bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulation of FBW7 in malignant lymphoproliferative disorders
Authors: Wan Xin , Guo Wei , Zhan Zhumei , Bai Ou
Published: November 2022

The ubiquitin-proteasome system (UPS) is involved in various aspects of cell processes, including cell proliferation, differentiation, and cell cycle progression. F-box and WD repeat domain-containing protein 7 (FBW7), as a key component of UPS proteins and a critical tumor suppressor in human cancers, controls proteasome-mediated degradation by ubiquitinating oncoproteins such as c-Myc, Mcl-1, cyclin E, and Notch. It also plays a role in the development of various cancers, including solid and hematological malignancies, such as T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. This comprehensive review emphasizes the functions, substrates, and expression of FBW7 in malignant lymphoproliferative disorders.
TRPV1 in dorsal root ganglion contributed to bone cancer pain
Authors: Chen Wen , Li Hongping , Hao Xiaowan , Liu Cunzhi
Published: November 2022

Tumor growth in situ or bone metastases in cancer patients all can induce bone cancer pain. It is frequently occurred in patients with breast, prostate, and lung cancer. Because of the lack of effective treatment, bone cancer pain causes depression, anxiety, fatigue, and sleep disturbances in cancer patients, disrupts the daily quality of life, and results in huge economic and psychological burden. Over the past years, transient receptor potential channels (TRPs), especially TRP vanilloid 1 (TRPV1) in dorsal root ganglion (DRG), have been considered to be involved in bone cancer pain. The characteristic of TRPV1 had been well studied. The mechanisms under TRPV1 regulation in DRG with bone cancer pain are complex, including inflammatory mediators, endogenous formaldehyde, and other mechanisms. In the present review, we summarize the role and potential mechanism of TRPV1 in DRG in bone cancer pain. As the primary sensory neurons, targeting the TRPV1 channel in DRG, might have fewer side effects than in central. We hope systematically understand of TRPV1 modulation in DRG will bring more effective strategy.
Mechanistic modeling as an explanatory tool for clinical treatment of chronic catatonia
Authors: Roberts Patrick D. , Conour James
Published: November 2022

Mathematical modeling of neural systems is an effective means to integrate complex information about the brain into a numerical tool that can help explain observations. However, the use of neural models to inform clinical decisions has been limited. In this study, we use a simple model of brain circuitry, the Wilson-Cowan model, to predict changes in a clinical measure for catatonia, the Bush-Francis Catatonia Rating Scale, for use in clinical treatment of schizophrenia. This computational tool can then be used to better understand mechanisms of action for pharmaceutical treatments, and to fine-tune dosage in individual cases. We present the conditions of clinical care for a residential patient cohort, and describe methods for synthesizing data to demonstrated the functioning of the model. We then show that the model can be used to explain effect sizes of treatments and estimate outcomes for combinations of medications. We conclude with a demonstration of how this model could be personalized for individual patients to inform ongoing treatment protocols.
Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models
Authors: Cai Xiao-Jun , Li Rui-Dong , Li Jian-Hua , Tao Yi-Feng , Zhang Quan-Bao , Shen Cong-Huan , Zhang Xiao-Fei , Wang Zheng-Xin , Jiao Zheng
Published: November 2022

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms.

Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis–Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens.

Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h−1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (Vmax) of the nonlinear MM model was 6.62 mg day−1; the average concentration at steady state at half-Vmax (Km) was 6.46 ng ml−1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations.

Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.
Ameliorative effect of Berberidis radix polysaccharide selenium nanoparticles against carbon tetrachloride induced oxidative stress and inflammation
Authors: Gao Fei , Liu Huimin , Han Hao , Wang Xin , Qu Lihua , Liu Congmin , Tian Xuemei , Hou Ranran
Published: November 2022

