The French compassionate programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant

Background The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (CF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for people with CF carrying one of 177 rare variants. Methods An observational study was conducted to evaluate the effectiveness of ETI in people with CF with advanced lung disease who were not eligible for ETI in Europe. All patients with no F508del variant and advanced lung disease (defined as having a percent predicted forced expiratory volume (ppFEV1) <40% and/or being under evaluation for lung transplantation) and enrolled in the French compassionate programme initiated ETI at recommended doses. Effectiveness was evaluated by a centralised adjudication committee at 4–6 weeks in terms of clinical manifestations, sweat chloride concentration and ppFEV1. Results Among the first 84 people with CF included in the programme, ETI was effective in 45 (54%), and 39 (46%) were considered to be nonresponders. Among the responders, 22 (49%) out of 45 carried a CFTR variant that is not currently approved by the FDA for ETI eligibility. Important clinical benefits, including suspending the indication for lung transplantation, a significant decrease in sweat chloride concentration by a median (interquartile range (IQR)) −30 (−14–−43) mmol·L−1 (n=42; p<0.0001) and an improvement in ppFEV1 by +10.0 (6.0–20.5) percentage points (n=44; p<0.0001), were observed in those for whom treatment was effective. Conclusion Clinical benefits were observed in a large subset of people with CF with advanced lung disease and CFTR variants not currently approved for ETI. A large subset of people with cystic fibrosis and advanced lung disease but no F508del variant may respond to elexacaftor/tezacaftor/ivacaftor. The observed clinical benefits seem comparable to those described in patients with the F508del variant. https://bit.ly/3YATRfQ
Interannual variations of intense typhoon activity

Abstract This study attempts to determine the possible causes of the interannual variations of intense tropical cyclones (TCs, or typhoons) in the western North Pacific (WNP, defined here as the region 0–40◦N, 120–180◦E). It is found that such variations cannot be explained by those of sea-surface temperature averaged over the same region. Rather, in years with a high frequency of occurrence of intense typhoons (inferred from high values of accumulated cyclone energy, or ACE), both the dynamic and thermodynamic conditions in the atmosphere, especially in the southeastern part of the WNP, are favourable for the formation of TCs. On the other hand, these conditions are not conducive for TC formation in years with small number of intense typhoons (low values of ACE). The temporal coefficients of the empirical orthogonal functions of the relative vorticity anomalies in the lower troposphere, the vertical zonal shear and the moist static energy correlate very well with ACE. The ACE is also significantly correlated with the Nino3.4 SST anomalies. It is concluded that the interannual variations of intense typhoons in the WNP are likely caused to a large extent by changes in the planetary-scale atmospheric circulation and thermodynamic structure associated with the El Ni˜no phenomenon.
Characterization of terahertz emission from a dc-biased filament in air

We demonstrate that the terahertz emission from a dc-biased filament can be regarded as a sum of an elliptically polarized terahertz source (generated by a filament without external electric field) and a linearly polarized terahertz source induced by the external electric field applied to the filament. The peak frequency and linewidth of the linearly polarized terahertz source are related to the average plasma density of the filament.
The correlations between steady-state concentration, duration of action and molecular weight of GLP-1RAs and their efficacy and gastrointestinal side effects in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

ABSTRACT Background To assess the influence of steady-state concentration, duration of action and molecular weight of glucagon-like peptide-1 receptor (GLP-1RA) on efficacy and gastrointestinal (GI) side effects in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to April 2022. Randomized controlled trials (RCTs) comparing GLP-1RA versus non-GLP-1RA agents in patients with T2DM were included. Sensitivity analyses on steady-state concentration, duration of action and molecular weight of GLP-1RA were conducted. Results 113 RCTs were included. Greater HbA1c reduction between GLP-1RA users versus non-GLP-1RA users was observed in the high-steady-state-concentration stratum and long-acting stratum compared with the low-steady-state-concentration stratum (Psubgroup difference = 0.0004) and short-acting stratum (Psubgroup difference<0.0001). The risk of GI adverse events in GLP-1RA users versus non-GLP-1RA users was decreased in the high-steady-state-concentration stratum, long-acting stratum and heavy-molecular-weight stratum compared with low-steady-state-concentration stratum (Psubgroup difference<0.0001), short-acting stratum (Psubgroup difference = 0.002) and light-molecular-weight stratum (Psubgroup difference = 0.0008). Conclusion GLP-1RA with high steady-state concentration and long duration of action showed better hypoglycemic effect. GLP-1RA with high steady-state concentration, long duration of action and heavy molecular weight was associated with lower risk of GI adverse events.
Low-Fire Processing and Dielectric Properties of TiO2 with MnOX–CuO

Effects of MnOx–CuO (MC) on densification and dielectric properties of TiO2 ceramics have been investigated. The densification temperature of TiO2 is greatly reduced from 1100–1200°C for pure rutile down to 900°C with the presence of >3 wt% MC. This is caused by the liquid phase sintering taking place at the interface between CuO in the MC and rutile during firing. For the samples with 3–20 wt% MC, a high relative sintered density of >95% is obtained at 900°C and the resulting dielectric composites have a dielectric constant and loss at 1 MHz in the range of 80–100 and 0.05–0.2%, respectively.
School Truants and Truancy Motivation Sorted out with Multidimensional Scaling

