bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular glue CELMoD compounds are regulators of cereblon conformation
Authors: Watson Edmond R. , Novick Scott , Matyskiela Mary E. , Chamberlain Philip P. , H. de la Peña Andres , Zhu Jinyi , Tran Eileen , Griffin Patrick R. , Wertz Ingrid E. , Lander Gabriel C.
Published: November 2022

Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN’s thalidomide-binding domain (TBD), but the allostery of drug-induced neosubstrate binding remains unclear. We performed cryo–electron microscopy analyses of the DNA damage-binding protein 1 (DDB1)–CRBN apo complex and compared these structures with DDB1-CRBN in the presence of CELMoD compounds alone and complexed with neosubstrates. Association of CELMoD compounds to the TBD is necessary and sufficient for triggering CRBN allosteric rearrangement from an open conformation to the canonical closed conformation. The neosubstrate Ikaros only stably associates with the closed CRBN conformation, illustrating the importance of allostery for CELMoD compound efficacy and informing structure-guided design strategies to improve therapeutic efficacy.
Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines
Authors: Cabellos Carmen , Guillem Lluïsa , Pelegrin Ivan , Tubau Fe , Ardanuy Carmen , Gudiol F. , Ariza J. , Viladrich Pedro F.
Published: November 2022

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L.
Respiratory Syncytial Virus Protects Bystander Cells against Influenza A Virus Infection by Triggering Secretion of Type I and Type III Interferons
Authors: Czerkies Maciej , Kochańczyk Marek , Korwek Zbigniew , Prus Wiktor , Lipniacki Tomasz
Published: November 2022

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are common recurrent respiratory infectants that show a relatively high coincidence. We demonstrated that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation.
Complete Genome Sequences of Grapevine Red Globe Virus in Japan
Authors: Yamamoto Toya , Sato Haruka , Suzuki Takumi , Miyazaki Akio , Kitazawa Yugo , Maejima Kensaku , Namba Shigetou , Yamaji Yasuyuki
Published: November 2022

Two complete and three partial genome sequences of grapevine red globe virus (GRGV) from grapevines (
Vitis
spp.) in Japan were determined.
Multimorbidity and out-of-pocket expenditure for medicines in China and India
Authors: La Dennis Tuan Vu , Zhao Yang , Arokiasamy Perianayagam , Atun Rifat , Mercer Stewart , Marthias Tiara , McPake Barbara , Pati Sanghamitra , Palladino Raffaele , Lee John Tayu
Published: November 2022

Introduction

Using nationally representative survey data from China and India, this study examined (1) the distribution and patterns of multimorbidity in relation to socioeconomic status and (2) association between multimorbidity and out-of-pocket expenditure (OOPE) for medicines by socioeconomic groups.

Methods

Secondary data analysis of adult population aged 45 years and older from WHO Study on Global Ageing and Adult Health (SAGE) India 2015 (n=7397) and China Health and Retirement Longitudinal Study (CHARLS) 2015 (n=11 570). Log-linear, two-parts, zero-inflated and quantile regression models were performed to assess the association between multimorbidity and OOPE for medicines in both countries. Quantile regression was adopted to assess the observed relationship across OOPE distributions.

Results

Based on 14 (11 self-reported) and 9 (8 self-reported) long-term conditions in the CHARLS and SAGE datasets, respectively, the prevalence of multimorbidity in the adult population aged 45 and older was found to be 63.4% in China and 42.2% in India. Of those with any long-term health condition, 38.6% in China and 20.9% in India had complex multimorbidity. Multimorbidity was significantly associated with higher OOPE for medicines in both countries (p<0.05); an additional physical long-term condition was associated with a 18.8% increase in OOPE for medicine in China (p<0.05) and a 20.9% increase in India (p<0.05). Liver disease was associated with highest increase in OOPE for medicines in China (61.6%) and stroke in India (131.6%). Diabetes had the second largest increase (China: 58.4%, India: 91.6%) in OOPE for medicines in both countries.

Conclusion

Multimorbidity was associated with substantially higher OOPE for medicines in China and India compared with those without multimorbidity. Our findings provide supporting evidence of the need to improve financial protection for populations with an increased burden of chronic diseases in low-income and middle-income countries.
Communication about medication management during patient–physician consultations in primary care: a participant observation study
Authors: Adelsjö Igor , Nilsson Lina , Hellström Amanda , Ekstedt Mirjam , Lehnbom Elin Christina
Published: November 2022

Objective

To explore communication about medication management during annual consultations in primary care. Design: passive participant observations of primary care consultations.

Setting

Two primary care centres in southern Sweden.

Participants

Consultations between 18 patients (over the age of 60 years) with chronic diseases and 10 general practitioners (GPs) were observed, audio-recorded, transcribed and analysed using content analysis.

Results

Four categories emerged: communication barriers, striving for a shared understanding of medication management, evaluation of the current medication treatment and the plan ahead and behavioural changes in relation to medication management. Misunderstandings in communication, failure to report changes in the medication treatment and use of generic substitutes complicated mutual understanding and agreement on continued treatment. The need for behavioural changes to reduce the need for medication treatment was recognised but should be explored further.

