Functional interrogation of DNA damage response variants with base editing screens.

Mutations in DNA damage response (DDR) genes endanger genome integrity and predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base editing screens, we identify > 2,000 sgRNAs that generate nucleotide variants in 86 DDR genes, resulting in altered cellular fitness upon DNA damage. Among those variants, we discover loss- and gain-of-function mutants in the Tudor domain of the DDR regulator 53BP1 that define a non-canonical surface required for binding the deubiquitinase USP28. Moreover, we characterize variants of the TRAIP ubiquitin ligase that define a domain, whose loss renders cells resistant to topoisomerase I inhibition. Finally, we identify mutations in the ATM kinase with opposing genome stability phenotypes and loss-of-function mutations in the CHK2 kinase previously categorized as variants of uncertain significance for breast cancer. We anticipate that this resource will enable the discovery of additional DDR gene functions and expedite studies of DDR variants in human disease.

Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory.

Histone proteins affect gene expression through multiple mechanisms, including through exchange with histone variants. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. Most notably, widely expressed variants of H2B remain elusive. We applied recently developed antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters, and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Further, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a mechanism linking histone variants to chromatin accessibility, transcriptional regulation, neuronal function, and memory. This work further identifies a widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.

PURPOSE: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically. METHODS: This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. RESULTS: Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms. CONCLUSION: The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.

Optimization of synchrotron radiation parameters using swarm intelligence and evolutionary algorithms.

Alignment of each optical element at a synchrotron beamline takes days, even weeks, for each experiment costing valuable beam time. Evolutionary algorithms (EAs), efficient heuristic search methods based on Darwinian evolution, can be utilized for multi-objective optimization problems in different application areas. In this study, the flux and spot size of a synchrotron beam are optimized for two different experimental setups including optical elements such as lenses and mirrors. Calculations were carried out with the X-ray Tracer beamline simulator using swarm intelligence (SI) algorithms and for comparison the same setups were optimized with EAs. The EAs and SI algorithms used in this study for two different experimental setups are the Genetic Algorithm (GA), Non-dominated Sorting Genetic Algorithm II (NSGA-II), Particle Swarm Optimization (PSO) and Artificial Bee Colony (ABC). While one of the algorithms optimizes the lens position, the other focuses on optimizing the focal distances of Kirkpatrick-Baez mirrors. First, mono-objective evolutionary algorithms were used and the spot size or flux values checked separately. After comparison of mono-objective algorithms, the multi-objective evolutionary algorithm NSGA-II was run for both objectives - minimum spot size and maximum flux. Every algorithm configuration was run several times for Monte Carlo simulations since these processes generate random solutions and the simulator also produces solutions that are stochastic. The results show that the PSO algorithm gives the best values over all setups.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. RECENT FINDINGS: The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumption with the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2 years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

VISIBL-MS: A bilingual educational framework to increase awareness of early multiple sclerosis.

BACKGROUND: Despite advancements in treatments of multiple sclerosis (MS), there is a lack of awareness of early MS symptoms, especially in students and the public, contributing to delays in diagnosis and treatment. This review aims to identify gaps in tools to increase awareness and to provide a bilingual framework to facilitate recognition of early MS symptoms. METHODS: We performed a literature review to determine the use of English and Spanish mnemonics in MS education for medical students and patients. RESULTS: There is no educational tool to help remember the early signs of MS at present. Here we present a framework for early awareness encompassed in the bilingual mnemonics VISIBLY (English) and VISIBLE (Spanish). VISIBLY stands for (1) Vision changes: Painful vision loss, loss of color vision or double vision; (2) Belly or Back numbness and Balance issues; (3) Limb weakness or Numbness; (4), Young people. Spanish version is included in the manuscript. CONCLUSION: We posit that VISIBL-MS provides a framework for MS awareness that addresses the interconnection between language, culture, health literacy, and health outcomes and can be a useful educational tool to tackle the effects of health literacy on diverse communities.

MB38(M=Be and Zn): A Quasi-Planar Structure Rather Than A Core-Shell Octahedral Borospherene Structure.