A combination of established and novel multivariate techniques was applied to the problem of school truancy. Informants described 104 truants they were acquainted with by ranking the applicability of 73 motives and causes for absence from school. Individual rankings were analyzed in the context of a multidimensional representation of the motives, derived from sorting data provided by other informants. Each ranking was interpreted as a three-dimensional vector within this “similarity space” and as a profile of 10 weights indicating the contributions of 10 “hotspots” (broad themes summarizing the motives) located in the space. The broad spectrum of motivational profiles was subdivided using clustering techniques. Five main relatively homogeneous clusters emerged, of which two cover a previously recognized pattern of parent-condoned truancy, whereas the other three are related to recognized syndromes of adolescent delinquency. There may be considerable differences between these clusters in terms of developmental antecedents, prognosis, and most effective form of intervention.
The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes that reflect dietary intakes and fecal water content

ABSTRACT Obesity is a complex, multifactorial condition that is an important risk factor for noncommunicable diseases including cardiovascular disease and type 2 diabetes. While prevention and management require a healthy and energy balanced diet and adequate physical activity, the taxonomic composition and functional attributes of the colonic microbiota may have a supplementary role in the development of obesity. The taxonomic composition and metabolic capacity of the fecal microbiota of 286 women, resident in Auckland New Zealand, was determined by metagenomic analysis. Associations with BMI (obese, nonobese), body fat composition, and ethnicity (Pacific, n = 125; NZ European women [NZE], n = 161) were assessed using regression analyses. The fecal microbiotas were characterized by the presence of three distinctive enterotypes, with enterotype 1 represented in both Pacific and NZE women (39 and 61%, respectively), enterotype 2 mainly in Pacific women (84 and 16%) and enterotype 3 mainly in NZE women (13 and 87%). Enterotype 1 was characterized mainly by the relative abundances of butyrate producing species, Eubacterium rectale and Faecalibacterium prausnitzii, enterotype 2 by the relative abundances of lactic acid producing species, Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus ruminis, and enterotype 3 by the relative abundances of Subdoligranulum sp. , Akkermansia muciniphila, Ruminococcus bromii, and Methanobrevibacter smithii. Enterotypes were also associated with BMI, visceral fat %, and blood cholesterol. Habitual food group intake was estimated using a 5 day nonconsecutive estimated food record and a 30 day, 220 item semi-quantitative Food Frequency Questionnaire. Higher intake of ‘egg’ and ‘dairy’ products was associated with enterotype 3, whereas ‘non-starchy vegetables’, ‘nuts and seeds’ and ‘plant-based fats’ were positively associated with enterotype 1. In contrast, these same food groups were inversely associated with enterotype 2. Fecal water content, as a proxy for stool consistency/colonic transit time, was associated with microbiota taxonomic composition and gene pools reflective of particular bacterial biochemical pathways. The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes, most likely due to differential dietary intake and fecal consistency/colonic transit time. These parameters need to be considered in future analyses of human fecal microbiotas.
Debating well: Why don’t we, and how can we?

ABSTRACT This paper introduces the contributions of Alan Sugarman (US), Rachel Blass (Israel), Paul Denis (France), Luisa Perez (Uruguay), Bernard Reith (Switzerland) and David Tuckett (UK) to a debate on the question of how we can enable productive discussion about our scientific differences and why historically it has been so difficult for the discipline of psychoanalysis to initiate and sustain such discussions. By way of introduction the historical example of the Controversial Discussions in the British Psychoanalytic Society is briefly reviewed and several possible factors contributing to the difficulties are provisionally identified, including over-reliance on authority and tradition, eagerness to supervise on the basis of our own theoretical models rather than trying to understand those of others, the lack of clarity and consensus in our definitions of terms, a lack of mutual curiosity resulting in theoretical silos, an experienced threat to identity when adjustments to our positions are called for, and the lack of a methodology for undesrstanding and / or resolving differences.
Testing Time-Invariance of Variable Specificity in Repeated Measure Designs Using Structural Equation Modeling

A structural equation modeling method for examining time-invariance of variable specificity in longitudinal studies with multiple measures is outlined, which is developed within a confirmatory factor-analytic framework. The approach represents a likelihood ratio test for the hypothesis of stability in the specificity part of the residual term associated with repeated administration of each measure. The procedure can be used in the search for parsimonious versions of multiwave multiple-indicator models, to test for variable specificity in them, and to examine assumptions underlying particular parameter estimation procedures in repeated measure designs. The outlined method is illustrated with empirical data.
Peiminine regulates bone‐fat balance by canonical Wnt/β‐catenin pathway in an ovariectomized rat model

Peiminine is a major biologically active component of Fritillaria thunbergii Miq that exhibits good anticancer, antiinflammatory, and anti‐osteoclast effects. However, its effects on osteoporosis (OP) remain unknown. This study aimed to explore whether Peiminine was able to regulate osteogenesis and adipogenesis in ovariectomized (OVX) rat. The effects on the differentiation of bone marrow stem cells (BMSCs), function of Wnt/β‐catenin pathway, ALP activity, calcium nodule deposition, as well as adipocyte formation in vitro by Peiminine at different concentrations, were detected. The curative effects of Peiminine on the ovariectomy‐induced osteoporosis model by micro‐CT and bone histomorphology assays were analyzed. The promotion of osteogenic differentiation and inhibition of adipogenic differentiation by Peiminine (5–40 μg/mL) was detected and the optimum concentration was 20 μg/mL. Mechanistically, Peiminine regulated the fate of BMSCs in vitro, and activated Wnt/β‐catenin signaling pathway by restraining phosphorylation of β‐catenin and promoting the nuclear translocation of β‐catenin. Moreover, Peiminine prevented ovariectomy‐induced osteoporosis by alleviating trabecular bone loss and inhibiting adipose formation. Our data suggested that Peiminine could attenuate ovariectomy‐induced osteoporosis by alleviating trabecular bone loss and inhibiting adipose formation. These encouraging discoveries could lay the foundation for Peiminine to be a promising preventive treatment strategy for skeletal diseases, such as osteoporosis.