bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study
Authors: Märtson Anne-Grete , da Silva Ferreira Ana Rita , Veringa Anette , Liu Lei , Wardill Hannah R. , Junier Lenneke A. T. , van der Werf Tjip S. , Harmsen Hermie J. M. , Sturkenboom Marieke G. G. , Span Lambert F. , Tissing Wim J. E. , Alffenaar Jan-Willem C.
Published: January 2023

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54–64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.
The Tol-Pal system of Acinetobacter baumannii is important for cell morphology, antibiotic resistance and virulence
Authors: Hubloher Josephine Joy , Van der Sande Lisa , Schaudinn Christoph , Müller Volker , Averhoff Beate
Published: January 2023

Acinetobacter baumannii is an opportunistic human pathogen that has become a global threat to healthcare institutions. This Gram-negative bacterium is one of the most successful human pathogens worldwide and responsible for hospital-acquired infections. This is due to its outstanding potential to adapt to very different environments, to persist in the human host and most important, its ability to develop multidrug resistance. Our combined approach of genomic and phenotypic analyses led to the identification of the envelope spanning Tol-Pal system in A. baumannii. We found that the deletion of the tolQ, tolR, tolA, tolB, and pal genes affects cell morphology and increases antibiotic sensitivity, such as the ∆tol-pal mutant exhibits a significantly increased gentamicin and bacitracin sensitivity. Furthermore, Galleria mellonella caterpillar killing assays revealed that the ∆tol-pal mutant exhibits a decreased killing phenotype. Taken together, our findings suggest that the Tol-Pal system is important for cell morphology, antibiotic resistance, and virulence of A. baumannii.
An ensemble-based framework for user behaviour anomaly detection and classification for cybersecurity
Authors: Folino Gianluigi , Otranto Godano Carla , Pisani Francesco Sergio
Published: January 2023

Nowadays, the speed of the user and application logs is so quick that it is almost impossible to analyse them in real time without using high-performance systems and platforms. In cybersecurity, human behaviour is responsible directly or indirectly for the most common attacks (i.e. ransomware and phishing). To monitor user behaviour, it is necessary to process fast user logs coming from different and heterogeneous sources, having part of the data or some entire sources missing. A framework based on the elastic stack (ELK) to process and store log data in real time from different users and applications is proposed for this aim. This system generates an ensemble of models to classify user behaviour and detect anomalies in real time, exploiting the advantages of the ELK-based software architecture and of the Kubernetes platform. In addition, a distributed evolutionary algorithm is used to classify the users by exploiting their digital footprints derived from many data sources. Experiments conducted on two real-life data sets verify the approach’s goodness in detecting anomalies in user behaviour, coping with missing data and lowering the number of false alarms.
Baseline and usual cardiorespiratory fitness and the risk of chronic kidney disease: A prospective study and meta-analysis of published observational cohort studies
Authors: Kunutsor Setor K. , Isiozor Nzechukwu M. , Myers Jonathan , Seidu Samuel , Khunti Kamlesh , Laukkanen Jari A.
Published: January 2023

Chronic kidney disease (CKD) is a global public health burden but is largely preventable. Few studies have reported an association between high levels of cardiorespiratory fitness (CRF) and decreased risk of CKD. However, some relevant aspects of the association, such as the dose-response relationship and the long-term relevance of CRF levels to CKD, have yet to be addressed. We, therefore, aimed to quantify the nature and magnitude of the association between CRF and CKD in a cohort of 2099 men aged 42-61 years with normal kidney function at baseline. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% CIs) were estimated for the incidence of CKD. Correction for within-person variability was made using data from repeat measurements of CRF taken 11 years after baseline. A total of 197 CKD events were recorded during a median follow-up of 25.8 years. The age-adjusted regression dilution ratio for CRF was 0.59 (95% CI: 0.53-0.65). The risk of CKD decreased in a graded fashion with increasing CRF. Comparing extreme tertiles of CRF, the HR (95% CI) for CKD was 0.67 (0.46-0.97) following adjustment for several established and emerging risk factors. The corresponding adjusted HR (95% CI) was 0.51 (0.27-0.96) following correction for within-person variability. In a meta-analysis of five population-based cohort studies (including the current study) comprising 32,447 participants and 4,043 CKD cases, the fully-adjusted risk ratios (95% CIs) for CKD comparing extreme tertiles of baseline and long-term CRF values were 0.58 (0.46-0.73) and 0.40 (0.27-0.59), respectively. Findings from a new prospective study and pooled analysis of previous studies plus the new study indicate that high CRF levels are strongly and independently associated with a reduced risk of CKD and consistent with a linear dose-response relationship. Using single baseline measurements of CRF to investigate the association between CRF and CKD risk could considerably underestimate the true association.
Increased cellular senescence in doxorubicin-induced murine ovarian injury: effect of senolytics
Authors: Gao Yueyue , Wu Tong , Tang Xianan , Wen Jingyi , Zhang Yan , Zhang Jinjin , Wang Shixuan
Published: January 2023

