Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconstitution of Bam Complex-Mediated Assembly of a Trimeric Porin into Proteoliposomes

Porins are a widespread family of homotrimers that represent a substantial fraction of the total protein located in the OM of many proteobacteria. These proteins facilitate the nonspecific diffusion of small molecules across the outer membrane and strongly influence the susceptibility of bacteria to clinically used antibiotics. ABSTRACT Many integral membrane proteins form oligomeric complexes, but the assembly of these structures is poorly understood. Here, we show that the assembly of OmpC, a trimeric porin that resides in the Escherichia coli outer membrane (OM), can be reconstituted in vitro. Although we observed the insertion of both urea-denatured and in vitro-synthesized OmpC into pure lipid vesicles at physiological pH, the protein assembled only into dead-end dimers. In contrast, in vitro-synthesized OmpC was inserted into proteoliposomes that contained the barrel assembly machinery (Bam) complex, a conserved heterooligomer that catalyzes protein integration into the bacterial OM, and folded into heat-stable trimers by passing through a short-lived dimeric intermediate. Interestingly, complete OmpC assembly was also dependent on the addition of lipopolysaccharide (LPS), a glycolipid located exclusively in the OM. Our results strongly suggest that trimeric porins form through a stepwise process that requires the integration of the protein into the OM in an assembly-competent state. Furthermore, our results provide surprising evidence that interaction with LPS is required not only for trimerization but also for the productive insertion of individual subunits into the lipid bilayer. IMPORTANCE Porins are a widespread family of homotrimers that represent a substantial fraction of the total protein located in the OM of many Proteobacteria. These proteins facilitate the nonspecific diffusion of small molecules across the outer membrane and strongly influence the susceptibility of bacteria to clinically used antibiotics. The assembly of porins and the mechanism by which they are integrated into the outer membrane, however, are poorly understood. Here, we show that assembly can be completely reconstituted in vitro and requires only phospholipid vesicles containing the Bam complex, a molecular chaperone, and LPS. Furthermore, by showing that LPS binding is required for membrane insertion, our results demonstrate that a native lipid promotes a specific stage of porin biogenesis.
Commercial Off-The-Shelf Video Games for Reducing Stress and Anxiety: Systematic Review

Background Using commercial off-the-shelf video games rather than custom-made computer games could have several advantages for reducing stress and anxiety, including their low cost, advanced graphics, and the possibility to reach millions of individuals worldwide. However, it is important to emphasize that not all commercial video games are equal, and their effects strongly depend on specific characteristics of the games. Objective The aim of this systematic review was to describe the literature on the use of commercial off-the-shelf video games for diminishing stress and anxiety, examining the research outcomes along with critical variables related to computer game characteristics (ie, genre, platform, time of play). Methods A systematic search of the literature was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The search databases were PsycINFO, Web of Science, Medline, IEEExplore, and the Cochrane Library. The search string was: [(“video game*”) OR (“computer game*”)] AND [(“stress”) OR (“anxiety”) OR (“relaxation”)] AND [(“study”) OR (“trial”) OR (“training”)]. Results A total of 28 studies met the inclusion criteria for the publication period 2006-2021. The findings demonstrate the benefit of commercial off-the-shelf video games for reducing stress in children, adults, and older adults. The majority of the retrieved studies recruited young adults, and fewer studies have involved children, middle-aged adults, and older adults. In addition to exergames and casual video games, other genres of commercial off-the-shelf games helped to reduce stress and anxiety. Conclusions Efficacy in reducing stress and anxiety has been demonstrated not only for exergames and casual video games but also for other genres such as action games, action-adventure games, and augmented reality games. Various gaming platforms, including consoles, PCs, smartphones, mobile consoles, and virtual reality systems, have been used with positive results. Finally, even single and short sessions of play had benefits in reducing stress and anxiety. Trial Registration International Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY202130081; https://inplasy.com/? s=INPLASY202130081
Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case–control study

ABSTRACT Objectives: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). Design: Case–control study. Setting: Osaka University Hospital. Participants: Patients with possible iNPH underwent a CSF tap test. Measurements: Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. Results: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. Conclusions: A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.
Characterization of carotenoid biosynthetic pathway genes in the pea aphid (Acyrthosiphon pisum) revealed by heterologous complementation and RNA interference assays