In a recent paper (ChemPhysChem, 2023, 24, e202200947), based on the results computed using DFT method, the perfect core-shell octahedral configuration Be@B38 and Zn@B38 was reported to be the global minima of the MB38(M=Be and Zn) clusters. However, this paper presents the lower energy structures of MB38(M=Be and Zn) clusters as a quasi-planar configuration, the Be atom is found to reside on the convex surface of the quasi-planar B38 isomer, while the Zn atom tends to be attached to the top three B atoms of the quasi-planar B38 isomer. Our results show that quasi-planar MB38(M=Be and Zn) at DFT method have lower energy than core-shell octahedral configuration M@B38(M=Be and Zn). Natural atomic charges, valence electron density, electron localization function (ELF) analyses identify the MB38(M=Be and Zn) to be charge transfer complexes (Be2+B382-and Be1+B381-) and suggest primarily the electrostatic interactions between doped atom and B38 fragment. The photoelectron spectra of the corresponding anionic structures were simulated, providing theoretical basis for future structural identification.

Transport of dust across the Solar System: Constraints on the spatial origin of individual micrometeorites from cosmic-ray exposure.

The origin of micrometeorites (MMs) from asteroids and comets is well-established, but the relative contribution from these two classes remains poorly resolved. Likewise, determining the precise origin of individual MMs is an open challenge. Here, cosmic-ray exposure ages are used to resolve the spatial origins of 12 MMs collected from urban areas and Antarctica. Their 26Al and 10Be concentration, produced during cosmic-ray irradiation in space, were measured by accelerator mass spectrometry. These data are compared to results from a model simulating the transport and irradiation of the MM precursors in space. This model, for the first time, considers a variety of orbits, precursor particle sizes, compositions and densities and incorporates non-isotropic solar and galactic cosmic-ray flux profiles, depth-dependent production rates, as well as spherical evaporation during atmospheric entry. While the origin for six MMs remains ambiguous, two MMs show a preferential tendency towards an origin in the Inner Solar System (Near Earth Objects to the Asteroid Belt) and four towards an origin in the Outer Solar System (Jupiter Family Comets to the Kuiper Belt). These findings challenge the notion that dust originating from the Outer Solar System is unlikely to survive long-term transport and delivery to the terrestrial planets. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Comprehensive characterization of organics in oil sands process water in constructed mesocosms utilizing multiple analytical methods.

This study aims to provide a thorough characterization of dissolved organics in oil sands process water (OSPW) in field-based aquatic mesocosms at both molecular and bulk measurement levels using multiple analytical methods. In a 3-year outdoor mesocosm experiment, the analysis of naphthenic acid (NA) species was conducted using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS). The results revealed the removal of both total NAs (38% and 35%) and classical NAs (O2-NAs, 58% and 49%) in undiluted and half-diluted OSPW, respectively. The increased ratios of oxidized NAs (O3-O6 NAs) to classical NAs suggested a transformation trend. The results also indicated that O2-NAs with higher carbon number and lower double bond equivalent (DBE) were more easily degraded in the mesocosm systems. Biomimetic extraction using solid-phase microextraction (BE-SPME) measurement displayed 26% (undiluted OSPW) and 30% (half-diluted OSPW) decrease in total bioavailable organics over 3 years. Naphthenic acids fraction compounds (NAFCs) obtained by liquid-liquid extraction (LLE) were also determined using Fourier transform infrared spectroscopy (FTIR). Reduction in acute toxicity for undiluted (43%) and half-diluted (26%) OSPW was observed over 3 years, which are well correlated with the decreases of NAs and BE-SPME concentrations. Moreover, BE-SPME values were found to be linearly correlated with total NAs concentrations (r = 0.96) and NAFCs (r = 0.96). Additionally, the linear relationships of individual O2-O6 NA species and BE-SPME concentrations unveiled the changes in the relative abundances of O2-O6 NA species in total bioavailable organics over time in the mesocosms. The present study has provided comprehensive insights by integrating various analytical methods, contributing valuable information for assessing the effectiveness of aquatic mesocosm systems in studying the temporal changes of organics in OSPW.

Bacillus velezensis BE2 controls wheat and barley diseases by direct antagonism and induced systemic resistance.

