bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico analyses and experimental validation of the MHC class-I restricted epitopes of Ebolavirus GP
Authors: Liu Yang , Sun Baozeng , Wang Jiawei , Sun Hao , Lu Zhenhua , Chen Longyu , Lan Mingfu , Xu Jiahao , Pan Jingyu , Shi Jingqi , Sun Yuanjie , Zhang Xiyang , Wang Jing , Jiang Dongbo , Yang Kun
Published: February 2022

Ebolavirus (EBOV) causes an extremely high mortality and prevalence disease called Ebola virus disease (EVD). There is only one glycoprotein (GP) on the virus particle surface, which mediates entry into the host cell. Major histocompatibility complex (MHC) class-I restricted cluster of differentiation 8 (CD8+) T cell responses are important antiviral immune responses. Therefore, it is of great importance to understand EBOV GP-specific MHC class-I restricted epitopes within immunogenicity. In this study, computational approaches were employed to predict the dominant MHC class-I molecule epitopes of EBOV GP for mouse H2 and major alleles of human leukocyte antigen (HLA) class-I supertypes. Our results yielded 42 dominant epitopes in H2 haplotypes and 301 dominant epitopes in HLA class-I haplotypes. After validation by enzyme-linked immunospot (ELISpot) assay, in-depth analyses to ascertain their nature of conservation, immunogenicity, and docking with the corresponding MHC class-I molecules were undertaken. Our study predicted MHC class-I restricted epitopes that may aid the advancement of anti-EBOV immune responses. An integrated strategy of epitope prediction, validation and comparative analyses was postulated, which is promising for epitope-based immunotherapy development and application to viral epidemics.
Identification and biochemical characterization of a heteromeric cis-prenyltransferase from the thermophilic archaeon Archaeoglobus fulgidus
Authors: Sompiyachoke Kitty , Nagasaka Arisa , Ito Tomokazu , Hemmi Hisashi
Published: February 2022

cis-Prenyltransferases (cPTs) form linear polyprenyl pyrophosphates, the precursors of polyprenyl or dolichyl phosphates that are essential for cell function in all living organisms. Polyprenyl phosphate serves as a sugar carrier for peptidoglycan cell wall synthesis in bacteria, a role that dolichyl phosphate performs analogously for protein glycosylation in eukaryotes and archaea. Bacterial cPTs are characterized by their homodimeric structure, while cPTs from eukaryotes usually require two distantly homologous subunits for enzymatic activity. This study identifies the subunits of heteromeric cPT, Af1219 and Af0707, from a thermophilic sulphur-reducing archaeon, Archaeoglobus fulgidus. Both subunits are indispensable for cPT activity, and their protein–protein interactions were demonstrated by a pulldown assay. Gel filtration chromatography and chemical cross-linking experiments suggest that Af1219 and Af0707 likely form a heterotetramer complex. Although this expected subunit composition agrees with a reported heterotetrameric structure of human hCIT/NgBR cPT complex, the similarity of the quaternary structures is likely a result of convergent evolution.
Cosmology behind the mask: constraining the parameters of ΛCDM with the unmasked galaxy density field from VIPERS
Authors: Estrada N , Granett B R , Guzzo L
Published: February 2022

Galaxy redshift surveys are designed to map cosmic structures in three dimensions for large-scale structure studies. Nevertheless, limitations due to sampling and the survey window are unavoidable and degrade the cosmological constraints. We present an analysis of the VIMOS Public Extragalactic Redshift Survey (VIPERS) over the redshift range 0.6 < z < 1 that is optimized to extract the cosmological parameters while fully accounting for the complex survey geometry. We employ the Gibbs sampling algorithm to iteratively draw samples of the galaxy density field in redshift space, the galaxy bias, the matter density, baryon fraction, and growth-rate parameter fσ8 based on a multivariate Gaussian likelihood and prior on the density field. Despite the high number of degrees of freedom, the samples converge to the joint posterior distribution and give self-consistent constraints on the model parameters. We validate the approach using VIPERS mock galaxy catalogues. Although the uncertainty is underestimated by the Gaussian likelihood on the scales that we consider by 50 per cent, the dispersion of the results from the mock catalogues gives a robust error estimate. We find that the precision of the results matches those of the traditional analyses applied to the VIPERS data that use more constrained models. By relaxing the model assumptions, we confirm that the data deliver consistent constraints on the ΛCDM model. This work provides a case-study for the application of maximum-likelihood analyses for the next generation of galaxy redshift surveys.
Leverage on small-scale primordial non-Gaussianity through cross-correlations between CMB E-mode and μ-distortion anisotropies
Authors: Remazeilles Mathieu , Ravenni Andrea , Chluba Jens
Published: February 2022

