bluuebunny/crossref_metadata_2025 huggingface dataset:
The concept of dynamicity of martial arts office building design with environmentally friendly
Authors: Kharismawardani N , Hayati A
Published: April 2022

The demand for office building for the sports branch of martial arts in Indonesia has increasingly risen in line with the rapid development of the international arena. For the administrative region, including the province of East Java, a martial arts head office is essential the administrative duties and management of the sports organisation. A martial arts office is an office to accommodate administrative and management tasks. It also requires facilities for users who mostly have an athletic background and are physically fit and well-being. Therefore, this paper aims to explore and propose architectural designs of martial arts’ administrative office from finding the idea, determining the design’s parameters and concept to formal design transformation. Presenting big ideas by translating the character and value of sport is applied during the design process and considering the green design approach to provide building’s energy-efficient. The result proposes a building design that expresses the dynamicity of sport’s value and characters. The building is also designed by reducing negative impacts on the environment and maximise energy saving.
Shape exploration through airflow simulation for reducing dust in apartment design
Authors: Maharani R T , Ekasiwi S N N , Samodra FX T B
Published: April 2022

Dust is a particle in the air which at certain concentrations can be harmful to human health. Therefore, in designing buildings, we need to consider forms that can reduce dust exposure. The design process, which uses a force-based framework, was carried out to design an apartment located in a very dusty industrial area. Shape exploration is done using simulation software. The process of exploring the basic form of an apartment with a courtyard type is realized by forming a surface that is easy to flow through by wind, namely by making a sloping surface, so that the wind easily removes dust, so it does not enter the room.
Study on non-equilibrium solidification microstructure of Al–Cu3–Si–Mg alloy by MMDF
Authors: Wu Tong , Xing Shuming , Liu Xin
Published: April 2022

Al–Cu3–Si–Mg wheel hubs were prepared by molten metals die forging (MMDF). The as-cast microstructure morphology of the alloy formed under pressure was observed by optical microscope and scanning electron microscope. The granular phases θ (Al2Cu) were distributed in the α–Al grains, and the cross phases β (Mg2Si) grew near the grain boundary in the α–Al grains. Polygonal compounds φ (AlxTi9La2Ce6Cu) and irregular eutectic structures mainly formed by (α + Al2Cu) eutectic formed under non-equilibrium solidification were found at the grain boundaries. Q (Al5Cu2Mg8Si6) phases were found at the intersection of grain boundaries. With the increase of pressure, the proportion of irregular eutectic structures (α + Al2Cu) decreased from 7.3% to 5.2%. Combined with microstructure analysis and thermodynamic software analysis, the non-equilibrium solidification path was determined as follows: L → L + φ → L + α + φ → L + (α + e) + α + φ → (α + e) + Q + α + φ → (α + e) + Q + [α + θ] + φ → (α + e) + Q + [α + θ + β] + φ
Wear mechanism of Nomex/PTFE fiber reinforced composites
Authors: Jian Liu , Fei Lu , Tiantian He , Xianjuan Pang , Yongzhen Zhang
Published: April 2022

This paper is aimed at the problems of abnormal tribological damage and fluctuation of tribological performance in the self-lubricating composite serving in heavy load spherical plain bearing in aerospace field. The Nomex/PTFE fiber reinforced composite was used to carry out a reciprocating block on ring tribological test, investigating the tribological performance of the material and its wear evolution. Results show that the influence of oscillating frequency on material wear is obviously higher than that of load under high load condition (more than 90 MPa or 180 kN). Under a certain load and frequency condition, friction temperature is a key factor to affect wear behavior of the material. Friction heat plays a dominant role in the process of worn out failure of the material. Too high friction temperature greatly weakens the friction and wear performance, resulting in material failure in a short time. Thermal fatigue is the main tribological damage mode of the material under the high load and high frequency condition, with local worn out occurred. This finding was also verified by SEM analysis of the worn surface and wear debris.
Enhanced damping and thermal conductivity of hBN/silicone rubber composites via strong interfacial action
Authors: Ren Fengmei , Yang Zizheng , Ma Haihong , Zhou Zhengfa , Xu Weibing
Published: April 2022

