bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of coupled neural oscillations using near-periodic inputs
Authors: Toth Kaitlyn , Wilson Dan
Published: March 2022

Deep brain stimulation (DBS) is a commonly used treatment for medication resistant Parkinson’s disease and is an emerging treatment for other neurological disorders. More recently, phase-specific adaptive DBS (aDBS), whereby the application of stimulation is locked to a particular phase of tremor, has been proposed as a strategy to improve therapeutic efficacy and decrease side effects. In this work, in the context of these phase-specific aDBS strategies, we investigate the dynamical behavior of large populations of coupled neurons in response to near-periodic stimulation, namely, stimulation that is periodic except for a slowly changing amplitude and phase offset that can be used to coordinate the timing of applied input with a specified phase of model oscillations. Using an adaptive phase-amplitude reduction strategy, we illustrate that for a large population of oscillatory neurons, the temporal evolution of the associated phase distribution in response to near-periodic forcing can be captured using a reduced order model with four state variables. Subsequently, we devise and validate a closed-loop control strategy to disrupt synchronization caused by coupling. Additionally, we identify strategies for implementing the proposed control strategy in situations where underlying model equations are unavailable by estimating the necessary terms of the reduced order equations in real-time from observables.
Coupling, lifetimes, and “strong coupling” maps for single molecules at plasmonic interfaces
Authors: Mondal Monosij , Ochoa Maicol A. , Sukharev Maxim , Nitzan Abraham
Published: March 2022

The interaction between excited states of a molecule and excited states of a metal nanostructure (e.g., plasmons) leads to hybrid states with modified optical properties. When plasmon resonance is swept through molecular transition frequency, an avoided crossing may be observed, which is often regarded as a signature of strong coupling between plasmons and molecules. Such strong coupling is expected to be realized when 2|⟨U⟩|/ℏΓ > 1, where ⟨U⟩ and Γ are the molecule–plasmon coupling and the spectral width of the optical transition, respectively. Because both ⟨U⟩ and Γ strongly increase with decreasing distance between a molecule and a plasmonic structure, it is not obvious that this condition can be satisfied for any molecule–metal surface distance. In this work, we investigate the behavior of ⟨U⟩ and Γ for several geometries. Surprisingly, we find that if the only contributions to Γ are lifetime broadenings associated with the radiative and nonradiative relaxation of a single molecular vibronic transition, including effects on molecular radiative and nonradiative lifetimes induced by the metal, the criterion 2|⟨U⟩|/ℏΓ > 1 is easily satisfied by many configurations irrespective of the metal–molecule distance. This implies that the Rabi splitting can be observed in such structures if other sources of broadening are suppressed. Additionally, when the molecule–metal surface distance is varied keeping all other molecular and metal parameters constant, this behavior is mitigated due to the spectral shift associated with the same molecule–plasmon interaction, making the observation of Rabi splitting more challenging.
Plasmon-induced excitation energy transfer in silver nanoparticle dimers: A real-time TDDFTB investigation
Authors: Liu Zhen , Oviedo M. Belén , Wong Bryan M. , Aikens Christine M.
Published: March 2022

Using real-time quantum dynamics calculations, we perform theoretical investigations of light-induced interactions and electronic excitation transfer in a silver nanoparticle dimer. Real-time time-dependent density functional tight-binding (RT-TDDFTB) calculations provide details of the quantum dynamical processes at an electronic/atomistic level with attosecond resolution. The computational efficiency of RT-TDDFTB allows us to examine electronic dynamics up to picosecond time scales. With time scales varying over six orders of magnitude, we provide insight into interactions between the nanoparticle and laser and between nanoparticles. Our results show that the coupling between nanoparticle monomers is dependent on the separation distance between the nanoparticles in the dimer. As the interparticle distance is varied, the dipole–dipole interactions and electronic excitation transfer mechanisms are markedly different. At large distances (from 50 to 20 Å), the energy transfer from NP1 to NP2 becomes more efficient as the interparticle distance decreases. The total dipole moment of the Ag14 nanoparticle dimer increases linearly at an interparticle distance of 20 Å and reaches its maximum after 1.2 ps. The electronic excitation transfer is also the most efficient at 20 Å. At short distances, back-transfer effects reduce the ability of the dimer and NP1 to accept energy from the incident electric field. We attribute the distance-dependent features of the nanoparticle dimer to the beating between the laser acting on NP1 and the back transfer from NP2 to NP1.
Ab initio Cu alloy design for high-gradient accelerating structures
Authors: Wang Gaoxue , Simakov Evgenya I. , Perez Danny
Published: March 2022

Operation of normal conducting accelerator structures at high accelerating gradients is beneficial for many accelerator applications in basic science, industry, medicine, and National Security. RF breakdown is the major factor that limits the achievable accelerating gradients. Previous experiments on copper (Cu) have demonstrated that RF breakdown probability can be significantly decreased by hardening the material and alloying Cu with solutes such as silver (Ag). In this paper, we propose a figure-of-merit (FOM) that characterizes the ability of Cu alloys to withstand high-gradients. The FOM represents a trade-off between hardening through solid solution strengthening and the additional thermal stress induced by incremental RF pulse heating resulting from changes in electronic properties induced by alloying. We performed high-throughput ab initio calculations and computed the FOM for a large number of binary Cu alloys. Several promising candidate alloys for high-gradient accelerating structures were identified, such as CuAg, CuCd, CuHg, CuAu, CuIn, and CuMg. CuAg alloys have previously exhibited low RF breakdown rates in experiments. The results provide guidance for selecting alloys for the future high-gradient normal conducting accelerating structures operating at very high gradients.
A new digital single-axis fluxgate magnetometer according to the cobalt-based amorphous effects
Authors: Yang Ruiping , Wang Hongpeng , Liu Huan , Luo Wang , Ge Jian , Dong Haobin
Published: March 2022