Wheat and barley rank among the main crops cultivated on a global scale, providing the essential nutritional foundation for both humans and animals. Nevertheless, these crops are vulnerable to several fungal diseases, such as Septoria tritici blotch and net blotch, which significantly reduce yields by adversely affecting leaves and grain quality. To mitigate the effect of these diseases, chemical fungicides have proven to be genuinely effective; however, they impose a serious environmental burden. Currently, biocontrol agents have attracted attention as a sustainable alternative to fungicides, offering an eco-friendly option. The study aimed to assess the efficacy of Bacillus velezensis BE2 in reducing disease symptoms caused by Zymoseptoria tritici and Pyrenophora teres. This bacterium exhibited significant antagonistic effects in vitro by suppressing fungal development when pathogens and the beneficial strain were in direct confrontation. These findings were subsequently confirmed through microscopic analysis, which illustrated the strain's capacity to inhibit spore germination and mycelial growth in both pathogens. Additionally, the study analysed the cell-free supernatant of the bacterium using UPLC-MS (ultra-performance liquid chromatography-mass spectrometry). The results revealed that strain BE2 produces, among other metabolites, different families of cyclic lipopeptides that may be involved in biocontrol. Furthermore, the beneficial effects of strain BE2 in planta were assessed by quantifying the fungal DNA content directly at the leaf level after bacterization, using two different application methods (foliar and drenching). The results indicated that applying the beneficial bacterium at the root level significantly reduced pathogens pressure. Finally, gene expression analysis of different markers showed that BE2 application induced a priming effect within the first hours after infection. KEY POINTS: • BE2 managed Z. tritici and P. teres by direct antagonism and induced systemic resistance. • Strain BE2 produced seven metabolite families, including three cyclic lipopeptides. • Application of strain BE2 at the root level triggered plant defense mechanisms.

PBPK model-based gender-specific risk assessment of N-nitrosodimethylamine (NDMA) using human biomonitoring data.

Despite several screening levels for NDMA reported in water, soil, air, and drugs, the human risk assessment using biomonitoring concentrations has not been performed. In this study, gender-specific exposure guidance values were determined in humans, then biomonitoring measurements in healthy Korean subjects (32 men and 40 women) were compared to the exposure guidance values to evaluate the current exposure level to NDMA. For the human risk assessment of NDMA, the gender-specific physiologically based pharmacokinetic (PBPK) model was developed in humans using proper physiological parameters, partition coefficients, and biochemical parameters. Using the PBPK model, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty on the single model predictions. The PBPK modeling and Monte Carlo simulation allowed the estimation of the relationship between external dose and blood concentration for the risk assessment. The procedure for the human risk assessment was summarized as follows: (1) estimating a steady-state blood concentration (Cavg) corresponding to the daily no observed adverse effect level (NOAEL) administration in rats; (2) applying uncertainty factors (UFs) for deriving the human Cavg; (3) determining the exposure guidance values as screening criteria; (4) interpreting the human biomonitoring measurements by forward and reverse dosimetry approaches. Using the biomonitoring concentrations, current daily exposures to NDMA were estimated to be 3.95 µg/day/kg for men and 10.60 µg/day/kg for women, respectively. The result of the study could be used as a basis for implementing further risk management and regulatory decision-making for NDMA.

YouTube as a source of recognizing acute stroke; progress in 2 years.

BACKGROUND: YouTube™ has a great role in providing information, which includes educational videos, to more than 2 billion users, making it the second most popular application in the world. BE-FAST is a modified version of the FAST mnemonic and is used to detect acute ischemic stroke by the patients or their relatives. The purpose of this study is to assess the overall usefulness of the information of YouTube in patients to realize an acute stroke attack. METHODS: YouTube was searched for the following five terms: "stroke", ''stroke diagnosis", "stroke signs", "brain attack" and "what is stroke" in November 2021 and May 2023, separately. Two independent neurology specialists scored each video by using Global Quality Scale (GQS). RESULTS: Among the total of 150 videos, the number that met inclusion criteria was 91 for the November 2021 search and 104 for the May 2023 search. For the 2021 search, in 30 videos (33%), the FAST mnemonic or its contents were noticed, whereas BE-FAST was mentioned in only four videos (4.4%). For the 2023 search, the FAST mnemonic or its contents were noticed in 36 videos (34.6%) and BE-FAST was mentioned in 11 videos (10.6%). Among the 2021 and 2023 searches, the mean GQS values were 3.09 and 2.96 points, 50 (54.8%) vs. 56 (53.8%) videos rated 3.5 points or higher (high quality), respectively. GQS scores of the videos mentioning balance, eyes, face, arms, speech, and time, the basic and advanced information about radiology and treatment, and mentioning FAST, BE-FAST, and TPA were significantly higher. CONCLUSION: We conclude that YouTube is not yet a very useful tool for patients to realize that they may have acute ischemic stroke, though over the years; information available on social media for healthcare information and education has improved.

Neogene continental denudation and the beryllium conundrum.