High integration and miniaturization of electronic systems require thermal conductivity and mechanical damping materials. In this study, hexagonal boron nitride (hBN) particles were modified by vinyltrimethoxysilane (V171) and hexadecyltrimethoxysilane (N3116) for comparing, and described as V171-hBN and N3116-hBN, respectively. The pristine and surface modified hBN were filled in vinylmethylpolysiloxane (VMQ), and then vulcanized to fabricate hBN/silicone rubber composites. The damping properties of V171-hBN/silicone rubber composites were significantly higher than that of pristine hBN/silicone rubber composites, while N3116-hBN/silicone rubber composites were in contrast. The strong interfacial action in V171-hBN/silicone rubber composites came from the chemical bond by vinyl groups on the surface of V171-hBN taking part in the vulcanization of VMQ. This strong interfacial action led the deformation of hBN, and the internal friction between layers of hBN significantly increased to dissipate more energy. As a result, V171-hBN/silicone rubber composites with excellent damping and thermal conductivity as well as good mechanical properties were obtained.
Aggregation sheaves for greedy modal decompositions
Authors: Robinson Michael
Published: April 2022

This article develops a new theoretical basis for decomposing signals that are formed by the linear superposition of a finite number of modes. Each mode depends linearly on the weights within the superposition and nonlinearly upon several other parameters. The particular focus of this article is upon finding both the weights and the parameters when the number of modes is not known in advance. This article introduces a novel mathematical formalism, aggregation sheaves, and shows how they characterize the behavior of greedy algorithms that attempt to solve modal decomposition problems. It is shown that minimizing the local consistency radius within the aggregation sheaf is guaranteed to solve all modal decomposition problems. Since the modes may or may not be well-separated, a greedy algorithm that identifies the most distinct modes first may not work reliably.
Mobility, nightlights and air pollution during the early phases of the SARS-CoV-2 pandemic
Authors: Schweikert A E , Flanagan R R , Bui J T , L’Her G F , Kerber S W , Elvidge C D , Deinert M R
Published: April 2022

The SARS-CoV-2 pandemic dramatically shifted daily life in the United States during 2020. The release of high spatial and temporal resolution cell phone data presented a unique opportunity to study the correlation between mobility, electricity use, and tropospheric NO2. While many studies have identified trends of changes in air pollution in locations with reduced mobility due to Covid-19-related restrictions, these studies fall short of assessing whether these trends are statistically significant. Here we analyze if, and how much, mobility, nighttime light and NO2 concentrations correlate. We analyze seven geographically diverse metropolitan areas in the United States (Atlanta, Austin, Boston, Denver, Los Angeles, New York City, Phoenix) in the first half of 2020. Using statistical tests of significance, we find that there is a strong correlation between NO2 levels and nighttime light during February-July 2020 in all urban centers. Mobility and NO2 are correlated strongly in four of the seven urban areas investigated. Together, these results suggest that policies aimed at limiting anthropogenic emissions from fixed (power generation) and mobile (traffic) NO2 sources have an effect on air quality but additional factors should also be considered.
Effects of antidot lattices density on transport features in zigzag graphene nanoribbons
Authors: Zhang Xiaowei , Liu Yuliang
Published: April 2022

Creating antidot lattices in graphene nanoribbons (GNRs) can significantly modify the electronic transport features and may open up an avenue to many practical applications. We here study the effects of antidot lattices on two-terminal transport in GNRs with zigzag edges (ZGNRs), based on the tight-binding method in combination with Green’s function formalism. The antidots in this work are set to be hexagonal structure. For the case of two antidots arranging in ZGNRs, many conductance resonances are found and they become denser and shaper with the increasing of the separation between antidots. However, no any effective transport gap is observed around Fermi energy. For the case of multi-antidots structure, each resonance shows a (m − 1)-splitting, where m is the number of antidots. The analysis on local density of states indicates that all of resonances are related to the quasi-standing waves in ZGNRs. To obtain an effective and stable transport gap, we suggest keeping a dense array of such antidots in ZGNRs. The computed results show that the transport gap decreases very rapidly as the separation between antidots increases. These results might guide the design of the future graphene-based devices.
Collective effects and synchronization of demand in real-time demand response
Authors: Han Chengyuan , Witthaut Dirk , Gorjão Leonardo Rydin , Böttcher Philipp C
Published: April 2022