Fluxgate sensors are currently widely used for weak magnetic field measurement because of their relatively great performance, such as resolution, power consumption, and measurement of vector magnetic fields directly. Since the analog fluxgate sensor has some drawbacks, e.g., it would be influenced by the noise of the analog circuit. Hence, in recent years, the analog circuit is gradually inclined to be realized by digital processing in which the software parameter adjustment is employed to replace the analog components, which can greatly improve the flexibility of the design. This paper proposes a digital single-axis fluxgate sensor according to the cobalt-based amorphous effect. To be specific, the analog signal output by the fluxgate is sampled directly by an analog-to-digital converter to obtain the signal waveform in digital form after amplification. The demodulation, filtering, and integration of the signal are all solved by mathematical algorithms. Based on the working principle of the fluxgate sensor, the selection of the magnetic core material and coil winding method of the fluxgate sensor probe is introduced in detail. The design and function of the excitation circuit and preamplifier circuit, as well as the specific realization of digital signal processing, are described. Finally, the performance test of the digital fluxgate sensor was performed under laboratory conditions, and the magnetic anomaly detection comparison experiment was performed outdoors with commercial fluxgate sensors. To sum up, the linearity of the digital single-axis fluxgate sensor is better than 1 × 10−5, and the root mean square noise value is below 0.1 nT. At the same time, it has good magnetic field tracking performance and is extremely sensitive to the magnetic field of the measurement area.
Strong four-phonon scattering in monolayer and hydrogenated bilayer BAs with horizontal mirror symmetry
Authors: Yu Cuiqian , Hu Yanxiao , He Jia , Lu Shuang , Li Dengfeng , Chen Jie
Published: March 2022

Recently, the important role of high-order anharmonic phonon–phonon interactions has been revealed in several materials, such as cubic boron arsenide (BAs), in which the wide phononic energy gap is found to be a critical factor causing the importance of four-phonon scattering. In this work, by solving the Boltzmann transport equation, we show that the four-phonon scattering has a significant impact on the thermal transport in honeycomb structured monolayer BAs (m-BAs) and its hydrogenated bilayer counterparts (bi-BAs). The lattice thermal conductivity (κL) values of all these structures are reduced after considering four-phonon scattering. Particularly, a huge drop in κL as large as 80% is observed for m-BAs compared to the case without four-phonon scattering, which is mainly caused by the suppression of phonon lifetimes. More interestingly, as opposed to the case of graphene, κL of m-BAs is abnormally lower than its bi-BAs counterparts, which is attributed to the much larger phonon scattering rate in m-BAs compared to that in bi-BAs. By further comparing BAs sheets with and without horizontal mirror symmetry, it is found that the contribution of flexural acoustic phonon exhibits most significant reduction in both mi-BAs and bi-BAs with horizontal mirror symmetry after including four-phonon scattering. This work provides physical understanding of the role of mirror symmetry and high-order phonon scattering on the thermal transport in two-dimensional materials.
General embedded cluster protocol for accurate modeling of oxygen vacancies in metal-oxides
Authors: Shi Benjamin X. , Kapil Venkat , Zen Andrea , Chen Ji , Alavi Ali , Michaelides Angelos
Published: March 2022

The O vacancy (Ov) formation energy, EOv, is an important property of a metal-oxide, governing its performance in applications such as fuel cells or heterogeneous catalysis. These defects are routinely studied with density functional theory (DFT). However, it is well-recognized that standard DFT formulations (e.g., the generalized gradient approximation) are insufficient for modeling the Ov, requiring higher levels of theory. The embedded cluster method offers a promising approach to compute EOv accurately, giving access to all electronic structure methods. Central to this approach is the construction of quantum(-mechanically treated) clusters placed within suitable embedding environments. Unfortunately, current approaches to constructing the quantum clusters either require large system sizes, preventing application of high-level methods, or require significant manual input, preventing investigations of multiple systems simultaneously. In this work, we present a systematic and general quantum cluster design protocol that can determine small converged quantum clusters for studying the Ov in metal-oxides with accurate methods, such as local coupled cluster with single, double, and perturbative triple excitations. We apply this protocol to study the Ov in the bulk and surface planes of rutile TiO2 and rock salt MgO, producing the first accurate and well-converged determinations of EOv with this method. These reference values are used to benchmark exchange–correlation functionals in DFT, and we find that all the studied functionals underestimate EOv, with the average error decreasing along the rungs of Jacob’s ladder. This protocol is automatable for high-throughput calculations and can be generalized to study other point defects or adsorbates.
Tripling of western US particulate pollution from wildfires in a warming climate
Authors: Xie Yuanyu , Lin Meiyun , Decharme Bertrand , Delire Christine , Horowitz Larry W. , Lawrence David M. , Li Fang , Séférian Roland
Published: March 2022