Conclusion

Several pitfalls, including miscommunication and inaccurate medication lists, for safe medication management were identified. The purpose of annual consultations should be clarified, individual treatment plans could be used more actively during primary care consultations and efforts are needed to improve verbal communication and information continuity.
Sensor-based gait training to reduce contact time for runners with exercise-related lower leg pain: a randomised controlled trial
Authors: DeJong Lempke Alexandra F , Stephens Stephanie L , Fish Pamela N , Thompson Xavier D , Hart Joseph M , Hryvniak David J , Rodu Jordan S , Hertel Jay
Published: November 2022

Objectives

To assess the effects of a 4-week randomised controlled trial comparing an outdoor gait-training programme to reduce contact time in conjunction with home exercises (contact time gait-training feedback with home exercises (FBHE)) to home exercises (HEs) alone for runners with exercise-related lower leg pain on sensor-derived biomechanics and patient-reported outcomes.

Design

Randomised controlled trial.

Setting

Laboratory and field-based study.

Participants

20 runners with exercise-related lower leg pain were randomly allocated into FBHE (4 male (M), 6 female (F), 23±4 years, 22.0±4.3 kg/m2) or HE groups (3 M, 7 F, 25±5 years, 23.6±3.9 kg/m2).

Interventions

Both groups completed eight sessions of HEs over 4 weeks. The FBHE group received vibrotactile feedback through wearable sensors to reduce contact time during outdoor running.

Primary and secondary outcome measures

Patient-reported outcome measures (PROMs) and outdoor gait assessments were conducted for both groups at baseline and 4 weeks. PROMs were repeated at 6 weeks, and feedback retention was assessed at 6 weeks for the FBHE group. Repeated measures analyses of variance were used to assess the influence of group and timepoint on primary outcomes.

Results

The FBHE group reported increased function and recovery on PROMs beyond the HE group at 6 weeks (p<0.001). There was a significant group by time interaction for Global Rating of Change (p=0.004) and contact time (p=0.002); the FBHE group reported greater subjective improvement and reduced contact time at 4 and 6 weeks compared with the HE group and compared with baseline. The FBHE group had increased cadence (mean difference: 7 steps/min, p=0.01) at 4 weeks during outdoor running compared with baseline.

Conclusion

FBHE was more effective than HE alone for runners with exercise-related lower leg pain, manifested with improved PROMs, reduced contact time and increased cadence.

Trial registration number

NCT04270565.
FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy
Authors: Choueiri Toni K , Kluger Harriet , George Saby , Tykodi Scott S , Kuzel Timothy M , Perets Ruth , Nair Suresh , Procopio Giuseppe , Carducci Michael A , Castonguay Vincent , Folefac Edmund , Lee Chung-Han , Hotte Sebastien J. , Miller, Wilson H , Saggi Shruti Shally , Lee Chung-Wei , Desilva Heshani , Bhagavatheeswaran Prabhu , Motzer Robert J , Escudier Bernard
Published: November 2022

Background

The role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab. For enrollment in track 2 (reported here), patients with histologically confirmed clear cell aRCC, Karnofsky performance status ≥70%, and life expectancy ≥3 months who had previously progressed after IO (anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)) therapy were eligible. Previous treatment with anti-CTLA-4 therapy plus anti-PD-1/PD-L1 therapy precluded eligibility for enrollment in the nivolumab plus ipilimumab arm. Patients were treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for up to 2 years or until progression, toxicity, or protocol-specified discontinuation. The primary outcome measures were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Secondary outcomes were safety and tolerability up to 2 years. Overall survival (OS) was a tertiary/exploratory endpoint. Overall, 46 patients were included with a median follow-up of 33.8 months. The ORR was 17.4% (95% CI, 7.8 to 31.4) with eight (17.4%) patients achieving partial response. Stable disease was achieved in 19 (41.3%) patients, while 14 (30.4%) had progressive disease. Median DOR (range) was 16.4 (2.1+ to 27.0+) months. The PFS rate at 24 weeks was 43.2%, and median OS was 23.8 (95% CI, 13.2 to not reached) months. Grade 3–4 immune-mediated adverse events were reported in seven (15.2%) patients. No treatment-related deaths were reported. Patients with aRCC treated with nivolumab plus ipilimumab may derive durable clinical benefit after progression on previous IO therapies, including heavily pretreated patients, with a manageable safety profile that was consistent with previously published safety outcomes. These outcomes contribute to the knowledge of optimal sequencing of IO therapies for patients with aRCC with high unmet needs.

Trial registration number

NCT02996110.
Cancer palliative care referral: patients’ and family caregivers’ perspectives – a systematic review
Authors: Patra Lipika , Ghoshal Arunangshu , Damani Anuja , Salins Naveen
Published: November 2022

Background

Despite the evidence of palliative care benefits, referrals are infrequent and delayed. Patients and their caregivers are essential stakeholders in the referral process with valuable perspectives. This review systematically explored their perceived facilitators and barriers to palliative care referral.