Multifield inflation models and non-Bunch–Davies vacuum initial conditions both predict sizeable non-Gaussian primordial perturbations and anisotropic μ-type spectral distortions of the cosmic microwave background (CMB) blackbody. While CMB anisotropies allow us to probe non-Gaussianity at wavenumbers $k\simeq 0.05\, {\rm Mpc^{-1}}$, μ-distortion anisotropies are related to non-Gaussianity of primordial perturbation modes with much larger wavenumbers, $k\simeq 740\, {\rm Mpc^{-1}}$. Through cross-correlations between CMB and μ-distortion anisotropies, one can therefore shed light on the aforementioned inflation models. We investigate the ability of a future CMB satellite imager like LiteBIRD to measure μT and μE cross-power spectra between anisotropic μ-distortions and CMB temperature and E-mode polarization anisotropies in the presence of foregrounds, and derive LiteBIRD forecasts on ${f_{\rm NL}^\mu (k\simeq 740\, {\rm Mpc^{-1}})}$. We show that μE cross-correlations with CMB polarization provide more constraining power on $f_{\rm NL}^\mu$ than μT cross-correlations in the presence of foregrounds, and the joint combination of μT and μE observables adds further leverage to the detection of small-scale primordial non-Gaussianity. For multifield inflation, we find that LiteBIRD would detect ${f_{\rm NL}^\mu }=4500$ at 5σ significance after foreground removal, and achieve a minimum error of ${\sigma (f_{\rm NL}^\mu =0) \simeq 800}$ at 68 per cent CL by combining CMB temperature and polarization. Due to the huge dynamic range of wavenumbers between CMB and μ-distortion anisotropies, such large $f^\mu _{\rm NL}$ values would still be consistent with current CMB constraints in the case of very mild scale dependence of primordial non-Gaussianity. Anisotropic spectral distortions thus provide a new path, complementary to CMB B-modes, to probe inflation with LiteBIRD.
Full-scale Randomized Trial Comparing Acceptance and Commitment Therapy Telephone-Delivered Coaching With Standard Telephone-Delivered Coaching Among Medicare/Uninsured Quitline Callers
Authors: Bricker Jonathan B , Sullivan Brianna M , Mull Kristin E , Torres Alula J , Carpenter Kelly M
Published: February 2022

Introduction

The aim of this study was to compare Acceptance and Commitment Therapy (ACT) telephone-delivered coaching with standard quitline (QL) telephone-delivered coaching.

Methods

Medicare/uninsured adults (analyzable sample N = 1170) who smoked at least 10 cigarettes per day were recruited from Optum, a major US provider of QL services, in a two-arm stratified double-blind randomized trial with main outcome of self-reported missing = smoking 30-day point prevalence abstinence (PPA) at the 12-month follow-up. Participants were mean (SD) age 47.4 (12.7), 61% female, and 72% white race. Five sessions of telephone-delivered ACT or QL interventions were offered. Both arms included combined nicotine patch (4 weeks) and gum or lozenge (2 weeks).

Results

The 12-month follow-up data retention rate was 67.8%. ACT participants reported their treatment was more useful for quitting smoking (92.0% for ACT vs. 82.3% for QL; odds ratio [OR] = 2.48; 95% confidence interval [CI]: 1.53 to 4.00). Both arms had similar 12-month cessation outcomes (missing = smoking 30-day PPA: 24.6% for ACT vs. 28.8% for QL; OR =.81; 95% CI: 0.62 to 1.05) and the ACT arm trended toward greater reductions in number cigarettes smoked per day (−5.6 for ACT vs. −1.7 QL, among smokers; p = .075).

Conclusions

ACT telephone-delivered coaching was more satisfying, engaging, and was as effective as standard QL telephone-delivered coaching. ACT may help those who fail to quit after standard coaching or who choose not to use nicotine replacement therapy.

Implications

In a sample of Medicare and uninsured QL callers, a large randomized trial with long-term follow-up showed that ACT) telephone-delivered coaching was more satisfying, engaging, and was as effective as standard QL telephone-delivered coaching—which has followed the same behavior change approach since the 1990s. This newer model of coaching might be a welcome addition to QL services.
Rubisco regulation in response to altered carbon status in the cyanobacteriumSynechococcus elongatusPCC 7942
Authors: Singh Amit K , Santos-Merino María , Sakkos Jonathan K , Walker Berkley J , Ducat Daniel C
Published: February 2022

Photosynthetic organisms possess a variety of mechanisms to achieve balance between absorbed light (source) and the capacity to metabolically utilize or dissipate this energy (sink). While regulatory processes that detect changes in metabolic status/balance are relatively well studied in plants, analogous pathways remain poorly characterized in photosynthetic microbes. Here, we explored systemic changes that result from alterations in carbon availability in the model cyanobacterium Synechococcus elongatus PCC 7942 by taking advantage of an engineered strain where influx/efflux of a central carbon metabolite, sucrose, can be regulated experimentally. We observed that induction of a high-flux sucrose export pathway leads to depletion of internal carbon storage pools (glycogen) and concurrent increases in estimates of photosynthetic activity. Further, a proteome-wide analysis and fluorescence reporter-based analysis revealed that upregulated factors following the activation of the metabolic sink are concentrated on ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) and auxiliary modules involved in Rubisco maturation. Carboxysome number and Rubisco activity also increased following engagement of sucrose secretion. Conversely, reversing the flux of sucrose by feeding exogenous sucrose through the heterologous transporter resulted in increased glycogen pools, decreased Rubisco abundance, and carboxysome reorganization. Our data suggest that Rubisco activity and organization are key variables connected to regulatory pathways involved in metabolic balancing in cyanobacteria.
Correction to black hole radiation due to pair annihilation
Authors: Shafiee Moslem
Published: February 2022