Significance

Record-setting fires in the western United States over the last decade caused severe air pollution, loss of human life, and property damage. Enhanced drought and increased biomass in a warmer climate may fuel larger and more frequent wildfires in the coming decades. Applying an empirical statistical model to fires projected by Earth System Models including climate–ecosystem–socioeconomic interactions, we show that fine particulate pollution over the US Pacific Northwest could double to triple during late summer to fall by the late 21st century under intermediate- and low-mitigation scenarios. The historic fires and resulting pollution extremes of 2017–2020 could occur every 3 to 5 y under 21st-century climate change, posing challenges for air quality management and threatening public health.
Shared in planta population and transcriptomic features of nonpathogenic members of endophytic phyllosphere microbiota
Authors: Velásquez André C. , Huguet-Tapia José C. , He Sheng Yang
Published: March 2022

Significance

Plants evolved in an environment colonized by a vast number of microbes, which collectively constitute the plant microbiota. The majority of microbiota taxa are nonpathogenic and may be beneficial to plants under certain ecological or environmental conditions. We conducted experiments to understand the features of long-term interactions of nonpathogenic microbiota members with plants. We found that a multiplication–death equilibrium explained the shared long-term static populations of nonpathogenic bacteria and that in planta bacterial transcriptomic signatures were characteristic of the stationary phase, a physiological state in which stress protection responses are induced. These results may have significant implications in understanding the bulk of “nonpathogenic” plant–microbiota interactions that occur in agricultural and natural ecosystems.
Optical sectioning of unlabeled samples using bright-field microscopy
Authors: Gutiérrez-Medina Braulio
Published: March 2022

The bright-field (BF) optical microscope is a traditional bioimaging tool that has been recently tested for depth discrimination during evaluation of specimen morphology; however, existing approaches require dedicated instrumentation or extensive computer modeling. We report a direct method for three-dimensional (3D) imaging in BF microscopy, applicable to label-free samples, where we use Köhler illumination in the coherent regime and conventional digital image processing filters to achieve optical sectioning. By visualizing fungal, animal tissue, and plant samples and comparing with light-sheet fluorescence microscopy imaging, we demonstrate the accuracy and applicability of the method, showing how the standard microscope is an effective 3D imaging device.
Hydroxyapatite nanoparticles promote mitochondrial-based pyroptosis via activating calcium homeostasis and redox imbalance in vascular smooth muscle cells
Authors: Xia Yubin , Li Bohou , Zhang Fengxia , Wu Qiong , Wen Sichun , Jiang Nan , Liu Ding , Huang Cong , Liu Shuangxin
Published: March 2022

Hydroxyapatite nanoparticles (HAP) have been widely used in various fields because of their natural biological origin and functional properties. The emerging evidence on their toxicities has attracted research interest. HAP-induced vascular smooth muscle cell (VSMC) damage is a key step in vascular calcification (VC), particularly in patients with chronic kidney disease. However, the injury effects and mechanism of action of HAP on VSMCs have not been extensively investigated. This study comprehensively characterized commercially available HAP and investigated its adverse biological effects in cultured A7R5 cells. In vitro experiments revealed that internalized HAP was localized in lysosomes, followed by the release of Ca2+ owing to the low pH microenvironment. Upon Ca2+ homeostasis, Ca2+ enters the mitochondria, leading to the simultaneous generation of reactive oxygen species (ROS). ROS subsequently attack mitochondrial transmembrane potentials, promote mitochondrial ROS production, and oxidize mitochondrial DNA (Ox-mtDNA). Mitochondrial permeability-transition pores open, followed by the release of more Ox-mtDNA from the mitochondria into the cytosol due to the redox imbalance. This activates NLRP3/caspase-1/gasdermin D-dependent pyroptosis and finally excretes inflammatory factors to induce VC; an antioxidant could rescue this process. It has been suggested that HAP could induce an imbalance in intracellular Ca2+ homeostasis in A7R5 cells, followed by the promotion of mitochondrial dysfunction and cell pyroptosis, finally enhancing VC. To detect the in vivo toxicity of HAP, mice were treated with Cy7-labelled HAP NPs for 24 h. In vivo results also demonstrated that HAP accumulated in the kidneys, accompined with increased Ca concentration, upregulated oxidative stress-related factor and kidney damage. Overall, our research elucidates the mechanism of calcium homeostasis and redox imbalance, providing insights into the prevention of HAP-induced cell death.
On electric field measurements based on intensity ratio of 1
−
and 2
+
systems of nitrogen in discharges with high specific deposited energy
Authors: Lepikhin N D , Popov N A , Starikovskaia S M
Published: March 2022

Analysis of optical emission spectroscopy (OES) in application to the measurements of the electric field has been performed for the nanosecond capillary discharge in molecular nitrogen at moderate gas pressure at high specific energy deposition. Significant discrepancy between results of electric field measurements by OES technique and capacitive probe measurements is demonstrated. Decay rates of excited species as well as rotation structure of corresponding optical transitions are used to identify possible population/depopulation channels of the

N

2

+

(

B

2

Σ

u

+

) and N2(C3Π
u
) states. Kinetic calculations taking into account additional quenching of the