Methods

4 subject-specific databases (PubMed, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and EMBASE), 3 multidisciplinary databases (SCOPUS, Web of Science and Cochrane database) and 11 journals from 1 January 1990 to 31 May 2022 were searched; and scored for their methodological rigour using Hawker’s tool. Findings were synthesised using Popay’s Narrative Synthesis method and interpreted using decision-making theory.

Results

4 themes were generated from 14 studies: (1) The timing of referral should be right and communication must be comprehensive. Delays in initiating serious illness conversations, prognostication, and decision-making hindered referral. In contrast, the presence of symptoms facilitated it. (2) Referral was equated to death, and as an inferior form of treatment, a rebranding might mitigate the stigma. (3) Referral made families feel emotional and devastated; explanation and team initiatives enabled the normalisation and positive coping. (4) Long-term holistic palliative care facilitated a positive care experience and a sense of reassurance and satisfaction, enabling a smooth transition from curative to comfort care. The late referral was associated with perceived inadequate symptom management, diminished quality of life and death and complicated bereavement issues.

Conclusion

Patients’ and caregivers’ predisposition to palliative care engagement was influenced by timely referral, comprehensive communication, perception and stigma about palliative care. Longitudinal association with the palliative care team mitigated negative perceptions and improved satisfaction and coping.

PROSPERO registration number

CRD42018091481.
Sentinel responses of Arctic freshwater systems to climate: linkages, evidence, and a roadmap for future research
Authors: Saros Jasmine E. , Arp Christopher D. , Bouchard Frédéric , Comte Jérôme , Couture Raoul-Marie , Dean Joshua F. , Lafrenière Melissa , MacIntyre Sally , McGowan Suzanne , Rautio Milla , Prater Clay , Tank Suzanne E. , Walvoord Michelle , Wickland Kimberly P. , Antoniades Dermot , Ayala-Borda Paola , Canario Joao , Drake Travis W. , Folhas Diogo , Hazuková Václava , Kivilä Henriikka , Klanten Yohanna , Lamoureux Scott , Laurion Isabelle , Pilla Rachel M. , Vonk Jorien E. , Zolkos Scott , Vincent Warwick F.
Published: November 2022

While the sentinel nature of freshwater systems is now well recognized, widespread integration of freshwater processes and patterns into our understanding of broader climate-driven Arctic terrestrial ecosystem change has been slow. We review the current understanding across Arctic freshwater systems of key sentinel responses to climate, which are attributes of these systems with demonstrated and sensitive responses to climate forcing. These include ice regimes, temperature and thermal structure, river baseflow, lake area and water level, permafrost-derived dissolved ions and nutrients, carbon mobilization (dissolved organic carbon, greenhouse gases, and radiocarbon), dissolved oxygen concentrations, lake trophic state, various aquatic organisms and their traits, and invasive species. For each sentinel, our objectives are to clarify linkages to climate, describe key insights already gained, and provide suggestions for future research based on current knowledge gaps. We suggest that tracking key responses in Arctic freshwater systems will expand understanding of the breadth and depth of climate-driven Arctic ecosystem changes, provide early indicators of looming, broader changes across the landscape, and improve protection of freshwater biodiversity and resources.
Single-cell genomics illustrates heterogeneous phenotypes of myocardial fibroblasts under ischemic insults
Authors: Thankam Finosh G. , La Vy , Agrawal Devendra K.
Published: November 2022

Myocardial regenerative strategies are promising where the choice of ideal cell population is crucial for successful translational applications. Herein, we explored the regenerative/repair responses of infarct zone cardiac fibroblast(s) (CF) by unveiling their phenotype heterogeneity at single-cell resolution. CF were isolated from the infarct zone of Yucatan miniswine that suffered myocardial infarction, cultured under simulated ischemic and reperfusion, and grouped into control, ischemia, and ischemia/reperfusion. The single-cell RNA sequencing analysis revealed 19 unique cell clusters suggesting distinct subpopulations. The status of gene expression (log2 fold change (log2 FC) > 2 and log2 FC < −2) was used to define the characteristics of each cluster unveiling with diverse features, including the pro-survival/cardioprotective (Clusters 1, 3, 5, 9, and 18), vasculoprotective (Clusters 2 and 5), anti-inflammatory (Clusters 4 and 17), proliferative (Clusters 4 and 5), nonproliferative (Clusters 6, 8, 11, 16, 17, and 18), proinflammatory (Cluster 6), profibrotic/pathologic (Clusters 8 and 19), antihypertrophic (Clusters 8 and 10), extracellular matrix restorative (Clusters 9 and 12), angiogenic (Cluster 16), and normal (Clusters 7 and 15) phenotypes. Further understanding of these unique phenotypes of CF will provide significant translational opportunities for myocardial regeneration and cardiac management.
Observational imprints of our lost twin anti-universe
Authors: Barroso Bellido Samuel , Da̧browski Mariusz P.
Published: November 2022