Berberidis radix polysaccharide (BRP) extracted as capping agents was applied to prepare BRP-selenium nanoparticles (BRP-SeNPs) in the redox reaction system of sodium selenite and ascorbic acid. The stability and characterization of BRP-SeNPs were investigated by physical analysis method. The results revealed that BRP were tightly wrapped on the surface of SeNPs by forming C-O⋯Se bonds or hydrogen bonding interaction (O-H⋯Se). BRP-SeNPs presented irregular, fragmented and smooth surface morphology and polycrystalline nanoring structure, and its particle size was 89.4 nm in the optimal preparation condition. The pharmacologic functions of BRP-SeNPs were explored in vitro and in vivo. The results showed that BRP-SeNPs could heighten the cell viabilities and the enzyme activity of GSH-Px and decrease the content of MDA on H2O2-induced AML-12 cells injury model. In vivo tests, the results displayed that BRP-SeNPs could increase the body weight of mice, promote the enzyme activity like SOD and GSH-Px, decrease the liver organ index and the hepatic function index such as ALT, AST, CYP2E1, reduce the content of MDA, and relieve the proinflammation factors of NO, IL-1β and TNF-α in CCl4-induced mice injury model. Liver tissue histopathological studies corroborated the improvement of BRP-SeNPs on liver of CCl4-induced mice. The results of Western blot showed that BRP-SeNPs could attenuate oxidant stress by the Nrf2/Keap1/MKP1/JNK pathways, and downregulate the proinflammatory factors by TLR4/MAPK pathway. These findings suggested that BRP-SeNPs possess the hepatoprotection and have the potential to be a green liver-protecting and auxiliary liver inflammation drugs.
A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects
Authors: Matloka Mikolaj , Janowska Sylwia , Pankiewicz Piotr , Kokhanovska Sofiya , Kos Tomasz , Hołuj Małgorzata , Rutkowska-Wlodarczyk Izabela , Abramski Krzysztof , Janicka Monika , Jakubowski Piotr , Świątkiewicz Maciej , Welniak-Kaminska Marlena , Hucz-Kalitowska Joanna , Dera Paulina , Bojarski Lukasz , Grieb Paweł , Popik Piotr , Wieczorek Maciej , Pieczykolan Jerzy
Published: November 2022

Background: Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, in vivo.

Methods: The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets. Cardiotoxicity in vitro was evaluated in human ether-a-go-go related gene (hERG)-potassium channel-overexpressing cells by the patch-clamp method and by assessing key parameters in 3D cardiac spheroids. Cytotoxicity was determined in H1299, HepG2 and SH-SY5Y cell lines. The Ames test was used for genotoxicity analyses. During in vivo studies, CPL500036 was administered by oral gavage. CPL500036 exposure were determined by liquid chromatography–tandem mass spectrometry and plasma protein binding was assessed. The bar test was employed to assess catalepsy. Prolactin and glucose levels in rat blood were measured by ELISAs and glucometers, respectively. Cardiovascular safety in vivo was investigated in dogs using a telemetry method.

Results: CPL500036 inhibited PDE10A at an IC50 of 1 nM, and interacted only with the muscarinic M2 receptor as a negative allosteric modulator with an IC50 of 9.2 µM. Despite inhibiting hERG tail current at an IC25 of 3.2 μM, cardiovascular adverse effects were not observed in human cardiac 3D spheroids or in vivo. Cytotoxicity in vitro was observed only at > 60 μM and genotoxicity was not recorded during the Ames test. CPL500036 presented good bioavailability and penetration into the brain. CPL500036 elicited catalepsy at 0.6 mg/kg, but hyperprolactinemia or hyperglycemic effects were not observed in doses up to 3 mg/kg.

Conclusion: CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate.
Trident: A dual oxygenation and fluorescence imaging platform for real-time and quantitative surgical guidance
Authors: Ségaud Silvère , Baratelli Luca , Felli Eric , Bannone Elisa , Cinelli Lorenzo , Rodríguez-Luna María Rita , Okamoto Nariaki , Keller Deborah S , de Mathelin Michel , Lecler Sylvain , Diana Michele , Gioux Sylvain
Published: November 2022

Despite recent technological progress in surgical guidance, current intraoperative assessment of tissue that should be removed (e.g., cancer) or avoided (e.g., nerves) is still performed subjectively. Optical imaging is a non-contact, non-invasive modality that has the potential to provide feedback regarding the condition of living tissues by imaging either an exogenously administered contrast agent or endogenous constituents such as hemoglobin, water, and lipids. As such, optical imaging is an attractive modality to provide physiologically and structurally relevant information for decision-making in real-time during surgery. The Trident imaging platform has been designed for real-time surgical guidance using state-of-the-art optical imaging. This platform is capable of dual exogenous and endogenous imaging owing to a unique filter and source combination, allowing to take advantage of both imaging modalities. This platform makes use of a real-time and quantitative imaging method working in the spatial frequency domain, called Single Snapshot imaging of Optical Properties (SSOP). The Trident imaging platform is designed to comply with all relevant standards for clinical use. In this manuscript, we first introduce the rationale for developing the Trident imaging platform. We then describe fluorescence and endogenous imaging modalities where we present the details of the design, assess the performance of the platform on the bench. Finally, we perform the validation of the platform during an in vivo preclinical experiment. Altogether, this work lays the foundation for translating state-of-the-art optical imaging technology to the clinic.
Circular RNAs: Emerging players in the pathogenesis of keloid
Authors: Yu Xin , Zhu Xueqing , Li Linfeng , Gao Guangcheng
Published: November 2022

