bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflection and transmission of plane waves in stressed media with an imperfectly bonded interface
Authors: Li Wenqiang , Hu Hengshan
Published: January 2023

The reflection and transmission of elastic waves are of great significance for predicting reservoir physical properties, interpreting seismic data and detecting crustal structures. Most studies only consider the initial vertical stress state when studying the reflection and transmission of elastic waves at imperfectly bonded interfaces, but few studies consider the influence of initial stress on boundary conditions. Moreover, the effect of initial stress on the energy distribution of elastic waves at imperfectly bonded interfaces has rarely been investigated. We propose a unified method to calculate the energy reflection and transmission coefficients for different incident waves at welded or imperfectly bonded interfaces in stressed media. The effects of initial stress on the equation of motion, the elastic properties of the medium and the boundary conditions at the interface are considered. The elastic properties of rocks under initial stress are described by acoustoelasticity theory. In addition, we define a new stress tensor to modify the linear-slip model for describing boundary conditions at the imperfectly bonded interface in the presence of initial stress. Numerical results show that the energy reflection and transmission coefficients at the non-welded interface in stressed media depend on the elastic properties of the incident and transmitted media, the initial stress, the type and magnitude of the interfacial compliance and the frequency and propagation direction of the incident wave. The initial vertical and horizontal stresses dominate the reflection and transmission coefficients at small and large angles, respectively. The discontinuity in displacement across the imperfectly bonded boundary results in the frequency dependence of the reflection and transmission coefficients. Imperfect bonding enhances P-wave and SV-wave energy reflection and weakens P-wave energy transmission. However, imperfect bonding can enhance the energy transmission of the SV wave for the imperfectly bonded interface with high contrast between tangential and normal compliance and a resonance peak appears at a specific frequency. We also notice that imperfectly bonded interfaces with interfacial compliance less than $1.0 \times {10}^{ - 11}$ m Pa−1 can be regarded as welded interfaces in the seismic frequency band (lower than 100 Hz). In addition, the initial stress greatly influences the reflection coefficients at high frequencies and the transmission coefficients at low frequencies. The initial vertical stress can reduce the energy transmission of SV waves at imperfectly bonded interfaces. In contrast, the initial horizontal stress can significantly increase the energy transmission of low-frequency SV waves and may lead to the disappearance of the resonant peak in the transmission coefficients.
The role of DNA methylation in the maintenance of phenotypic variation induced by grafting chimerism inBrassica
Authors: Liu Ke , Wang Tingjin , Xiao Duohong , Liu Bin , Yang Yang , Xu Kexin , Qi Zhenyu , Wang Yan , Li Junxing , Xiang Xun , Yuan Lu , Chen Liping
Published: January 2023

Grafting facilitates the interaction between heterologous cells with different genomes, resulting in abundant phenotypic variation, which provides opportunities for crop improvement. However, how grafting-induced variation occurs and is transmitted to progeny remains elusive. A graft chimera, especially a periclinal chimera, which has genetically distinct cell layers throughout the plant, is an excellent model to probe the molecular mechanisms of grafting-induced variation maintenance. Here we regenerated a plant from the T-cell layer of a periclinal chimera, TCC (where the apical meristem was artificially divided into three cell layers – from outside to inside, L1, L2, and L3; T = Tuber mustard, C = red Cabbage), named rTTT0 (r = regenerated). Compared with the control (rsTTT, s = self-grafted), rTTT0 had multiple phenotypic variations, especially leaf shape variation, which could be maintained in sexual progeny. Transcriptomes were analyzed and 58 phenotypic variation-associated genes were identified. Whole-genome bisulfite sequencing analyses revealed that the methylome of rTTT0 was changed, and the CG methylation level was significantly increased by 8.74%. In rTTT0, the coding gene bodies are hypermethylated in the CG context, while their promoter regions are hypomethylated in the non-CG context. DNA methylation changes in the leaf shape variation-associated coding genes, ARF10, IAA20, ROF1, and TPR2, were maintained for five generations of rTTT0. Interestingly, grafting chimerism also affected transcription of the microRNA gene (MIR), among which the DNA methylation levels of the promoters of three MIRs associated with leaf shape variation were changed in rTTT0, and the DNA methylation modification of MIR319 was maintained to the fifth generation of selfed progeny of rTTT0 (rTTT5). These findings demonstrate that DNA methylation of coding and non-coding genes plays an important role in heterologous cell interaction-induced variation formation and its transgenerational inheritance.
A randomized superiority clinical trial: metronidazole improved the efficacy of high-dose dual therapy inHelicobacter pylorirescue treatment
Authors: Ding Zhao-Hui , Huang Yu , Chen Jin-Nan , Luo Lai-Sheng , Zhang Wei , Liang Xiao , Lu Hong
Published: January 2023

Background and objectives

High-dose dual therapy [proton pump inhibitor (PPI) + amoxicillin] is recommended as a Helicobacter pylori rescue treatment. However, its efficacy is still controversial. The aim of this study was to evaluate the efficacy and safety of triple therapy containing high dose of PPI and amoxicillin plus metronidazole compared with dual therapy in rescue treatment.

