Miracle-dz/UniFAR-FTUs huggingface dataset:
T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis

ABSTRACT Bordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the Bordetella type III chaperone of BtrA. In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node.
Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non‐high‐grade serous ovarian carcinomas

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision‐making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high‐grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non‐HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high‐grade endometrioid (3/20; 15%), low‐grade endometrioid (1/40; 2.5%), low‐grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re‐evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non‐HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53‐abnormal high‐grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53‐wildtype low‐grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non‐causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high‐grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype‐directed sequencing. Furthermore, in‐depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2‐related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Mimicry in misophonia: A large-scale survey of prevalence and relationship with trigger sounds.

BACKGROUND Misophonia is often referred to as a disorder that is characterized by excessive negative emotional responses, including anger and anxiety, to "trigger sounds" which are typically day-to-day sounds, such as those generated from people eating, chewing, and breathing. Misophonia (literally "hatred of sounds") has commonly been understood within an auditory processing framework where sounds cause distress due to aberrant processing in the auditory and emotional systems of the brain. However, a recent proposal suggests that it is the perceived action (e.g., mouth movement in eating/chewing sounds as triggers) of the trigger person, and not the sounds per se, that drives the distress in misophonia. Since observation or listening to sounds of actions of others are known to prompt mimicry in perceivers, we hypothesized that mimicking the action of the trigger person may be prevalent in misophonia. Apart from a few case studies and anecdotal information, a relation between mimicking and misophonia has not been systematically evaluated. METHOD In this work, we addressed this limitation by collecting data on misophonia symptoms and mimicry behavior using online questionnaires from 676 participants. RESULTS Analysis of these data shows that (i) more than 45% of individuals with misophonia reported mimicry, indicating its wide prevalence, (ii) the tendency to mimic varies in direct proportion to misophonia severity, (iii) compared to other human and environmental sounds, trigger sounds of eating and chewing are more likely to trigger mimicking, and (iv) the act of mimicking provides some degree of relief from distress to people with misophonia. CONCLUSION This study shows prevalence of mimicry and its relation to misophonia severity and trigger types. The theoretical framework of misophonia needs to incorporate the phenomenon of mimicry and its effect on management of misophonia distress.
Conservative treatment using laser diode and systemic chemotherapy for early‐stage bilateral retinoblastoma: A 14‐year prospective cohort study

Abstract Background Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long‐term follow‐up is scarce, especially in low‐resource countries. Aims This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low‐resource settings. Methods and results A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three‐agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4–20) months, 34 eyes were in group B (68%). The median follow‐up time was 60 (60–84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan–Meier analysis found the overall globe‐salvage rate at 5 years of 91.9% (95% CI: 80.1%–97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%–90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p = .007, AOR = 8.098, 95% CI: 1.79–36.53) which also shows less enucleation than a type 3 scar (p = .002, AOR = 0.06, 95% CI: 0.01–0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded. Conclusion Conservative treatment of early‐stage RB is safe and effective. Long‐term, thorough follow‐ups of patients post‐treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.
Maternal and fetal outcomes of acute pancreatitis in pregnancy: a population-based study

Background Acute pancreatitis during pregnancy can have negative effects on both the mother and the fetus. The primary aim of this study is to evaluate the trends, maternal and fetal outcomes, and associated comorbidities of acute pancreatitis during pregnancy using data from the USA National Inpatient Sample (NIS) database. Methods This study is a retrospective analysis of hospital discharge records from the NIS database from 2009 to 2019. Results Delivery patients with acute pancreatitis faced a higher risk of maternal mortality (AOR 91.02, 95% CI 28.47–291.06), postpartum hemorrhage (AOR 1.59, 95% CI 1.02–2.49), and hypertensive complications (defined as preeclampsia, eclampsia, or HELLP syndrome) (AOR 3.42, 95% CI 2.56–4.56) compared to those without acute pancreatitis. Moreover, we saw an increased incidence of preterm labor (AOR 3.94, 95% CI 3.02–5.12) and fetal death (AOR 3.12, 95% CI 1.76–5.53). Rates of fetal restriction and large fetal size were comparable. Additionally, the acute pancreatitis group showed higher rates of acute kidney injury (4.2% vs. 0.06%; AOR, 31.02, 95% CI 12.50–76.98), severe sepsis (0.8% vs. 0.01%; AOR, 34.49, 95% CI 7.67–155.14), and respiratory failure (2.4% vs. 0.06%; AOR, 20.77, 95% CI (8.55–50.41). There were no significant differences in maternal and perinatal outcomes in biliary pancreatitis after the intervention compared to conservative treatment. Conclusion Acute pancreatitis during pregnancy can have negative effects on both the mother and fetus. Treatment for biliary pancreatitis does not affect maternal and fetal outcomes. An interdisciplinary approach is essential to ensure optimal outcomes for mothers and their offspring in these cases.
Epigenetic regulation limits competence of pluripotent stem cell‐derived oocytes

Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro‐generated oocytes remains low. Here, we perform a comprehensive comparison of mouse germ cell development in vitro over all culture steps versus in vivo with the goal to understand mechanisms underlying poor oocyte quality. We show that the in vitro differentiation of primordial germ cells to growing oocytes and subsequent follicle growth is critical for competence for preimplantation development. Systematic transcriptome analysis of single oocytes that were subjected to different culture steps identifies genes that are normally upregulated during oocyte growth to be susceptible for misregulation during in vitro oogenesis. Many misregulated genes are Polycomb targets. Deregulation of Polycomb repression is therefore a key cause and the earliest defect known in in vitro oocyte differentiation. Conversely, structurally normal in vitro‐derived oocytes fail at zygotic genome activation and show abnormal acquisition of 5‐hydroxymethylcytosine on maternal chromosomes. Our data identify epigenetic regulation at an early stage of oogenesis limiting developmental competence and suggest opportunities for future improvements.
Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection

ABSTRACT Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = −0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia–Shigella and the lower abundance of Methylobacterium–Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and “healthy” controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression. Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and “healthy” controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.
Plant Traits and Soil Chemical Variables During a Secondary Vegetation Succession in Abandoned Fields on the Loess Plateau

Species dynamics in terms of both plant biological traits, ecological strategies and species richness as well as soil chemical variables during a secondary succession in abandoned fields on the Loess Plateau along a temporal sere from 3 a to 149 a were studied. The results indicated that (1) Soil total C and N increased while soil pH, total K and Na decreased with years since abandonment. No noticeable trend was found in the case of soil P along the successional sere. On the other hand, total CaO of the surface layer (0-10 cm) decreased, but that of the two deeper layers (20-30 cm, 40-50 cm) increased with years since abandonment. Soil C, N, K and P decreased, while Na, CaO and soil pH increased with increasing soil depth. (2) Species richness peaked at both mid_stage of the successional sere and the intermediate portion of soil chemical variables gradient. (3) An ideal dominant species in the early successional stage were annuals with stable seed pool, CR_life strategy, S_regeneration strategy, and strong competitive ability on relatively poor soil, while perennials capable of intensive lateral spread and colonal ability, requiring high nutrient supply, and having C_life strategy would be the dominant species in the subsequent stages. Plant traits, such as perennial_life history, C_, CR_, SC_, SR_, S_ and R_life strategies, W_, S_, Bs_ VBs_ and V_regeneration strategies, were over_represented throughout the whole sere among the other species. (4) Some traits, such as C_, SC_life strategies, ability of clonality, perennial_life history, well_developed lateral spread ability, V_ and VBs_regeneration strategies, seed animal dispersal mode, flowering time of autumn, fruit types of legumen and nut, were more or less correlated with increased soil total C, N and K, while S_, SR_, R_, CR_life strategies, annual_, biannual_life history, non_clonal ability, S_regeneration strategy, poor lateral spread ability, and fruit types of utricle, capsule were associated with increased soil total Na, CaO and pH. The results suggested that steppes should be the dominant native vegetation coinciding with the large_scaled eco_climatic conditions on the Loess Plateau.
Thermal and Subsidence History of the Labrador and West Greenland Continental Margins