Circular RNAs (circRNAs) are a new type of non-coding RNAs originating from precursor messenger RNAs. Recent research has confirmed that circRNAs play a significant role in various biological and pathological processes, including cell viability, migration, and apoptosis. Emerging studies have demonstrated that the deregulated circRNA–miRNA–mRNA interaction network plays a key role in the development of many diseases. Increasing evidence has highlighted the role of ncRNAs (mainly miRNAs and lncRNAs) in the pathogenesis of keloids. Recently, several publications also indicated that circRNAs contribute to keloid development. The discovery of circRNAs changed the current understanding of the biology of keloids It is crucial to elucidate a circRNA–miRNA–mRNA network to understand the pathological mechanism of keloids. In the present review, we summarize the aberrant expression of regulatory roles of circRNAs in keloids. We discuss the potential clinical application of circRNAs in the diagnosis and treatment of keloids.
Streamlined single-molecule RNA-FISH of core clock mRNAs in clock neurons in whole mount Drosophila brains
Authors: Yuan Ye , Padilla Marc-Antonio , Clark Dunham , Yadlapalli Swathi
Published: November 2022

Circadian clocks are ∼24-h timekeepers that control rhythms in almost all aspects of our behavior and physiology. While it is well known that subcellular localization of core clock proteins plays a critical role in circadian regulation, very little is known about the spatiotemporal organization of core clock mRNAs and its role in generating ∼24-h circadian rhythms. Here we describe a streamlined single molecule Fluorescence In Situ Hybridization (smFISH) protocol and a fully automated analysis pipeline to precisely quantify the number and subcellular location of mRNAs of Clock, a core circadian transcription factor, in individual clock neurons in whole mount Drosophila adult brains. Specifically, we used ∼48 fluorescent oligonucleotide probes that can bind to an individual Clock mRNA molecule, which can then be detected as a diffraction-limited spot. Further, we developed a machine learning-based approach for 3-D cell segmentation, based on a pretrained encoder-decoder convolutional neural network, to automatically identify the cytoplasm and nuclei of clock neurons. We combined our segmentation model with a spot counting algorithm to detect Clock mRNA spots in individual clock neurons. Our results demonstrate that the number of Clock mRNA molecules cycle in large ventral lateral clock neurons (lLNvs) with peak levels at ZT4 (4 h after lights are turned on) with ∼80 molecules/neuron and trough levels at ZT16 with ∼30 molecules/neuron. Our streamlined smFISH protocol and deep learning-based analysis pipeline can be employed to quantify the number and subcellular location of any mRNA in individual clock neurons in Drosophila brains. Further, this method can open mechanistic and functional studies into how spatiotemporal localization of clock mRNAs affect circadian rhythms.
A tale of two stories: COVID-19 and disability. A critical scoping review of the literature on the effects of the pandemic among athletes with disabilities and para-athletes
Authors: Puce Luca , Trabelsi Khaled , Ammar Achraf , Jabbour Georges , Marinelli Lucio , Mori Laura , Kong Jude Dzevela , Tsigalou Christina , Cotellessa Filippo , Schenone Cristina , Samanipour Mohammad Hossein , Biz Carlo , Ruggieri Pietro , Trompetto Carlo , Bragazzi Nicola Luigi
Published: November 2022

The still ongoing COVID-19 pandemic has dramatically impacted athletes, and, in particular, para-athletes and athletes with disabilities. However, there is no scholarly appraisal on this topic. Therefore, a critical scoping review of the literature was conducted. We were able to retrieve sixteen relevant studies. The sample size ranged from 4 to 183. Most studies were observational, cross-sectional, and questionnaire-based surveys, two studies were interventional, and two were longitudinal. One study was a technical feasibility study. Almost all studies were conducted as single-country studies, with the exception of one multi-country investigation. Five major topics/themes could be identified: namely, 1) impact of COVID-19-induced confinement on training and lifestyles in athletes with disabilities/para-athletes; 2) impact of COVID-19-induced confinement on mental health in athletes with disabilities/para-athletes; 3) impact of COVID-19-induced confinement on performance outcomes in athletes with disabilities/para-athletes; 4) risk of contracting COVID-19 among athletes with disabilities/para-athletes; and, finally, 5) impact of COVID-19 infection on athletes with disabilities/para-athletes. The scholarly literature assessed was highly heterogeneous, with contrasting findings, and various methodological limitations. Based on our considerations, we recommend that standardized, reliable tools should be utilized and new, specific questionnaires should be created, tested for reliability, and validated. High-quality, multi-center, cross-countries, longitudinal surveys should be conducted to overcome current shortcomings. Involving all relevant actors and stakeholders, including various national and international Paralympic Committees, as a few studies have done, is fundamental: community-led, participatory research can help identify gaps in the current knowledge about sports-related practices among the population of athletes with disabilities during an unprecedented period of measures undertaken that have significantly affected everyday life. Moreover, this could advance the field, by capturing the needs of para-athletes and athletes with disabilities and enabling the design of a truly “disability-inclusive response” to COVID-19 and similar future conditions/situations. Furthermore, follow-up studies on COVID-19-infected para-athletes and athletes with disabilities should be conducted. Evidence of long-term effects of COVID-19 is available only for able-bodied athletes, for whom cardiorespiratory residual alterations and mental health issues a long time after COVID-19 have been described.
Transcriptome profiling revealed salt stress-responsive genes in Lilium pumilum bulbs
Authors: So Kyongsok , Pak Unil , Sun Shaoying , Wang Yiping , Yan Hao , Zhang Yanni
Published: November 2022