N

2

+

(

B

2

Σ

u

+

) and N2(C3Π
u
) states by electrons, additional population of

N

2

+

(

B

2

Σ

u

+

) by electron impact from the ground state of the molecular ion and by a reaction of excited N2(

A

3

Σ

u

+

) with the ground state of

N

2

+

describes adequately behavior of experimentally measured emission of both considered systems.
Physics of plasma jets and interaction with surfaces: review on modelling and experiments
Authors: Viegas Pedro , Slikboer Elmar , Bonaventura Zdenek , Guaitella Olivier , Sobota Ana , Bourdon Anne
Published: March 2022

Plasma jets are sources of repetitive and stable ionization waves, meant for applications where they interact with surfaces of different characteristics. As such, plasma jets provide an ideal testbed for the study of transient reproducible streamer discharge dynamics, particularly in inhomogeneous gaseous mixtures, and of plasma–surface interactions. This topical review addresses the physics of plasma jets and their interactions with surfaces through a pedagogical approach. The state-of-the-art of numerical models and diagnostic techniques to describe helium jets is presented, along with the benchmarking of different experimental measurements in literature and recent efforts for direct comparisons between simulations and measurements. This exposure is focussed on the most fundamental physical quantities determining discharge dynamics, such as the electric field, the mean electron energy and the electron number density, as well as the charging of targets. The physics of plasma jets is described for jet systems of increasing complexity, showing the effect of the different components (tube, electrodes, gas mixing in the plume, target) of the jet system on discharge dynamics. Focussing on coaxial helium kHz plasma jets powered by rectangular pulses of applied voltage, physical phenomena imposed by different targets on the discharge, such as discharge acceleration, surface spreading, the return stroke and the charge relaxation event, are explained and reviewed. Finally, open questions and perspectives for the physics of plasma jets and interactions with surfaces are outlined.
A topological flux trap: Majorana bound states at screw dislocations
Authors: Rex Stefan , Willa Roland
Published: March 2022

The engineering of non-trivial topology in superconducting heterostructures is a very challenging task. Reducing the number of components in the system would facilitate the creation of the long-sought Majorana bound states. Here, we explore a route toward emergent topology in a trivial superconductor without a need for other proximitized materials. Specifically, we show that a vortex hosting an even number of flux quanta is capable of forming a quasi-one-dimensional topological sub-system that can be mapped to the Kitaev wire, if the vortex is trapped at a screw dislocation. This crystallographic defect breaks inversion symmetry and thereby threads a local spin–orbit coupling through the superconductor. The vortex-dislocation pair in the otherwise trivial bulk can harbor a pair of Majorana bound states located at the two surface terminations. We explain the topological transition in terms of a band inversion in the Caroli-de Gennes-Matricon vortex bound states and discuss favorable material parameters.
The canonical ring of a stacky curve
Authors: Voight John , Zureick-Brown David
Published: March 2022

Generalizing the classical theorems of Max Noether and Petri, we describe generators and relations for the canonical ring of a stacky curve, including an explicit Gröbner basis. We work in a general algebro-geometric context and treat log canonical and spin canonical rings as well. As an application, we give an explicit presentation for graded rings of modular forms arising from finite-area quotients of the upper half-plane by Fuchsian groups.
Systematically mapping gray matter abnormal patterns in drug-naïve first-episode schizophrenia from childhood to adolescence
Authors: Fan Yun-Shuang , Xu Yong , Li Qiang , Chen Yuyan , Guo Xiaonan , Yang Siqi , Guo Jing , Sheng Wei , Wang Chong , Gao Qing , Chen Huafu
Published: March 2022

Background

Schizophrenia originates early in neurodevelopment, underscoring the need to elaborate on anomalies in the still maturing brain of early-onset schizophrenia (EOS).

Methods

Gray matter (GM) volumes were evaluated in 94 antipsychotic-naïve first-episode EOS patients and 100 typically developing (TD) controls. The anatomical profiles of changing GM deficits in EOS were detected using 2-way analyses of variance with diagnosis and age as factors, and its timing was further charted using stage-specific group comparisons. Interregional relationships of GM alterations were established using structural covariance network analyses.

Results

Antagonistic interaction results suggested dynamic GM abnormalities of the left fusiform gyrus, inferior occipital gyrus, and lingual gyrus in EOS. These regions comprise a dominating part of the ventral stream, a ventral occipitotemporal (vOT) network engaged in early social information processing. GM abnormalities were mainly located in the vOT regions in childhood-onset patients, whereas in the rostral prefrontal cortex (rPFC) in adolescent-onset patients. Moreover, compared with TD controls, patients’ GM synchronization with the ventral stream was disrupted in widespread high-order social perception regions including the rPFC and salience network.

Conclusions

The current findings reveal age-related anatomical abnormalities of the social perception system in pediatric patients with schizophrenia.
Adherence Measured Using Electronic Dose Monitoring is Associated with Emergent Antiretroviral Resistance and Poor Outcomes in People with Human Immunodeficiency Virus/AIDS and Multidrug-Resistant Tuberculosis
Authors: Bateman Mark , Wolf Allison , Chimukangara Benjamin , Brust James C M , Lessells Richard , Amico Rivet , Boodhram Resha , Singh Nalini , Orrell Catherine , Friedland Gerald , Naidoo Kogieleum , Padayatchi Nesri , O’Donnell Max R
Published: March 2022

Background

Medication adherence is known to challenge treatment of human immunodeficiency virus (HIV)/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that adherence using electronic dose monitoring (EDM) would identify an antiretroviral therapy (ART) adherence threshold for emergent ART resistance and predict treatment outcomes in patients with MDR-TB and HIV on ART and bedaquiline-containing TB regimens.