Reconstructing Cenozoic history of continental silicate weathering is crucial for understanding Earth's carbon cycle and greenhouse history. The question of whether continental silicate weathering increased during the late Cenozoic, setting the stage for glacial cycles, has remained controversial for decades. Whereas numerous independent proxies of weathering in ocean sediments (e.g., Li, Sr, and Os isotopes) have been interpreted to indicate that the continental silicate weathering rate increased in the late Cenozoic, beryllium isotopes in seawater have stood out as an important exception. Beryllium isotopes have been interpreted to indicate stable continental weathering and/or denudation rates over the last 12 Myr. Here we present a Be cycle model whose results show that variations in the 9Be weathering flux are counterbalanced by near-coastal scavenging while the cosmogenic 10Be flux from the upper atmosphere stays constant. As a result, predicted seawater 10Be/9Be ratios remain nearly constant even when global denudation and Be weathering rates increase by three orders of magnitude. Moreover, 10Be/9Be records allow for up to an 11-fold increase in Be weathering and denudation rates over the late Cenozoic, consistent with estimates from other proxies. The large increase in continental weathering indicated by multiple proxies further suggests that the increased CO2 consumption by continental weathering, driven by mountain-building events, was counterbalanced by other geological processes to prevent a runaway icehouse condition during the late Cenozoic. These processes could include enhanced carbonate dissolution via pyrite weathering, accelerated oxidation of fossil organic carbon, and/or reduced basalt weathering as the climate cooled.

The intrabulbar or extrabulbar growth pattern and its surgical outcomes of jugular foramen paragangliomas.

OBJECTIVE: This study is to define a subclassification system of jugular foramen paragangliomas (JFPs) and to demonstrate corresponding microsurgical outcomes of JFPs. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: We conducted a retrospective review of the clinical data of 44 patients with JFPs who underwent surgical management. Extrabulbar(Be) tumor and intrabulbar(Bi) tumor are defined based on the growth patterns, receiver operating characteristic (ROC) curves of the imaging profile were generated and was confirmed based on intraoperative findings. Area Under Curve (AUC), accuracy, sensitivity, and specificity for diagnostic imaging were revealed. We also compared the correlation between the two growth patterns with Fisch's classification, blood loss, lower cranial nerves (LCNs) deficit. RESULTS: There are 27 (69%) cases of Bi tumor and 17 (39%) cases of Be tumor. Significant radiomics features between the two growth patterns were demonstrated, ROC curves achieved excellent AUCs for MRI sequences (T1W1 MRI, MR contrast-enhanced sequence, MR complex sequences and MR complex + DSA by 0.833, 0.833, 0.875, 0.944) and had statistically significant in diagnosis of two growth patterns (P<0.05). There was no statistical correlation between growth patterns of JFPs and intra-operative blood loss. Preoperative LCNs deficits and Fisch's classification of tumors were correlated with the growth patterns of JFPs (P < 0.05). CONCLUSION: We proposetd two growth patterns of JFPs in term of the inferior petrous sinus involvement. Identification of Bi or Be growth patterns preoperatively is helpful to design optimal surgical strategies and minimize postoperative complications.

Contention-Less Multi-Link Synchronous Transmission for Throughput Enhancement and Heterogeneous Fairness in Wi-Fi 7.

Multi-link operation (MLO) is a new and essential mechanism of IEEE 802.11be Extremely High Throughput (Wi-Fi 7) that can increase throughput and decrease latency in Wireless Local Area Networks (WLANs). The MLO enables a Multi-Link Device (MLD) to perform Simultaneous Transmission and Reception (STR) in different frequency bands. However, not all MLDs can support STR due to cross-link or in-device coexistence interference, while an STR-unable MLD (NSTR-MLD) can transmit multiple frames simultaneously in more than two links. This study focuses on the problems when NSTR-MLDs share a link with Single-Link Devices (SLDs). We propose a Contention-Less Synchronous Transmission (CLST) mechanism to improve fairness between NSTR-MLDs and SLDs while increasing the total network throughput. The proposed mechanism classifies links as MLD Dominant Links (MDLs) and Heterogeneous Coexistence Links (HCLs). In the proposed mechanism, an NSTR-MLD obtains a Synchronous Transmission Token (STT) through a virtual channel contention in the HCL but does not actually transmit a frame in the HCL, which is compensated for by a synchronous transmission triggered in the MDL. Moreover, the CLST mechanism allows additional subsequent transmissions up to the accumulated STT without further contention. Extensive simulation results confirm the outstanding performance of the CLST mechanism in terms of total throughput and fairness compared to existing synchronous transmission mechanisms.

Multi-Omics Approaches for Freshness Estimation and Detection of Illicit Conservation Treatments in Sea Bass (Dicentrarchus Labrax): Data Fusion Applications.