Carotenoids are involved in many essential physiological functions and are produced from geranylgeranyl pyrophosphate through synthase, desaturase, and cyclase activities. In the pea aphid (Acyrthosiphon pisum), the duplication of carotenoid biosynthetic genes, including carotenoid synthases/cyclases (ApCscA–C) and desaturases (ApCdeA–D), through horizontal gene transfer from fungi has been detected, and ApCdeB has known dehydrogenation functions. However, whether other genes contribute to aphid carotenoid biosynthesis, and its specific regulatory pathway, remains unclear. In the current study, functional analyses of seven genes were performed using heterologous complementation and RNA interference assays. The bifunctional enzymes ApCscA–C were responsible for the synthase of phytoene, and ApCscC may also have a cyclase activity. ApCdeA, ApCdeC, and ApCdeD had diverse dehydrogenation functions. ApCdeA catalyzed the enzymatic conversion of phytoene to neurosporene (three‐step product), ApCdeC catalyzed the enzymatic conversion of phytoene to ζ‐carotene (two‐step product), and ApCdeD catalyzed the enzymatic conversion of phytoene to lycopene (four‐step product). Silencing of ApCscs reduced the expression levels of ApCdes, and silencing these carotenoid biosynthetic genes reduced the α‐, β‐, and γ‐carotene levels, as well as the total carotenoid level. The results suggest that these genes were activated and led to carotenoid biosynthesis in the pea aphid.
Building a Caring Arts Program with Oncology Patients: From Inception to Impact

A Caring Arts Program (CAP) was inspired and carried out by the vision of an in-resident nurse-artist and the chief nursing officer in a private, not-for-profit health system. Together they envisioned a program that would impact family, patients, and staff while improving patient/family care practices. The impact of the CAP was evaluated through mixed methods which included stories, fieldnotes, comments, and the Listen360(R) which rates patient satisfaction scores. The synergy between the evaluations and the attempt to understand what creates patient satisfaction using creative arts was a prime objective of this article. The qualitative results represented by field notes and written patient comments revealed a positive impact on participants. The quantitative results demonstrated an improvement in patient satisfaction scores during the time of the project. The positive trend in the scores combined with the qualitative stories and interviews suggests that the CAP contributed to the improvement in patient satisfaction at Baptist MD Anderson Cancer Center. During a worldwide pandemic, supporting human caring and self-expression was more critical than ever.
The roles of antimicrobial resistance, phage diversity, isolation source and selection in shaping the genomic architecture of Bacillus anthracis

Bacillus anthracis, the causative agent of anthrax disease, is a worldwide threat to livestock, wildlife and public health. While analyses of genetic data from across the globe have increased our understanding of this bacterium’s population genomic structure, the influence of selective pressures on this successful pathogen is not well understood. In this study, we investigate the effects of antimicrobial resistance, phage diversity, geography and isolation source in shaping population genomic structure. We also identify a suite of candidate genes potentially under selection, driving patterns of diversity across 356 globally extant B. anthracis genomes. We report ten antimicrobial resistance genes and 11 different prophage sequences, resulting in the first large-scale documentation of these genetic anomalies for this pathogen. Results of random forest classification suggest genomic structure may be driven by a combination of antimicrobial resistance, geography and isolation source, specific to the population cluster examined. We found strong evidence that a recombination event linked to a gene involved in protein synthesis may be responsible for phenotypic differences between comparatively disparate populations. We also offer a list of genes for further examination of B. anthracis evolution, based on high-impact single nucleotide polymorphisms (SNPs) and clustered mutations. The information presented here sheds new light on the factors driving genomic structure in this notorious pathogen and may act as a road map for future studies aimed at understanding functional differences in terms of B. anthracis biogeography, virulence and evolution.
Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline

ABSTRACT Introduction: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports. Methods: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 (“agree moderately”) or 6 (“agree strongly”). Reporting elements that ≥70% of panelists rated as “agree moderately” or “agree strongly” were considered to have achieved consensus. Results: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report. Discussion: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.
Bimodal multispectral imaging system with cloud-based machine learning algorithm for real-time screening and detection of oral potentially malignant lesions and biopsy guidance