We consider observational consequences of the entanglement between our universe and a hypothetical twin anti-universe in the third quantization scheme of the canonical quantum gravity in order to make such a scenario falsifiable. Based on our recent and unique investigations we select some special form of the interuniversal interaction which allows the entanglement entropy of the pair of universes to diverge at the critical points of their classical evolution where the specific behaviour of the Hubble parameter plays the key role. We find that the modification of the cosmic microwave background (CMB) power spectrum due to the entanglement with our twin anti-universe for such models is enlarged for small modeskand small multipole numbersl. Our specific form of the interaction is then constrained by the Planck satellite data giving the interaction coupling constant bound to be$$\lambda _o\lesssim {\mathcal {O}}(10^{-56})\,\text {s}^{-3}$$λo≲O(10-56)s-3which is small, but not negligible compared to the inflationary contribution. Some other coupling functions which allow more critical points are also briefly commented on in the context of their observational effect on CMB and other prospective observational data.
An isotropic extension of Einstein’s universe solution through gravitational decoupling
Authors: Andrade J. , Santana D.
Published: November 2022

In this work, we use the gravitational decoupling framework through the extended minimal geometric deformation to construct and study a new interior isotropic extension of Einstein’s universe solution. The resulting model fulfills the fundamental physical acceptance conditions. As well, we study the energy exchange between the Einstein’s fluid distribution and an extra perfect fluid which supports the resulting isotropic stellar configuration.
Bifurcation Analysis of a Size-Structured Population Model
Authors: Cai Yuting , Wang Chuncheng , Fan Dejun
Published: November 2022

In this paper, a size-structured population model is studied. Choosing the coefficient of birth function as the varying parameter, we prove the existence of Hopf bifurcation and discuss the bifurcation properties, such as the direction of Hopf bifurcation and the stability of bifurcated periodic solutions. The methods used in this paper include Hopf bifurcation theorem, center manifold theorem and normal form theory for the abstract Cauchy problems in a nondense domain. Numerical simulations are finally carried out to show the theoretical results.
Endless Process of Bifurcations in Delay Differential Equations
Authors: Kashchenko Ilia
Published: November 2022

The paper is devoted to studying the singularly perturbed equations and systems with one or multiple delays. In focus is a bifurcation effect that, as the small parameter present in the system tends to zero, an endless process of forward and backward bifurcations repetition occur. To describe this effect and give its analytical background, we use the analog of the normal form, the quasinormal form, a nonlinear partial differential equation that regularly depends on a small parameter. The solutions of the quasinormal form give the main part of the asymptotic approximation of the solution of the differential equation with delay. Also effects of endless process of bifurcations is demonstrated in detail in two examples. In the first example, we consider second order equation with large delay, and in the second example — first order equation with two delays.
Periodic Peakons and Compacton Families of the Hirota-Type Peakon Equation
Authors: Han Maoan , Chen Guanrong , Li Jibin
Published: November 2022

In this paper, the methodologies of dynamical systems and singular traveling wave theory developed by [Li & Chen, 2007] are applied to find the solutions in the form of [Formula: see text] for the Hirota-type peakon equation posed by [Anco & Mobasheramini, 2017; Anco et al., 2021]. For the function [Formula: see text] therein, under the parameter conditions of [Formula: see text] [Formula: see text] or [Formula: see text], the existence of some possible bounded solutions (solitary wave solutions, periodic wave solutions and periodic peakons, as well as compactons) is proved, with exact explicit parametric representations obtained, except for the peakon solution.
Review of "Design Thinking in Technical Communication: Solving Problems through Making and Collaboration by Jason C. K. Tham" Tham, J. C. K. (2021). Routledge.
Authors: Pellegrini Mason
Published: November 2022

The use of design thinking (DT) as a pedagogical and problem-solving strategy has been gaining interest in technical and professional communication (TPC) for years, and Jason Tham'sDesign Thinking in Technical Communicationis the best and most comprehensive statement on this topic that our discipline has created yet. The book first overviews its central concepts (DT and "making"), then illustrates very concretely how those concepts can improve pedagogy, social advocacy, and collaboration in TPC. All the book's chapters (except the conclusion and first chapter) contain empirical elements, which Tham uses to support his points.
Source-free Unsupervised Domain Adaptation with Trusted Pseudo Samples
Authors: Tian Qing , Peng Shun , Ma Tinghuai
Published: November 2022

Source-free unsupervised domain adaptation (SFUDA)
aims to accomplish the task of adaptation to the target domain by utilizing pre-trained source domain model and unlabeled target domain samples, without directly accessing any source domain data. Although many SFUDA works use the pseudo-labeling strategy to improve the accuracy of pseudo-labels in the target domain, these strategies ignore the influence of domain shift on calculating the reference distribution of pseudo-labels. In this article, we propose a novel kind of SFUDA with trusted pseudo samples (SFUDA-TPS), which uses reliable feature reference distribution to solve the SFUDA problem. In SFUDA-TPS, we design a target feature correcting classifier to alleviate the problem of feature reference distribution deviating from target domain samples distribution. On this basis, the more reliable feature reference distribution is calculated by selecting the target domain samples with a high amount of information, i.e., low entropy in the fixed source domain classifier and target feature correcting classifier. The implicit alignment between the source domain and target domain is realized by learning the source domain distributions hidden in the fixed source domain classifier. Experimental evaluations illustrate the effectiveness of our proposed method in solving SFUDA tasks.
A method of named entity recognition for Tigrinya
Authors: Yohannes Hailemariam Mehari , Amagasa Toshiyuki
Published: November 2022