Methods

Two hundred and sixty-eight patients who failed at least two courses of H. pylori treatment were recruited and randomly allocated into two 14-day groups: esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily plus metronidazole 400 mg three times daily (EAM group); or esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily (EA group). The agar-dilution method was performed as an antibiotic susceptibility test. The 13C urea breath test was used to assess H. pylori eradication at 6 weeks after the treatment. The study was registered at clinicaltrials.gov (NCT04024527).

Results

H. pylori eradication rates in the EAM group were 85.8% (115/134, 95% CI 79.9%–91.7%) in ITT analysis and 92.6% (113/122, 95% CI 87.9%–97.3%) in PP analysis, significantly higher than those of the EA group, which were 73.1% (98/134, 95% CI 65.6%–80.6%) and 83.1% (98/118, 95% CI 76.8%–89.8%) (P = 0.005, 0.011). Resistance rates of amoxicillin and metronidazole were 6.6% (13/196) and 89.8% (176/196). Metronidazole resistance did not affect the eradication rates in the EAM group. Both groups had similar moderate and severe adverse events and similar compliance.

Conclusions

A triple therapy containing high dose of PPI and amoxicillin plus metronidazole could be a potential rescue therapy worldwide even in a high metronidazole-resistance region.
Recommendations for Epstein-Barr virus–based screening for nasopharyngeal cancer in high- and intermediate-risk regions
Authors: Lam W K Jacky , King Ann D , Miller Jacob A , Liu Zhiwei , Yu Kelly J , Chua Melvin L K , Ma Brigette B Y , Chen Ming Yuan , Pinsky Benjamin A , Lou Pei-Jen , Woo John K S , Hsu Wan-Lun , Simon Julia , Doolan Denise L , Waterboer Tim , Hui Edwin P , Li Hui , Tsang Raymond K , Wong Kenneth C W , Goh Julian P , Vlantis Alexander C , Ai Qi Yong , Wong Lun M , Abdullah Victor , Lin Jin Ching , Chen Chien-Jen , Pfeiffer Ruth M , Le Quynh-Thu , Lee Anne W M , Ji Mingfang , Cao Sumei , Ma Jun , Chan Anthony T C , Chan K C Allen , Hildesheim Allan
Published: January 2023

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)–based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.
International politics of migration in times of ‘crisis’ and beyond the COVID-19 pandemic
Authors: Koinova Maria , Düvell Franck , Kalantzi Foteini , de Jong Sara , Kaunert Christian , Marchand Marianne H
Published: January 2023

A much-anticipated end of the COVID-19 pandemic is on the horizon. It is important to reflect on the ways in which the pandemic has impacted the international politics of migration and especially on the migration-security nexus, which is still little understood but affecting policies and population movements with future implications. How the pandemic has shaped tradeoffs between securitization of migration, health, and economic concerns in governing migration? What are the new trends emerging from the pandemic on the migration-security nexus? And how can we study these in the coming years? This Research Note features insights from scholars associated with the British International Studies Association’s working group on the ‘International Politics of Migration, Refugees and Diaspora’. They argue that the pandemic has exacerbated tendencies for migration control beyond reinforcing nation-state borders, namely through foregrounding ‘riskification’ of migration discourses and practices, adding to an earlier existing securitization of migration considered as a ‘threat’. Digital controls at borders and beyond were ramped up, as were racial tropes and discrimination against migrants and mobile persons more generally. These trends deepen the restrictions on liberal freedoms during a period of global democratic backsliding, but also trigger a counter-movement where the visibility of migrants as ‘key workers’ and their deservingness in host societies has been enhanced, and diasporas became more connected to their countries of origin. This Research Note finds that enhanced controls, on the one side, and openings for visibility of migrants and transnational connectivity of diasporas, on the other, are worthy to study in the future as political trends per se. Yet, it would be also interesting to study them as interconnected in a dual movement of simultaneous restriction and inclusion, and in an interdependent world where the power of nation-states has been reasserted due to the pandemic, but migrant transnationalism has remained largely intact.
Kepler K2Campaign 9 – II. First space-based discovery of an exoplanet using microlensing
Authors: Specht D , Poleski R , Penny M T , Kerins E , McDonald I , Lee Chung-Uk , Udalski A , Bond I A , Shvartzvald Y , Zang Weicheng , Street R A , Hogg D W , Gaudi B S , Barclay T , Barentsen G , Howell S B , Mullally F , Henderson C B , Bryson S T , Caldwell D A , Haas M R , Van Cleve J E , Larson K , McCalmont K , Peterson C , Putnam D , Ross S , Packard M , Reedy L , Albrow Michael D , Chung Sun-Ju , Kil Jung Youn , Gould Andrew , Han Cheongho , Hwang Kyu-Ha , Ryu Yoon-Hyun , Shin In-Gu , Yang Hongjing , Yee Jennifer C , Cha Sang-Mok , Kim Dong-Jin , Kim Seung-Lee , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W , Szymański M K , Soszyński I , Ulaczyk K , Pietrukowicz P , Kozłowski Sz , Skowron J , Mróz P , Mao Shude , Fouqué Pascal , Zhu Wei , Abe F , Barry R , Bennett D P , Bhattacharya A , Fukui A , Fujii H , Hirao Y , Itow Y , Kirikawa R , Kondo I , Koshimoto N , Matsubara Y , Matsumoto S , Miyazaki S , Muraki Y , Olmschenk G , Ranc C , Okamura A , Rattenbury N J , Satoh Y , Sumi T , Suzuki D , Silva S I , Toda T , Tristram P J , Vandorou A , Yama H , Beichman C , Bryden G , Calchi Novati S
Published: January 2023