Future energy systems will be dominated by variable renewable power generation and interconnected sectors, leading to rapidly growing complexity. Flexible elements are required to balance the variability of renewable power sources, including backup generators and storage devices, but also flexible consumers. Demand response (DR) aims to adapt the demand to the variable generation, in particular by shifting the load in time. In this article, we provide a detailed statistic analysis of the collective operation of many DR units. We establish and simulate a model for load shifting in response to real-time electricity pricing using local storage systems. We show that DR drives load shifting as desired but also induces strong collective effects that may threaten system stability. The load of individual households synchronizes, leading to extreme demand peaks. We provide a detailed statistical analysis of the grid load and quantify both the likelihood and extent of extreme demand peaks.
InClass nets: independent classifier networks for nonparametric estimation of conditional independence mixture models and unsupervised classification
Authors: Matchev Konstantin T , Shyamsundar Prasanth
Published: April 2022

Conditional independence mixture models (CIMMs) are an important class of statistical models used in many fields of science. We introduce a novel unsupervised machine learning technique called the independent classifier networks (InClass nets) technique for the nonparameteric estimation of CIMMs. InClass nets consist of multiple independent classifier neural networks (NNs), which are trained simultaneously using suitable cost functions. Leveraging the ability of NNs to handle high-dimensional data, the conditionally independent variates of the model are allowed to be individually high-dimensional, which is the main advantage of the proposed technique over existing non-machine-learning-based approaches. Two new theorems on the nonparametric identifiability of bivariate CIMMs are derived in the form of a necessary and a (different) sufficient condition for a bivariate CIMM to be identifiable. We use the InClass nets technique to perform CIMM estimation successfully for several examples. We provide a public implementation as a Python package called RainDancesVI.
Public fast charging infrastructure for battery electric trucks—a model-based network for Germany
Authors: Speth Daniel , Plötz Patrick , Funke Simon , Vallarella Emanuel
Published: April 2022

Globally, road freight accounts for 40% of the CO2 emissions in the transport sector, mainly from heavy-duty vehicles (HDVs). All the major truck markets have introduced fuel efficiency regulations for HDV, and the more ambitious regulations require the introduction of zero-emission HDV, for which battery electric trucks (BEVs) are a promising candidate. However, frequent long-distance trips require a dense public high-power charging network if BEV are to meet today's operating schedules in logistics. Here, we develop a model for public BEV high-power fast-charging that uses widely available traffic count data as input and combines this with on-site queueing models. We apply the model to Germany and obtain a fast-charging network where average waiting times do not exceed 5 min. For 15% BEV in the truck stock and 50% public charging, the model shows 267 charging locations, each with 2–8 charging points per location, for a dense network with 50 km distance between charging locations. We calculated 142 charging locations with 2–13 charging points for a wider network with 100 km distance between locations. Our results help to design future charging infrastructure for electric road freight transport.
Platelet reactivity testing in peripheral artery disease
Authors: Zhang Youqi , Chou Jennifer W , Huang Wan-Ting , Derry Katrina , Humber Doug
Published: April 2022

Purpose

Oral antiplatelet therapy is routinely used to prevent adverse cardiovascular events in patients with peripheral artery disease (PAD). Several laboratory tests are available to quantify the degree of platelet inhibition following antiplatelet therapy. This article aims to provide a review of the literature surrounding platelet functional testing in patients with PAD receiving oral P2Y12 inhibitors and to offer guidance to clinicians for the use and interpretation of these tests.

A literature search of PubMed and the Web of Science Core Collection database was conducted. All studies that performed platelet function testing and reported clinical outcomes in patients with PAD were included. Evaluation of the data suggests that, among the available testing strategies, the VerifyNow platelet reactivity unit (PRU) test is the most widely used. Despite numerous investigations attempting to define a laboratory threshold indicating suboptimal response to antiplatelet therapy, controversy exists about which PRU value best correlates with cardiovascular outcomes (ie, mortality, stent thrombosis, etc). In the PAD literature, the most commonly used PRU thresholds are 208 or higher and 235 or higher. Nonetheless, adjusting antiplatelet regimens based on suboptimal P2Y12 reactivity values has yet to be proven useful in reducing the incidence of adverse cardiovascular outcomes. This review examines platelet function testing in patients with PAD and discusses the interpretation and application of these tests when monitoring the safety and efficacy of P2Y12 inhibitors.