Methods

A prospective cohort of adults with MDR-TB and HIV on ART and initiating MDR-TB treatment with bedaquiline were enrolled at a public hospital in KwaZulu-Natal, South Africa (PRAXIS Study). Participants received separate EDM devices that measure adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over 6 months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline and 2 and 6 months on samples with HIV RNA ≥1000 copies/mL.

Results

From November 2016 through February 2018, 198 persons with MDR-TB and HIV were enrolled and followed (median, 17.2 months; interquartile range, 12.2–19.6). Eleven percent had baseline ART resistance mutations, and 7.5% developed emergent ART resistance at 6 months. ART adherence was independently associated with ART resistance and mortality. Modeling identified a significant (P < .001), linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold.

Conclusions

Our findings highlight the need for ART resistance testing, especially in patients with MDR-TB and HIV, which is currently not the standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality.

Clinical Trials Registration

NCT03162107.
The impact of digital interventions on antimicrobial stewardship in hospitals: a qualitative synthesis of systematic reviews
Authors: Van Dort Bethany A , Penm Jonathan , Ritchie Angus , Baysari Melissa T
Published: March 2022

Background

Antimicrobial stewardship (AMS) programmes in hospitals support optimal antimicrobial use by utilizing strategies such as restriction policies and education. Several systematic reviews on digital interventions supporting AMS have been conducted but they have focused on specific interventions and outcomes.

Objectives

To provide a systematic overview and synthesis of evidence on the effectiveness of digital interventions to improve antimicrobial prescribing and monitoring in hospitals.

Methods

Multiple databases were searched from 2010 onwards. Review papers were eligible if they included studies that examined the effectiveness of AMS digital interventions in an inpatient hospital setting. Papers were excluded if they were not systematic reviews, were limited to a paediatric setting, or were not in English.

Results

Eight systematic reviews were included for data extraction. A large number of digital interventions were evaluated, with a strong focus on clinical decision support. Due to the heterogeneity of the interventions and outcome measures, a meta-analysis could not be performed. The majority of reviews reported that digital interventions reduced antimicrobial use and improved antimicrobial appropriateness. The impact of digital interventions on clinical outcomes was inconsistent.

Conclusions

Digital interventions reduce antimicrobial use and improve antimicrobial appropriateness in hospitals, but no firm conclusions can be drawn about the degree to which different types of digital interventions achieve these outcomes. Evaluation of sociotechnical aspects of digital intervention implementation is limited, despite the critical role that user acceptance, uptake and feasibility play in ensuring improvements in AMS are achieved with digital health.
Prognostic value of the Kyoto Prognostic Index in higher-risk diffuse large B-cell lymphomas treated by upfront autologous stem cell transplantation in JCOG0908 trial
Authors: Kobayashi Tsutomu , Yamamoto Kazuhito , Kagami Yoshitoyo , Machida Ryunosuke , Miyazaki Kana , Nakamura Shigeo , Kuroda Junya , Maruyama Dai , Nagai Hirokazu
Published: March 2022

Background

There is currently no standard prognostic model optimized for the patients with diffuse large B-cell lymphoma (DLBCL) treated with upfront intensive immunochemotherapy including autologous stem cell transplantation (ASCT). The Kyoto Prognostic Index (KPI) has been proposed as a novel prognostic model for DLBCL, which can accurately identify especially high-risk patients. In this study, we investigated the prognostic value of the KPI in JCOG0908 trial in which higher-risk DLBCL patients defined by the conventional International Prognostic Index (IPI) were treated with upfront high dose therapy followed by ASCT.

Methods

Fifty-eight patients with DLBCL, not otherwise specified, enrolled in JCOG0908 and confirmed by the central pathological review were analyzed. The Kaplan–Meier method was used to estimate the probabilities of overall survival (OS) and progression-free survival (PFS). We compared the discrimination ability of the KPI with that of the IPI.

Results

According to KPI, 3-year OS and PFS rates were 86.7% and 76.7% in low-intermediate, 73.3% and 60.0% in high-intermediate, and 61.5% and 46.2% in high-risk group. According to IPI, 3-year OS and PFS rates were 75.0% and 50.0% in low-intermediate, 82.9% and 74.3% in high-intermediate, and 63.6% and 54.5% in high-risk group. The concordance-indices of KPI and IPI were 0.642 and 0.580 for OS and 0.606 and 0.606 for PFS.

