Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacterial Outer Membrane Proteins Are Targeted to the Bam Complex by Two Parallel Mechanisms

Proteins that are embedded in the outer membrane of Gram-negative bacteria (OMPs) play an important role in protecting the cell from harmful chemicals. OMPs share a architecture and often contain a conserved sequence motif (β motif) of unknown function. ABSTRACT Membrane proteins that are integrated into the outer membrane of Gram-negative bacteria typically contain a unique “β barrel” structure that serves as a membrane spanning segment. A conserved “β signal” motif is located at the C terminus of the β barrel of many outer membrane proteins (OMPs), but the function of this sequence is unclear. We found that mutations in the β signal slightly delayed the assembly of three model Escherichia coli OMPs by reducing their affinity for the barrel assembly machinery (Bam) complex, a heterooligomer that catalyzes β barrel insertion, and led to the degradation of a fraction of the protein in the periplasm. Interestingly, the absence of the periplasmic chaperone SurA amplified the effect of the mutations and caused the complete degradation of the mutant proteins. In contrast, the absence of another periplasmic chaperone (Skp) suppressed the effect of the mutations and considerably enhanced the efficiency of assembly. Our results reveal the existence of two parallel OMP targeting mechanisms that rely on a cis-acting peptide (the β signal) and a trans-acting factor (SurA), respectively. Our results also challenge the long-standing view that periplasmic chaperones are redundant and provide evidence that they have specialized functions. IMPORTANCE Proteins that are embedded in the outer membrane of Gram-negative bacteria (OMPs) play an important role in protecting the cell from harmful chemicals. OMPs share a common architecture and often contain a conserved sequence motif (β motif) of unknown function. Although OMPs are escorted to the outer membrane by proteins called chaperones, the exact function of the chaperones is also unclear. Here, we show that the β motif and the chaperone SurA both target OMPs to the β barrel insertion machinery in the outer membrane. In contrast, the chaperone Skp delivers unintegrated OMPs to protein degradation complexes. Our results challenge the long-standing view that chaperones are functionally redundant and strongly suggest that they have specialized roles in OMP targeting and quality control.
A shared frailty model for multivariate longitudinal data on adverse event of radiation therapy

Oral mucositis is an inflammatory adverse event when treating head and neck cancer patients with radiation therapy (RT). The severity of its occurrence is believed to mainly depend on its site and the distribution of a cumulative radiation dose in the mouth area. The motivating study investigating differences in radiosensitivities (mucositis progression) at distinct sites where the severity of mucositis is assessed regularly at eight distinct sites on an ordinal scale results in multivariate longitudinal data and thus poses certain challenges. To deal with the multivariate longitudinal data in this particular setting, we take a time‐to‐event approach focusing on the first occurrence of severe mucositis at the distinct sites using the fact that the site‐specific cumulative radiation dose thought to be the main driver of oral mucositis develops over time. Thereby, we may address multivariate longitudinal processes in a simpler and more compact fashion. In this article, to find out differences in mucositis progression at eight distinct sites we propose a shared frailty model for multivariate parallel processes within individuals. The shared frailty model directly incorporating ‘process indicators’ as covariates turns out to adequately explain the differences in the parallel processes (here, mucositis progressions at distinct sites) while taking individual effects into account. The parallel result with the one from the previous analysis based on the same data but conducted with an alternative statistical methodology shows adequacy of the proposed approach.
Biobased Polyurethane Composite Foams Reinforced with Plum Stones and Silanized Plum Stones

In the following study, ground plum stones and silanized ground plum stones were used as natural fillers for novel polyurethane (PUR) composite foams. The impact of 1, 2, and 5 wt. % of fillers on the cellular structure, foaming parameters, and mechanical, thermomechanical, and thermal properties of produced foams were assessed. The results showed that the silanization process leads to acquiring fillers with a smoother surface compared to unmodified filler. The results also showed that the morphology of the obtained materials is affected by the type and content of filler. Moreover, the modified PUR foams showed improved properties. For example, compared with the reference foam (PUR_REF), the foam with the addition of 1 wt. % of unmodified plum filler showed better mechanical properties, such as higher compressive strength (~8% improvement) and better flexural strength (~6% improvement). The addition of silanized plum filler improved the thermal stability and hydrophobic character of PUR foams. This work shows the relationship between the mechanical, thermal, and application properties of the obtained PUR composites depending on the modification of the filler used during synthesis.
Association between Microbiota and Nasal Mucosal Diseases in terms of Immunity

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.
Effect of Nitrogen Ion Implantation on the Cavitation Erosion Resistance and Cobalt-Based Solid Solution Phase Transformations of HIPed Stellite 6