Conclusion

Although platelet functional tests may be simple to use, clinical trials thus far have failed to show benefit from therapy adjustments based on test results. Clinicians should be cautioned against relying on this test result alone and should instead consider a combination of laboratory, clinical, and patient-specific factors when adjusting P2Y12 inhibitor therapy in clinical practice.
Eravacycline infusion–related hypoesthesia: A case report
Authors: Miller R Briley , McClure Kinsey M , Stewart Robby G , Shealy Stephanie C , Brown Krishnan , Bookstaver P Brandon
Published: April 2022

Purpose

Eravacycline (ERV) is often used for drug-resistant gram-negative and nontuberculous mycobacteria (NTM) infections, but infusion site reactions are a potential adverse effect. We report a case of severe hypoesthesia secondary to ERV infusion.

A 74-year-old man presented with dyspnea, shortness of breath, and hemoptysis after being treated for community-acquired pneumonia. On the basis of respiratory cultures performed several weeks before the index hospitalization, he was diagnosed with Mycobacterium chelonae pneumonia. On hospital day (HD) 2, the infectious diseases consult team, guided by susceptibilities, initiated a regimen of azithromycin, levofloxacin, and ERV 80 mg (1 mg/kg) intravenously every 12 hours infused over 1 hour in 250 mL of normal saline. Approximately 25 minutes after the ERV infusion began, the patient reported tingling and numbness in his fingers, hands, and mouth, with shooting pain in his head. Symptoms resolved with cessation of the ERV infusion. On HD 3, the same ERV dose and volume was administered with an extended infusion time of 2 hours. The patient experienced the same reaction after 58 minutes, which ceased shortly after the infusion was stopped. Use of ERV was subsequently discontinued. The Naranjo adverse drug reaction probability scale score was 9, indicating a definite reaction. A review of the Food and Drug Administration Adverse Event Reporting System through March 2021 identified 22 ERV-associated events. Among these, 18% appear to be related to ERV infusions. Published results from phase 3 clinical trials did not document any hypoesthesia. It is unknown whether there is a correlation between concentration, dose, or infusion time and associated reactions.

Conclusion

This is a unique case of severe hypoesthesia secondary to ERV infusion leading to drug discontinuation. More data are needed to determine effective mitigation strategies.
MTD: a unique pipeline for host and meta-transcriptome joint and integrative analyses of RNA-seq data
Authors: Wu Fei , Liu Yao-Zhong , Ling Binhua
Published: April 2022

Ribonucleic acid (RNA)-seq data contain not only host transcriptomes but also nonhost information that comprises transcripts from active microbiota in the host cells. Therefore, joint and integrative analyses of both host and meta-transcriptome can reveal gene expression of the microbial community in a given sample as well as the correlative and interactive dynamics of the host response to the microbiome. However, there are no convenient tools that can systemically analyze host–microbiota interactions through simultaneously quantifying the host and meta-transcriptome in the same sample at the tissue and the single-cell level. This poses a challenge for interested researchers with limited expertise in bioinformatics. Here, we developed a software pipeline that can comprehensively and synergistically analyze and correlate the host and meta-transcriptome in a single sample using bulk and single-cell RNA-seq data. This pipeline, named meta-transcriptome detector (MTD), can extensively identify and quantify microbiome, including viruses, bacteria, protozoa, fungi, plasmids and vectors, in the host cells and correlate the microbiome with the host transcriptome. MTD is easy to install and run, involving only a few lines of simple commands. It offers researchers with unique genomics insights into host responses to microorganisms.
ELIXIR biovalidator for semantic validation of life science metadata
Authors: Liyanage Isuru , Burdett Tony , Droesbeke Bert , Erdos Karoly , Fernandez Rolando , Gray Alasdair , Haseeb Muhammad , Jupp Simon , Penim Flavia , Pommier Cyril , Rocca-Serra Philippe , Courtot Mélanie , Coppens Frederik
Published: April 2022

To advance biomedical research, increasingly large amounts of complex data need to be discovered and integrated. This requires syntactic and semantic validation to ensure shared understanding of relevant entities. This article describes the ELIXIR biovalidator, which extends the syntactic validation of the widely used AJV library with ontology-based validation of JSON documents.

Availability and implementation

Source code: https://github.com/elixir-europe/biovalidator, Release: v1.9.1, License: Apache License 2.0, Deployed at: https://www.ebi.ac.uk/biosamples/schema/validator/validate.