We present K2-2016-BLG-0005Lb, a densely sampled, planetary binary caustic-crossing microlensing event found from a blind search of data gathered from Campaign 9 of the Kepler K2 mission (K2C9). K2-2016-BLG-0005Lb is the first bound microlensing exoplanet discovered from space-based data. The event has caustic entry and exit points that are resolved in the K2C9 data, enabling the lens-source relative proper motion to be measured. We have fitted a binary microlens model to the Kepler data and to simultaneous observations from multiple ground-based surveys. Whilst the ground-based data only sparsely sample the binary caustic, they provide a clear detection of parallax that allows us to break completely the microlensing mass-position-velocity degeneracy and measure the planet’s mass directly. We find a host mass of 0.58 ± 0.04 M⊙ and a planetary mass of 1.1 ± 0.1 MJ. The system lies at a distance of 5.2 ± 0.2 kpc from Earth towards the Galactic bulge, more than twice the distance of the previous most distant planet found by Kepler. The sky-projected separation of the planet from its host is found to be 4.2 ± 0.3 au which, for circular orbits, deprojects to a host separation $a = 4.4^{+1.9}_{-0.4}$ au and orbital period $P = 13^{+9}_{-2}$ yr. This makes K2-2016-BLG-0005Lb a close Jupiter analogue orbiting a low-mass host star. According to current planet formation models, this system is very close to the host mass threshold below which Jupiters are not expected to form. Upcoming space-based exoplanet microlensing surveys by NASA’s Nancy Grace Roman Space Telescope and, possibly, ESA’s Euclid mission, will provide demanding tests of current planet formation models.
Spectral difference method with a posteriori limiting: application to the Euler equations in one and two space dimensions
Authors: Velasco Romero David A , Han-Veiga Maria , Teyssier Romain
Published: January 2023

We present a new numerical scheme which combines the spectral difference (SD) method up to arbitrary high order with a-posteriori limiting using the classical MUSCL-Hancock scheme as fallback scheme. It delivers very accurate solutions in smooth regions of the flow while capturing sharp discontinuities without spurious oscillations. We exploit the strict equivalence between the SD scheme and a finite-volume scheme based on the SD control volumes to enable a straightforward limiting strategy. At the end of each stage of our high-order time-integration ADER (Arbitrary high order using Derivatives) scheme, we check if the high-order solution is admissible under a number of numerical and physical criteria. If not, we replace the high-order fluxes of the troubled cells by fluxes from our robust second-order MUSCL (Monotonic Upstream-centered Scheme for Conservation Laws) fallback scheme. We apply our method to a suite of test problems for the one-dimensional and two-dimensional Euler equations. We demonstrate that this combination of SD and ADER provides a virtually arbitrary high order of accuracy while at the same time preserving good sub-element shock capturing capabilities.
Revealing determinants of translation efficiency via whole-gene codon randomization and machine learning
Authors: Nieuwkoop Thijs , Terlouw Barbara R , Stevens Katherine G , Scheltema Richard A , de Ridder Dick , van der Oost John , Claassens Nico J
Published: January 2023

It has been known for decades that codon usage contributes to translation efficiency and hence to protein production levels. However, its role in protein synthesis is still only partly understood. This lack of understanding hampers the design of synthetic genes for efficient protein production. In this study, we generated a synonymous codon-randomized library of the complete coding sequence of red fluorescent protein. Protein production levels and the full coding sequences were determined for 1459 gene variants in Escherichia coli. Using different machine learning approaches, these data were used to reveal correlations between codon usage and protein production. Interestingly, protein production levels can be relatively accurately predicted (Pearson correlation of 0.762) by a Random Forest model that only relies on the sequence information of the first eight codons. In this region, close to the translation initiation site, mRNA secondary structure rather than Codon Adaptation Index (CAI) is the key determinant of protein production. This study clearly demonstrates the key role of codons at the start of the coding sequence. Furthermore, these results imply that commonly used CAI-based codon optimization of the full coding sequence is not a very effective strategy. One should rather focus on optimizing protein production via reducing mRNA secondary structure formation with the first few codons.
Improving Early Recognition of Coccidioidomycosis in Urgent Care Clinics: Analysis of an Implemented Education Program
Authors: Pu Jie , Miranda Valerie , Minior Devin , Reynolds Shane , Rayhorn Benjamin , Ellingson Katherine D , Galgiani John N
Published: January 2023

Background

Only 0.2% of coccidioidomycosis (CM) diagnoses were made in patients (pts) with pneumonia (PNA) in urgent care (UC), because they were not being tested for CM. Our objective in this study was to improve CM testing rates.