Conclusions

The KPI may be a suitable predictor of outcome than the IPI for patients with higher-risk DLBCL treated with upfront intensive immunochemotherapy including ASCT.
Management of breast cancer in older patients
Authors: Sawaki Masataka , Shimomura Akihiko , Shien Tadahiko , Iwata Hiroji
Published: March 2022

Japanese women have the highest life expectancy in the world and breast cancer is the most prevalent cancer among them. However, little data are available to support the evidence-based clinical management due to the fact that older adults are commonly excluded from most clinical trials. In Japan the rate of other cause of death in older patient was about a half, then we should consider whether or not breast cancer may affect the patient’s life expectancy to avoid either overtreatment or undertreatment. Although management principles in older patients may be similar with those of younger age, these differences would be caused by relatively short life expectancy, some comorbidity, drug interactions and low functional status. Then, their treatment needs to be individualized. To this end, employing a comprehensive geriatric assessment may be advantageous, which enables to evaluate patient vulnerability from several different aspects, to predict adverse events of chemotherapy and to identify geriatric problems in advance so that extra support and modified treatment can be provided. Before treatment we should assess the patient’s goals and values regarding the management of the cancer, especially on balancing survival benefit with immediate quality of life impairment due to anti-cancer therapy. In Japan Clinical Oncology Group (JCOG) , a randomized controlled trial for older patients with advanced stage HER2-positive breast cancer is ongoing as an inferiority design including geriatric assessment (JCOG1607, HARB TEA study). Best practice, current management and how to approach decision making in older patients with breast cancer are summarized.
Using old and new approaches: determining physical properties of brown dwarfs with empirical relations and machine learning models
Authors: Feeser S Jean , Best William M J
Published: March 2022

We investigate applications of machine learning models to directly infer physical properties of brown dwarfs from their photometry and spectra using The Cannon. We demonstrate that absolute magnitudes, spectral types, and spectral indices can be determined from low-resolution SpeX prism spectra of L and T dwarfs without trigonometric parallax measurements and with precisions competitive with commonly used methods. For T dwarfs with sufficiently precise spectra and photometry, bolometric luminosities and effective temperatures can be determined at precisions comparable to methods that use polynomial relations as a function of absolute magnitudes. We also provide new and updated polynomial relations for absolute magnitudes as a function of spectral types L0–T8 in 14 bands spanning Pan-STARRS rP1 to AllWISE W3, using a volume-limited sample of 256 brown dwarfs defined entirely by parallaxes. These include the first relations for brown dwarfs using Pan-STARRS1 photometry and the first for several infrared bands using a volume-limited sample. We find that our novel method with The Cannon can infer absolute magnitudes with equal or smaller uncertainties than the polynomial relations that depend on trigonometric parallax measurements.
Racial Differences in Patients Undergoing Anterior Cervical Discectomy and Fusion
Authors: Woodard Thaddeus K. , Cortese Brian D. , Gupta Sachin , Mohanty Sarthak , Casper David S. , Saifi Comron
Published: March 2022

Study Design:

This was a retrospective chart review.

Objective:

The objective of this study was to examine disparities within patients undergoing anterior cervical discectomy and fusion (ACDF) at a multi-site tertiary referral center with specific focus on factors related to length of stay (LOS).

Summary of Background Data:

There are previously described racial disparities in spinal surgery outcomes and quality metrics.

Methods:

A total of 278 consecutive patients undergoing ACDF by 8 different surgeons over a 5-year period were identified retrospectively. Demographic data, including age at time of surgery, sex, smoking status, and self-identified race [White or African American (AA)], as well as surgical data and postoperative course were recorded. Preoperative health status was recorded, and comorbidities were scored by the Charlson Comorbidity Index. Univariable and multivariable linear regression models were employed to quantify the degree to which a patient’s LOS was related to their self-identified race, demographics, and perioperative clinical data.

Results:

Of the 278 patients who received an ACDF, 71.6% (199) self-identified as White and 28.4% (79) identified as AA. AA patients were more likely to have an ACDF due to myelopathy, while White patients were more likely to have an ACDF due to radiculopathy (P=0.001). AA patients had longer LOS by an average of half a day (P=0.001) and experienced a larger percentage of extended stays (P=0.002). AA patients experienced longer overall operation times on average (P=0.001) across all different levels of fusion. AA race was not an independent driver of LOS (β=0.186; P=0.246).

Conclusions:

As hypothesized, and consistent with previous literature on racial surgical disparities, AA race was associated with increased LOS, increased operative times, and increased indication of myelopathy in this study. Additional research is necessary to evaluate the underlying social determinants of health and other factors that may contribute to this study’s results.

Level of Evidence:

Level III.
Microscopic Anterior Cervical Discectomy and Fusion Versus Posterior Percutaneous Endoscopic Cervical Keyhole Foraminotomy for Single-level Unilateral Cervical Radiculopathy
Authors: Guo Linlin , Wang Jiajing , Zhao Zhen , Li Jing , Zhao Hongyang , Gao Yong , Chen Chao
Published: March 2022

Study Design:

A systematic review and meta-analysis.

Objective:

The objective of this study was to compare the safety of microscopic anterior cervical discectomy and fusion (MI-ACDF) and posterior percutaneous endoscopic keyhole foraminotomy (PPEKF) in patients diagnosed with single-level unilateral cervical radiculopathy.

Summary of Background Data:

After conservative treatment, the symptoms will be relieved in about 90% of cervical radiculopathy patients. For the other one tenth of patients, surgical treatment is needed. The overall complication rate of MI-ACDF and PPEKF ranges from 0% to 25%, and the reoperation rate ranges from 0% to 20%.