Supplementary information

Supplementary data are available at Bioinformatics online.
Impact of protein conformational diversity on AlphaFold predictions
Authors: Saldaño Tadeo , Escobedo Nahuel , Marchetti Julia , Zea Diego Javier , Mac Donagh Juan , Velez Rueda Ana Julia , Gonik Eduardo , García Melani Agustina , Novomisky Nechcoff Julieta , Salas Martín N , Peters Tomás , Demitroff Nicolás , Fernandez Alberti Sebastian , Palopoli Nicolas , Fornasari Maria Silvina , Parisi Gustavo
Published: April 2022

Motivation

After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm.

Results

Using a curated collection of apo–holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo–holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.

Availability and implementation

Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021.

Supplementary information

Supplementary data are available at Bioinformatics online.
Central stress processing, T-cell responsivity to stress hormones and disease severity in multiple sclerosis
Authors: Brasanac Jelena , Hetzer Stefan , Asseyer Susanna , Kuchling Joseph , Bellmann-Strobl Judith , Ritter Kristin , Gamradt Stefanie , Scheel Michael , Haynes John-Dylan , Brandt Alexander U. , Paul Friedemann , Gold Stefan M. , Weygandt Martin
Published: April 2022

Epidemiological, clinical and neuroscientific studies support a link between psychobiological stress and multiple sclerosis. Neuroimaging suggests that blunted central stress processing goes along with higher multiple sclerosis severity, neuroendocrine studies suggest that blunted immune system sensitivity to stress hormones is linked to stronger neuroinflammation. Until now, however, no effort has been made to elucidate whether central stress processing and immune system sensitivity to stress hormones are related in a disease-specific fashion, and if so, whether this relation is clinically meaningful. Consequently, we conducted two functional MRI analyses based on a total of 39 persons with multiple sclerosis and 25 healthy persons. Motivated by findings of an altered interplay between neuroendocrine stress processing and T-cell glucocorticoid sensitivity in multiple sclerosis, we searched for neural networks whose stress task-evoked activity is differentially linked to peripheral T-cell glucocorticoid signalling in patients versus healthy persons as a potential indicator of disease-specific CNS–immune crosstalk. Subsequently, we tested whether this activity is simultaneously related to disease severity. We found that activity of a network comprising right anterior insula, right fusiform gyrus, left midcingulate and lingual gyrus was differentially coupled to T-cell glucocorticoid signalling across groups. This network’s activity was simultaneously linked to patients’ lesion volume, clinical disability and information-processing speed. Complementary analyses revealed that T-cell glucocorticoid signalling was not directly linked to disease severity. Our findings show that alterations in the coupling between central stress processing and T-cell stress hormone sensitivity are related to key severity measures of multiple sclerosis.
Altered spontaneous cortical activity predicts pain perception in individuals with cerebral palsy
Authors: Trevarrow Michael P. , Reelfs Anna , Ott Lauren R. , Penhale Samantha H. , Lew Brandon J. , Goeller Jessica , Wilson Tony W. , Kurz Max J.
Published: April 2022

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2–4 Hz), theta (5–7 Hz), alpha (8–12 Hz), beta (15–29 Hz), low gamma (30–59 Hz) and high gamma (60–90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all pFWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (P = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.
Tinnitus: at a crossroad between phantom perception and sleep
Authors: Milinski Linus , Nodal Fernando R. , Vyazovskiy Vladyslav V. , Bajo Victoria M.
Published: April 2022

Sensory disconnection from the environment is a hallmark of sleep and is crucial for sleep maintenance. It remains unclear, however, whether internally generated percepts—phantom percepts—may overcome such disconnection and, in turn, how sleep and its effect on sensory processing and brain plasticity may affect the function of the specific neural networks underlying such phenomena. A major hurdle in addressing this relationship is the methodological difficulty to study sensory phantoms, due to their subjective nature and lack of control over the parameters or neural activity underlying that percept. Here, we explore the most prevalent phantom percept, subjective tinnitus—or tinnitus for short—as a model to investigate this. Tinnitus is the permanent perception of a sound with no identifiable corresponding acoustic source. This review offers a novel perspective on the functional interaction between brain activity across the sleep–wake cycle and tinnitus. We discuss characteristic features of brain activity during tinnitus in the awake and the sleeping brain and explore its effect on sleep functions and homeostasis. We ask whether local changes in cortical activity in tinnitus may overcome sensory disconnection and prevent the occurrence of global restorative sleep and, in turn, how accumulating sleep pressure may temporarily alleviate the persistence of a phantom sound. Beyond an acute interaction between sleep and neural activity, we discuss how the effects of sleep on brain plasticity may contribute to aberrant neural circuit activity and promote tinnitus consolidation. Tinnitus represents a unique window into understanding the role of sleep in sensory processing. Clarification of the underlying relationship may offer novel insights into therapeutic interventions in tinnitus management.
Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient
Authors: Teitelbaum Daniel , Elligsen Marion , Katz Kevin , Lam Philip W , Lo Jennifer , MacFadden Derek , Vermeiren Christie , Daneman Nick
Published: April 2022

Background

Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients.