We consider the emission of charged scalar particles from a Schwarzschild black hole. It is shown that these particles can interact with each other through pair annihilation and, as a result, produce photons. These photons make a correction to the spectrum of photons that are directly emitted from the black hole. By solving the field equations using the Wentzel–Kramers–Brillouin approximation, the pair annihilation rate is taken into account for the most probable case, i.e. the first order, and therefore the correction will be of the order of e2. Considering this scenario, we show that most interactions take place near the event horizon of the black hole, yet the number of interactions is not large enough to make a noticeable modification in the radiation spectrum of particles.
Non-rapid eye movement sleep instability in adults with epilepsy: a systematic review and meta-analysis of cyclic alternating pattern
Authors: Yeh Wei-Chih , Lin Huan-Jan , Li Ying-Sheng , Chien Ching-Fang , Wu Meng-Ni , Liou Li-Min , Hsieh Cheng-Fang , Hsu Chung-Yao
Published: February 2022

Study Objectives

Epilepsy is characterized by disrupted sleep architecture. Studies on sleep macro- and microstructure revealed that patients with epilepsy experience disturbed rapid eye movement (REM) sleep; however, no consensus has been reached on non-REM (NREM) sleep changes. Cyclic alternating pattern (CAP) is a marker of sleep instability that occurs only during NREM sleep. This meta-analysis investigated CAP differences between patients with epilepsy and healthy controls.

Methods

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in searching PubMed, Embase, and Cochrane Central database for studies comparing polysomnographic sleep microstructures between patients with epilepsy and healthy controls. A meta-analysis using a random-effects model was performed. We compared CAP rates, percentages of phase A1, A2, A3 subtypes, and phase B durations between patients with epilepsy and healthy controls.

Results

A total of 11 studies, including 209 patients with epilepsy and 197 healthy controls, fulfilled the eligibility criteria. Compared with healthy controls, patients with epilepsy had significantly increased CAP rates and decreased A1 subtype percentages, and patients with sleep-related epilepsy had increased A3 subtype percentages. Subgroup analyses revealed that antiseizure medications (ASMs) decreased CAP rates and increased phase B durations but did not affect the microstates of phase A in patients with sleep-related epilepsy.

Conclusions

This meta-analysis detected statistically significant differences in CAP parameters between patients with epilepsy and healthy controls. Our findings suggest patients with epilepsy experience NREM sleep instability. ASMs treatment may decrease NREM instability but did not alter the microstates of phase A.
Systems-level audit and feedback interventions to improve oncology care: a scoping review
Authors: Hobden Breanne , Turon Heidi , Fakes Kristy , Cameron Emilie , Sanson-Fisher Rob
Published: February 2022

Lay Summary

Auditing clinical practice and providing performance feedback is commonly used as a method of monitoring and attempting to improve the quality of healthcare. The scope of the research evidence on audit and feedback strategies to improve patient care across an oncology treatment centers is currently unclear. A scoping review of the literature was conducted to explore the research in this area. After assessing included studies for scientific rigor, only four intervention studies were considered to use a sound research design. The low number of studies make it difficult to draw clear conclusions about the effectiveness of systems-level audit and feedback. This area represents an important field for future research.
How COVID-19 impacted child and family health and healthcare: a mixed-methods study incorporating family voices
Authors: Heerman William J , Gross Rachel , Lampkin Jacarra , Nmoh Ashley , Eatwell Sagen , Delamater Alan M , Sanders Lee , Rothman Russell L , Yin H Shonna , Perrin Eliana M , Flower Kori B
Published: February 2022

To describe how social disruptions caused by the COVID-19 pandemic impacted child access to healthcare and child health behaviors in 2020. We used mixed-methods to conduct surveys and in-depth interviews with English- and Spanish-speaking parents of young children from five geographic regions in the USA. Participants completed the COVID-19 Exposure and Family Impact Survey (CEFIS). Semistructured telephone interviews were conducted between August and October 2020. Of the 72 parents interviewed, 45.8% of participants were Hispanic, 20.8% Black (non-Hispanic), and 19.4% White (non-Hispanic). On the CEFIS, the average (SD) number of social/family disruptions reported was 10.5 (3.8) out of 25. Qualitative analysis revealed multiple levels of themes that influenced accessing healthcare during the pandemic, including two broad contextual themes: (a) lack of trustworthiness of medical system/governmental organizations, and (b) uncertainty due to lack of consistency across multiple sources of information. This context influenced two themes that shaped the social and emotional environments in which participants accessed healthcare: (a) fear and anxiety and (b) social isolation. However, the pandemic also had some positive impacts on families: over 80% indicated that the pandemic made it “a lot” or “a little” better to care for their new infants. Social and family disruptions due to COVID-19 were common. These disruptions contributed to social isolation and fear, and adversely impacted multiple aspects of child and family health and access to healthcare. Some parents of infants reported improvements in specific health domains such as parenting, possibly due to spending more time together.
A delayed diagnosis of high-grade spondylolisthesis
Authors: Kolenko Ana Maria G. , Bauer Jennifer M.
Published: February 2022