Lilium pumilum is an important ornamental, culinary and medicinal bulbous plants with salt tolerance. However, salt tolerance of lily, particularly the bulb, has been studied relatively little, which brings challenges to the cultivation of lily varieties with high salt tolerance. Here, we performed transcriptome sequencing on the bulb organs of L. pumilum under salt stress treatment, analyzed differential gene expressed levels and then identified several key genes associated with salt stress tolerance at genome-wide scale. For the first time, we revealed the obvious response against salt stress for L. pumilum bulb organs, while distinct from those for root organs. Several key genes obtained through transcriptome analysis and DEG screening include NF-YB3 transcription factor, metallothionein type 2 protein, vicilin like seed storage protein and bidirectional sugar transporter SWEET14. Rather than typical ROS scavengers like superoxide dismutase, peroxidase, and glutathione transferase, non-typical ROS scavengers such as the metallothionein type 2 protein, and vicilin like seed storage protein were upregulated in our work. The bidirectional sugar transporter SWEET14 protein and the hormone signaling proteins such as E3-ubiquitin protein ligases, PYL4 and protein phosphatase 2C were also upregulated, suggesting the role of sugars and hormones in the bulb organ responses to salt stress. Co-expression analysis of the DEGs further confirmed that NF-YB3 transcription factor acted as a hub gene, suggesting that salt stress can promote flowering of L. pumilum. Taken together, we identified important candidate genes associated with salt tolerance of the L. pumilum bulb organs, which may provide the excellent basis for further in-depth salt tolerance mechanisms of the lily bulbs.
Electrochemical fingerprinting sensor for plant phylogenetic investigation: A case of sclerophyllous oak
Authors: Hu Jun , Shen Yin , Zheng Yuhong , Zhou Wei , Karimi-maleh Hassan , Liu Qing , Fu Li
Published: November 2022

Electrochemical fingerprinting can collect the electrochemical behavior of electrochemically active molecules in plant tissues, so it is regarded as a new plant analysis technology. Because the signal of electrochemical fingerprinting is positively correlated with the amount and type of electrochemically active molecules in plant tissues, it can also be used to reflect genetic differences between different species. Previous electrochemical fingerprinting techniques have been frequently used in phylogenetic studies of herbaceous plants. In this work, 19 Quercus species (17 evergreen or semi evergreen species and 2 deciduous species) were selected for investigation. The results indicated the electrochemical fingerprint of some species share similar features but can be distinguished after changing the recording condition (extraction solvent and electrolyte). The two sets of electrochemical fingerprint data can be used to construct different pattern recognition technology, which further speeds up the recognition efficiency. These electrochemical fingerprints were further used in phylogenetic investigations. The phylogenetic results deduced from electrochemical fingerprinting were divided mainly into three clusters. These can provide evidence for some of these arguments as well as new results.
The effectiveness and associated factors of online psychotherapy on COVID-19 related distress: A systematic review and meta-analysis
Authors: Chi Danni , Zhang Yuanyuan , Zhou Dongsheng , Xu Guozhang , Bian Guolin
Published: November 2022

Objective

A quantitative synthesis of online psychotherapies' effectiveness in managing COVID-19 related distress is lacking. This study aimed to estimate online psychological interventions' effectiveness and associated factors on COVID-19 related psychological distress.

Methods

Multi-databases including PubMed, EBSCO, ProQuest, and Cochrane were searched repeatedly till the end of June 2022. Hand-picking was also utilized for relevant papers. Depression, anxiety, stress, and quality of sleep were evaluated as outcomes. The risk of bias was evaluated using the Cochrane tool. Data analyses were conducted through Review Manager (version 5.4.1).

Results

A total of 13 studies involving 1,897 participants were included for meta-analysis. Results showed that online psychotherapy significantly reduced the levels of depression [standard mean difference, SMD = −0.45, 95% CI (−0.69, −0.20)], anxiety [SMD = −0.67, 95% CI (−0.99, −0.36)], and stress [SMD = −0.73, 95% CI (−1.11, −0.34)], but not quality of sleep [SMD = −0.53, 95% CI (−1.23, 0.17)]. In addition, guided therapies were more effective than self-help ones on reducing levels of anxiety (χ2 = 5.58, p = 0.02, and I2 = 82.1%), and ≤ 2 weeks' daily interventions were more effective on treating depression than 2-month weekly interventions (χ2 = 7.97, p = 0.005, I2 = 87.5%).