Methods

This was a time series of clinician practice before and after an intervention that occurred at UC clinics in Phoenix and Tucson Arizona. All patients in UC were >18 years old. We included information about CM in periodic educational activities for clinicians. Coccidioidal serologic testing (CST), CST results, and their relation to International Classification of Diseases, Tenth Revision (ICD-10) codes were extracted from medical records.

Results

Urgent care received 2.1 million visits from 1.5 million patients. The CST orders per 104 visits increased from 5.5 to 19.8 (P < .0001). Percentage positive CSTs were highest for August, November, and December (17.0%) versus other months (10.6%). Positive CSTs were associated with PNA ICD-10 codes, and, independently, for Erythema nodosum (EN) which had the highest positivity rate (61.4%). Testing of PNA pts increased on first visits and on second visits when the first CST was negative. Yearly rates of PNA due to CM ranged from 17.3% to 26.0%. Despite this improvement, CST was still not done for over three quarters of pts with PNA. This was a noncomparative study.

Conclusions

Routine quality improvement activities have significantly but only partially improved rates of testing pts with PNA for CM in UC clinics located in a highly endemic area. Innovative strategies may be needed to improve current practice. Also in our region, EN, independent of PNA, is a strong predictor of CM.
Escalation of civil war in Nepal: The role of local poverty, inequality and caste polarization
Authors: Sharma Hari , Gibson John
Published: January 2023

A growing literature examines the effects of poverty, inequality and polarization on civil war but analyses typically use spatially aggregated data. Many civil wars exhibit great spatial heterogeneity so very local effects may be obscured. We study Nepal’s civil war that escalated sharply from 2001 to contribute evidence on these local effects. We combine geo-coded data on 15 000 conflict deaths spread over a decade with small-area estimates of poverty and inequality for almost 4000 localities in Nepal. We model the likelihood of a locality being affected by conflict and the intensity of the conflict, in terms of the number of deaths. Higher local poverty rates are negatively related to an increased risk of conflict and deaths, due to a shift in strategy by the rebels to target richer middle class and urban areas for accessing resources to win the war. Local relative wealth inequality is postively associated with the escalation of conflict, suggesting that relative wellbeing affects decisions about rebellion and conflict. Caste polarization also raises conflict risk and deaths, especially where dominant caste groups were more numerous. These support an agnostic view that poverty is neither a necessary nor sufficient condition for the escalation of civil conflict. The strategy used by the rebels in Nepal saw the conflict escalate away from poor areas even as conflict was more likely in unequal and caste-polarized areas.
Community engagement and sustainability: Two cases of implementation of mini-grids in Lesotho
Authors: Tsoeu-Ntokoane Seroala , Kali Moeketsi , Lemaire Xavier
Published: January 2023

Based on a survey of two Lesotho communities, this study assessed the type of governance of energy that favours the emergence of energy democracy or community energy. It established that the centralized energy governance of Semonkong seems less effective in solving conflicts compared to the decentralized energy governance of Ha-Makebe. Poor communication and lack of will to respond to community needs caused dissatisfaction and misunderstanding towards the centralized energy project. The study found that the decentralized energy project was more likely to be sustainable because it was characterized by community participation and engagement. The findings also revealed that the satisfaction of energy consumers results from a consistent supply of energy accompanied by responsiveness to community needs as opposed to a cheap inconsistent electricity supply. The implications are that the Semonkong plant's sustainability is at risk, and the project may collapse unless the Government of Lesotho, in the short term, engages with the community regarding its concerns.
Crystal structure of the membrane (M) protein from a bat betacoronavirus
Authors: Wang Xiaodong , Yang Yuwei , Sun Ziyi , Zhou Xiaoming
Published: January 2023

The membrane (M) protein is the most abundant structural protein of coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2, and plays a central role in virus assembly through its interaction with various partner proteins. However, mechanistic details about how M protein interacts with others remain elusive due to lack of high-resolution structures. Here, we present the first crystal structure of a betacoronavirus M protein from Pipistrellus bat coronavirus HKU5 (batCOV5-M), which is closely related to MERS-CoV, SARS-CoV, and SARS-CoV-2 M proteins. Furthermore, an interaction analysis indicates that the carboxy-terminus of the batCOV5 nucleocapsid (N) protein mediates its interaction with batCOV5-M. Combined with a computational docking analysis an M–N interaction model is proposed, providing insight into the mechanism of M protein–mediated protein interactions.
Inapparent infections shape the transmission heterogeneity of dengue
Authors: Vazquez-Prokopec Gonzalo M , Morrison Amy C , Paz-Soldan Valerie , Stoddard Steven T , Koval William , Waller Lance A , Alex Perkins T , Lloyd Alun L , Astete Helvio , Elder John , Scott Thomas W , Kitron Uriel
Published: January 2023