Ovarian injury caused by chemotherapy can lead to early menopause, infertility, and even premature senility in female cancer patients, impairing the quality of life and overall health of the cancer survivors seriously. However, there is still a lack of effective protection strategies against such injury. Cellular senescence can be induced by chemotherapeutic agents in multiple organs and may corrode the structure and function of normal tissues. We hypothesized that the widely used first-line chemotherapy drug, doxorubicin, could increase senescent cell burden in normal ovarian tissue during the therapeutic process and that elimination of senescent cells with senolytics would ameliorate doxorubicin-induced ovarian injury. Here, we demonstrated an accumulation of cellular senescence in doxorubicin-treated ovaries through detecting p16 and p21 expression levels and senescence-associated β-galactosidase (SA-β-gal) activity as well as senescence-associated secretory phenotype (SASP) factors. Short-term intervention with the classic senolytic combination dasatinib and quercetin (DQ) or fisetin significantly reduced the load of senescent cells in ovaries after doxorubicin treatment. However, neither DQ nor fisetin alleviated doxorubicin-related ovarian dysfunction. Further experiments showed that ovarian apoptosis and fibrosis following doxorubicin exposure could not be improved by senolytics. Collectively, our study shows that senolytic treatment can eliminate accumulated senescent cells, but cannot reverse the massive follicle loss and ovarian stromal fibrosis caused by doxorubicin, suggesting that cellular senescence may not be one of the key mechanisms in doxorubicin-induced ovarian injury.
Disparities in Social Insurance Participation and Urban Identification Among In-situ Urbanized Residents in China
Authors: Gong Lin , Chen Juan
Published: January 2023

China’s in-situ urbanization implies a phenomenon where rural populations become new urbanites as their land was reclassified as urban. While studies have suggested that social insurance may play a role in encouraging urban identification, empirical evidence in this field remains scarce. Highlighting the identity construction experience of in-situ urbanized residents, this study assesses the efficacy of major health and pension insurance in promoting a sense of urban identity in the context of China’s rapid urbanization. We analyze data from the 2018 Urbanization and Quality of Life Survey (N = 3,229) conducted in 40 localities that undergo in-situ urbanization. Results of multi-level modelling show that those participating in urban insurance schemes such as the Urban Employee Basic Medical Insurance (UEBMI) are more likely to identify as urban. Enrollment in the New Rural Social Pension Scheme (NRSPS), however, is negatively associated with urban identification. There are also variations associated with the interaction of social insurance and hukou status. To promote future urban integration of in-situ urbanized residents, it is vital to build an equitable, efficient, and equal-access social insurance system in urbanizing China.
Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity
Authors: Ibrahim Fouad Ghadha
Published: January 2023

Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.
Health-Related Social Control and Perceived Stress Among High-Risk Latina Mothers with Type 2 Diabetes and Their At-Risk Adult Daughters
Authors: Cervantes-Ortega Maribel , Palma Anton M. , Rook Karen S. , Biegler Kelly A. , Davis Katelyn C. , Janio Emily A. , Kilgore David B. , Dow Emily , Ngo-Metzger Quyen , Sorkin Dara H.
Published: January 2023

Background

Diabetes-related multi-morbidity and cultural factors place Latinas with diabetes at increased risk for stress, which can threaten illness management. Families provide an ideal focus for interventions that seek to strengthen interpersonal resources for illness management and, in the process, to reduce stress. The current study sought to examine whether participating in a dyadic intervention was associated with reduced perceived stress and, furthermore, whether this association was mediated by persuasion and pressure, two forms of health-related social control.

Method

Latina mothers with diabetes and their at-risk adult daughters participated in either (1) a dyadic intervention that encouraged constructive collaboration to improve health behaviors and reduce stress, or (2) a usual-care minimal control condition. Actor-partner interdependence model analysis was used to estimate the effect of the intervention on dyads’ perceived stress, and mother-daughter ratings of health-related social control as potential mediators.

Results

Results revealed that participating in the intervention was associated with significantly reduced perceived stress for daughters, but not for mothers (β =  − 3.00, p = 0.02; β =  − 0.57, p = 0.67, respectively). Analyses also indicated that the association between the intervention and perceived stress was mediated by persuasion, such that mothers’ who experienced more health-related persuasion exhibited significantly less post-intervention perceived stress (indirect effect =  − 1.52, 95% CI = [− 3.12, − 0.39]). Pressure exerted by others, however, did not evidence a mediating mechanism for either mothers or daughters.

