Miracle-dz/UniFAR-FTUs huggingface dataset:
Carers' experiences of involuntary admission under mental health legislation: systematic review and qualitative meta-synthesis

Background Carers are key providers of care and support to mental health patients and mental health policies consistently mandate carer involvement. Understanding carers' experiences of and views about assessment for involuntary admission and subsequent detention is crucial to efforts to improve policy and practice. Aims We aimed to synthesise qualitative evidence of carers' experiences of the assessment and detention of their family and friends under mental health legislation. Method We searched five bibliographic databases, reference lists and citations. Studies were included if they collected data using qualitative methods and the patients were aged 18 or older; reported on carer experiences of assessment or detention under mental health legislation anywhere in the world; and were published in peer-reviewed journals. We used meta-synthesis. Results The review included 23 papers. Themes were consistent across time and setting and related to the emotional impact of detention; the availability of support for carers; the extent to which carers felt involved in decision-making; relationships with patients and staff during detention; and the quality of care provided to patients. Carers often described conflicting feelings of relief coupled with distress and anxiety about how the patient might cope and respond. Carers also spoke about the need for timely and accessible information, supportive and trusting relationships with mental health professionals, and of involvement as partners in care. Conclusions Research is needed to explore whether and how health service and other interventions can improve the involvement and support of carers prior to, during and after the detention of family members and friends.
Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane

1-[2-[({[2-/3-(Alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium/azepan- ium oxalates or dichlorides (alkoxy = butoxy to heptyloxy) were recently described as very promising antimycobacterial agents. These compounds were tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. 1-[3-(Dipropylammonio)-2-({[3-(pentyloxy-/hexyloxy-/heptyloxy)phenyl]carbamoyl}oxy)propyl]pyrrolidinium dichlorides showed high activity against staphylococci and enterococci comparable with or higher than that of used controls (clinically used antibiotics and antiseptics). The screening of the cytotoxicity of the compounds as well as the used controls was performed using human monocytic leukemia cells. IC50 values of the most effective compounds ranged from ca. 3.5 to 6.3 µM, thus, it can be stated that the antimicrobial effect is closely connected with their cytotoxicity. The antibacterial activity is based on the surface activity of the compounds that are influenced by the length of their alkoxy side chain, the size of the azacyclic system, and hydro-lipophilic properties, as proven by in vitro experiments and chemometric principal component analyses. Synergistic studies showed the increased activity of oxacillin, gentamicin, and vancomycin, which could be explained by the direct activity of the compounds against the bacterial cell wall. All these compounds demonstrate excellent antibiofilm activity, when they inhibit and disrupt the biofilm of S. aureus in concentrations close to minimum inhibitory concentrations against planktonic cells. Expected interactions of the compounds with the cytoplasmic membrane are proven by in vitro crystal violet uptake assays.
The impact of attachment security on death preparation in advanced cancer: The role of couple communication

Attachment security protects psychological well‐being in patients with advanced cancer, but its effect on death preparation in this population has not been demonstrated. We examined the relationship of attachment security to death preparation in advanced cancer and tested whether couple communication mediates this relationship and whether gender and age moderate this mediating effect, using longitudinal data from a psychotherapy trial.
Sertoli Cell Tumors of the Testes: Systematic Literature Review and Meta-Analysis of Outcomes in 435 Patients.

BACKGROUND Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes. MATERIALS AND METHODS Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected. RESULTS Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission. CONCLUSION Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission. IMPLICATIONS FOR PRACTICE Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.
Elderly people: propensity to be vaccinated for seasonal influenza in Italy

ABSTRACT Seasonal influenza continues to be a major cause of illness and death. Vaccination is the most cost-effective prophylaxis to prevent the disease and it is particularly important for people who are at high risk of serious complications derived from influenza, especially for people ≥65 years. In Italy, the influenza vaccination program has been unsuccessful with low rates of uptake in people ≥65 years. We analyzed all the community ≥65 years of the Health Promoting Agency (HPA) of Brescia (northern Italy) to evaluate the propensity attitudes toward influenza vaccination among people ≥65 years in four consecutive seasonal influenza campaigns (from 2014/2015 to 2017/2018). Information about subjects were retrieved from administrative databases. Data from 952,822 records were analyzed. The prevalence of vaccinated subjects in the four campaigns was 38.6%, 33.7%, 37.7%, and 40.1%, respectively. Among vaccinated people, the frequencies of individuals aged 65–69.9 years were lower than the frequencies of those in the other age classes, with highest frequencies of vaccinated people in the 75–79.9 years age-class. Overall, males showed a slightly higher propensity to be vaccinated and the propensity toward vaccination increased with age in both genders. Suffering from a chronic disease increased the propensity to vaccination; hypertension had the highest impact on the propensity whereas suffering from vasculopathy has the opposite effect. The value of this study is the possibility to know the factors that might indicate a propensity to get an influenza vaccination and to consider a different approach to people ≥65 years with the characteristics indicating a lower propensity to vaccination.
Cultural Determinants of Cancer Fatalism and Cancer Prevention Behaviors among Asians in Singapore