Conclusion

Online psychological interventions effectively reduced COVID-19 related depression, anxiety, and stress levels, and the effectiveness was influenced by settings like guidance and duration and frequency.

Systematic review registration

https://inplasy.com/inplasy-2022-7-0081/, identifier: INPLASY202270081.
Metabolic syndrome and cognition: A systematic review across cognitive domains and a bibliometric analysis
Authors: Koutsonida Myrto , Markozannes Georgios , Bouras Emmanouil , Aretouli Eleni , Tsilidis Konstantinos K.
Published: November 2022

The aim of this review is to investigate the association between metabolic syndrome (MetS) and cognitive decline in distinct cognitive domains, and to perform a complementary study description through the bibliometric analysis. PubMed and Scopus databases were searched from inception to 15 December 2021 to identify longitudinal studies that examined the association of MetS with incident decline, in order to prevent reverse causality. The Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was used to conduct the present systematic review. Thirty studies were included and results were analyzed across the cognitive domains of global cognition, memory, executive functions, attention, visuoconstructive abilities, and language. The majority of the studies reviewed did not report statistically significant results for most cognitive domains investigated, and decline in specific cognitive domains was not consistently associated with the presence of MetS. Meta-analyses were not conducted due to the high degree of between-study heterogeneity regarding the MetS definitions, the cognitive domains examined, the specific tests used for each cognitive domain and the different measures of association used. Bibliometric analysis revealed that most studies are conducted by research teams from USA and China, and that cognitive tasks that reflect real-life abilities are rarely examined. Future studies should employ larger sample sizes, longer follow-up periods, a global consensus for MetS definition and standardized tests of the above mentioned cognitive domains as well as problem-solving tasks with high sensitivity and specificity to clarify the impact of MetS on cognition and its underlying mechanisms.
Why do people with similar levels of internal control differ in their likelihood to commit fraud? Analysis of the moderating effect of perceived opportunity to commit fraud
Authors: Sun Xiaonan , Chen Yan
Published: November 2022

This research focuses on one of the three components of the fraud triangle, namely opportunity, and empirically tests the tendency to commit fraud. The perceived opportunity to commit fraud can be considered in terms of temptation and obstacles. This research employs concepts from cognitive psychology, i.e., desire and motivation for action, which affect people’s decision-making processes when presented with an opportunity to commit fraud. Questionnaires were used to analyze the tendency to commit fraud. First, dispositional differences among people differing in self-control were observed, which may influence the likelihood of fraudulent behavior. That is, low self-control mediates the relationship between self-regard and fraud tendency. Second, strong relationships of both personal disposition and self-efficacy with the tendency to commit fraud were revealed; high self-efficacy enhances the tendency to commit fraud. This research offers a new psychological perspective on fraud opportunity, and showing for the first time that fraud can be reduced not only by improved internal control and external supervision, as suggested in previous studies, but also by changing people’s perceptions of fraud opportunity, given the fallibility of both internal control and external supervision.
Use of central nervous system drugs in combination with selective serotonin reuptake inhibitor treatment: A Bayesian screening study for risk of suicidal behavior
Authors: Lagerberg Tyra , Sjölander Arvid , Gibbons Robert D. , Quinn Patrick D. , D’Onofrio Brian M. , Hellner Clara , Lichtenstein Paul , Fazel Seena , Chang Zheng
Published: November 2022

Background

Using other central nervous system (CNS) medications in combination with selective serotonin reuptake inhibitor (SSRI) treatment is common. Despite this, there is limited evidence on the impact on suicidal behavior of combining specific medications. We aim to provide evidence on signals for suicidal behavior risk when initiating CNS drugs during and outside of SSRI treatment.

Materials and methods

Using a linkage of Swedish national registers, we identified a national cohort of SSRI users aged 6–59 years residing in Sweden 2006–2013. We used a two-stage Bayesian Poisson model to estimate the incidence rate ratio (IRR) of suicidal behavior in periods up to 90 days before and after a CNS drug initiation during SSRI treatment, while accounting for multiple testing. For comparison, and to assess whether there were interactions between SSRIs and other CNS drugs, we also estimated the IRR of initiating the CNS drug without SSRI treatment.

Results

We identified 53 common CNS drugs initiated during SSRI treatment, dispensed to 262,721 individuals. We found 20 CNS drugs with statistically significant IRRs. Of these, two showed a greater risk of suicidal behavior after versus before initiating the CNS drug (alprazolam, IRR = 1.39; flunitrazepam, IRR = 1.83). We found several novel signals of drugs that were statistically significantly associated with a reduction in the suicidal behavior risk. We did not find evidence of harmful interactions between SSRIs and the selected CNS drugs.