Abstract The first order subsidence and thermal characteristics of the Labrador continental margin, the northern Labrador Sea and the central West Greenland margin along Davis Strait are investigated using a one-dimensional, finite element model, calibrated with measured thermal properties of sediments from borehole samples. The model is a variation of the McKenzie stretching model, which allows differing amounts of extension in the upper and lower lithosphere, and it assumes that heat transport is by thermal conduction. Model predictions are tested using bottom-hole temperature, and geochemical and paleoenvironmental data from 27 industry wells. An instantaneous, depth-dependent extension model is generally consistent with the observed geological constraints. Predicted heat flow ranges from 40 to 50mW/m2 for the Labrador Shelf and 50 to 60mW/m2 for the northern Labrador Sea-Davis Strait region. For most of the wells, the model predicts maximum water depths during the Paleocene and Eocene, in qualitative agreement with interpreted paleobathymetry. Crustal extension, β, ranges from 1.20 to 2.15 for the Labrador Shelf-northern Labrador Sea wells, and from approximately 1.6 to 1.9 for the central West Greenland margin. Subcrustal lithospheric extension, δ, varies from approximately 1 to 3 times the amount of crustal thinning in most of the wells, β estimates are biased by the presence of basement topography and reflect local changes in crustal thickness rather than true crustal extension. Thermal predictions appear to depend most strongly on estimates of δ which, in turn, depend on the quality and resolution of paleobathymetry data. Profiles across the Labrador Shelf and in the northern Labrador Sea are used to study variations in the timing and position of the petroleum generation zone and are related to specific hydrocarbon occurrences. This zone varies temporally and spatially along the margin, but its present-day thickness is predicted to increase seaward from the Labrador coastline, with progressively younger sediments becoming mature toward the shelf edge. Calculations for the northern Labrador Sea imply that gas and condensate have been locally generated from organic-rich Paleocene shales since Late Miocene time. Potential oil source rocks of Eocene age are predicted to occur within the oil window beneath the outer part of the Labrador Shelf. Mature Upper Cretaceous to Paleocene mudstones with oil and gas potential were encountered in two wells on the West Greenland margin, and should be at the threshold for peak hydrocarbon generation in deeper parts of the basin.
A factorization of the GJMS operators of special Einstein products and applications

We show that the GJMS operators of a special Einstein product factor as a composition of second- and fourth-order differential operators. In particular, our formula applies to the Riemannian product $H^{\ell} \times S^{d-\ell}$. We also show that there is an integer $D = D(k,\ell)$ such that if $d \geq D$, then for any special Einstein product $N^\ell \times M^{d-\ell}$, the Green's function for the GJMS operator of order $2k$ is positive. As a result, these products give new examples of closed Riemannian manifolds for which the $Q_{2k}$-Yamabe problem is solvable.
The Lorenz ratio as a guide to scattering contributions to Planckian transport

In many physical situations in which many-body assemblies exist at temperature $T$, a characteristic quantum-mechanical time scale of approximately $\hbar/k_{B}T$ can be identified in both theory and experiment, leading to speculation that it may be the shortest meaningful time in such circumstances. When this behaviour is investigated by probing the scattering rate of strongly interacting electrons in metals, it is clear that in some cases only electron-electron scattering can be its cause, while in others it arises from high-temperature scattering of electrons from quantised lattice vibrations, i.e. phonons. In metallic oxides, which are among the most studied materials, analysis of electrical transport does not satisfactorily identify the relevant scattering mechanism at 'high' temperatures near room temperature. We employ a contactless optical method to measure thermal diffusivity in two Ru-based layered perovskites, Sr$_3$Ru$_2$O$_7$ and Sr$_2$RuO$_4$, and use the measurements to extract the dimensionless Lorenz ratio. By comparing our results to the literature data on both conventional and unconventional metals we show how the analysis of high-temperature thermal transport can both give important insight into dominant scattering mechanisms, and be offered as a stringent test of theories attempting to explain anomalous scattering.
Solutions to the KP hierarchy with an elliptic background

A class of"elliptic soliton"solutions of the Kadomtsev-Petviashvili hierarchy, which includes a determinantal solution of Li and Zhang, is described in terms of pseudo-differential operator formulation. In our approach, the Li-Zhang solution is obtained by repeatedly applying the Darboux transformation to a stationary solution. Real-valued solutions are discussed and various examples that display web-like patterns are presented.
Comments on the double cone wormhole

In this paper we revisit the double cone wormhole introduced by Saad, Shenker and Stanford (SSS), which was shown to reproduce the ramp in the spectral form factor. As a first approximation we can say that this solution computes $\textrm{Tr}[e^{-iKT}]$, a trace of the"evolution"operator that generates Schwarzschild time translations on the two sided wormhole geometry. This point of view leads to a simple way to compute the normalization factor of the wormhole. When we have bulk matter fields, SSS suggested using a modified evolution $\tilde K$ which involves a slightly complex geometry, so that we are really computing $\textrm{Tr}[e^{-i\tilde{K}T}]$. We argue that, for general black holes, the spectrum of $\tilde K$ is given by quasinormal mode frequencies. We explain that this reproduces various features that were previously predicted from the spectral form factor on hydrodynamics grounds. We also give a general algebraic construction of the modified boost in terms of operators constructed from half sided modular inclusions. For the special case of JT gravity, we work out the backreaction of matter on the geometry of the double cone and find that it deforms the geometry in an undesirable direction. We finally give some comments on the possible physical interpretation of $\tilde K$.