Spondylolysis, or pars defect, occurs in nearly half of children with back pain. Despite the marked prevalence, diagnosis of spondylolysis with spondylolisthesis often is delayed or missed secondary to referred pain and uncharacteristic presentation. This article describes an 8-year-old patient with 15 months of right heel pain who was initially treated by her primary care provider for presumed Sever disease before being referred to orthopedics. After orthopedic consultation, she was diagnosed with a high-grade spondylolisthesis with L5 nerve root compression. Although spondylolysis is an infrequent diagnosis, particularly in a patient this young, missing the diagnosis can significantly reduce a patient's quality of life.
Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis
Authors: Yu Hongmin , Luo Haiping , Liu Xunbi
Published: February 2022

The key regulatory roles of circular RNAs (circRNAs) in human diseases have been demonstrated, including breast cancer (BC). The purpose of this study is to explore the role of circ_0102273, a newly discovered circRNA, in BC progression. The expression levels of circ_0102273, microRNA (miR)-1236-3p and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) were determined by quantitative real-time PCR. Cell proliferation, migration and invasion were measured using colony formation assay, EdU staining, wound healing assay and transwell assay. Glucose consumption, lactate production and ATP level were detected to evaluate cell glycolysis. The interaction between miR-1236-3p and circ_0102273 or PFKFB3 was confirmed by dual-luciferase reporter assay and RIP assay. Additionally, western blot analysis was utilized for measuring PFKFB3 protein expression. In-vivo experiments were performed to further explore the function of circ_0102273 in BC tumorigenesis. Our data showed that circ_0102273 was highly expressed in BC tumor tissues and cells, and its downregulation could inhibit BC cell proliferation, metastasis and glycolysis. MiR-1236-3p was confirmed to be sponged by circ_0102273, and its inhibitor could reverse the negative regulation of sh-circ_0102273 on BC cell proliferation, metastasis and glycolysis. PFKFB3 could be targeted by miR-1236-3p, and its expression could be positively regulated by circ_0102273. In addition, miR-1236-3p could suppress BC cell proliferation, metastasis and glycolysis, while this effect could be abolished by PFKFB3. Furthermore, circ_0102273 knockdown also had been discovered to reduce BC tumorigenesis in vivo. In summary, our research proposed that circ_0102273 might be a potential target for BC treatment, which could inhibit BC proliferation, metastasis and glycolysis through the miR-1236-3p/PFKFB3 axis.
3,3′-Diindolylmethane induces ferroptosis by BAP1–IP3R axis in BGC-823 gastric cancer cells
Authors: Ye Yang , Li Xue , Feng Guoquan , Ma Ying , Ye Fen , Shen Haijun , Sun Kang , Lu Rongzhu , Miao Shuhan
Published: February 2022

To investigate the effect and potential mechanism of 3,3′-diindolylmethane (DIM) on ferroptosis against gastric cancer, cells proliferation, lipid reactive oxygen species (ROS) and GSH level were measured in the BGC-823 gastric cancer cells after DIM treatment. Western blotting was used to detect the expression of SLC7A11, GPX4, IP3R and BAP1. Results showed that DIM could induce ferroptosis in the BGC-823 gastric cancer cells via upregulating lipid-ROS level and decreasing GSH generation. Besides, DIM also significantly reduced the protein level of SLC7A11 and GPX4, which was an important regulator of ferroptosis. In addition, DIM promoted the protein level of BAP1 and IP3R in a concentration-dependent manner in the BGC-823 gastric cancer cells. The knockdown of BAP1 could reduce IP3R level and DIM-induced ferroptosis of gastric cancer cells. Taken together, these results indicated that DIM could induce ferroptosis to exert anti-cancer effects via BAP1–IP3R axis, suggesting its effective therapeutic potential in gastric cancer.
Anti-tumoral effect of beta-blockers on prostate and bladder cancer cells via mitogen-activated protein kinase pathways
Authors: Özler Serkan , Pazarci Percin
Published: February 2022

The incidence of prostate cancer in the world is increasing every year. Death caused by prostate cancer is increased by 13% in men between 1980 and 2005. It is the second leading cause of cancer death in men after lung cancer. Bladder cancer is the second most common of urological malignancies. Most of the bladder cancers are treated with transurethral resection. Even great efforts have been made in the treatment of bladder cancer over the past years, it still remains as a major health problem. New therapeutic approaches are required to prevent the development and metastasis of these diseases. Experimental and clinical studies have shown potential beneficial effects of co-administration of beta-adrenergic receptor antagonists (beta-blockers) during cancer therapy. This study aimed to investigate the anti-tumor activity of beta-blockers on prostate and bladder cancer. Prostate and bladder cancer cell lines were cultured and treated with beta-blocker (propranolol). Then, protein levels and activity of apoptotic pathway mediators and mitogen-activated protein kinase (MAPK) pathway mediators were analyzed by ELISA. Propranolol treatment elevated the activity of caspase-3 and expression of bax, Wee1, GADD153 and apoptosis-inducing factor, but decreased bcl-2 which is an antiapoptotic protein. Propranolol treatment also inhibited ERK and JNK activity. This study showed that propranolol will help to inhibit prostate and bladder cancer by activating apoptotic pathway and by inhibiting MAPK pathway. This is the first study investigating the apoptotic effect of propranolol via MAPK on prostate and bladder cancer.
Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report
Authors: Deng Youjun , Yang Chenglin , Liu Wenyi , Cai Songhua , Guo Xiaotong
Published: February 2022