Materials and Methods:

Electronic retrieval of studies from PubMed, Embase, and Cochrane Library was performed to identify comparative or single-arm studies on MI-ACDF and PPEKF. A total of 24 studies were included in our meta-analysis by screening according to the inclusion and exclusion criteria. After data extraction and quality assessment of the included studies, a meta-analysis was performed by using the R software. The pooled incidences of efficient rate, total complication rate, and reoperation rate were calculated.

Results:

A total of 24 studies with 1345 patients (MI-ACDF: 644, PPEKF: 701) were identified. There was no significantly statistical difference in pooled patient effective rate (MI-ACDF: 94.3% vs. PPEKF: 93.3%, P=0.625), total complication rate (MI-ACDF: 7.1% vs. PPEKF: 4.7%, P=0.198), and reoperation rate (MI-ACDF: 1.8% vs. PPEKF: 1.1%, P=0.312). However, the common complications of the 2 procedures were different. The most common complications of MI-ACDF were dysphagia and vertebral body sinking, whereas the most common complication of PPEKF was nerve root palsy.

Conclusions:

Both MI-ACDF and PPEKF can provide a relatively safe and reliable treatment for single-level unilateral cervical radiculopathy. The 2 techniques are not significantly different in terms of effective rate, total complication rate, and reoperation rate.
Early Plasma Nuclear DNA, Mitochondrial DNA, and Nucleosome Concentrations Are Associated With Acute Kidney Injury in Critically Ill Trauma Patients
Authors: Faust Hilary E. , Oniyide Oluwatosin , Wang Yiyue , Forker Caitlin M. , Dunn Thomas , Yang Wei , Lanken Paul N. , Sims Carrie A. , Yehya Nadir , Christie Jason D. , Meyer Nuala J. , Reilly John P. , Mangalmurti Nilam S. , Shashaty Michael G. S.
Published: March 2022

OBJECTIVES:

Circulating nucleic acids, alone and in complex with histones as nucleosomes, have been proposed to link systemic inflammation and coagulation after trauma to acute kidney injury (AKI). We sought to determine the association of circulating nucleic acids measured at multiple time points after trauma with AKI risk.

DESIGN:

We conducted a prospective cohort study of trauma patients, collecting plasma on presentation and at 6, 12, 24, and 48 hours, defining AKI over the first 6 days by Kidney Disease Improving Global Outcomes serum creatinine and dialysis criteria. We determined kinetics of plasma mitochondrial DNA (mtDNA), nuclear DNA (nDNA), and nucleosome levels across time points and associations with AKI using multivariable linear mixed-effects models, adjusted for injury characteristics and blood transfusions. We evaluated the association of presentation nucleic acid damage-associated molecular patterns (DAMP) concentrations with subsequent AKI, adjusting for injury severity using multivariable logistic regression.

SETTING:

Academic level I trauma center.

PATIENTS:

Trauma patients (n = 55) requiring intensive care for greater than or equal to 24 hours after presentation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

AKI developed in 17 patients (31%), a median of 12.0 hours (interquartile range, 6.2–24.1 hr) after presentation. mtDNA demonstrated a time-varying association with AKI (p = 0.022, interaction with time point), with differences by AKI status not emerging until 24 hours (β = 0.97 [95% CI, 0.03–1.90] log copies/uL; p = 0.043). Patients who developed AKI had higher nDNA across all time points (overall β = 1.41 log copies/uL [0.86–1.95 log copies/uL]; p < 0.001), and presentation levels were significantly associated with subsequent AKI (odds ratio [OR], 2.55 [1.36–4.78] per log copy/uL; p = 0.003). Patients with AKI had higher nucleosome levels at presentation (β = 0.32 [0.00–0.63] arbitrary unit; p = 0.048), a difference that was more pronounced at 24 hours (β = 0.41 [0.06–0.76]; p = 0.021) and 48 hours (β = 0.71 [0.35–1.08]; p < 0.001) (p = 0.075, interaction with time point).

CONCLUSIONS:

Plasma nucleic acid DAMPs have distinct kinetics and associations with AKI in critically ill trauma patients. nDNA at presentation predicts subsequent AKI and may be amenable to targeted therapies in this population.
MYCOBACTERIUM ABSCESSUS SCLERAL BUCKLE INFECTION
Authors: Cai Sophie , Song Ailin , Borkar Durga S.
Published: March 2022

Purpose:

To report the successful management of a rare case of Mycobacterium abscessus scleral buckle infection.

Methods:

Case report.

Results:

A 63-year-old woman with a history of sarcoid anterior uveitis and macula-off retinal detachment repaired by scleral buckle and pars plana vitrectomy presented with eye pain, redness, and purulent drainage in the left eye. Slit-lamp examination showed superonasal scleral buckle exposure, purulent conjunctival discharge, corneal edema, nongranulomatous keratic precipitates, and anterior chamber cell and flare. The patient underwent urgent scleral buckle removal. Intraoperatively, an area of scleral thinning without perforation underneath the exposed buckle was discovered and covered with a scleral patch graft, and an amniotic membrane graft was used to cover an area of bare sclera with significant conjunctival scarring and retraction. Cultures grew M. abscessus panresistant except to amikacin. After 6 weeks of fortified amikacin drops and a long taper of topical steroid therapy for persistent postoperative anterior uveitis, the patient's symptoms resolved.