Methods

Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type.

Results

Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals.

Conclusions

Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study
Authors: Gazit Sivan , Shlezinger Roei , Perez Galit , Lotan Roni , Peretz Asaf , Ben-Tov Amir , Herzel Esma , Alapi Hillel , Cohen Dani , Muhsen Khitam , Chodick Gabriel , Patalon Tal
Published: April 2022

Background

Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity.

Methods

A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel.

Results

SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease.

Conclusions

Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.
The chromosome-level genome assembly of Gentiana dahurica (Gentianaceae) provides insights into gentiopicroside biosynthesis
Authors: Li Ting , Yu Xi , Ren Yumeng , Kang Minghui , Yang Wenjie , Feng Landi , Hu Quanjun
Published: April 2022

Gentiana dahurica Fisch. is a perennial herb of the family Gentianaceae. This species is used as a traditional Tibetan medicine because of its rich gentiopicroside constituents. Here, we generate a high-quality, chromosome-level genome of G. dahurica with a total length of 1,416.54 Mb. Comparative genomic analyses showed that G. dahurica shared one whole-genome duplication (WGD) event with Gelsemium sempervirens of the family Gelsemiaceaei and had one additional species-specific WGD after the ancient whole-genome triplication with other eudicots. Further transcriptome analyses identified numerous enzyme coding genes and the transcription factors related to gentiopicroside biosynthesis. A set of candidate cytochrome P450 genes were identified for being involved in biosynthetic shifts from swertiamarin to gentiopicroside. Both gene expressions and the contents measured by high-performance liquid chromatography indicated that the gentiopicrosides were mainly synthesized in the rhizomes with the highest contents. In addition, we found that two above-mentioned WGDs, contributed greatly to the identified candidate genes involving in gentiopicroside biosynthesis. The first reference genome of Gentianaceae we generated here will definitely accelerate evolutionary, ecological, and pharmaceutical studies of this family.
Frontiering International Relations: Narrating US Policy in the Asia Pacific
Authors: Turner Oliver
Published: April 2022

This article reintegrates the frontier into debates about contemporary global affairs. Its analytical focus is the United States, because despite widespread agreement that it constitutes a “frontier nation,” we lack clear explanations of what the American frontier is today and what role(s) it occupies in US politics and foreign policy. To resolve this, the article ontologically reconceptualizes the frontier, arguing that it first constitutes a narrative, rather than a spatial, construct. Instead of conquering a once self-evident frontier, the United States has a long-standing tradition of narrative “frontiering” as the ideational (re)production of frontiers. The frontier has been most consistently understood not in terms of territory but ideas, with Washington's modern-day “frontiers of freedom”—notably in the Asia Pacific—as real and consequential as those of the past. The frontier-as-narrative represents a performative act about what the United States is and how it should engage at peripheral borderlands of its identity. Beyond the United States, frontiers are created and actioned anew to reshape international affairs.
Gene Regulatory Evolution in Cold-Adapted Fly Populations Neutralizes Plasticity and May Undermine Genetic Canalization
Authors: Huang Yuheng , Lack Justin B. , Hoppel Grant T. , Pool John E.
Published: April 2022

The relationships between adaptive evolution, phenotypic plasticity, and canalization remain incompletely understood. Theoretical and empirical studies have made conflicting arguments on whether adaptive evolution may enhance or oppose the plastic response. Gene regulatory traits offer excellent potential to study the relationship between plasticity and adaptation, and they can now be studied at the transcriptomic level. Here, we take advantage of three closely related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. We measure the transcriptome-wide plasticity in gene expression levels and alternative splicing (intron usage) between warm and cold laboratory environments. We find that suspected adaptive changes in both gene expression and alternative splicing tend to neutralize the ancestral plastic response. Further, we investigate the hypothesis that adaptive evolution can lead to decanalization of selected gene regulatory traits. We find strong evidence that suspected adaptive gene expression (but not splicing) changes in cold-adapted populations are more vulnerable to the genetic perturbation of inbreeding than putatively neutral changes. We find some evidence that these patterns may reflect a loss of genetic canalization accompanying adaptation, although other processes including hitchhiking recessive deleterious variants may contribute as well. Our findings augment our understanding of genetic and environmental effects on gene regulation in the context of adaptive evolution.
Race, Childhood Socioeconomic Status, and Region of Childhood Residence as Intersectional Life-Course Predictors of Cognitive Aging in the United States
Authors: Reynolds Addam , Greenfield Emily A , Moorman Sara , Reyes Laurent
Published: April 2022