Conclusion

Several of the detected signals for reduced risk correspond to drugs where there is previous evidence of benefit for antidepressant augmentation (e.g., olanzapine, quetiapine, lithium, buspirone, and mirtazapine). Novel signals of reduced suicidal behavior risk, including for lamotrigine, valproic acid, risperidone, and melatonin, warrant further investigation.
Association of sleep characteristics with renal function in menopausal women without recognized chronic kidney disease
Authors: Tong Jianqian , Li Changbin , Hu Jiangshan , Teng Yincheng , Zhou Yang , Tao Minfang
Published: November 2022

Objective

To delineate the association between sleep characteristics and renal function in peri-post menopause free of Chronic kidney disease (CKD) as well as cardiometabolic and hormone indicators.

Methods

Cross-sectional data from a total of 823 Han-Chinese women aged 40–67 years who visited the Menopause Clinic in the Shanghai Sixth People’s Hospital from November 2011 to November 2020 were analyzed through the Pittsburgh Sleep Quality Index (PSQI) and serum cystatin C (Cys-C). Logistic regression models were used to assess the association between cumulative/each sleep parameter and renal function after adjusting for cardiometabolic variables.

Results

After confounding factors, we identified that poor perceived sleep quality, shorter sleep duration (<6 h), low sleep efficiency (<75%), delayed sleep latency and worse sleep disturbance elevated more than doubled the odds ratio for declining renal function (≥0.91 mg/dL, the highest Cys-C) in postmenopause in a graded fashion. Meanwhile, multiple logistic regression analysis revealed that sleep disorder (PSQI ≥ 8), late postmenopause, highest quartile independently increased the odds ratio for declining renal function (OR 2.007, 95% CI: 1.408–2.861, OR = 3.287, 95%CI: 3.425–8.889, OR = 2.345, 95% CI: 1.310–4.199, respectively), while participants with menopausal hormone replacement (MHT) lower the odds of declining renal function (OR = 0.486, 95% CI: 0.324–0.728).

Conclusion

The findings proposed that maintaining good sleep quality should be attached great importance to postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as MHT of renal disease progression in postmenopausal women.
Attenuated initial serum ferritin concentration in critically ill coronavirus disease 2019 geriatric patients with comorbid psychiatric conditions
Authors: Abulseoud Osama A. , Yehia Asmaa , Egol Claudine J. , Nettey Victor N. , Aly Mohamed , Qu Yihuai , Skolnik Aaron B. , Grill Marie F. , Sen Ayan , Schneekloth Terry D.
Published: November 2022

We examined the effects of psychiatric comorbidity, sex, and ICU admission on serum ferritin concentration in 628 elderly patients (79.7 ± 8.5 years) with positive SARS-CoV-2 PCR test. Hospitalization was required in 96% of patients and 17% required ICU admission. Patients with COVID-19 and psychiatric comorbidities (n = 212) compared to patients without psychiatric comorbidities (n = 416) had significantly lower ferritin concentration (570.4 ± 900.1 vs. 744.1 ± 965, P = 0.029), a greater incidence of delirium (22.6 vs. 14.4%, P = 0.013) and higher mortality (35.3 vs. 27.6%, P = 0.015). Furthermore, we found significant effects for sex (P = 0.002) and ICU admission (P = 0.007). Among patients without comorbid psychiatric conditions, males had significantly higher ferritin compared to females (1,098.3 ± 78.4 vs. 651.5 ± 94.4, P < 0.001). ICU patients without comorbid psychiatric conditions had significantly higher serum ferritin compared to ICU patients with comorbid psychiatric conditions: (1,126.6 ± 110.7 vs. 668.6 ± 156.5, P < 0.001). Our results suggest that the presence of comorbid psychiatric conditions in elderly patients with COVID-19 is associated with higher rates of delirium and mortality and lower ferritin levels during severe illness. Whether high serum ferritin is protective during severe infection requires further investigation.
The interrelationship between physical activity intensity, cardiorespiratory fitness, and executive function in middle-aged adults: An observational study of office workers
Authors: Wang Rui , Ekblom Maria M. , Arvidsson Daniel , Fridolfsson Jonatan , Börjesson Mats , Ekblom Örjan
Published: November 2022

Background

Previous evidence supports a beneficial effect of physical activity on executive function across the whole lifespan. Yet, the interrelationships of the intensities of physical activity, cardiorespiratory fitness, and executive function require further investigation in adults.

Aim

Using unfiltered accelerometry data and high-resolution intensity classification, we sought to estimate the associations of physical activity with cardiorespiratory fitness and executive function in adult office workers.

Methods

We included 343 full-time office workers (mean age: 42.41 years, range of age: 36−49 years). Executive function was assessed using Stroop, Trail making tests (part-B), and 2-back tests, and a composite score was produced to reflect the general executive function performance. Physical activity was assessed using the Actigraph GT3X+-monitor, worn by each participant for seven days at the hip. Raw accelerometry data were processed by the 10 Hz frequency extended method and divided into 22 intensity bins and sleep time. Cardiorespiratory fitness was estimated using the submaximal Ekblom-Bak cycle ergometer test. Data were analyzed using partial least squares regressions.