This paper proposes a method for Named-Entity Recognition (NER) for a low-resource language, Tigrinya, using a pre-trained language model. Tigrinya is a morphologically rich, although one of the underrepresented in the field of NLP. This is mainly due to the limited amount of annotated data available. To address this problem, we present the first publicly available datasets of NER for Tigrinya containing two versions, namely, (V1 and V2) annotated manually. The V1 and V2 datasets contain 69,309 and 40,627 tokens, respectively, where the annotations are based on the CoNLL 2003 Beginning, Inside, and Outside (BIO) tagging schema. Specifically, we develop a new pre-trained language model for Tigrinya based on RoBERTa, which we refer to as TigRoBERTa. Our model is then fine-tuned on down-stream tasks on a more specific target NER and POS tasks with limited data. Finally, we further enhance the model performance by applying semi-supervised self-training using unlabeled data. The experimental results show that the method achieved 84% F1-score for NER and 92% accuracy for POS tagging, which is better than or comparable to the baseline method based on the CNN-BiLSTM-CRF.
Design of Ternary Logic Circuits using Pseudo N-type CNTFETs
Authors: RatanKumar S. V. , Rao L. Koteswara , Kumar M. Kiran
Published: November 2022

In this paper, a novel method is presented to design ternary logic circuits for nanoelectronics applications. The ternary logic is a best alternative to the binary logic because it offers reduced interconnects, faster operating speed and reduced chip area. The digital logic circuit designs are developed using Pseudo N-type carbon nanotube field effect transistors (CNTFETs). The threshold voltage of CNTFETs is altered by the CNT diameter that is defined by the chirality vector. The ternary inverters such as standard inverter (SI), positive inverter (PI) and negative inverter (NI) and ternary basic gates such as AND, NAND, OR and NOR gates are designed. Furthermore, the half adder circuits developed which assists to develop complex circuit schematics. The proposed ternary schematics are designed and simulated using the HSPICE simulator. Moreover, the performance of the proposed circuits are investigated in terms of delay, power dissipation and power delay product (PDP) and compared with the existing circuits. It is observed that the proposed circuits show average performance improvement up to 47.48% over the existing circuits.
Mechanism of Gas Desorption in Coal Particles under Different Positive Pressures: Experiments and Numerical Model
Authors: Han Enguang
Published: November 2022

The inaccurate calculation of the gas lost is the principal cause of inaccurate determinations of the coalbed methane content via air reverse circulation sampling (ARCS). The positive pressure environment has a significant impact on gas desorption during the sampling process. To obtain the gas desorption mechanism of coal particles under positive pressure, positive pressure desorption experiments were conducted on coal samples with different particle sizes under different adsorption equilibrium pressures using a self-designed positive pressure desorption experimental device. And a positive diffusion model for coal particles was established, in which the diffusion coefficient was calculated based on the results of the positive desorption experiments. The diffusion model was then used to simulate the diffusion capacity of coal particles and compared with the test data. The results show that the responses of the positive pressure desorption and atmospheric pressure desorption to the adsorption equilibrium pressure are similar. The gas desorption velocity increases as the adsorption equilibrium pressure increases. Positive pressure can effectively inhibit gas desorption. The initial gas desorption velocity decreases as the positive pressure and coal particle size increase. Concurrently, the entire sample desorption process during ARCS can be divided into three stages: a slow desorption stage, an accelerated desorption stage, and an atmospheric desorption stage. The relationship between the diffusion coefficient and the positive pressure exhibits an exponential distribution, and the positive pressure diffusion model can describe the gas diffusion from coal particles well. The results of this study could help to establish a gas loss compensation model for the ARCS process.
Plasma‐Based Metabolomics Profiling of High‐Risk Human Papillomavirus and their Emerging Roles in the Progression of Cervical Cancer
Authors: Chen Aozheng , Xu Min , Chen Jing , Chen Tingting , Wang Qin , Zhang Runjie , Qiu Jin
Published: November 2022