EGFR exon 20 insertion mutation is a rare mutation subtype of EGFR mutations, with no approved treatment in China so far. The clinical treatments of advanced EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) are mainly based on EGFR-TKI, chemotherapy, ICI, and other therapies. However, the efficacy is not satisfactory. Aumolertinib is the third-generation EGFR-TKI independently developed in China, which has shown excellent efficacy and safety in phase 2 and 3 clinical trials. This study aimed to share a case of applying aumolertinib as the core combined with other treatments for a patient with multiple metastases in NSCLC with an uncommon site of EGFR exon 20 insertion mutations. The comprehensive treatment benefited the patient in terms of 10 months of progression-free survival and a significant improvement in quality of life. We discussed whether we could further explore the potential of aumolertinib in treating EGFR exon 20 insertion mutations through this case report.
Clinical Grade Manufacture of CYAD-101, a NKG2D-based, First in Class, Non–Gene-edited Allogeneic CAR T-Cell Therapy
Authors: Michaux Alexandre , Mauën Sébastien , Breman Eytan , Dheur Marie-Sophie , Twyffels Laure , Saerens Laura , Jacques-Hespel Céline , Gauthy Emilie , Agaugué Sophie , Gilham David E. , Sotiropoulou Panagiota A.
Published: February 2022

Allogeneic chimeric antigen receptor (CAR) T holds the promise of taking this therapeutic approach to broader patient populations while avoiding the intensive manufacturing demands of autologous cell products. One limitation to delivering an allogeneic CAR T is T-cell receptor (TCR) driven toxicity. In this work, the expression of a peptide to interfere with TCR signaling was assessed for the generation of allogeneic CAR T cells. The expression of a truncated CD3ζ peptide was shown to incorporate into the TCR complex and to result in blunted TCR responses. When coexpressed with a natural killer group 2D (NKG2D) CAR, the allogeneic T cells (called CYAD-101) failed to induce graft-versus-host disease in mouse models while maintaining antitumor activity driven by the CAR in vitro and in vivo. Two clinical grade discrete batches of CYAD-101 cells were produced of single donor apheresis resulting in 48 billion CAR T cells sufficient for the entire dose-escalation phase of the proposed clinical trial. The 2 batches showed high consistency producing a predominantly CD4+T-cell population that displayed an effector/central memory phenotype with no evidence of exhaustion markers expression. These clinical grade CYAD-101 cells secreted cytokines and chemokines in response to ligands expressing target cells in vitro, demonstrating effector function through the CAR. Moreover, CYAD-101 cells failed to respond to TCR stimulation, indicating a lack of allogeneic potential. This bank of clinical grade, non–gene-edited, allogeneic CYAD-101 cells are used in the alloSHRINK clinical trial (NCT03692429).
Clinical suspicion of sarcopenic obesity and probable sarcopenic obesity in Colombian women with a history of surgical menopause: a cross-sectional study
Authors: Monterrosa-Castro Álvaro , Prada-Tobar María , Monterrosa-Blanco Angélica , Pérez-Romero Diana , Salas-Becerra Cindy , Redondo-Mendoza Velia
Published: February 2022

Objectives:

To identify the frequency of clinical suspicion of sarcopenic obesity (CSSO) and probable sarcopenic obesity (PSO) and to estimate the association between them and surgical menopause.

Methods:

A cross-sectional study carried out in women residing in Colombia, ages 60 to 75 years. Body mass index, the SARC-F scale, SARC-CalF < 31, and SARC-CalF <33 versions adding the calf circumference measurement in the last two were used to identify CSSO. Muscle strength measurement was added to the above measures to establish PSO. Surgical menopause was defined in women who underwent bilateral oophorectomy simultaneously with hysterectomy before natural menopause. Adjusted and unadjusted logistic regression were performed between CSSO or PSO with surgical menopause, bilateral oophorectomy after natural menopause, and abdominal hysterectomy with ovarian preservation. All participants provided informed consent. P < 0.05 was statistically significant.

Results:

Seven hundred women 67.0 ± 4.8 years old were included; 23.7% were obese, 68.1% had reduced muscle strength, and 4.2% had surgical menopause. CSSO was found in 3.0% with SARC-F and with SARC-CalF < 31; whereas 2.0% were found with SARC-CalF <33. PSO was found in 2.4%, 1.5%, and 2.2% with SARC-F, SARC-CalF <31, and SARC-CalF <33, respectively. Surgical menopause was associated with PSO but was not associated with CSSO. Bilateral oophorectomy after menopause and hysterectomy with ovarian preservation were not associated with CSSO or PSO.

Conclusions:

In a group of older adult women, the frequency of CSSO was up to 3.0% and PSO up to 2.4%. Surgical menopause was statistically significantly associated with PSO. On the contrary, CSSO was not associated.
Mental health and quality of life in postmenopausal women as a function of retrospective menopause symptom severity
Authors: Hooper Savannah C. , Marshall Victoria B. , Becker Carolyn B. , LaCroix Andrea Z. , Keel Pamela K. , Kilpela Lisa S.
Published: February 2022

Objectives:

Perimenopause is commonly viewed as a window of vulnerability for developing psychiatric and eating disorders, especially for women who experience severe symptoms. However, menopausal symptoms may have a lasting effect on older women's mental health and quality of life (QOL) into postmenopause. The current study examined older (60+) postmenopausal women's mental health and QOL as a function of retrospective menopausal symptom severity.