Results

In adults, cardiorespiratory fitness was closely correlated with a wide range of absolute physical activity intensity patterns. A higher level of executive function in adults was associated with both higher absolute physical activity intensities and cardiorespiratory fitness, which was independent of age, sex, and education levels. A very weak association between intensities, fitness, and executive function was observed in high-fit adults. Among low-fit adults, although a positive association started already toward the upper end of moderate intensity, there still appeared to be an association between intensities, cardiorespiratory fitness, and executive function. That is, cardiorespiratory fitness may mediate the association between absolute physical activity intensities and executive function up to a certain level.

Conclusion

The maintenance of executive function in adulthood was related to both physical activity intensities and cardiorespiratory fitness, while their interrelationship was not equal across fitness levels. It is highly recommended to consider the cardiorespiratory fitness level in future studies that focus on executive functions in aging as well when designing individualized physical activity training programs.
Media impacts recovery of Salmonella enterica and Enterococcus faecium NRRL B2354 from whole black peppercorns, basil leaves, and chia seeds treated with antimicrobial gasses
Authors: Garcia Jose O , Wason Surabhi , Subbiah Jeyamkondan , Eifert Joseph , Strawn Laura K. , Ponder Monica A.
Published: November 2022

Salmonella enterica contamination of low water activity foods (LWAFs) has resulted in recalls of spices, herbs, and seeds and outbreaks of salmonellosis. To improve the safety of these ready-to-eat products, new treatment methods, including fumigation with chlorine dioxide (ClO2) or hydrogen peroxide (H2O2) gas are being explored, and effectiveness determined. To prevent overestimation of treatment effectiveness, it is vital that recovery methods should accurately quantify all viable cells, even those injured. This study evaluated different media and supplements for the recovery of multiple strains of S. enterica and Enterococcus faecium NRRL B2354, from ClO2 or H2O2 treated black peppercorns, dried basil leaves, and chia seeds. Also, this study aimed to compare the log reduction of these two microorganisms to evaluate E. faecium NRRL B2354, as a surrogate for S. enterica. On average, recovery of S. enterica was improved by 1 log CFU from ClO2 and H2O2 treated LWAFs when a non-selective but differential media containing tryptic soy agar with yeast extract, ammonium iron citrate and sodium thiosulfate (MTSAYE) was used, when compared to plating on XLD (p < 0.05). Furthermore, addition of sodium pyruvate, ferrous sulfate, or 3’3’-thiodiproionate supplements to MTSAYE did not show increased recovery of either S. enterica or E. faecium NRRL B2354 (p > 0.05). On each treatment and LWAF combination tested, there was no significant difference between the log reduction of S. enterica and E. faecium NRRL B2354, indicating its suitability as a surrogate under the test conditions.
Predictors of sustainment of two distinct nutrition and physical activity programs in early care and education
Authors: Swindle Taren , Bellows Laura L. , Mitchell Virginia , Johnson Susan L. , Shakya Samjhana , Zhang Dong , Selig James P. , Whiteside-Mansell Leanne , Curran Geoffrey M.
Published: November 2022

Introduction

The goal of the present study was to investigate factors associated with sustainment of two evidence-based programs for nutrition promotion in early care and education (ECE) settings – Food Friends (FF) and Together, We Inspire Smart Eating (WISE).

Materials and methods

In a cross-sectional study design, ECE directors (N = 55) from centers that had previously been trained in WISE or FF completed a survey. Program-specific measures included Steckler's Perception of Innovations, the Program Sustainability Assessment Tool (PSAT), and the Organizational Readiness for Change Assessment (ORCA). For our primary outcomes, two measures of sustainment were examined: Nutrition Continued Practice (i.e., the use of or general focus on nutrition programs) and Program Fidelity (i.e., how well centers used specific evidence-based practices of WISE or FF). Multiple regression was used to determine the association of these outcomes with program, years since last implementation, and overall scores on predictors. Follow-up correlation analyses were used to investigate outcome relationships with context submeasures due to high intercorrelations between predictor submeasures.

Results

Nutrition Continued Practice was significantly predicted by program and overall PSAT score. WISE programs had significantly higher Nutrition Continued Practice scores than FF program (p = 0.03). All subscales of the PSAT (e.g., environmental support, funding stability, organizational capacity, program adaptation, communications, and strategic planning) were significantly correlated with Nutrition Continued Practice (all rs > 0.30, all ps < 0.03). Program Fidelity was significantly predicted by PSAT and Steckler Perception of Innovation scores. All subscales of the PSAT were strongly positively correlated with Program Fidelity (all rs > 0.48, all ps < 0.001); relative advantage (r = 0.54, p < 0.001) and level of institutionalization (r = 0.61, p < 0.001) were positively correlated with Program Fidelity.