Transmission heterogeneity, whereby a disproportionate fraction of pathogen transmission events result from a small number of individuals or geographic locations, is an inherent property of many, if not most, infectious disease systems. For vector-borne diseases, transmission heterogeneity is inferred from the distribution of the number of vectors per host, which could lead to significant bias in situations where vector abundance and transmission risk at the household do not correlate, as is the case with dengue virus (DENV). We used data from a contact tracing study to quantify the distribution of DENV acute infections within human activity spaces (AS), the collection of residential locations an individual routinely visits, and quantified measures of virus transmission heterogeneity from two consecutive dengue outbreaks (DENV-4 and DENV-2) that occurred in the city of Iquitos, Peru. Negative-binomial distributions and Pareto fractions showed evidence of strong overdispersion in the number of DENV infections by AS and identified super-spreading units (SSUs): i.e. AS where most infections occurred. Approximately 8% of AS were identified as SSUs, contributing to more than 50% of DENV infections. SSU occurrence was associated more with DENV-2 infection than with DENV-4, a predominance of inapparent infections (74% of all infections), households with high Aedes aegypti mosquito abundance, and high host susceptibility to the circulating DENV serotype. Marked heterogeneity in dengue case distribution, and the role of inapparent infections in defining it, highlight major challenges faced by reactive interventions if those transmission units contributing the most to transmission are not identified, prioritized, and effectively treated.
Participatory governance in megaprojects: the Lyon–Turin high-speed railway among structure, agency, and democratic participation
Authors: Esposito Giovanni , Felicetti Andrea , Terlizzi Andrea
Published: January 2023

Megaprojects are increasingly common across countries and attract substantial political attention from a variety of actors. Recent studies have highlighted the need to move from an understanding of megaprojects as linear and rational processes towards a more nuanced approach that accounts for non-linear and conflictual aspects. Participatory governance is often proposed as a valuable resource in this regard. In this paper, we investigate the setting and design of two participatory venues operating in the context of the implementation of the Lyon-Turin high-speed railway megaproject: the Italian Observatory for the Turin-Lyon Railway and the French Public Inquiry. Empirical evidence shows that the Italian case featured substantial structural barriers to effective democratic participation. As for the French case, while better designed and implanted in its context, it featured important agentic limitations that undermined its democratic potential. On the basis of our case study, we therefore argue that both the Observatory for the Turin-Lyon Railway and Public Inquiry failed to promote democratic participation. We thus propose a deliberative approach to (the study of) of megaprojects. Whereas deliberative democratic ideas command growing interest across disciplines, these have found only limited application in the study of megaprojects. We contend that a deliberative democratic approach holds promise to improve the democratic and epistemic qualities of decision making on megaprojects.
Clawback Provisions and Firm Risk
Authors: Babenko Ilona , Bennett Benjamin , Bizjak John M , Coles Jeffrey L , Sandvik Jason J
Published: January 2023

Many of the events that trigger clawback provisions are associated with risky corporate policies and variable performance outcomes. We propose and test the hypothesis that clawback provisions motivate managers to reduce firm risk. Panel ordinary least squares, general method of moments with instrumental variables, and propensity square matching models all indicate that clawback provisions decrease the volatility of stock returns. The channels that connect clawback presence to firm risk include more conservative investment and financial policies. The clawback-induced reduction in risk-taking appears to benefit shareholders on average. The gains from reduced risk-taking are larger for firms with fewer growth options, lower R&D, and prior wrongdoing. (JEL G32, G34, J33, M41, M52, M55)
HIV reservoir: antiviral immune responses and immune interventions for curing HIV infection
Authors: Li Shuang , Moog Christiane , Zhang Tong , Su Bin
Published: January 2023

Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.
Association of apolipoprotein E epsilon 4 and cognitive impairment in adults living with human immunodeficiency virus: a meta-analysis
Authors: Mu Tingting , Wei Jiaqi , Sun Jun , Jin Junyan , Zhang Tong , Wu Hao , Su Bin
Published: January 2023

Background:

It is controversial whether the apolipoprotein E epsilon 4 allele (APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH).

Methods:

Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables.

Results:

Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates (k) = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers (P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = −0.51, 95% CI = [−0.76, −0.25], P < 0.001, k = 4, I
2 = 0%), learning (SMD = −0.52, 95% CI = [−0.75, −0.28], P < 0.001, k = 5, I
2 = 0%), executive function (SMD = −0.41, 95% CI = [−0.59, −0.23], P < 0.001, k = 8, I
2 = 0%), memory (SMD = −0.41, 95% CI = [−0.61, −0.20], P < 0.001, k = 10, I
2 = 36%), attention/working memory (SMD = −0.34, 95% CI = [−0.54, −0.14], P = 0.001, k = 6, I
2 = 0%), speed of information processing (SMD = −0.34, 95% CI = [−0.53, −0.16], P < 0.001, k = 8, I
2 = 0%), and motor function (SMD = −0.19, 95% CI = [−0.38, −0.01], P = 0.04, k = 7, I
2 = 0%).