Methods:

Participants were recruited via public online postings and included 227 postmenopausal women, ages 60 to 94 years old (M = 68.84, SD = 6.53). Participants completed an online questionnaire to assess past menopausal symptoms as well as current depression, anxiety, sleep difficulties, binge eating, QOL, and demographics. The relation between the retrospective severity of menopausal symptoms and mental health/QOL was evaluated using linear regressions, while controlling for demographic covariates.

Results:

Retrospective menopause symptom severity was significantly associated with depression, sleep difficulties, binge eating severity, and most QOL measures. Regarding covariates, having a psychiatric history was significantly associated with all outcome variables, except for anxiety. Time since menopause and body mass index were significantly associated with binge eating severity. Regarding specific symptom subgroups, psychological and somato-vegetative symptoms were most associated with mental health and QOL.

Conclusion:

The menopausal transition is a significant change in a woman's life and the challenges of menopausal symptoms can have lasting impacts on women's health. It is imperative that future research seeks to further understand the lasting impacts of this transition on the lives of older women to ensure proper interventions are implemented for successful aging.
Machine Learning to Assess for Acute Myocardial Infarction Within 30 Minutes
Authors: McCord James , Gibbs Joseph , Hudson Michael , Moyer Michele , Jacobsen Gordon , Murtagh Gillian , Nowak Richard
Published: February 2022

Variations in high-sensitivity cardiac troponin I by age and sex along with various sampling times can make the evaluation for acute myocardial infarction (AMI) challenging. Machine learning integrates these variables to allow a more accurate evaluation for possible AMI. The goal was to test the diagnostic and prognostic utility of a machine learning algorithm in the evaluation of possible AMI. We applied a machine learning algorithm (myocardial-ischemic-injury-index [MI3]) that incorporates age, sex, and high-sensitivity cardiac troponin I levels at time 0 and 30 minutes in 529 patients evaluated for possible AMI in a single urban emergency department. MI3 generates an index value from 0 to 100 reflecting the likelihood of AMI. Patients were followed at 30–45 days for major adverse cardiac events (MACEs). There were 42 (7.9%) patients that had an AMI. Patients were divided into 3 groups by the MI3 score: low-risk (≤ 3.13), intermediate-risk (> 3.13–51.0), and high-risk (> 51.0). The sensitivity for AMI was 100% with a MI3 value ≤ 3.13 and 353 (67%) ruled-out for AMI at 30 minutes. At 30–45 days, there were 2 (0.6%) MACEs (2 noncardiac deaths) in the low-risk group, in the intermediate-risk group 4 (3.0%) MACEs (3 AMIs, 1 cardiac death), and in the high-risk group 4 (9.1%) MACEs (4 AMIs, 2 cardiac deaths). The MI3 algorithm had 100% sensitivity for AMI at 30 minutes and identified a low-risk cohort who may be considered for early discharge.
Update on Myopia Control: The US Perspective
Authors: Rhee Michelle K.
Published: February 2022

Myopia is a global epidemic on the rise, garnering increased attention, particularly in therapeutics and prevention, and the field of myopia control. This study reviews the current management options including contact lenses, spectacles, atropine, and environmental and behavioral modifications. Particular attention is given to the US perspective.
Epidemiology, Microbiology, and Genetics of Contact Lens–Related and Non–Contact Lens-Related Infectious Keratitis
Authors: Stapleton Fiona , Shrestha Gauri S. , Vijay Ajay K. , Carnt Nicole
Published: February 2022

Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non–CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CL-related and non–CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity.
Premature acute coronary syndrome: understanding the early onset
Authors: Menezes Fernandes Raquel , Mota Teresa , Costa Hugo , Bispo João , Azevedo Pedro , Bento Dina , Guedes João , Carvalho Daniela , Marques Nuno , Santos Walter , Mimoso Jorge , de Jesus Ilídio ,   On behalf of the Portuguese Registry of Acute Coronary Syndromes (ProACS) investigators
Published: February 2022

Introduction

Acute coronary syndrome (ACS) is less frequent in young adults, but it has become a significant health problem, associated with the increasing prevalence of modifiable risk factors.

Objectives

To characterize patients admitted with premature ACS, comparing with those with nonpremature ACS.

Methods

We performed a retrospective study encompassing patients of the Portuguese Registry (ProACS), comparing two groups: one composed of men less than 55 and women less than 65 years old; and other with men ≥55 and women ≥65 years old at the ACS admission. The primary endpoint was the composite of in-hospital mortality, stroke and myocardial reinfarction (re-MI).

Results

A total of 29 870 patients were enrolled and 25% had premature ACS, with a mean age of 50 ± 7 years old. They had a larger prevalence of smoking habits, obesity and dyslipidemia. ST-segment elevation MI (STEMI) was the main admission diagnosis in young patients and coronary angiogram mainly revealed one vessel disease in this subgroup. They had a lower Killip-Kimball (KK) class and mostly preserved left ventricular ejection fraction (LVEF). Composite endpoint was more frequent in nonpremature ACS patients. Nonpremature age, presentation with syncope or cardiac arrest, KK class >1, multivessel disease and LVEF <40% were independent predictors of the primary endpoint (P < 0.001). Younger patients had lower rates of in-hospital all-cause mortality, re-MI and stroke. One-year all-cause mortality and 1-year cardiovascular and non-cardiovascular readmissions were also lower.