Conclusion

These findings buttress existing research suggesting that persuasion, or others’ attempts to increase participants’ healthy behaviors in an uncritical way, may be a driving force in reducing perceived stress levels.
Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial
Authors: Johnson Matthew G. , Strizki Julie M. , Brown Michelle L. , Wan Hong , Shamsuddin Hala H. , Ramgopal Moti , Florescu Diana F. , Delobel Pierre , Khaertynova Ilsiyar , Flores José F. , Fouche Leon F. , Chang Shan-Chwen , Williams-Diaz Angela , Du Jiejun , Grobler Jay A. , Paschke Amanda , De Anda Carisa
Published: January 2023

Purpose

Immunocompromised patients have a potentially increased risk for progression to severe COVID-19 and prolonged replication of SARS-CoV-2. This post hoc analysis examined outcomes among immunocompromised participants in the MOVe-OUT trial.

Methods

In phase 3 of MOVe-OUT, non-hospitalized at-risk adults with mild-to-moderate COVID-19 were randomized to receive molnupiravir 800 mg or placebo twice daily for 5 days. Immunocompromised participants were identified based on prior/concomitant medications and/or medical history. All-cause hospitalization/death, adverse events, SARS-CoV-2 titers, infectivity, and RNA sequences were compared between immunocompromised participants who received molnupiravir or placebo and with non-immunocompromised participants.

Results

Fifty-five of 1408 participants were considered immunocompromised. Compared to placebo, fewer molnupiravir-treated immunocompromised participants were hospitalized/died through Day 29 (22.6% [7/31] vs. 8.3% [2/24]), with fewer adverse events (45.2% [14/31] vs. 25.0% [6/24]). A larger mean change from baseline in SARS-CoV-2 RNA was observed with molnupiravir compared to placebo in non-immunocompromised participants (least squares mean [LSM] difference Day 5:  – 0.31, 95% confidence interval [CI]  – 0.47 to  – 0.15), while the mean change was comparable between treatment groups in immunocompromised participants (LSM difference Day 5: 0.23, 95% CI  – 0.71 to 1.17). Molnupiravir treatment was associated with increased clearance of infectious virus. Increased errors in viral nucleotide sequences in post-baseline samples compared to placebo support molnupiravir’s mechanism of action and were not associated with observation of novel treatment-emergent amino acid substitutions in immunocompromised participants.

Conclusion

Although the study population was small, these data suggest that molnupiravir treatment for mild-to-moderate COVID-19 in non-hospitalized immunocompromised adults is efficacious and safe and quickly reduces infectious SARS-CoV-2.

ClinicalTrials.gov Registration Number

NCT04575597.
Barriers and enablers associated with participation in a home-based pragmatic exercise snacking program in older adults delivered and monitored by Amazon Alexa: a qualitative study
Authors: Jansons Paul , Fyfe Jackson J. , Dalla Via Jack , Daly Robin M. , Scott David
Published: January 2023

Background

‘Exercise snacking’, which is characterised by shorter and more frequent exercise bouts compared with traditional exercise guidelines, may be an acceptable strategy for increasing physical activity and reducing sedentary behaviour in older adults.

Aim

The aim of this study was to evaluate the enablers and barriers for older adults associated with participation in a home-based exercise snacking program delivered and monitored using an Amazon Echo Show 5 device (Alexa).

Methods

This study used an interpretive description qualitative design to conduct semi-structured interviews following a 12-week pilot study in 15 adults aged 60–89 years with at least one chronic condition. All participants were prescribed a home based, individualised, lower limb focussed ‘exercise snacking’ program (involving ≤ 10 min of bodyweight exercises 2–4 times per day) delivered and monitored by an Alexa. Qualitative interview data were analysed using thematic analysis.

Results

All 15 participants (mean age 70.3 years) attended the semi-structured interview. Themes including time efficiency, flexibility, perceived health benefits, and motivation were enablers for participation in the ‘exercise snacking’ program. A lack of upper body exercises and omission of exercise equipment in the program, as well as a lack of time and motivation for performing exercise snacks three or more times per day, were barriers to participation.