From the wide range of engineering materials traditional Stellite 6 (cobalt alloy) exhibits excellent resistance to cavitation erosion (CE). Nonetheless, the influence of ion implantation of cobalt alloys on the CE behaviour has not been completely clarified by the literature. Thus, this work investigates the effect of nitrogen ion implantation (NII) of HIPed Stellite 6 on the improvement of resistance to CE. Finally, the cobalt-rich matrix phase transformations due to both NII and cavitation load were studied. The CE resistance of stellites ion-implanted by 120 keV N+ ions two fluences: 5 × 1016 cm−2 and 1 × 1017 cm−2 were comparatively analysed with the unimplanted stellite and AISI 304 stainless steel. CE tests were conducted according to ASTM G32 with stationary specimen method. Erosion rate curves and mean depth of erosion confirm that the nitrogen-implanted HIPed Stellite 6 two times exceeds the resistance to CE than unimplanted stellite, and has almost ten times higher CE reference than stainless steel. The X-ray diffraction (XRD) confirms that NII of HIPed Stellite 6 favours transformation of the ε(hcp) to γ(fcc) structure. Unimplanted stellite ε-rich matrix is less prone to plastic deformation than γ and consequently, increase of γ phase effectively holds carbides in cobalt matrix and prevents Cr7C3 debonding. This phenomenon elongates three times the CE incubation stage, slows erosion rate and mitigates the material loss. Metastable γ structure formed by ion implantation consumes the cavitation load for work-hardening and γ → ε martensitic transformation. In further CE stages, phases transform as for unimplanted alloy namely, the cavitation-inducted recovery process, removal of strain, dislocations resulting in increase of γ phase. The CE mechanism was investigated using a surface profilometer, atomic force microscopy, SEM-EDS and XRD. HIPed Stellite 6 wear behaviour relies on the plastic deformation of cobalt matrix, starting at Cr7C3/matrix interfaces. Once the Cr7C3 particles lose from the matrix restrain, they debond from matrix and are removed from the material. Carbides detachment creates cavitation pits which initiate cracks propagation through cobalt matrix, that leads to loss of matrix phase and as a result the CE proceeds with a detachment of massive chunk of materials.
Association of sarcopenia with mortality and end‐stage renal disease in those with chronic kidney disease: a UK Biobank study

Sarcopenia, a degenerative and generalized skeletal muscle disorder involving the loss of muscle function and mass, is an under‐recognized problem in clinical practice, particularly in chronic kidney disease (CKD). We aimed to investigate the prevalence of sarcopenia in individuals with CKD, its risk factors, and its association with all‐cause mortality and progression to end‐stage renal disease (ESRD).
ERCC1 Is a Predictive Biomarker for Non-small Cell Lung Cancer But Is Antibody-dependent

Background/Aim: To predict the efficacy of platinum-containing chemotherapy, ERCC1 expression levels were investigated. Studies have shown changes in the performance of anti-ERCC1 antibodies; therefore, predicting chemotherapy efficacy by immunohistochemical assessment of ERCC1 is controversial. Patients and Methods: Twenty-eight patients who received platinum-containing chemotherapy and underwent computed tomography evaluation 6-9 weeks after therapy initiation were retrospectively identified. The tumor samples were evaluated in 2012 and 2018 using the latest anti-ERCC1 antibodies available at those times. Results: In 2012, the ERCC1 H-score was significantly higher in patients with disease progression than in patients without disease progression (p=0.019). Although the same trend was shown in 2018, there were some inconsistent results between the 2012 and 2018 samples. Conclusion: Patients with tumors showing low ERCC1 expression had a better disease control rate on platinum-containing chemotherapy. However, since the performance of the antibody changed over time, standardized technology to evaluate ERCC1 expression is needed.
Cytoplasmic-only Expression of Maspin Predicts Unfavorable Prognosis in Patients With Pancreatic Ductal Adenocarcinoma

Background/Aim: Maspin is a tumor-suppressor protein expressed in >90% of pancreatic ductal adenocarcinoma (PDAC) cases. We aimed to assess the prognostic value of subcellular localization of maspin. Patients and Methods: Ninety-two resected PDAC specimens were immunohistochemically analyzed. Cytoplasmic-only expression observed in >10% of the tumor was defined as maspin-positive. Results: The maspin-positive status (21.7%) was inversely correlated with well-differentiated histological type and indicated a shorter recurrence-free survival (RFS) and overall survival (OS). Cox’s multivariate analysis showed that maspin-positive status was an independent factor for shorter RFS and OS. Maspin was localized to cytoplasm in AsPC-1 cells, but to both nucleus and cytoplasm in BxPC-3 cells. In AsPC-1 cells, cell invasion was significantly reduced in response to maspin suppression via transfection with siRNA targeting maspin, whereas no reduction was observed in BxPC-3 cells. Conclusion: Cytoplasmic-only expression of maspin could be an independent unfavorable prognostic indicator for patients with PDAC.
Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease

In vivo IL-17A activity is elevated in active tuberculosis and may be a therapeutic target to attenuate disease-associated immunopathology. IL-luminating active tuberculosis disease Immune responses at the site of Mycobacterium tuberculosis (Mtb) infection can dictate pathogenesis within the infected individual and likelihood of transmission to others. However, the understanding of immunological distinctions between active, latent, and cured tuberculosis disease has been limited to assessment of peripheral blood of patients. Here, Pollara et al. evaluated immune response gene signatures in individuals with active, latent, or cured Mtb infection at the site of a tuberculin skin test, which reflects the immune response at the site of infection. The authors found that active disease, but not latent or cured disease, was associated with exaggerated interleukin-17A (IL-17A) activity and neutrophil recruitment. Thus, IL-17A may represent a therapeutic target for active Mtb infection. Host immune responses at the site of Mycobacterium tuberculosis infection can mediate pathogenesis of tuberculosis (TB) and onward transmission of infection. We hypothesized that pathological immune responses would be enriched at the site of host-pathogen interactions modeled by a standardized tuberculin skin test (TST) challenge in patients with active TB compared to those without disease, and interrogated immune responses by genome-wide transcriptional profiling. We show exaggerated interleukin-17A (IL-17A) and T helper 17 (TH17) responses among 48 individuals with active TB compared to 191 with latent TB infection, associated with increased neutrophil recruitment and matrix metalloproteinase-1 expression, both involved in TB pathogenesis. Curative antimicrobial treatment reversed these observed changes. Increased IL-1β and IL-6 responses to mycobacterial stimulation were evident both in circulating monocytes and in molecular changes at the site of TST in individuals with active TB, supporting a model in which monocyte-derived IL-1β and IL-6 promote TH17 differentiation within tissues. Modulation of these cytokine pathways may provide a rational strategy for host-directed therapy in active TB.
Yttrium-90 Radioembolization for Hepatocellular Carcinoma: Virtual Tumor Absorbed Dose as a Predictor of Complete Response

Background/Aim: To evaluate the impact of virtual tumor absorbed dose (vTAD) on tumor response in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization. Patients and Methods: The institutional review board approved this retrospective single center study, which comprised 100 patients with nodular HCC who underwent yttrium-90 radioembolization between November 2015 and December 2019. The vTAD was calculated assuming that all infused microspheres were distributed only in the tumor. The ability of mean absorbed dose (mAD) and vTAD in predicting complete response were evaluated by receiver operating characteristic (ROC) curve analyses. Results: The mAD was 263.9 Gy ± 125.8, and the mean vTAD was 2005.8 Gy ± 2348.9. In terms of tumor response, 63 patients had complete response, 25 partial response, and 12 stable disease. For predicting complete response, ROC curve analyses revealed that the area under the curve (AUC) value of the vTAD was significantly higher (p<0.001) than that of the mAD. Multivariate analysis revealed that Child–Pugh class A5, unilobar disease, and vTAD (>952 Gy) were significant factors in predicting complete response. Conclusion: High vTAD (>952 Gy) plays a significant role in complete response in patients with nodular HCC.
Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas and Correlation With Preoperative Laboratory Findings

Background/Aim: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. Patients and Methods: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. Results: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. Conclusion: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.
Advanced Stages and Increased Need for Adjuvant Treatments in Breast Cancer Patients: The Effect of the One-year COVID-19 Pandemic

Background/Aim: The COVID-19 lockdown includes restrictive measures and temporary health system reorganization. Resources were shifted to COVID-19 patients, screening programs were temporary suspended, and oncological care suffered slow-down. The aim of the study was to evaluate the impact of these measures on breast cancer patients. Patients and Methods: All breast cancer patients referred to our unit from February 21, 2019 to February 21, 2021 were enrolled. Type of treatments and surgery, TNM, tumor diameter, and predictive and prognostic factors were analyzed. Results: Out of 445 patients with a breast cancer diagnosis, 182 (40.9%) were enrolled in the COVID-19 group (from February 21, 2010 to February 21, 2021). These patients were compared with 263 (59.1%) patients pre-COVID-19. Tumor diameters were bigger in the COVID-19 group. Type of surgery and N staging were statistically significantly different. Extreme advanced disease incidence was significantly different between the groups (2.7% COVID-19 group vs. 0 pre-COVID-19 group, p=0.011). Incidence of post-surgical radiation-therapy was higher in the COVID-19 group. Other variables analyzed were comparable without a statistically significant difference. Conclusion: COVID-19 led to increased tumor dimensions, advanced N-staging, and increased need for adjuvant treatments in breast cancer.
Aneurysmal Fibrous Histiocytoma: A Large Soft Tissue Tumor with Metastases Treated with Palliative Radiation Therapy and Targeted Therapy