Conclusions

Premature ACS affects 25% of the ACS population, mostly presenting with STEMI, but generally associated with better clinical evolution. Nevertheless, prevention measures are essential to correct modifiable cardiovascular risk factors and reduce coronary events.
Dynamic Mortality Risk Predictions for Children in ICUs: Development and Validation of Machine Learning Models*
Authors: Trujillo Rivera Eduardo A. , Chamberlain James M. , Patel Anita K. , Morizono Hiroki , Heneghan Julia A. , Pollack Murray M.
Published: February 2022

OBJECTIVES:

Assess a machine learning method of serially updated mortality risk.

DESIGN:

Retrospective analysis of a national database (Health Facts; Cerner Corporation, Kansas City, MO).

SETTING:

Hospitals caring for children in ICUs.

PATIENTS:

A total of 27,354 admissions cared for in ICUs from 2009 to 2018.

INTERVENTIONS:

None.

MAIN OUTCOME:

Hospital mortality risk estimates determined at 6-hour time periods during care in the ICU. Models were truncated at 180 hours due to decreased sample size secondary to discharges and deaths.

MEASUREMENTS AND MAIN RESULTS:

The Criticality Index, based on physiology, therapy, and care intensity, was computed for each admission for each time period and calibrated to hospital mortality risk (Criticality Index-Mortality [CI-M]) at each of 29 time periods (initial assessment: 6 hr; last assessment: 180 hr). Performance metrics and clinical validity were determined from the held-out test sample (n = 3,453, 13%). Discrimination assessed with the area under the receiver operating characteristic curve was 0.852 (95% CI, 0.843–0.861) overall and greater than or equal to 0.80 for all individual time periods. Calibration assessed by the Hosmer-Lemeshow goodness-of-fit test showed good fit overall (p = 0.196) and was statistically not significant for 28 of the 29 time periods. Calibration plots for all models revealed the intercept ranged from–-0.002 to 0.009, the slope ranged from 0.867 to 1.415, and the R
2 ranged from 0.862 to 0.989. Clinical validity assessed using population trajectories and changes in the risk status of admissions (clinical volatility) revealed clinical trajectories consistent with clinical expectations and greater clinical volatility in deaths than survivors (p < 0.001).

CONCLUSIONS:

Machine learning models incorporating physiology, therapy, and care intensity can track changes in hospital mortality risk during intensive care. The CI-M’s framework and modeling method are potentially applicable to monitoring clinical improvement and deterioration in real time.
Choosing antibiotic therapy for severe community-acquired pneumonia
Authors: Martin-Loeches Ignacio , Garduno Alexis , Povoa Pedro , Nseir Saad
Published: February 2022

Purpose of review

Community-acquired pneumonia (CAP) is known as a major worldwide health concern considering it has been shown to account for 78% of infection-related deaths in the USA. It is a common cause for hospitalization with a continued incidence rise in the elderly, high mortality rate and long-term sequelae in critically ill patients. Severe CAP (sCAP) is an accepted terminology used to describe ICU admitted patients with CAP. The aim of this review is to further report on the major advances in treatment for patients with sCAP including new antibiotic treatments despite macrolide resistance as seen in the ICU, and multifaceted antibiotic stewardship interventions that may lead to the reduction broad-spectrum antibiotic use in CAP.

Recent findings

We aim to examine the most recent findings in order to determine appropriate empirical antibiotic choices, timing regimens and evidence for clinical effectiveness. This will be addressed by focusing on the use combination therapies, the usefulness of severity scores and the difficulty to treat multidrug-resistant pathogens, including gram negatives such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Relevant reports referenced within included randomized controlled trials, meta-analyses, observational studies, systematic reviews and international guidelines where applicable.

New antibiotics have been recently launched with direct agent-specific properties that have been shown to avoid the overuse of previous broad-spectrum antibiotics when treating patients sCAP. Although narrow-spectrum antibiotics are now recommended and imperative in improving a patients’ prognosis, there are also some considerations when prescribing antibiotics that are beyond the spectrum. There is a need to implement effective policies of de-escalation to avoid antibiotic resistance and the risk for developing subsequent infections by combining informed clinical judgement and the application of biomarkers. Reaching clinical stability and avoidance of treatment failure are the most important pillars in treatment success.
Do Orthognathic Patients and Persons Without Facial Deformities Have Different Visual Attention to Menton Deviation?
Authors: Liu Kai , Wang Xinxi , Abdelrehem Ahmed , Zhang Yujie , Guo Yuxiang , Wang Xudong
Published: February 2022

Purpose:

This study aimed to quantify how menton deviation influenced facial visual attention of orthognathic patients and persons without facial deformities, and to explore differences between them.

Materials and Methods:

The visual scanning paths of 260 participants (Group I, 130 orthognathic participants; Group II, 130 participants without facial deformities) while observing images reflecting normal subjects and those with different menton deviation degrees were recorded with an eye-tracking device. The fixation duration [FD] and first fixation time [FFT]) on the areas of interest for each group were compared.