Background and Objectives

Race, childhood socioeconomic status (cSES), and region of childhood residence are each associated with later-life cognition, but no studies have examined how the confluence of these factors influences later-life cognitive performance. Guided by intersectionality theory, we examined individuals’ social positionality across these dimensions as a predictor of cognitive performance in later life among non-Hispanic White (NHW) and non-Hispanic Black (NHB) older adults.

Research Design and Methods

We used data from the 2010–2016 waves of the Health and Retirement Study with participants aged 65 and older in 2010. We employed growth curve modeling to estimate associations among race, cSES, and region of childhood residence, as well as their interactions, and cognitive performance at baseline and over time.

Results

Identifying as NHB, residing in the South, and having lower cSES each were associated with poorer later-life cognition at baseline. Childhood residence in the South was an especially strong risk factor for poorer cognition among NHBs. Among NHWs, higher cSES was associated with better baseline cognitive performance, especially among those from the South. NHBs from the South demonstrated a small advantage of higher cSES, but regardless of cSES, NHBs from the South had lower levels of baseline cognitive scores compared to all other subgroups. We observed steeper declines in cognitive performance over the 6-year study period among participants who lived in the South as children.

Discussion and Implications

Our findings suggest that intersectional social positions across race, cSES, and region of childhood residence primarily influence baseline cognition in later life. Results implicate the importance of attention to multiple life-course social positions in the context of racism within social policies and other initiatives to promote equity in later-life brain health.
Peach fruit PpNAC1 activates PpFAD3-1 transcription to provide ω-3 fatty acids for the synthesis of short-chain flavor volatiles
Authors: Jin Zhengnan , Wang Jiaojiao , Cao Xiangmei , Wei Chunyan , Kuang Jianfei , Chen Kunsong , Zhang Bo
Published: April 2022

Volatile organic compounds (VOCs) derived from fatty acids are major contributors to fruit flavor and affect human preferences. The ω-3 fatty acid linolenic acid 3 (18:3) serves as an important precursor for synthesis of (E)-2-hexenal and (Z)-3-hexenol. These short-chain C6 VOCs provide unique fresh notes in multiple fruit species. Metabolic engineering to improve fruit aroma requires knowledge of the regulation of fatty acid-derived VOCs. Here, we determined that ripe fruit-specific expression of PpFAD3-1 contributes to 18:3 synthesis in peach fruit. However, no significant increases in (E)-2-hexenal and (Z)-3-hexenol were detected after overexpressing PpFAD3-1. Interestingly, overexpressing the PpNAC1 transcription factor increased the content of 18:3 and enhanced the production of its derived volatiles. Moreover, induced expression of genes responsible for downstream VOC synthesis was observed for transgenic tomato fruit overexpressing PpNAC1, but not for transgenic fruit overexpressing PpFAD3-1. Electrophoretic mobility shift and ChIP-Seq assays showed that PpNAC1 activated PpFAD3-1 expression via binding to its promoter. Therefore, PpNAC1 plays an important role in modulating fatty acid flux to produce fruit flavor-related VOCs. In addition to PpNAC1, PpFAD3-1 expression was also associated with epigenetic modifications during peach fruit ripening. Taken together, our results provide new insights into the molecular mechanisms regulating biosynthesis of fatty acid and short-chain VOCs in fruit.
Is Salt at Fault? Dietary Salt Consumption and Inflammatory Bowel Disease
Authors: Kuang Rebecca , O’Keefe Stephen J D , Ramos del Aguila de Rivers Claudia , Koutroumpakis Filippos , Binion David G
Published: April 2022