Conclusion

While ‘exercise snacking’ is acceptable for older adults, future trials should provide equipment (e.g. adjustable dumbbells, exercise bands), prescribe whole-body exercise programs, and establish strategies to support participation in more than three exercise snacks per day.
Cooperative coevolutionary differential evolution with linkage measurement minimization for large-scale optimization problems in noisy environments
Authors: Zhong Rui , Zhang Enzhi , Munetomo Masaharu
Published: January 2023

Many optimization problems suffer from noise, and the noise combined with the large-scale attributes makes the problem complexity explode. Cooperative coevolution (CC) based on divide and conquer decomposes the problems and solves the sub-problems alternately, which is a popular framework for solving large-scale optimization problems (LSOPs). Many studies show that the CC framework is sensitive to decomposition, and the high-accuracy decomposition methods such as differential grouping (DG), DG2, and recursive DG (RDG) are extremely sensitive to sampling accuracy, which will fail to detect the interactions in noisy environments. Therefore, solving LSOPs in noisy environments based on the CC framework faces unprecedented challenges. In this paper, we propose a novel decomposition method named linkage measurement minimization (LMM). We regard the decomposition problem as a combinatorial optimization problem and design the linkage measurement function (LMF) based on Linkage Identification by non-linearity check for real-coded GA (LINC-R). A detailed theoretical analysis explains why our proposal can determine the interactions in noisy environments. In the optimization, we introduce an advanced optimizer named modified differential evolution with distance-based selection (MDE-DS), and the various mutation strategy and distance-based selection endow MDE-DS with strong anti-noise ability. Numerical experiments show that our proposal is competitive with the state-of-the-art decomposition methods in noisy environments, and the introduction of MDE-DS can accelerate the optimization in noisy environments significantly.
A hybrid recommender system using topic modeling and prefixspan algorithm in social media
Authors: Noorian Avval Ali Akbar , Harounabadi Ali
Published: January 2023

Route schema is difficult to plan for tourists, because they demand to pick points of interest (POI) in unknown areas that align with their preferences and limitations. This research proposes a novel personalized method for POI route recommendation that employs contextual data. The proposed approach enhances the existing methods by considering user preferences and multifaceted tourism contexts. Due to the sparsity of the data, the proposed method employs two-level clustering (DBSCAN based on the Manhattan distance) that reduces the time to discover POI. In specific, this approach utilizes the following: first, a topic pattern model is employed to discover the users’ attraction diffusion while improving the user–user similarity model using a novel asymmetric schema. Second, it has used explicit demographic information to alleviate the cold start issue, and third, it proposes a new strategy for assessing user preferences and also combined the context parameters in the form of a vector model with the Term Frequency Inverse Document Frequency technique to find contexts’ similarity. Furthermore, our framework discovers a list of optimal candidate trips by involving personalized POIs in sequential patterns’ mining (SPM); also, it used an adjusted forgotten function to involve the date context of each trip. Based on two datasets (Flickr and Gowalla), our methodology beats other prior approaches in F-score, RMSE, MAP, and NDCG factors in the experimental evaluation.
A methodology framework for bipartite network modeling
Authors: Liew Chin Ying , Labadin Jane , Kok Woon Chee , Eze Monday Okpoto
Published: January 2023

The graph-theoretic based studies employing bipartite network approach mostly focus on surveying the statistical properties of the structure and behavior of the network systems under the domain of complex network analysis. They aim to provide the big-picture-view insights of a networked system by looking into the dynamic interaction and relationship among the vertices. Nonetheless, incorporating the features of individual vertex and capturing the dynamic interaction of the heterogeneous local rules governing each of them in the studies is lacking. The methodology in achieving this could hardly be found. Consequently, this study intends to propose a methodology framework that considers the influence of heterogeneous features of each node to the overall network behavior in modeling real-world bipartite network system. The proposed framework consists of three main stages with principal processes detailed in each stage, and three libraries of techniques to guide the modeling activities. It is iterative and process-oriented in nature and allows future network expansion. Two case studies from the domain of communicable disease in epidemiology and habitat suitability in ecology employing this framework are also presented. The results obtained suggest that the methodology could serve as a generic framework in advancing the current state of the art of bipartite network approach.

Graphical Abstract
Drivers’ EEG Responses to Different Distraction Tasks
Authors: Li Guofa , Wu Xiaojian , Eichberger Arno , Green Paul , Olaverri-Monreal Cristina , Yan Weiquan , Qin Yechen , Li Yuezhi
Published: January 2023

Driver distraction has been deemed a major cause of traffic accidents. However, drivers’ brain response activities to different distraction types have not been well investigated. The purpose of this study is to investigate the response of electroencephalography (EEG) activities to different distraction tasks. In the conducted simulation tests, three secondary tasks (i.e., a clock task, a 2-back task, and a navigation task) are designed to induce different types of driver distractions. Twenty-four participants are recruited for the designed tests, and differences in drivers’ brain response activities concerning distraction types are investigated. The results show that the differences in comprehensive distraction are more significant than that in single cognitive distraction. Friedman test and post hoc two-tailed Nemenyi test are conducted to further identify the differences in band activities among brain regions. The results show that the theta energy in the frontal lobe is significantly higher than that in other brain regions in distracted driving, whereas the alpha energy in the temporal lobe significantly decreases compared to other brain regions. These results provide theoretical references for the development of distraction detection systems based on EEG signals.
Borders on the Move
Authors: Waters Leslie
Published: January 2023