Results:

Although Group I devoted longer FD to the lower face than the Group II when observing a normal face (P < 0.05), a menton deviation of 3°D was associated with a significantly longer FD and earlier FFT for both groups (P < 0.05). As the severity of the menton deviation increased, this trend became more obvious, and the visual attention paid to the eyes and nose decreased (FD decreased, FFT delayed), especially for Group II (P < 0.05).

Conclusions:

A menton deviation of 3° can induce abnormally increased visual attention to the lower face in both orthognathic patients and persons without facial deformities. With increased menton deviation, this trend will be more obvious, and the visual attention to the eyes and nose will also be affected, especially for persons without facial deformities, attention to the eyes will be significantly reduced.
Time to Move on: HLA Matching Should Be Reconsidered in Modern Deceased Donor Kidney Allocation
Authors: Gramlick Madelyn E. , Trevillian Paul , Palazzi Kerrin L. , Heer Munish K.
Published: February 2022

Background.

HLA matching has been the cornerstone of deceased donor kidney allocation policies worldwide but can lead to racial inequity. Although HLA matching has been shown to improve clinical outcomes, the long-term impacts of nonallogenic factors are being increasingly recognized. This has led some transplant programs to include points for nonallogenic factors, for example, age. Our study looks at long-term graft and patient outcomes based on allocation cohorts rather than individual number of HLA mismatches.

Methods.

Using the Australia and New Zealand Dialysis and Transplant Registry, we analyzed 7440 adult deceased donor transplant events from 2000 to 2018. Transplants were classified as HLA matched or nonmatched according to the OrganMatch score and the local allocation algorithms. Graft function was studied with linear mixed modeling and graft rejection with logistic and binomial regression. Time to graft failure and recipient survival were examined with Kaplan–Meier curve and Cox regression models.

Results.

Forty percent of transplants were HLA matched. Mean glomerular filtration rate was 1.76 mL/min/1.73 m2 higher in the matched transplants (P < 0.001). Matched transplants had longer time to graft failure (15.9 versus 12.7 y; P < 0.001) and improved recipient survival (risk of death hazard ratio, 0.83; P = 0.003). Matched recipients spent less time on dialysis (28.1 versus 44.8 mo; P < 0.001), and this significantly contributed to the benefits seen in graft loss and recipient survival. Caucasian recipients were more likely to receive a matched transplant than non-Caucasians.

Conclusions.

Matched transplants showed benefits in graft and recipient outcomes; however, some of these results were of small magnitude, whereas others seemed to be due in part to a reduction in time on dialysis. The benefit for the matched cohort came at the expense of the nonmatched cohort, who spent longer on dialysis and were more likely to be of a minority racial background.
Glycosaminoglycan binding by arboviruses: a cautionary tale
Authors: Alcorn Maria D. H. , Klimstra William B.
Published: February 2022

Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematophagous arthropod blood meal but they must also bind sufficiently to cellular structures on divergent organisms such that productive infection can be initiated and viremia generated. Sulfated polysaccharides of the glycosaminoglycan (GAG) groups, primarily heparan sulfate (HS), have been identified as cell attachment moieties for many arboviruses. Original identification of GAG binding as a phenotype of arboviruses appeared to involve this attribute arising solely as a consequence of adaptation of virus isolates to growth in cell culture. However, more recently, naturally circulating strains of at least one arbovirus, eastern equine encephalitis, have been shown to bind HS efficiently and the GAG binding phenotype continues to be associated with arbovirus infection in published studies. If GAGs are attachment receptors for many naturally circulating arboviruses, this could lead to development of broad-spectrum antiviral therapies through blocking of the virus–GAG interaction. This review summarizes the available data for GAG/HS binding as a phenotype of naturally circulating arbovirus strains emphasizing the importance of avoiding tissue culture amplification and artifactual phenotypes during their isolation.
SARS-CoV-2 Viroporins Activate The NLRP3-Inflammasome Via The Mitochondrial Permeability Transition Pore
Authors: Guarnieri Joseph W. , Angelin Alessia , Murdock Deborah G. , Portluri Prasanth , Lie Timothy , Wallace Douglas C.
Published: February 2022

Cytokine storm precipitated by activation of the host innate immune defenses is a major cause of COVID19 death. To elucidate how SARS-CoV-2 initiates this inflammatory process, we studied viroporin proteins E and Orf3a (2-E+2-3a). Expression of 2-E+2-3a in human 293T cells resulted in increased cytosolic Ca++ and then elevated mitochondrial Ca++, taken up through the MUCi11-sensitive mitochondrial calcium uniporter (MCU). Increased mitochondrial Ca++ resulted in stimulation of mitochondrial reactive oxygen species (mROS) production, which was blocked by mitochondrially-targeted catalase or MnTBAP. To determined how mROS activates the inflammasome, we transformed 293T cells with NLRP3, ASC, pro-caspase-1 and pro-IL-1β plus used THP1 derived macrophages to monitor the secretion of mature IL-1β. This revealed that mROS activates a factor that is released via the NIM811-sensitive mitochondrial permeability pore (mtPTP) to activate the inflammasome. Hence, interventions targeting mROS and the mtPTP may mitigate the severity of COVID19 cytokine storms.