Conclusions:

Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific. Meta analysis registration: PROSPERO, CRD 42021257775.
Safety and immunogenicity of COVID-19 vaccination in immunocompromised patients
Authors: Song Jin-Wen , Hu Wei , Shen Lili , Wang Fu-Sheng
Published: January 2023

The coronavirus disease 2019 (COVID-19) pandemic poses a great threat to public health. Individuals who are immunocompromised because of the progression of the primary disease or receiving immunosuppressive medications are prone to severe COVID-19 complications and poor outcomes. Abundant data have shown that many COVID-19 vaccines are safe and effective in large-scale populations; however, these clinical trials have excluded immunocompromised populations. Available evidence indicates that immunocompromised populations have a blunted immune response to other vaccines, raising concerns regarding the efficacy of COVID-19 vaccination in these populations. Thus, there is an urgent need to delineate the efficacy of COVID-19 vaccines in these vulnerable populations. Here, we review the characteristics of specific humoral and cellular responses to COVID-19 vaccination in immunocompromised populations, including HIV-infected patients and those receiving immunosuppressive treatment, especially solid organ transplant recipients and those undergoing anti-CD20 treatment. We also addressed the challenges that immunocompromised populations are facing in the future pandemic and the need for basic and clinical translational studies to highlight the best vaccination strategies for these populations.
Resource: A Cellular Developmental Taxonomy of the Bone Marrow Mesenchymal Stem Cell Population in Mice
Authors: Pisterzi Paola , Chen Lanpeng , van Dijk Claire , Wevers Michiel J. W. , Bindels Eric J. M. , Raaijmakers Marc H. G. P.
Published: January 2023

Mesenchymal stem cells (MSCs) play pivotal roles in tissue (re)generation. In the murine bone marrow, they are thought to reside within the Sca-1+ CD51+ bone marrow stromal cell population. Here, using scRNAseq, we aimed to delineate the cellularheterogeneity of this MSC-enriched population throughout development. At the fetal stage, the MSC population is relatively homogeneous with subsets predicted to contain stem/progenitor cells, based on transcriptional modeling and marker expression. These subsets decline in relative size throughout life, with postnatal emergence of specialized clusters, including hematopoietic stem/progenitor cell (HSPC) niches. In fetal development, these stromal HSPC niches are lacking, but subsets of endothelial cells express HSPC factors, suggesting that they may provide initial niches for emerging hematopoiesis. This cellular taxonomy of the MSC population upon development is anticipated to provide a resource aiding the prospective identification of cellular subsets and molecular mechanisms driving bone marrow (re)generation.
Acute kidney injury development and impact on clinical and economic outcomes in patients with cirrhosis: an observational cohort study over a 10-year period
Authors: Alshogran Osama Y. , Altawalbeh Shoroq M. , Almestarihi Eman M.
Published: January 2023

Objectives

Acute kidney injury (AKI) is a severe complication that is associated with significant morbidity and mortality in hospitalized cirrhotic patients. Data about AKI incidence and outcomes in patients with cirrhosis is scarce in the Middle East region. This study explored the incidence and impact of AKI on clinical and economic outcomes in cirrhosis.

Methods

This was a retrospective cohort study of cirrhosis patients admitted to an educational hospital in Jordan during the years 2012–2022. Demographics, clinical and biochemical information, and charges were retrieved from medical electronic records. Logistic regression models were conducted to evaluate predictors of AKI and mortality in cirrhosis adjusting for covariates. Hospital charges were also described.

Results

A total of 380 cirrhosis patients were included with an AKI incidence of 27.9%. Male sex, elevated baseline serum creatinine, presence of spontaneous bacterial peritonitis, and higher comorbidity score were independently associated with AKI development (P < 0.05). The hospital mortality rate was markedly higher for patients with AKI versus those without AKI (51.9% vs. 6.2%, respectively; P < 0.001). AKI was associated independently with higher odds of hospital death (OR = 5.83, P < 0.001), prolongation of the median hospital stays by 5 days (P < 0.001), more clinical complications, and increased total hospital charges per admission by $2500.

Conclusion

AKI is prevalent in cirrhosis patients, and it is associated with increased mortality, hospitalization, and cost. This burden in cirrhosis emphasizes the need for early identification of patients at high risk of AKI and applying prompt and effective management approaches, aiming at improving outcomes.
Inhibiting miR-186-5p relieves traumatic brain injury by regulating insulin-like growth factor-I-NLRP3/ASC/caspase-1 signaling pathway
Authors: Nie Ying , Wang Feng
Published: January 2023