High‐risk human papillomavirus (HR‐HPV) is the main etiological factor for cervical cancer. Accumulating evidence has suggested the active role of metabolites in the initiation and progression of cancers. This study explored the plasma metabolic profiles of HPV‐16 positive (HPV16 (+)), HPV‐18 positive (HPV18 (+)), and HPV negative (CTL) individuals using a nontargeted metabolomics approach. C8 ceramide‐1‐Phosphate (d18 : 1/8 : 0) was found to inhibit cervical cancer cell proliferation and migration in vitro, evidenced by CCK8 experiments, a cell migration test, RT‐qPCR, and western blotting. The underlying mechanism demonstrated that C8 inhibited proliferation and migration in cervical cancer cells via the MAPK/JNK1 signaling pathway. These findings may contribute to the clinical treatment of HR‐HPV‐induced cervical cancer by intervening in its initiation and progression.
Exosome-Based Theranostics for Liver Diseases
Authors: Luo Nianan , Li Jiangbin , Dong Rui , Lu Jianguo
Published: November 2022

Exosomes are small extracellular vesicles that can be secreted by any type of cell, released into almost all biological fluids, and extracted from anybody fluid such as blood, urine, saliva, and amniotic fluid. The theranostic role of exosome in liver diseases has been widely studied in recent years. In this review, we briefly introduce the biological characteristics of exosomes and then focus on the theranostics of exosomes in liver diseases, specifically gene delivery associated with liver diseases.
Application Value of Combined Detection of Anti-β2-GPI, ACL, and Lupus Anticoagulant in the Diagnosis of Patients with Antiphospholipid Syndrome
Authors: Peng Li , Ding Hong , Yang Milan , Cheng Yangyan , Luo Xiaoyan , Fan Xin , Jiao Wei
Published: November 2022

Objective. To investigate the application value of combined detection of anti-beta 2-glycoprotein I antibody (anti-β2-GPI), anti-cardiolipin antibody (ACL), and lupus anticoagulant (LA) in the diagnosis of patients with antiphospholipid syndrome (APS). Methods. 30 APS patients in our hospital between Jan. 2020 and Jan. 2021 were chosen as the experimental group, and 30 healthy persons with normal physical examination during the same period were selected as the control group The anti-β2-GPI and ACL indexes of both groups were detected by enzyme-linked immunosorbent assay (ELISA), with the LA levels tested by modified dilute Russell’s viper venom time (dRVVT) and LA ratio calculated. The diagnostic efficacy of single detection and combined detection was analyzed by plotting the receiver operating characteristic (ROC) curve. Results. The serum indexes in the experimental group were remarkably higher than those in the control group (

P
<
0.001

). ROC curve analysis suggested that in the diagnosis of APS, the area under the ROC curve by detecting anti-β2-GPI, ACL, LA ratio alone and simultaneously were 0.517, 0.583, 0.683, and 0.817 respectively, and the combined detection of the three had remarkably higher sensitivity and specificity than those of each single detection. Conclusion. The indexes of anti-β2-GPI, ACL, and LA ratio were highly expressed in APS patients, and the combined detection of the three has high diagnostic value and can effectively screen and assist the diagnosis of APS.
Risk Factors for Exacerbations in School-Age Children with Asthma
Authors: Yavuz S. Tolga , Koc Ozan , Kaya Guven , Gülec Mustafa
Published: November 2022

Introduction: Awareness of risk factors for asthma exacerbation can reduce the morbidity and mortality of the disease. The current study aimed to investigate the risk factors associated with current asthma exacerbations in school-age children. Methods: This study enrolled children who were admitted to a tertiary outpatient paediatric allergy and asthma department and were diagnosed with asthma. Patients and their caregivers underwent an interviewer-administered questionnaire, which obtained information regarding the demographic features and parameters to determine environmental exposures along with previous disease history. Laboratory examinations, including complete blood count with differential, total IgE levels, skin prick tests, and pulmonary function tests, were also performed. Results: A total of 431 children (288 male, 66.8%) with a median age (interquartile range) of 8.1 (6.3–11.2) years were included, among whom 265 (61.5%) had aeroallergen sensitization. Asthma was controlled, partially controlled, and uncontrolled in 154 (35.7%), 53 (12.3%), and 143 (33.2%) patients, respectively. A total of 81 patients (18.8%) experienced asthma exacerbation. Multivariate logistic regression analysis revealed that a history of asthma exacerbation within the last year (odds ratio [confidence interval]) (20.73 [9.95–43.20]; p < 0.001), a shorter asthma duration (<2.5 years) (2.58 [1.44–4.61]; p = 0.001), and a lack of regular controller therapy (4.12 [1.54–10.98]; p = 0.005) were associated with current asthma exacerbation. Discussion/Conclusion: Awareness of risk factors for asthma exacerbation may help physicians treat school-age children with asthma by providing prompt and rational interventions in order to prevent asthma exacerbations.
Extracellular Vesicles Derived from Human Bone Marrow Stem Cells Inhibit Acute Lymphoblastic Leukemia Cell Growth by Inhibiting MAPK Pathway via the miR-29b-3p/GDF15 Axis
Authors: Zhou Li , Shan Zhe , Fan Jiangsha
Published: November 2022