An examination of territorial changes between Czechoslovakia and Hungary and their effects on the local populations of the borderlands in the World War II era.
Developing a quality measure to assess use of antibiotic medications for respiratory conditions
Authors: Melville Brandi L. , Musser Taylor , Fishman Ezra , Rainis Danielle , Byron Sepheen C.
Published: January 2023

Objective:

Antibiotics are essential medications for treating life-threatening infections. However, incorrect prescribing can lead to adverse events and contribute to antibiotic resistance. We sought to develop a utilization quality measure that could be used by health insurance plans to track overall prescribing for respiratory conditions.

Design:

A consensus-based process that included evidence review, testing, and stakeholder input was used to develop a measure and assess its usefulness for the Healthcare Effectiveness Data and Information Set (HEDIS), a national quality measurement tool.

Methods:

Guidelines and literature were reviewed to establish the rationale for the measure. The measure was tested in claims data for commercial, Medicaid and Medicare Advantage enrollees to assess feasibility of collecting and reporting needed information. The measure was vetted with multistakeholder advisory panels and posted for public comment to solicit wide input on relevance and usability.

Results:

Respiratory conditions are frequent reasons for outpatient care in the data assessed. On average, across all lines of business, the measure revealed that approximately one-third of outpatient visits for respiratory conditions are followed by antibiotics. Stakeholders supported the measure as a tool for monitoring antibiotic prescribing across health plans alongside existing measures that assess inappropriate prescribing for specific conditions. The final measure assesses the number of antibiotic prescriptions dispensed across all outpatient respiratory-related encounters at a health-plan level.

Conclusions:

The measure on antibiotic prescribing for respiratory conditions was relevant, feasible, and useful. Stakeholders strongly supported the newly developed measure and recommended its integration into HEDIS.
A Preliminary Examination of Treatment Barriers, Preferences, and Histories of Women with Symptoms of Social Anxiety Disorder
Authors: Black Julie. A. , Paparo Josephine , Wootton Bethany M.
Published: January 2023

Social anxiety disorder (SAD) is a common mental health condition that is characterised by a persistent fear of social or performance situations. Despite effective treatments being available, many individuals with SAD do not seek treatment or delay treatment seeking for many years. The aim of the present study was to examine treatment barriers, treatment histories, and cognitive behavioural therapy (CBT) delivery preferences in a sample of women with clinically relevant SAD symptoms. Ninety-nine women (Mage = 34.90, SD = 11.28) completed the online questionnaires and were included in the study. Participants were recruited from advertisements on community noticeboards and posts on social media. The results demonstrated that less than 5% of those who received psychological treatment in the past were likely to have received best-practice CBT. The most commonly cited barriers to accessing treatment for women with SAD related to direct costs (63%) and indirect costs (e.g., transport/childcare) (28%). The most preferred treatment delivery method overall was individual face-to-face treatment (70%). The study demonstrates a need to provide a variety of treatment options in order to enhance access to empirically supported treatment for women with SAD.
Securitising infectious disease outbreaks: The WHO and the visualisation of molecular life
Authors: Long Christopher
Published: January 2023

Following its exceptional response to the 2003 severe acute respiratory syndrome (SARS) outbreak, the World Health Organization (WHO) gained new powers to securitise infectious disease outbreaks via the revised 2005 International Health Regulations (IHRs) and the ability to declare a Public Health Emergency of International Concern (PHEIC). This article investigates the declaration of a PHEIC in relation to the 2009 H1N1 flu pandemic, the 2014–16 Ebola outbreak, and the ongoing COVID-19 pandemic. It argues that the securitisation of these outbreaks was dependent upon global surveillance networks that utilised genetic technologies to visualise the molecular characteristics and spread of the pathogen in question. Genetic evidence in these cases facilitated the creation of a securitised object by revealing the unique and ‘untypable’ nature of the H1N1 and SARS-CoV-2 viruses and made visible the widespread prevalence of Ebola across the population of West Africa. The power of this evidence draws from a societal perception of science as producing objective ‘facts’ about the world that objectivise their objects of concern and empower political actors in the implementation of their security agendas. As a result, scientific evidence provided by genetic technologies now plays a necessary and indispensable role in the securitisation of infectious disease outbreaks.
LINKING RADIOCARBON AND TROPHIC WEBS IN KARSTIC GROUNDWATER ECOSYSTEMS IN THE YUCATAN PENINSULA, MÉXICO
Authors: Solís C , Chávez-Solís E M , Rodríguez-Ceja M , Méndez-García C G , Ortíz E , Canto C , Martínez-Carrillo M A , Mascaró M
Published: January 2023