Aneurysmal fibrous histiocytoma (AFH) is a rare variant of cutaneous fibrous histiocytoma, with low malignant potential and infrequent metastatic progression. We present the case of a 19-year-old female with a large AFH of the neck metastatic to soft tissue and treated with radiation therapy and molecularly targeted therapy. To our knowledge, this is the first report describing either radiation therapy and palliation or the use of targeted therapy in this uncommon malignancy and can provide insight into future therapeutic strategies.
Functional genomics meta-analysis to identify gene set enrichment networks in cardiac hypertrophy

Abstract In order to take advantage of the continuously increasing number of transcriptome studies, it is important to develop strategies that integrate multiple expression datasets addressing the same biological question to allow a robust analysis. Here, we propose a meta-analysis framework that integrates enriched pathways identified through the Gene Set Enrichment Analysis (GSEA) approach and calculates for each meta-pathway an empirical p-value. Validation of our approach on benchmark datasets showed comparable or even better performance than existing methods and an increase in robustness with increasing number of integrated datasets. We then applied the meta-analysis framework to 15 functional genomics datasets of physiological and pathological cardiac hypertrophy. Within these datasets we grouped expression sets measured at time points that represent the same hallmarks of heart tissue remodeling (‘aggregated time points’) and performed meta-analysis on the expression sets assigned to each aggregated time point. To facilitate biological interpretation, results were visualized as gene set enrichment networks. Here, our meta-analysis framework identified well-known biological mechanisms associated with pathological cardiac hypertrophy (e.g., cardiomyocyte apoptosis, cardiac contractile dysfunction, and alteration in energy metabolism). In addition, results highlighted novel, potentially cardioprotective mechanisms in physiological cardiac hypertrophy involving the down-regulation of immune cell response, which are worth further investigation.
Alternations emerge and disappear: the network of dispossession constructions in the history of English

Abstract This paper focuses on two main issues regarding syntactic alternations and their development over time. On the one hand, it discusses the diachronic implications of alternations as involving multiple (rather than binary) choices. On the other hand, it shows that while studies are typically interested in the emergence of alternation relationships, there are also cases of diachronic loss of such. This is illustrated by zooming in on the history of a particular set of ditransitive verbs, viz. dispossession verbs such as steal or rob, and their connection to the well-known English dative alternation. Based on a quantitative analysis of different dispossession-constructions in corpora of Middle, Early Modern and Late Modern English, I demonstrate that the network of dispossession constructions has changed considerably over time — from a complex interaction between three overlapping patterns to a clear differentiation of two non-alternating constructions.
Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human Pathogenic Cryptococcus

The human pathogenic Cryptococcus species are the main agents of fungal meningitis in humans and the causes of other diseases collectively called cryptococcosis. There are at least eight evolutionary divergent lineages among these agents, with different lineages showing different geographic and/or ecological distributions. In this review, we describe the main strain typing methods that have been used to analyze the human pathogenic Cryptococcus and discuss how molecular markers derived from the various strain typing methods have impacted our understanding of not only cryptococcal epidemiology but also its evolutionary histories. These methods include serotyping, multilocus enzyme electrophoresis, electrophoretic karyotyping, random amplified polymorphic DNA, restriction fragment length polymorphism, PCR-fingerprinting, amplified fragment length polymorphism, multilocus microsatellite typing, single locus and multilocus sequence typing, matrix-assisted laser desorption/ionization time of flight mass spectrometry, and whole genome sequencing. The major findings and the advantages and disadvantages of each method are discussed. Together, while controversies remain, these strain typing methods have helped reveal (i) the broad phylogenetic pattern among these agents, (ii) the centers of origins for several lineages and their dispersal patterns, (iii) the distributions of genetic variation among geographic regions and ecological niches, (iv) recent hybridization among several lineages, and (v) specific mutations during infections within individual patients. However, significant challenges remain. Multilocus sequence typing and whole genome sequencing are emerging as the gold standards for continued strain typing and epidemiological investigations of cryptococcosis.