ABSTRACT This research aims to better understand cultural disparities in cancer prevention behaviors. To do this, we investigate how four cultural beliefs – optimism, pessimism, naïve dialecticism, and superstition – associate with cancer fatalism, which has been recognized as a major barrier to cancer prevention behaviors. Based on an online survey of 1,021 Singapore residents, the results reveal that cancer fatalism is positively associated with pessimism, naïve dialecticism and superstitions, and associated negatively with optimism. Mediation analyses further reveal that cancer fatalism is a significant mediator between these four cultural beliefs and four cancer prevention behaviors including fruit and vegetable intake, regular exercise, avoidance of smoking, and sunscreen use. This study offers theoretical insights into the understanding of how people develop cancer fatalism and practical guidance on the promotion of cancer prevention behaviors, particularly among Asian populations.
The PRT6 N‐degron pathway restricts VERNALIZATION 2 to endogenous hypoxic niches to modulate plant development

Summary VERNALIZATION2 (VRN2), an angiosperm‐specific subunit of the polycomb repressive complex 2 (PRC2), is an oxygen (O2)‐regulated target of the PCO branch of the PRT6 N‐degron pathway of ubiquitin‐mediated proteolysis. How this post‐translational regulation coordinates VRN2 activity remains to be fully established. Here we use Arabidopsis thaliana ecotypes, mutants and transgenic lines to determine how control of VRN2 stability contributes to its functions during plant development. VRN2 localizes to endogenous hypoxic regions in aerial and root tissues. In the shoot apex, VRN2 differentially modulates flowering time dependent on photoperiod, whilst its presence in lateral root primordia and the root apical meristem negatively regulates root system architecture. Ectopic accumulation of VRN2 does not enhance its effects on flowering, but does potentiate its repressive effects on root growth. In late‐flowering vernalization‐dependent ecotypes, VRN2 is only active outside meristems when its proteolysis is inhibited in response to cold exposure, as its function requires concomitant cold‐triggered increases in other PRC2 subunits and cofactors. We conclude that the O2‐sensitive N‐degron of VRN2 has a dual function, confining VRN2 to meristems and primordia, where it has specific developmental roles, whilst also permitting broad accumulation outside of meristems in response to environmental cues, leading to other functions.
Sorting nexin 17 (SNX17) links endosomal sorting to Eps15 homology domain protein 1 (EHD1)–mediated fission machinery

Following endocytosis, receptors that are internalized to sorting endosomes are sorted to different pathways, in part by sorting nexin (SNX) proteins. Notably, SNX17 interacts with a multitude of receptors in a sequence-specific manner to regulate their recycling. However, the mechanisms by which SNX17-labeled vesicles that contain sorted receptors bud and undergo vesicular fission from the sorting endosomes remain elusive. Recent studies suggest that a dynamin-homolog, Eps15 homology domain protein 1, catalyzes fission and releases endosome-derived vesicles for recycling to the plasma membrane. However, the mechanism by which EHD1 is coupled to various receptors and regulates their recycling remains unknown. Here we sought to characterize the mechanism by which EHD1 couples with SNX17 to regulate recycling of SNX17-interacting receptors. We hypothesized that SNX17 couples receptors to the EHD1 fission machinery in mammalian cells. Coimmunoprecipitation experiments and in vitro assays provided evidence that EHD1 and SNX17 directly interact. We also found that inducing internalization of a SNX17 cargo receptor, low-density lipoprotein receptor–related protein 1 (LRP1), led to recruitment of cytoplasmic EHD1 to endosomal membranes. Moreover, surface rendering and quantification of overlap volumes indicated that SNX17 and EHD1 partially colocalize on endosomes and that this overlap further increases upon LRP1 internalization. Additionally, SNX17-containing endosomes were larger in EHD1-depleted cells than in WT cells, suggesting that EHD1 depletion impairs SNX17-mediated endosomal fission. Our findings help clarify our current understanding of endocytic trafficking, providing significant additional insight into the process of endosomal fission and connecting the sorting and fission machineries.
Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. ABSTRACT Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.
Tephritidae fruit fly gut microbiome diversity, function and potential for applications

Abstract The family Tephritidae (order: Diptera), commonly known as fruit flies, comprises a widely distributed group of agricultural pests. The tephritid pests infest multiple species of fruits and vegetables, resulting in huge crop losses. Here, we summarize the composition and diversity of tephritid gut-associated bacteria communities and host intrinsic and environmental factors that influence the microbiome structures. Diverse members of Enterobacteriaceae, most commonly Klebsiella and Enterobacter bacteria, are prevalent in fruit flies guts. Roles played by gut bacteria in host nutrition, development, physiology and resistance to insecticides and pathogens are also addressed. This review provides an overview of fruit fly microbiome structure and points to diverse roles that it can play in fly physiology and survival. It also considers potential use of this knowledge for the control of economically important fruit flies, including the sterile insect technique and cue-lure baiting.
Clinical Features and Outcomes of Bloodstream Infections Caused by New Delhi Metallo-β-Lactamase–Producing Enterobacterales During a Regional Outbreak