Stable isotopes have been used historically to track food webs. Our approach used a combination of δ13C and radiocarbon (14C) dating to identify carbon sources in cave shrimp within caves of the Karstic Yucatan Peninsula, Mexico. Three sister species of stygobitic Typhlatya shrimps were collected from the cenote pool (cenote hereafter), cavern and cave hydro regions. New and previously reported 14C and δ13C values of whole tissues from the organisms were determined at the AMS laboratory (LEMA) of the Institute of Physics of the Universidad Nacional Autónoma de México. This new set of isotopic values of biomass and potential sources were incorporated into the Bayesian Mixing Modeling Software SIAR. In two hypothetical scenarios, the contribution from each feeding source among three species of the Typhlatya genus was determined. Slight differences were also observed between isotopic values of two groups of the same species collected in two distant cenote pools, suggesting this species may feed on a wider array of sources than previously found, and that the oligotrophic environment may have a strong influence on cave shrimp diet.
A general infrastructure for data-driven control design and implementation in tokamaks
Authors: Abbate Joseph , Conlin Rory , Shousha Ricardo , Erickson Keith , Kolemen Egemen
Published: January 2023

A general infrastructure for tokamak controllers based on data-driven neural net models is presented. The paradigm allows for more flexible choices of both the underlying model and the desired controlled variables and targets. The system is implemented and tested on the DIII-D tokamak, enacting simultaneous pressure and temperature control via a finite-set model-predictive controller. Traditional control methods such as proportional–integral–derivative (PID) have proven effective for decoupled control tasks, but scale poorly when trying to achieve more complicated goals such as full state control. This is exactly where model-based controllers succeed.
Adaptive robust control for Pendubot with matched–mismatched uncertainty via constraint-following
Authors: Wei Cui , Chen Ye-Hwa , Chai Tianyou , Fu Jun
Published: January 2023

The study presents an adaptive robust control method for the Pendubot subjects to matched and mismatched uncertainty. First, the control task is formatted as a reduced-dimension equality constraint of the system states. To handle the matched and mismatched uncertainties, an orthogonal decomposition method is employed to make the mismatched part disappear after decomposition. Based on the above, an adaptive robust control law based on constraint-following is devised. By the Lyapunov approach, it is rigorously proven that the proposed approach ensures the uniform boundedness and uniform ultimate boundedness of the closed-loop control system and thus renders approximate constraint-following, regardless of uncertainty. Simulation and experimental results are provided and discussed, demonstrating the good performance of the proposed approach.
Simulation Research on the Influence of Plasma Bubbles on Radio Wave Propagation
Authors: Ma Xin , Guo Peng , Wu Mengjie
Published: January 2023

Plasma bubbles are large‐scale irregular structures that often occur at equatorial latitudes, equatorial plasma bubbles (EPBs) affect the propagation of high‐frequency (HF) radio waves. Based on their main observational characteristics, a three‐dimensional (3D) model of EPBs was established, and a preliminary simulation of EPBs was performed. Three‐dimensional ray tracing can be used to simulate HF radio wave propagation. In this study, we consider EPBs at different scales, appearing at different times and different heights, and investigate the influence of EPBs on the propagation path of radio waves at low latitudes. The simulation results show that when they propagate through EPBs of different scales, the propagation paths of radio waves are completely different. Radio waves at 6, 8, and 10 MHz show obvious refraction; With an increase in EPB scale, the focusing effect of radio waves will diminish, and the focusing height will increase. The propagation of HF radio waves through EPB change with time as follows: partial penetration, partial reflection, and total penetration, the refraction effect of EPB on radio waves gradually decreases over time. When radio waves propagate through EPB at different heights, the simulation results show that EPB at an altitude of 200 km makes little impact on the radio waves. As the height of EPB increases, the radio waves will exhibit significant refraction, showing an obvious focusing effect.
Controlling Factors of Artificial Irregularities Triggered by Chemical Release at Low Latitude Ionosphere
Authors: Gao Jing‐Fan , Xu Zheng‐Wen , Guo Li‐Xin , Xue Kun , Zhao Hai‐Sheng
Published: January 2023