Conclusion:

Mycobacterium is an emerging causative agent of scleral buckle infections. Our report provides insights about the management of such cases.
Flavobacterium ammonificans sp. nov. and Flavobacterium ammoniigenes sp. nov., ammonifying bacteria isolated from surface river water
Authors: Watanabe Keiji , Kitamura Tatsumi , Ogata Yusuke , Shindo Chie , Suda Wataru
Published: March 2022

Three aerobic, Gram-stain-negative, non-motile, rod-shaped bacteria, designated as strains SHINM13T, GENT5T and GENT11 were isolated from surface river water (Saitama Prefecture, Japan). SHINM13T and GENT11 were positive for catalase, whereas GENT5T was negative. Phylogenetic analyses based on the 16S rRNA gene (1341 bp) or 40 marker gene (34,513 bp) sequences revealed that the strains formed distinct phylogenetic lineages within the genus

Flavobacterium

. The three strains shared 99.3–99.6 % 16S rRNA gene sequence similarity among each other. The average nucleotide identity by orthology (OrthoANI) and digital DNA–DNA hybridization (dDDH) values between strains SHINM13T and GENT11 were 96.56 and 82.1 %, respectively, and those between SHINM13T and GENT5T were 83.46 % and 52.9 %, respectively. The major cellular fatty acids were C15 : 1ω6c, iso-C15 : 0, iso-C15 : 1G, anteiso-C15 : 0 and iso-C15 : 0 3-OH. The major polar lipid was phosphatidylethanolamine. SHINM13T and GENT5T contained menaquinone-6 (MK-6) as the predominant respiratory quinone, and their DNA G+C contents were 34.4 and 35.1 mol%, respectively. Genome sequencing of the three isolates revealed a genome size of 2.26–2.40 Mbp. Furthermore, all three isolates converted dissolved organic nitrogen to ammonium during cell growth. On the basis of the results of phenotypic and phylogenetic analyses, strains SHINM13T and GENT11 and GENT5T represent two distinct novel species in the genus

Flavobacterium

, for which the names Flavobacterium ammonificans sp. nov. (type strain SHINM13T =JCM 34684T =NCIMB 15379T) and Flavobacterium ammoniigenes sp. nov. (type strain GENT5T =JCM 32249T=NCIMB 15380T) are proposed.
Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19
Authors: Mothes Ronja , Pascual-Reguant Anna , Koehler Ralf , Liebeskind Juliane , Liebheit Alina , Bauherr Sandy , Dittmayer Carsten , Laue Michael , von Manitius Regina , Elezkurtaj Sefer , Durek Pawel , Heinrich Frederik , Heinz Gitta Anne , Guerra Gabriela Maria , Obermayer Benedikt , Meinhardt Jenny , Ihlow Jana , Radke Josefine , Heppner Frank L. , Enghard Philipp , Stockmann Helena , Aschman Tom , Schneider Julia , Corman Victor , Sander Leif Erik , Mashreghi Mir-Farzin , Conrad Thomas , Hocke Andreas , Niesner Raluca A. , Radbruch Helena , Hauser Anja E.
Published: March 2022

Post-acute lung sequelae of COVID-19 are challenging many survivors across the world, yet the mechanisms behind are poorly understood. Our results delineate an inflammatory cascade of events occurring along disease progression within fibrovascular niches. It is initiated by endothelial dysfunction, followed by heme scavenging of CD163+ macrophages and production of CCL18. This chemokine synergizes with local CCL21 upregulation to influence the stromal composition favoring endothelial to mesenchymal transition. The local immune response is further modulated via recruitment of CCR7+ T cells into the expanding fibrovascular niche and imprinting an exhausted, T follicular helper–like phenotype in these cells. Eventually, this culminates in the formation of tertiary lymphoid structures, further perpetuating chronic inflammation. Thus, our work presents misdirected immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and leads to profound tissue repurposing and chronic inflammation.
High temperature increases centromere-mediated genome elimination frequency in Arabidopsis deficient in cenH3 or its assembly factor KNL2
Authors: Ahmadli Ulkar , Kalidass Manikandan , Khaitova Lucie Crhak , Fuchs Joerg , Cuacos Maria , Demidov Dmitri , Zuo Sheng , Pecinkova Jana , Mascher Martin , Ingouff Mathieu , Heckmann Stefan , Houben Andreas , Riha Karel , Lermontova Inna
Published: March 2022

Double haploid production is the most effective way of creating true-breeding lines in a single generation. In Arabidopsis, haploid induction via mutation of the centromere-specific histone H3 (cenH3) has been shown when outcrossed to wild-type. Here we report that a mutant of the cenH3 assembly factor KNL2 can be used as a haploid inducer. We elucidated that short temperature stress of the knl2 mutant increased the efficiency of haploid induction from 1 to 10%. Moreover, we have demonstrated that a point mutation in the CENPC-k motif of KNL2 is sufficient to generate haploid inducing lines, suggesting that haploid inducing lines in crops can be identified in a naturally occurring or chemically induced mutant population, avoiding the GMO approach at any stage. In addition, we have shown that the cenh3-4 mutant, which does not induce haploids under standard growth conditions, functions as a haploid inducer after exposure to short temperature stress.