Abstract. Significance: Screening and early detection of oral potentially malignant lesions (OPMLs) are of great significance in reducing the mortality rates associated with head and neck malignancies. Intra-oral multispectral optical imaging of tissues in conjunction with cloud-based machine learning (CBML) can be used to detect oral precancers at the point-of-care (POC) and guide the clinician to the most malignant site for biopsy. Aim: Develop a bimodal multispectral imaging system (BMIS) combining tissue autofluorescence and diffuse reflectance (DR) for mapping changes in oxygenated hemoglobin (HbO2) absorption in the oral mucosa, quantifying tissue abnormalities, and guiding biopsies. Approach: The hand-held widefield BMIS consisting of LEDs emitting at 405, 545, 575, and 610 nm, 5MPx monochrome camera, and proprietary Windows-based software was developed for image capture, processing, and analytics. The DR image ratio (R610/R545) was compared with pathologic classification to develop a CBML algorithm for real-time assessment of tissue status at the POC. Results: Sensitivity of 97.5% and specificity of 92.5% were achieved for discrimination of OPML from patient normal in 40 sites, whereas 82% sensitivity and 96.6% specificity were obtained for discrimination of abnormal (OPML + SCC) in 89 sites. Site-specific algorithms derived for buccal mucosa (27 sites) showed improved sensitivity and specificity of 96.3% for discrimination of OPML from normal. Conclusions: Assessment of oral cancer risk is possible by mapping of HbO2 absorption in tissues, and the BMIS system developed appears to be suitable for biopsy guidance and early detection of oral cancers.
Major depression and generalised anxiety disorder: An analysis of the effects of remission status and comorbidity on mother-infant emotional availability in the perinatal period.

BACKGROUND The effects of maternal depression on mother-infant relationship quality likely vary according to depression heterogeneity. We investigated the effects of different presentations of major depression on mother-infant emotional availability (EA). METHODS Data were obtained from 115 mother-infant dyads from a longitudinal pregnancy cohort. Disorders, symptoms, and antidepressant use were assessed in pregnancy and postpartum, and EA was observed 6-month postpartum. Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) were assessed using the Structured Clinical Interview for the DSM-5. A series of multivariate analyses of covariance analyses' examining the effects of disorder on EA were conducted. RESULTS After controlling for maternal age, antidepressant use, and postpartum depressive symptoms, MDD accounted for 20% of the variance in EA. In the MDD/GAD group, 93% of interactions were rated as emotionally unavailable, nearly threefold the comparison group rate. CONCLUSIONS Findings demonstrate that different presentations of major depression are associated with observed differences in mother-infant EA.
A Widespread Bacterial Secretion System with Diverse Substrates

The microbial constituency of a host-associated microbiome emerges from a complex physical and chemical interplay of microbial colonization factors, host surface conditions, and host immunological responses. To fill unique niches within a host, bacteria encode surface and secreted proteins that enable interactions with and responses to the host and cooccurring microbes. ABSTRACT In host-associated bacteria, surface and secreted proteins mediate acquisition of nutrients, interactions with host cells, and specificity of tissue localization. In Gram-negative bacteria, the mechanism by which many proteins cross and/or become tethered to the outer membrane remains unclear. The domain of unknown function 560 (DUF560) occurs in outer membrane proteins throughout Proteobacteria and has been implicated in host-bacterium interactions and lipoprotein surface exposure. We used sequence similarity networking to reveal three subfamilies of DUF560 homologs. One subfamily includes those DUF560 proteins experimentally characterized thus far: NilB, a host range determinant of the nematode-mutualist Xenorhabdus nematophila, and the surface lipoprotein assembly modulators Slam1 and Slam2, which facilitate lipoprotein surface exposure in Neisseria meningitidis (Y. Hooda, C. C. Lai, A. Judd, C. M. Buckwalter, et al., Nat Microbiol 1:16009, 2016, https://doi.org/10.1038/nmicrobiol.2016.9; Y. Hooda, C. C. L. Lai, T. F. Moraes, Front Cell Infect Microbiol 7:207, 2017, https://doi.org/10.3389/fcimb.2017.00207). We show that DUF560 proteins from a second subfamily facilitate secretion of soluble, nonlipidated proteins across the outer membrane. Using in silico analysis, we demonstrate that DUF560 gene complement correlates with bacterial environment at a macro level and host association at a species level. The DUF560 protein superfamily represents a newly characterized Gram-negative secretion system capable of lipoprotein surface exposure and soluble protein secretion with conserved roles in facilitating symbiosis. In light of these data, we propose that it be titled the type 11 secretion system (TXISS). IMPORTANCE The microbial constituency of a host-associated microbiome emerges from a complex physical and chemical interplay of microbial colonization factors, host surface conditions, and host immunological responses. To fill unique niches within a host, bacteria encode surface and secreted proteins that enable interactions with and responses to the host and co-occurring microbes. Bioinformatic predictions of putative bacterial colonization factor localization and function facilitate hypotheses about the potential of bacteria to engage in pathogenic, mutualistic, or commensal activities. This study uses publicly available genome sequence data alongside experimental results from Xenorhabdus nematophila to demonstrate a role for DUF560 family proteins in secretion of bacterial effectors of host interactions. Our research delineates a broadly distributed family of proteins and enables more accurate predictions of the localization of colonization factors throughout Proteobacteria.
Detecting Pb2+ by a ‘turn-on’ fluorescence sensor based on DNA functionalized magnetic nanocomposites