The chemical release for trigging instabilities is a challenging topic in the ionosphere since 1970s. It is a helpful tool to both recognize the physical mechanism for modeling space weather and mitigate adverse effects on technological systems. Based on the well‐developed instability simulation, the rate of change of total electron content index (ROTI) theory is employed as a diagnosis method in this paper. It is used to study the instability inducing effects or scintillation controlling effect of chemical release for the first time. The main controlling factors of the chemical release are investigated. It is found that the release amount, release altitude and the initial growth rate of the ambient ionosphere are of great importance to the instability evolution and consequent scintillation effects. First, the plasma bubble induced by chemical release will rise and penetrate to the upper ionosphere, no matter what the ambient growth rate is. However, the ambient growth rate will determine the induced scintillation regime. Second, the release altitude will significantly affect the instability evolving time and scintillation intensity. There only exist a threshold of the release amount for moderate scintillation. Finally, the release amount could dominate the bifurcation process, in which the plasma bubble will deform and extend laterally. It provides an insight into the scintillation effect induced by chemical release by using the ROTI estimation. As a result, this work is a step further for the challenging topic of chemical release, and so as to be helpful for the follow‐up active space experiments.
Ensemble Modeling of Radiation Belt Electron Acceleration by Chorus Waves: Dependence on Key Input Parameters
Authors: Hua Man , Bortnik Jacob , Kellerman Adam C. , Camporeale Enrico , Ma Qianli
Published: January 2023

We perform ensemble simulations of radiation belt electron acceleration using the quasi‐linear approach during the storm on 9 October 2012, where chorus waves dominated electron acceleration at L = 5.2. Based on a superposed epoch analysis of 11 similar storms when both multi‐MeV electron flux enhancements and chorus wave activities were observed by Van Allen Probes, we use percentiles to sample the normalized input distributions for the four key inputs to estimate their relative perturbations. Using 11 points in each input parameter including chorus wave amplitude Bw, chorus wave peak frequency fm, background magnetic field B0, and electron density Ne, we ran 114 simulations to quantify the impact of uncertainties in the input parameters on the resulting simulated electron acceleration by chorus. By comparing the simulations to observations, our ensemble simulations reveal that inaccuracies in all four input parameters significantly affect the simulated electron acceleration, with the largest simulation errors attributed to the uncertainties in Bw, Ne, and fm. The simulation can deviate from the observations by four orders of magnitude, while members with largest probability density (smallest perturbations in the input) provide reasonable estimations of output fluxes with log accuracy errors concentrated between ∼−2.0 and 0.5. Quantifying the uncertainties in our study is a prerequisite for the validation of our radiation belt electron model and improvements of accurate electron flux predictions.
In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma
Authors: Taniguchi Seiji , Matsui Takahiro , Kimura Kenji , Funaki Soichiro , Miyamoto Yu , Uchida Yutaka , Sudo Takao , Kikuta Junichi , Hara Tetsuya , Motooka Daisuke , Liu Yu-Chen , Okuzaki Daisuke , Morii Eiichi , Emoto Noriaki , Shintani Yasushi , Ishii Masaru
Published: January 2023

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.
High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform
Authors: Tham Cheng-Yong , Poon LaiFong , Yan TingDong , Koh Javier Yu Peng , Ramlee Muhammad Khairul , Teoh Vania Swee Imm , Zhang Suihan , Cai Yi , Hong Zebin , Lee Gina S. , Liu Jin , Song Hai Wei , Hwang William Ying Khee , Teh Bin Tean , Tan Patrick , Xu Lifeng , Koh Angela S. , Osato Motomi , Li Shang
Published: January 2023

Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length due to the lack of high-throughput method with nucleotide resolution for individual telomere. Here, we describe a workflow to capture telomeres using newly designed telobaits in human culture cell lines as well as clinical patient samples and measure their length accurately at nucleotide resolution using single-molecule real-time (SMRT) sequencing. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that are dispersed throughout the telomere repeat region. The presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which affects the binding of shelterin complexes at the chromosomal ends and telomere protection. These findings may have profound implications in human aging and diseases.
CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer
Authors: Tsujino Takuya , Takai Tomoaki , Hinohara Kunihiko , Gui Fu , Tsutsumi Takeshi , Bai Xiao , Miao Chenkui , Feng Chao , Gui Bin , Sztupinszki Zsofia , Simoneau Antoine , Xie Ning , Fazli Ladan , Dong Xuesen , Azuma Haruhito , Choudhury Atish D. , Mouw Kent W. , Szallasi Zoltan , Zou Lee , Kibel Adam S. , Jia Li
Published: January 2023