Conclusion

This study suggests that factors associated with the continued practice of program principles are partially distinct from those that are associated with the sustainment of specific practices driving program fidelity. Results suggest capacity building strategies may be important for both continued attention to nutrition and physical activity as well as sustaining fidelity to specific evidence-based practices.
Core functions of a financial navigation intervention: An in-depth assessment of the Lessening the Impact of Financial Toxicity (LIFT) intervention to inform adaptation and scale-up in diverse oncology care settings
Authors: Wheeler Stephanie B. , Birken Sarah A. , Wagi Cheyenne R. , Manning Michelle L. , Gellin Mindy , Padilla Neda , Rogers Cindy , Rodriguez Julia , Biddell Caitlin B. , Strom Carla , Bell Ronny Antonio , Rosenstein Donald L.
Published: November 2022

Background

Lessening the Impact of Financial Toxicity (LIFT) is an intervention designed to address financial toxicity (FT) and improve cancer care access and outcomes through financial navigation (FN). FN identifies patients at risk for FT, assesses eligibility for financial support, and develops strategies to cope with those costs. LIFT successfully reduced FT and improved care access in a preliminary study among patients with high levels of FT in a single large academic cancer center. Adapting LIFT requires distinguishing between core functions (components that are key to its implementation and effectiveness) and forms (specific activities that carry out core functions). Our objective was to complete the first stage of adaptation, identifying LIFT core functions.

Methods

We reviewed LIFT's protocol and internal standard-operating procedures. We then conducted 45–90 min in-depth interviews, using Kirk's method of identifying core functions, with key LIFT staff (N = 8), including the principal investigators. Interviews focused on participant roles and intervention implementation. Recorded interviews were transcribed verbatim. Using ATLAS.ti and a codebook based on the Model for Adaptation Design and Impact, we coded interview transcripts. Through thematic analysis, we then identified themes related to LIFT's intervention and implementation core functions. Two report back sessions with interview participants were incorporated to further refine themes.

Results

Six intervention core functions (i.e., what makes LIFT effective) and five implementation core functions (i.e., what facilitated LIFT's implementation) were identified to be sufficient to reduce FT. Intervention core functions included systematically cataloging knowledge and tracking patient-specific information related to eligibility criteria for FT relief. Repeat contacts between the financial navigator and participant created an ongoing relationship, removing common barriers to accessing resources. Implementation core functions included having engaged sites with the resources and willingness necessary to implement FN. Developing navigators' capabilities to implement LIFT—through training, an established case management system, and connections to peer navigators—were also identified as implementation core functions.

Conclusion

This study adds to the growing evidence on FN by characterizing intervention and implementation core functions, a critical step toward promoting LIFT's implementation and effectiveness.
Improving ionospheric predictability requires accurate simulation of the mesospheric polar vortex
Authors: Harvey V. Lynn , Randall Cora E. , Bailey Scott M. , Becker Erich , Chau Jorge L. , Cullens Chihoko Y. , Goncharenko Larisa P. , Gordley Larry L. , Hindley Neil P. , Lieberman Ruth S. , Liu Han-Li , Megner Linda , Palo Scott E. , Pedatella Nicholas M. , Siskind David E. , Sassi Fabrizio , Smith Anne K. , Stober Gunter , Stolle Claudia , Yue Jia
Published: November 2022

The mesospheric polar vortex (MPV) plays a critical role in coupling the atmosphere-ionosphere system, so its accurate simulation is imperative for robust predictions of the thermosphere and ionosphere. While the stratospheric polar vortex is widely understood and characterized, the mesospheric polar vortex is much less well-known and observed, a short-coming that must be addressed to improve predictability of the ionosphere. The winter MPV facilitates top-down coupling via the communication of high energy particle precipitation effects from the thermosphere down to the stratosphere, though the details of this mechanism are poorly understood. Coupling from the bottom-up involves gravity waves (GWs), planetary waves (PWs), and tidal interactions that are distinctly different and important during weak vs. strong vortex states, and yet remain poorly understood as well. Moreover, generation and modulation of GWs by the large wind shears at the vortex edge contribute to the generation of traveling atmospheric disturbances and traveling ionospheric disturbances. Unfortunately, representation of the MPV is generally not accurate in state-of-the-art general circulation models, even when compared to the limited observational data available. Models substantially underestimate eastward momentum at the top of the MPV, which limits the ability to predict upward effects in the thermosphere. The zonal wind bias responsible for this missing momentum in models has been attributed to deficiencies in the treatment of GWs and to an inaccurate representation of the high-latitude dynamics. In the coming decade, simulations of the MPV must be improved.