Sensitive and selective detection of the lead ion (Pb2+) plays an important role in terms of both human health and environmental protection, as the heavy metal is fairly ubiquitous and highly toxic. The highly stable fluorescence biosensor is composed of Fe3O4@TiO2 core–shell nanocomposites, functionalized with a carboxyl fluorescein labeled DNA. The morphology, physical and chemical properties of the sensing nanomaterials were studied by transmission electron microscopy, FT-IR spectroscopy (FT-IR), x-ray powder diffraction and vibrating sample magnetometer. UV–visible and fluorescence spectroscopy were used to characterize the fluorescein functionalized magnetic nanoparticles. The performance of Pb2+ detection displayed an excellent linearity (R 2 = 0.995) in the range of 10−10 to 5 × 10−9 ppm with a detection limit of 10−10 ppm, based on the optimization of the fabrication process and aptamers’ specification. The fluorescence biosensor has an accurate response, excellent recoveries and high adsorbent capacities. It was successfully applied for the determination of Pb2+ in contaminated water and serum samples; the detection of limit in both media were 10−10 ppm. These features ensure the potential use of aptamer functionalized magnetic nanocomposites as a new class of non-toxic biocompatible sensors for biological and environmental applications.
Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy.

Introduction: [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). We have optimized the radiolabeling protocol for a multidose formulation (27-28.8 GBq equivalent to 6-7 patient-doses) of [177Lu]Lu-PSMA-617 using [177Lu]Lu3+ produced via 176Lu(n,γ)177Lu route with moderate specific activity (0.66-0.81 GBq/μg). Methods: [177Lu]Lu-PSMA-617 was synthesized using moderate specific activity [177Lu]LuCl3 (0.74 GBq/μg) with PSMA-617 having metal-to-ligand molar ratio ∼1: 2.5 in CH3COONH4 buffer (0.1 M) containing gentisic acid at pH 4.0-4.5. Human prostate carcinoma cell line LNCaP cell (high PSMA expression) was used for in vitro cell-binding studies and generating tumor xenograft models in nude mice for tissue biodistribution studies. Several batches of the present formulation have been clinically administered in mCRPC patients (single patient dose: 4.44-5.55 GBq per cycle). Results: In this study we report a consistent and reproducible protocol for multidose formulations of [177Lu]Lu-PSMA-617 for adopting in a hospital radiopharmacy setting. Although the radiochemical yield of [177Lu]Lu-PSMA-617 was found to be 97.30% ± 1.03%, the radiochemical purity was 98.24% ± 0.50% (n = 19). In vitro and serum stability of [177Lu]Lu-PSMA-617 was retained up to 72 and 120 h after radiolabeling and upon storage at -20°C with a radioactive concentration between 0.37 and 0.74 GBq/mL upon using stabilizer concentration as low as 43-48 μg/mCi. Preclinical cell-binding studies of [177Lu]Lu-PSMA-617 revealed specific binding with LNCaP cells of 17.4% ± 2.4%. The uptake in LnCaP xenografted tumor (nude mice) was 7.5 ± 2.6% ID/g for ∼1.5-2.0 cm3 tumor volume at 24-h post-injection. Post-therapy (24 h) SPECT image of mCRPC patients with prior orchidectomy and various hormone therapy showed specific localization of [177Lu]Lu-PSMA-617 in the tumor region. Conclusions: Formulation of a ready-to-use multidose formulation of [177Lu]Lu-PSMA-617 was successfully achieved and the procedure was optimized for routine preparation at a hospital radiopharmacy set-up. High degree of localization of [177Lu]Lu-PSMA-617 in post-therapy SPECT scan and the post-therapeutic response confirms its therapeutic efficacy. Clinical Trials.gov ID: RPC/51/Minutes/Final dated 16th October, 2019.