Previous studies have shown that micro-RNA (miR)-186-5p can affect apoptosis of cells by regulating insulin-like growth factor-I (IGF-1). However, the role of miR-186-5p-IGF1 axis in traumatic brain injury (TBI), especially oxidative stress and neuroinflammatory response, remains to be further studied. Lipopolysaccharide (5 μg/mL) was used to activate microglia in vitro. The expression of miR-186-5p, IGF-1 was detected by quantitative reverse transcription PCR (qRT-PCR). ELISA and western blot were used to detect the inflammatory factors and oxidative stress. Western blot was used to detect apoptotic proteins (Bax, Bcl2 and C-caspase3), inflammatory proteins (iNOS and COX2), oxidative stress proteins (Nrf2 and HO-1) and NLRP3/apoptosis-associated speck-like protein containing a CARD (ASC)/caspase-1 inflammatory bodies. MiR-186-5p inhibitor could reduce the inflammatory factors and oxidative stress in BV2 treated with lipopolysaccharide, and reduce apoptosis. In addition, we also found that inhibition of miR-186-5p increased the expression of IGF-1, which is necessary for nervous system development. Luciferase activity assay confirmed that IGF-1 was the direct target gene of miR-186-5p. Inhibiting miR-186-5p, through upregulation IGF-1, attenuates the inflammatory factors, oxidative stress and by inhibiting NLRP3/ASC/caspase-1 signal pathway TBI in-vitro model.
Impact of Preoperative Extramammary Findings in Patients with Newly Diagnosed Breast Cancer
Authors: Gleckler Lauren , Roy Nikita , Bernstein Michelle , Balija Tara M , LaPlaca Caroline , Port Elisa , Bernik Stephanie
Published: January 2023

Background:

Breast MRI has been associated with significant rates of false positive findings. We aimed to determine the frequency of extra-mammary findings (EMFs) in newly diagnosed breast cancer patients on breast MRI with contrast and assess the significance of these findings and need for additional imaging and follow up.

Study Design:

Retrospective review of patients diagnosed with breast cancer from October 2018 – October 2019 was performed. Clinico-pathologic features were collected, including type of breast cancer, size, stage, and whether the patients had a breast MRI. Those who had MRI were included and MRI was reviewed to determine if EMFs were identified. Further imaging and follow up were assessed and recorded.

Results:

Of the 480 patients included in this cohort, 353 (74%) had invasive cancer while the remainder had DCIS. Two hundred and ninety patients (60%) underwent MRI, and 53/290 (18%) had EMFs on MRI. Of these, 28/53 (53%) underwent additional imaging to further evaluate findings. Two invasive procedures were performed (fine needle aspiration and thymectomy), and one malignancy was identified in the thymus. No metastatic breast cancer was identified in any patient.

Conclusions:

MRIs are frequently obtained for newly diagnosed breast cancer patients, and additional findings, especially extra-mammary, can be stressful for patients, and potentially lead to treatment delay if further evaluation is warranted. Our results demonstrate that incidental EMFs discovered via breast MRI are common and often lead to additional imaging studies. However, no metastatic lesions were found and only one separate malignancy was identified which did not affect breast cancer management. In patients with early-stage breast cancer, EMFs yield a very low rate of malignancy, providing high levels of reassurance and supporting the option of proceeding with surgery or treatment without delay.
Acoustic trapping and navigation of microrobots in the mouse brain vasculature
Authors: Fonseca Alexia Del Campo , Glück Chaim , Droux Jeanne , Ferry Yann , Frei Carole , Wegener Susanne , Weber Bruno , El Amki Mohamad , Ahmed Daniel
Published: January 2023

Many cerebrovascular and neurodegenerative diseases are currently challenging to treat due to the complex and delicate anatomy of the brain. The use of microrobots can create new opportunities in brain research due to their ability to access hard-to-reach regions and empower various biological applications; however, little is known about the functionality of microrobots in the brain, owing to their limited imaging modalities and intravascular challenges such as high blood flow velocities, osmotic pressures, and cellular responses. Here, we present an acoustic, non-invasive, biocompatible microrobot actuation system, forin vivonavigation in the bloodstream, in which microrobots are formed by lipid-shelled microbubbles that aggregate and propel under the force of acoustic irradiation. We investigated their capacitiesin vitrowithin a microfluidic 3D setup andin vivoin a living mouse brain. We show that microrobots can self-assemble and navigate upstream in the brain vasculature. Our microrobots achieved upstream velocities of up to 1.5 μm/s and overcame blood flows of ~10 mm/s. Our results prove that microbubble-based microrobots are scalable to the complex 3D living milieu.

Significance Statement

Numerous brain diseases, including ischemic stroke, Alzheimer’s disease, and glioblastoma, may benefit from local and targeted therapies. Although they show great promise, microrobots have not yet demonstrated successfulin vivonavigation inside the brain, as the challenging flow conditions and the complex 3D vascular network in the brain pose fundamental limitations. Here, we apply acoustically driven microrobots with the capacity for self-assembly and real-time navigation, including navigation against blood flow up to 10 mm/s, used for the first time inside the brain vasculature of a living mouse. The ultrasound manipulation of microrobots inside animal models provides a much-needed pathway for the advancement of preclinical research.
Talk To A Scientist: A Framework for a Webinar-Based Science Outreach Platform for Children
Authors: Mhade Shreeya , Kadam Snehal , Kaushik Karishma S
Published: January 2023