Fish freshness consists of complex endogenous and exogenous processes; therefore, the use of a few parameters to unravel illicit practices could be insufficient. Moreover, the development of strategies for the identification of such practices based on additives known to prevent and/or delay fish spoilage is still limited. The paper deals with the identification of the effect played by a Cafodos solution on the conservation state of sea bass at both short-term (3 h) and long-term (24 h). Controls and treated samples were characterized by a multi-omic approach involving proteomics, lipidomics, metabolomics, and metagenomics. Different parts of the fish samples were studied (muscle, skin, eye, and gills) and sampled through a non-invasive procedure based on EVA strips functionalized by ionic exchange resins. Data fusion methods were then applied to build models able to discriminate between controls and treated samples and identify the possible markers of the applied treatment. The approach was effective in the identification of the effect played by Cafodos that proved to be different in the short- and long-term and complex, involving proteins, lipids, and small molecules to a different extent.

The effect of desire to be liked and social appearance anxiety on aesthetic surgery acceptance in female nurses.

BACKGROUND: A rapid increase has been observed in aesthetic surgery procedures in recent years and it has been determined that females have more aesthetic procedures. While different groups of female groups were taken as a sample in the studies, no study on female nurses was found. In this study, it is thought that psychological reasons such as stress, anxiety, desire to be liked and lack of self-confidence that lead women to plastic surgery will reduce the professional performance of nurses and this situation will create additional workload for other colleagues. Therefore, the aim of the study is to reveal the effect of desire to be liked and social appearance anxiety on the acceptance of female nurses to plastic surgery. METHODS: The population of the cross-sectional study consisted of 243.565 nurses working in public, private and university hospitals in Turkey. A questionnaire form was used as a data collection tool in the study. In the first part of the form, there are statements aiming to reveal the socio-demographic characteristics, social media usage levels and aesthetic surgery experiences of nurses, and in the second part, there is a desire to be liked scale, social appearance anxiety scale and aesthetic surgery acceptance scale. The 1004 questionnaire forms collected as a result of the study were subjected to percentage, frequency, correlation and regression analysis. RESULTS: 41.2% of the nurses have had aesthetic procedures before and 68.4% of them want to have aesthetic procedures when there is an area they do not like in their body. A strong positive relationship was found between the desire to be liked, social appearance anxiety, and aesthetic surgery acceptance (r > 0.500, p < 0.01). Aesthetic surgery acceptance is affected by the desire to be liked and by social appearance anxiety. CONCLUSION: In the study, it was determined that social appearance anxiety and the desire to be liked led female nurses to plastic surgery. According to the results of similar studies conducted in different groups, it may be recommended that awareness training be organized both in schools and through digital media about the consequences of unnecessary plastic surgery.

The duty of care and the right to be cared for: is there a duty to treat the unvaccinated?

Vaccine hesitancy or refusal has been one of the major obstacles to herd immunity against Covid-19 in high-income countries and one of the causes for the emergence of variants. The refusal of people who are eligible for vaccination to receive vaccination creates an ethical dilemma between the duty of healthcare professionals (HCPs) to care for patients and their right to be taken care of. This paper argues for an extended social contract between patients and society wherein vaccination against Covid-19 is conceived as essential for the protection of the right of healthcare providers to be taken care of. Thus, a duty of care is only valid when those who can receive vaccination actually receive it. Whenever that is not the case, the continuing functioning of HCPs can only be perceived as supererogatory and not obligatory.

Likelihood Ratio Test and the Evidential Approach for 2 × 2 Tables.

Categorical data analysis of 2 × 2 contingency tables is extremely common, not least because they provide risk difference, risk ratio, odds ratio, and log odds statistics in medical research. A χ2 test analysis is most often used, although some researchers use likelihood ratio test (LRT) analysis. Does it matter which test is used? A review of the literature, examination of the theoretical foundations, and analyses of simulations and empirical data are used by this paper to argue that only the LRT should be used when we are interested in testing whether the binomial proportions are equal. This so-called test of independence is by far the most popular, meaning the χ2 test is widely misused. By contrast, the χ2 test should be reserved for where the data appear to match too closely a particular hypothesis (e.g., the null hypothesis), where the variance is of interest, and is less than expected. Low variance can be of interest in various scenarios, particularly in investigations of data integrity. Finally, it is argued that the evidential approach provides a consistent and coherent method that avoids the difficulties posed by significance testing. The approach facilitates the calculation of appropriate log likelihood ratios to suit our research aims, whether this is to test the proportions or to test the variance. The conclusions from this paper apply to larger contingency tables, including multi-way tables.