Introduction: Acute lymphoblastic leukemia (ALL) is a common hematologic neoplastic disease. This study discussed the effect of extracellular vesicles (EVs) released from bone marrow mesenchymal stem cells (BMSCs) on ALL cells and the mechanism. Methods: BMSCs-EVs were isolated by differential centrifugation and identified. The effect of BMSCs-EVs on ALL cell proliferation and apoptosis was evaluated. The expression of miR-29b-3p in ALL cells and EVs was detected. The uptake of EVs by ALL cells was observed. The effect of miR-29b-3p on ALL cell proliferation and apoptosis was assessed after silencing miR-29b-3p. The targeting relation of miR-29b-3p and GDF15 was analyzed by bioinformatics website and dual-luciferase assay. The role of GDF15 in proliferation and apoptosis of ALL cells was further confirmed, and Western blot assay was performed to measure MAPK pathway-related protein levels. Results: BMSC-derived EVs inhibited proliferation and promoted apoptosis of ALL cells, as shown by the up-regulation of caspase-3 and Bax expressions and down-regulation of Bcl-2 expression. EVs carried miR-29b-3p into ALL cells, upregulated miR-29b-3p expression in ALL cells, and inhibited GDF15 expression. Silencing of miR-29b-3p or overexpression of GDF15 partially reversed the effect of EVs. EVs inhibited the MAPK pathway through the miR-29b-3p/GDF15 axis. Conclusion: BMSCs-EVs carried miR-29b-3p into ALL cells, upregulated miR-29b-3p, and inhibited GDF15 to suppress the MAPK pathway and further inhibit proliferation and promote apoptosis of ALL cells.
Novel JAK2 Exon 14 Mutations L611S or N622Y in cis with JAK2V617F Are Associated with Distinct Clinical Phenotype of Polycythemia Vera and Concurrent Eosinophilia
Authors: Patel Ameet , Juskevicius Ridas , Mohan Sanjay
Published: November 2022

Eosinophilic phenotypes in polycythemia vera (PV) and essential thrombocythemia (ET) are rare and poorly characterized. Co-occurring JAK2 mutations in cis, specifically L611S or N622Y mutations, appear to result in a more aggressive clinical phenotype. PV/ET with eosinophilic phenotypes may require full next-generation sequencing to capture co-occurring mutations as opposed to more prevalent single-gene assays. These eosinophilic phenotypes are highly thrombotic and systemic symptoms appear responsive to early use of the janus kinase inhibitor ruxolitinib.
Ultrasensitive Troponin I and Incident Cardiovascular Disease
Authors: Empana Jean-Philippe , Lerner Ivan , Perier Marie-Cécile , Guibout Catherine , Jabre Patricia , Bailly Karine , Andrieu Muriel , Climie Rachel , van Sloten Thomas , Vedie Benoit , Geromin Daniela , Marijon Eloi , Thomas Frederique , Danchin Nicolas , Boutouyrie Pierre , Jouven Xavier
Published: November 2022

Background:

To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting.

Methods:

cTnI was analyzed in the baseline plasma (2008–2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale.

Results:

The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39–1.09). After a median follow-up of 8.34 years (interquartile range, 8.0–10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08–1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131–0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023–0.102]). Findings were consistent using the US pooled cohort risk equation.

Conclusions:

Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.
Intravascular Imaging for Guiding In‐Stent Restenosis and Stent Thrombosis Therapy
Authors: Erdogan Emrah , Bajaj Retesh , Lansky Alexandra , Mathur Anthony , Baumbach Andreas , Bourantas Christos V.
Published: November 2022

ABSTRACT: Advances in stent technology and the design of endovascular devices with thinner struts, anti‐inflammatory and antithrombotic polymers, and better drug kinetics have enhanced the safety and efficacy of the second‐generation drug‐eluting stents and broadened their use in the therapy of high‐risk patients and complex anatomies. However, despite these developments, in‐stent restenosis and stent thrombosis remain the Achilles' heel of percutaneous coronary intervention, with their cumulative incidence reaching up to 10% at 5 years following percutaneous coronary intervention. The treatment of stent failure poses challenges and is associated with a worse prognosis than conventional percutaneous coronary intervention. Several studies have recently highlighted the value of intravascular imaging in identifying causes of stent failure, underscored its role in treatment planning, and registries have shown that its use may be associated with better clinical outcomes. The present review aims to summarize the evidence in the field; it discusses the value of intravascular imaging in identifying the mechanisms of in‐stent restenosis and stent thrombosis in assessing the morphological characteristics of neointima tissue that appears to determine long‐term outcomes in evaluating procedural results, and presents the findings of studies supporting its value in guiding therapy in stent failure.
What Happened to the K–12 Education Labor Market During COVID? The Acute Need for Better Data Systems
Authors: Bleiberg Joshua F. , Kraft Matthew A.
Published: November 2022