Abstract Limited data about New Delhi metallo-β-lactamase (NDM) bacteremia are available. Blood isolates from 40 patients with NDM bacteremia were studied for antibiotic susceptibility and whole-genomic sequencing. NDM bacteremia has high 30-day mortality. In most cases, aztreonam-avibactam is active in vitro. Ceftazidime-avibactam plus aztreonam may represent a feasible therapeutic option.
Coordination-induced exfoliation to monolayer Bi-anchored MnB2 nanosheets for multimodal imaging-guided photothermal therapy of cancer

Background: Rapid advance in biomedicine has recently vitalized the development of multifunctional two-dimensional (2D) nanomaterials for cancer theranostics. However, it is still challenging to develop new strategy to produce new types of 2D nanomaterials with flexible structure and function for enhanced disease theranostics. Method: We explore the monolayer Bi-anchored manganese boride nanosheets (MBBN) as a new type of MBene (metal boride), and discover their unique near infrared (NIR)-photothermal and photoacoustic effects, X-ray absorption and MRI imaging properties, and develop them as a new nanotheranostic agent for multimodal imaging-guided photothermal therapy of cancer. A microwave-assisted chemical etching route was utilized to exfoliate the manganese boride bulk into the nanosheets-constructed flower-like manganese boride nanoparticle (MBN), and a coordination-induced exfoliation strategy was further developed to separate the MBN into the dispersive monolayer MBBN by the coordination between Bi and B on the surface, and the B-OH group on the surface of MBBN enabled facile surface modification with hyaluronic acid (HA) by the borate esterification reaction in favor of enhanced monodispersion and active tumor targeting. Result: The constructed MBBN displays superior NIR-photothermal conversion efficiency (η=59.4%) as well as high photothermal stability, and possesses versatile imaging functionality including photoacoustic, photothermal, CT and T1-wighted MRI imagings. In vitro and in vivo evaluations indicate that MBBN had high photothermal ablation and multimodal imaging performances, realizing high efficacy of imaging-guided cancer therapy. Conclusion: We have proposed new MBene concept and exfloliation strategy to impart the integration of structural modification and functional enhancement for cancer theranostics, which would open an avenue to facile fabrication and extended application of multifunctional 2D nanomaterials.
Design and Characterization of an “All-in-One” Lentiviral Vector System Combining Constitutive Anti-GD2 CAR Expression and Inducible Cytokines

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.
ORP3 phosphorylation regulates phosphatidylinositol 4-phosphate and Ca2+ dynamics at plasma membrane–ER contact sites

ABSTRACT Oxysterol-binding protein (OSBP)-related proteins (ORPs) mediate non-vesicular lipid transfer between intracellular membranes. Phosphoinositide (PI) gradients play important roles in the ability of OSBP and some ORPs to transfer cholesterol and phosphatidylserine between the endoplasmic reticulum (ER) and other organelle membranes. Here, we show that plasma membrane (PM) association of ORP3 (also known as OSBPL3), a poorly characterized ORP family member, is triggered by protein kinase C (PKC) activation, especially when combined with Ca2+ increases, and is determined by both PI(4,5)P2 and PI4P. After activation, ORP3 efficiently extracts PI4P and to a lesser extent phosphatidic acid from the PM, and slightly increases PM cholesterol levels. Full activation of ORP3 resulted in decreased PM PI4P levels and inhibited Ca2+ entry via the store-operated Ca2+ entry pathway. The C-terminal region of ORP3 that follows the strictly defined lipid transfer domain was found to be critical for the proper localization and function of the protein. Highlighted Article: The ORP3 protein controls plasma membrane PI4P levels and store-operated Ca2+ entry regulated by protein kinase C at PM–ER contact sites.
Rapid polarisation mapping in ferroelectrics using fourier masking.

Ferroelectric materials, and more specifically ferroelectric domain walls (DWs) have become an area of intense research in recent years. Novel physical phenomena have been discovered at these nanoscale topological polarisation discontinuities by mapping out the polarisation in each atomic unit cell around the DW in a scanning transmission electron microscope (STEM). However identifying these features requires an understanding of the polarisation in the overall domain structure of the TEM sample, which is often a time consuming process. Here a fast method of polarisation mapping in the TEM is presented, which can be applied to a range of ferroelectric materials. Due to the coupling of polarisation to spontaneous strain we can isolate different strain states and demonstrate the fast mapping of the domain structure in ferroelectric lead titanate (PTO). The method only requires a high resolution (HR) TEM or STEM image and is less sensitive to zone axis or local strain effects which may affect other techniques. Thus it is easily applicable to in-situ experiments. The complimentary benefits of Fourier masking with more advanced mapping strategies and its application to other materials are discussed. These results imply that Fourier masked polarisation mapping will be a useful tool for electron microscopists in streamlining their analysis of ferroelectric TEM samples. This article is protected by copyright. All rights reserved.