Prostate cancer harboring BRCA1/2 mutations are often exceptionally sensitive to PARP inhibitors. However, genomic alterations in other DNA damage response genes have not been consistently predictive of clinical response to PARP inhibition. Here, we perform genome-wide CRISPR-Cas9 knockout screens in BRCA1/2-proficient prostate cancer cells and identify previously unknown genes whose loss has a profound impact on PARP inhibitor response. Specifically, MMS22L deletion, frequently observed (up to 14%) in prostate cancer, renders cells hypersensitive to PARP inhibitors by disrupting RAD51 loading required for homologous recombination repair, although this response is TP53-dependent. Unexpectedly, loss of CHEK2 confers resistance rather than sensitivity to PARP inhibition through increased expression of BRCA2, a target of CHEK2-TP53-E2F7-mediated transcriptional repression. Combined PARP and ATR inhibition overcomes PARP inhibitor resistance caused by CHEK2 loss. Our findings may inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and support reevaluation of current biomarkers for PARP inhibition in prostate cancer.
Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke
Authors: Zhang Hongyuan , Zhao Zhiqiang , Sun Shengnan , Zhang Sen , Wang Yuequan , Zhang Xuanbo , Sun Jin , He Zhonggui , Zhang Shenwu , Luo Cong
Published: January 2023

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide. However, current drug therapeutics are compromised by narrow therapeutic windows, unsatisfactory thrombolysis effects, severe bleeding events, and high recurrence rates. In this study, we exploit a self-propelling nano-penetrator with high fuel loading and controllable motion features, which is molecularly co-assembled using a photothermal photosensitizer (DiR) and a photothermal-activable NO donor (BNN6). The precisely engineered nano-penetrator of the BNN6-DiR fuel pair shows distinct advantages in terms of NO productivity and autonomous motion under laser irradiation. In animal models of artery/vein thrombosis and acute ischemic stroke, the self‐fueled nano-penetrator enables self-navigated thrombus-homing accumulation, self-propelled clot deep penetration, fluorescence image-guided photothermal/mechanical thrombolysis, and NO-mediated prevention of thrombosis recurrence and acute ischemic stroke salvage. As expected, the molecularly self-fueled nano-penetrator displayed favorable therapeutic outcomes without bleeding risk compared to the clinically available thrombolytic drug. This study offers a facile, safe, and effective nonpharmaceutical modality towards the clinical treatment of thrombosis and ischemic stroke.
Porous organic polycarbene nanotrap for efficient and selective gold stripping from electronic waste
Authors: Li Xinghao , Wang Yong-Lei , Wen Jin , Zheng Linlin , Qian Cheng , Cheng Zhonghua , Zuo Hongyu , Yu Mingqing , Yuan Jiayin , Li Rong , Zhang Weiyi , Liao Yaozu
Published: January 2023

The role of N-heterocyclic carbene, a well-known reactive site, in chemical catalysis has long been studied. However, its unique binding and electron-donating properties have barely been explored in other research areas, such as metal capture. Herein, we report the design and preparation of a poly(ionic liquid)-derived porous organic polycarbene adsorbent with superior gold-capturing capability. With carbene sites in the porous network as the “nanotrap”, it exhibits an ultrahigh gold recovery capacity of 2.09 g/g. In-depth exploration of a complex metal ion environment in an electronic waste-extraction solution indicates that the polycarbene adsorbent possesses a significant gold recovery efficiency of 99.8%. X-ray photoelectron spectroscopy along with nuclear magnetic resonance spectroscopy reveals that the high performance of the polycarbene adsorbent results from the formation of robust metal-carbene bonds plus the ability to reduce nearby gold ions into nanoparticles. Density functional theory calculations indicate that energetically favourable multinuclear Au binding enhances adsorption as clusters. Life cycle assessment and cost analysis indicate that the synthesis of polycarbene adsorbents has potential for application in industrial-scale productions. These results reveal the potential to apply carbene chemistry to materials science and highlight porous organic polycarbene as a promising new material for precious metal recovery.
Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants
Authors: Bendall Emily E. , Callear Amy P. , Getz Amy , Goforth Kendra , Edwards Drew , Monto Arnold S. , Martin Emily T. , Lauring Adam S.
Published: January 2023

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection, receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here we compare the transmission bottleneck of non-VOC SARS-CoV-2 lineages to those of Alpha, Delta, and Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0–1 single nucleotide variants (iSNV). From 64 transmission pairs with detectable iSNV, we identify a per clade bottleneck of 1 (95% CI 1–1) for Alpha, Delta, and Omicron and 2 (95% CI 2–2) for non-VOC. These tight bottlenecks reflect the low diversity at the time of transmission, which may be more pronounced in rapidly transmissible variants. Tight bottlenecks will limit the development of highly mutated VOC in transmission chains, adding to the evidence that selection over prolonged infections may drive their evolution.