Given their future roles as citizens and decision makers, science outreach focused on children is important and relevant. We describe a scientist-led outreach platform (Talk To A Scientist), that uses a webinar-based approach to discuss a range of science topics with children (6-16 years). Based in India and led by two working scientists, Talk To A Scientist has been running for nearly 3 years, with a large and diverse reach across school students. In addition to webinars, the platform regularly hosts archived video content and weekly science activities, along with occasional summer family quizzes and age-specific webinars. We outline the framework used to build Talk To A Scientist, and discuss key considerations and challenges in the development and expansion of the program. We believe that the Talk To A Scientist outreach model focused on children can serve as a guideline for the implementation of similar platforms across diverse settings, and is amenable to a range of modifications to enhance engagement, sustain interest, and tailor outreach to specific groups.
Modeling the HIV epidemic in MSM in Cyprus: Reaching only the 95-95-95 cascade of care targets fails to reduce HIV incidence by 90% in 2030
Authors: Gountas I. , Pantavou K. , Siakalis G. , Demetriou A. , Demetriades I. , Nikolopoulos G. K.
Published: January 2023

Objectives

National responses should be improved and accelerated to meet the target of ending the Acquired ImmunoDeficiency Syndrome (AIDS) epidemic by 2030. In the Republic of Cyprus, Men who have Sex with Men (MSM) are disproportionately affected by Human Immunodeficiency Virus (HIV), accounting approximately for half of all annual HIV diagnoses. This study aims to assess the evolution of HIV incidence in MSM in Cyprus until 2030 under different scenarios.

Methods

A model of HIV transmission and progression was calibrated to Cypriot epidemiological data. Four scenarios were examined: status quo, two scenarios focusing on introducing Pre-Exposure Prophylaxis (PrEP), and a 90% HIV incidence reduction scenario.

Results

Reaching only the 95-95-95 HIV cascade of care (CoC) targets among MSM fails to achieve the 90% reduction in HIV incidence: the estimated reduction in 2030 compared to 2015 would be 48.6%. Initiating a PrEP intervention only for high risk MSM would cause a modest further reduction in HIV incidence. To meet the 90% HIV reduction target, PrEP should be expanded to both high and medium risk MSM and, after 2025, behavioral interventions should be implemented so as high risk MSM gradually move to the medium risk category.

Conclusions

Cyprus will not reach the HIV incidence reduction target by 2030 unless PrEP is gradually promoted and delivered to all high and medium risk MSM along with awareness and behavioral interventions.
Structure of the Native Chemotaxis Core Signalling Unit from E-gene lysedE. colicells
Authors: Cassidy C. Keith , Qin Zhuan , Frosio Thomas , Gosink Khoosheh , Yang Zhengyi , Sansom Mark S. P. , Stansfeld Phillip J. , Parkinson John S. , Zhang Peijun
Published: January 2023

Motile bacteria detect ambient chemical gradients and control their locomotion via conserved chemotaxis signaling networks, enabling cells to locate nutrients, potential hosts and other important biological niches. The sensory apparatus of the chemotaxis pathway is an array of core-signaling units (CSU) composed of transmembrane chemoreceptors, the histidine kinase CheA and an adaptor protein CheW. Although chemotaxis pathways represent the best understood signaling systems, a detailed mechanistic understanding of signal transduction has been hindered by the lack of a complete structural picture of the CSU and extended array. In this study, we present the structure of the complete CSU from phage E-gene lysedE. colicells, determined using cryo-electron tomography and sub-tomogram averaging to 12 Å resolution. Using AlphaFold2, we further predict the atomic structures of the CSU’s constituent proteins as well as key protein-protein interfaces, enabling the assembly an all-atom CSU model, which we conformationally refine using our cryoET map. Molecular dynamics simulations of the resulting model provide new insight into the periplasmic organization of the complex, including novel interactions between neighboring receptor ligand binding domains. Our results further elucidate previously unresolved interactions between individual CheA domains, including an anti-parallel P1 dimer and non-productive binding mode between P1 and P4, enhancing our understanding of the structural mechanisms underlying CheA signaling and regulation.
Mapping the 3D position of battery cathode particles in Bragg coherent diffractive imaging
Authors: Shabalin A. G. , Zhang M. , Yao W. , Rysov R. , Ren Z. , Lapkin D. , Kim Y.-Y. , Assalauova D. , Mukharamova N. , Sprung M. , Vartanyants I. A. , Meng Y. S. , Shpyrko O. G.
Published: January 2023

In Bragg coherent diffractive imaging, the precise location of the measured crystals in the interior of the sample is usually missing. Obtaining this information would help the study of the spatially dependent behavior of particles in the bulk of inhomogeneous samples, such as extra-thick battery cathodes. This work presents an approach to determine the 3D position of particles by precisely aligning them at the instrument axis of rotation. In the test experiment reported here, with a 60 µm-thick LiNi0.5Mn1.5O4 battery cathode, the particles were located with a precision of 20 µm in the out-of-plane direction, and the in-plane coordinates were determined with a precision of 1 µm.