Epidemiological trends have led to a growing consensus that diet plays a central role in the etiopathogenesis of inflammatory bowel diseases (IBD). A Western diet high in ultra-processed foods has been associated with an increased prevalence of IBD worldwide. Much attention has focused on components of the Western diet, including the high fat content, lack of fiber, added sugars, and use of additives, such as carrageenan and other emulsifiers. Less attention has been paid to the impact of high salt intake, an integral component of ultra-processed foods, which has increased dramatically in the US diet over the past 50 years. We review a growing body of literature linking the rise in dietary salt intake with the epidemiology of IBD, increased consumption of salt as a component of ultra-processed foods, high salt intake and imbalances in immune homeostasis, the effects of a high-salt diet on other inflammatory disorders, salt’s impact on animal colitis models, salt as an underrecognized component in diet modification–induced remission of IBD, and directions for future investigation.
Debt Overhang, Rollover Risk, and Corporate Investment: Evidence from the European Crisis
Authors: Kalemli-Özcan Şebnem , Laeven Luc , Moreno David
Published: April 2022

We quantify the role of financial leverage behind the sluggish post-crisis investment performance of European firms. We use a cross-country firm-bank matched database to identify separate roles for firm leverage, bank balance sheet weaknesses arising from sovereign risk, and aggregate demand conditions. We find that firms entering the crisis with higher debt levels reduce their investment more after the crisis. This negative effect is stronger for firms holding short-term debt in countries whose banks are weak due to sovereign stress, consistent with rollover risk being an important channel influencing investment. The negative effect of firm leverage on investment is also persistent for several years after the shock in the countries with sovereign stress. The corporate leverage channel can explain about 20% of the cumulative decline in aggregate private sector investment over the crisis period.
Reevaluation of the Role of Blocked Oropsylla hirsuta Prairie Dog Fleas (Siphonaptera: Ceratophyllidae) in Yersinia pestis (Enterobacterales: Enterobacteriaceae) Transmission
Authors: Miarinjara Adélaïde , Eads David A , Bland David M , Matchett Marc R , Biggins Dean E , Hinnebusch B Joseph
Published: April 2022

Prairie dogs in the western United States experience periodic epizootics of plague, caused by the flea-borne bacterial pathogen Yersinia pestis. An early study indicated that Oropsylla hirsuta (Baker), often the most abundant prairie dog flea vector of plague, seldom transmits Y. pestis by the classic blocked flea mechanism. More recently, an alternative early-phase mode of transmission has been proposed as the driving force behind prairie dog epizootics. In this study, using the same flea infection protocol used previously to evaluate early-phase transmission, we assessed the vector competence of O. hirsuta for both modes of transmission. Proventricular blockage was evident during the first two weeks after infection and transmission during this time was at least as efficient as early-phase transmission 2 d after infection. Thus, both modes of transmission likely contribute to plague epizootics in prairie dogs.
Rotating neutron stars without light cylinders
Authors: Lyutikov Maxim , Sharma Praveen
Published: April 2022

We find a class of twisted and differentially rotating neutron star magnetospheres that do not have a light cylinder, generate no wind, and thus do not spin-down. The magnetosphere is composed of embedded differentially rotating flux surfaces, with the angular velocity decreasing as Ω ∝ 1/r (equivalently, becoming smaller at the foot-points closer to the axis of rotation). For each given North–South self-similar twist profile there is a set of self-similar angular velocity profiles (limited from above) with a ‘smooth’, dipolar-like magnetic field structure extending to infinity. For spin parameters larger than some critical value, the light cylinder appears, magnetosphere opens up, and the wind is generated.
Transient two-pole accretion in the polar V496 UMa
Authors: Kennedy M R , Littlefield C , Garnavich P M
Published: April 2022

We report XMM–Newton and TESS observations of V496 UMa, an AM Herculis-type cataclysmic variable. The XMM–Newton observation reveals that at times, two poles on the white dwarf accrete simultaneously, but accretion on to the secondary magnetic pole is erratic and can nearly cease in less than one binary orbit (1.5 h). Modelling of the X-ray spectrum during the primary maximum reveals no change in the accretion structures on to the primary pole when accretion on to the secondary pole is disrupted, suggesting that the disruption of accretion on to the secondary pole may be caused by mass-transfer variations from the donor star. The TESS observation, which spanned eight weeks at a 2-min cadence, shows a stable, double-humped orbital modulation due to cyclotron emission from the post-shock region, while the observed times of maximum light show a slow systematic drift that does not correlate with the system’s overall brightness.