The COVID-19 pandemic upended the U.S. education system in ways that dramatically affected the jobs of K–12 employees. However, there remains considerable uncertainty about the nature and degree of staffing challenges during the pandemic. We draw on data from the Bureau of Labor Statistics (BLS) and State Education Agencies (SEA) to describe patterns in K–12 education employment and to highlight the limitations of available data. Data from the BLS suggest overall employment in the K–12 labor market declined by 9 percent at the onset of the pandemic and remained well below pre-pandemic levels more than two years later. SEA data suggest that teachers did not leave the profession en masse as many predicted, with turnover decreasing in the summer of 2020 and then increasing modestly in 2021 back to pre-pandemic levels. We explore possible explanations for these patterns including weak hiring through the summer of 2020 and high attrition among K–12 instructional support and noninstructional staff. State vacancy data also suggest that schools faced substantial challenges filling open positions during the 2021–22 academic year. Our analyses illustrate the imperative to build nationally representative, detailed, and timely data systems on the K–12 education labor market to better inform policy.
A remarkable new species of Hippeastrum (Amaryllidaceae) from the Serra da Mantiqueira, Southeastern Brazil
Authors: CAMPOS-ROCHA ANTONIO , DA SILVA MEDEIROS ALEXANDRE , MEEROW ALAN WILLIAM , ANDRE SANZ-VEIGA PRISCILA , KOCH INGRID , DUTILH JULIE HENRIETTE ANTOINETTE
Published: November 2022

Serra da Mantiqueira is the most important mountain range in eastern South America, known for its high levels of species richness and endemism. A new species of Amaryllidaceae endemic to the region was recently identified, described and illustrated herein. It can be recognized by its rupicolous habit, large bulbs, reaching 12 cm in diameter, annual, lorate leaves, white flowers with pink striations and perigonal tube up to 1.5 cm long. Comments on its habitat, conservation status, phenology data, photographs and illustrations are provided, as well as comparison with the most morphologically similar species. Known by only a single population, exposed to several types of threats and with limited guarantee of protection, Hippeastrum abatinguara is considered Critically Endangered. Additionally, a key to the species of Hippeastrum occurring in the Serra da Mantiqueira is presented, accompanied by photographs of these species in their natural habitats.
A Comparison of Beamforming and Direction Finding Algorithms (Beamscan and MUSIC) on a Linear Array HF Radar in a Medium to Low Wave Energy Environment
Authors: Cahl Douglas , Voulgaris George , Leonard Lynn
Published: November 2022

We assess the performance of three different algorithms for estimating surface ocean currents from two linear array HF radar systems. The delay-and-sum beamforming algorithm, commonly used with beamforming systems, is compared with two direction-finding algorithms: Multiple Signal Classification (MUSIC) and direction finding using beamforming (Beamscan). A 7-month dataset from two HF radar sites (CSW and GTN) on Long Bay, South Carolina (United States), is used to compare the different methods. The comparison is carried out on three locations (midpoint along the baseline and two locations with in situ Eulerian current data available) representing different steering angles. Beamforming produces surface current data that show high correlation near the radar boresight (R2 ≥ 0.79). At partially sheltered locations far from the radar boresight directions (59° and 48° for radar sites CSW and GTN, respectively) there is no correlation for CSW (R2 = 0) and the correlation is reduced significantly for GTN (R2 = 0.29). Beamscan performs similarly near the radar boresight (R2 = 0.8 and 0.85 for CSW and GTN, respectively) but better than beamforming far from the radar boresight (R2 = 0.52 and 0.32 for CSW and GTN, respectively). MUSIC’s performance, after significant tuning, is similar near the boresight (R2 = 0.78 and 0.84 for CSW and GTN) while worse than Beamscan but better than beamforming far from the boresight (R2 = 0.42 and 0.27 for CSW and GTN, respectively). Comparisons at the midpoint (baseline comparison) show the largest performance difference between methods. Beamforming (R2 = 0.01) is the worst performer, followed by MUSIC (R2 = 0.37) while Beamscan (R2 = 0.76) performs best.
Effectiveness of Suicide Safety Planning Interventions: A Systematic Review Informing Occupational Therapy
Authors: Marshall Carrie Anne , Crowley Pavlina , Carmichael Dave , Goldszmidt Rebecca , Aryobi Suliman , Holmes Julia , Easton Corinna , Isard Roxanne , Murphy Susanne
Published: November 2022

Background. Suicide safety planning (SSP) is a suicide prevention approach that involves developing a collaborative plan between a service provider such as an occupational therapist and a person who is at risk of suicide. Purpose. To synthesize effectiveness studies on SSP. Method. Using the Joanna Briggs Institute methodology, we conducted a systematic review of effectiveness studies including a: (1) title and abstract screening; (2) full-text review; (3) critical appraisal; and (4) narrative synthesis. Findings. We included 22 studies. Critical appraisal scores ranged from 38.5 to 92.3 (m = 63.7). The types of interventions included were: standard and enhanced SSP (n = 11); electronically delivered SSP (n = 5); and SSP integrated with other approaches (n = 6). Only three studies identified meaningful activity as a component of SSP. Evidence across a range of studies indicates that SSP is effective for reducing suicide behavior (SB) and ideation (SI). While some studies have demonstrated effectiveness for reducing symptoms of mental illness, promoting resilience and service use, the number of studies exploring these outcomes is currently limited. Implications. Occupational therapists support individuals expressing SI, and SSP is a necessary skill for practice.