bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear analysis of the synchronous reference frame phase-locked loop under unbalanced grid voltage
Authors: Ponomarev Anton , Hagenmeyer Veit , Gröll Lutz
Published: April 2024

The synchronous reference frame phase-locked loop (SRF-PLL), also called dqPLL, is an electric circuit commonly used in power electronics to estimate the phase angle of a three-phase AC grid. If the voltage is unbalanced, the PLL is modeled as a periodically forced nonlinear oscillator and is known in practice to converge to a steady oscillation. In the existing literature, the oscillation has been studied via linearization assuming a low level of unbalance. Aiming for stronger nonlocal statements, we present nonlinear analysis. We apply the method of autonomous comparison systems and incremental stability to show that the steady oscillation is unique and attractive in a wider neighborhood. Its lock-in domain is estimated using numerical phase portrait analysis. The oscillation is further approximated up to the terms of the second order in the unbalance factor—it yields an estimation of the time average of the PLL’s phase error which is not visible by linearization only. The results provide stability guarantees and can guide the tuning of SRF-PLL.
Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using a smartphone PPG app: the Dutch-GERAF study
Authors:   Dutch-GERAF investigators, Zwart Lennaert A. R. , Spruit Jocelyn R. , Hemels Martin E. W. , de Groot Joris R. , Pisters Ron , Riezebos Robert K. , Jansen René W. M. M.
Published: April 2024

Background

Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC).

Methods

This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients’ pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality.

Discussion

The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population.

Trial registration

NCT05337202.
Docker Container-Based Framework of Apache Kafka Node Ecosystem: Vehicle Tracking System by License Plate Recognition on Surveillance Camera Feeds
Authors: Kul Seda , Kumcu Sarper , Sayar Ahmet
Published: April 2024

Vehicle tracking and license plate recognition (LPR) over video surveillance cameras are essential intelligent traffic monitoring systems. Due to the enormous amount of data collected each day, it would be difficult to track vehicles by license plate in a real-world traffic setting. Large volumes of data processing, real-time request responses, and emergency scenario response may not be possible using conventional approaches. By combining license plate recognition with the docker container-based structure of the Apache Kafka node ecosystem, the suggested solution takes a novel approach to vehicle tracking. The primary components of our suggested framework for reading license plates are the identification of license plates and text data queries. License plate localization is performed with You Only Look Once version 3 (YOLOv3) and character recognition with Optical Character Recognition (OCR). The detected vehicle images with license plate results are published on related topics with Apache Kafka. Apache Kafka is a publish-subscribe (producers-consumers) messaging system and one of the most popular architectures used for streaming data. For each license plate search, a topic will be created in the framework where producers publish and consumers receive data. Thus, the workload of the operators will be reduced and they will be able to pay attention to more important events in traffic.
New correlations to estimate the rough fracture permeability using computational fluid dynamics simulation
Authors: Valizadeh Farshid , Ghaedi Mojtaba , Hemmati Sara , Feilizadeh Mehrzad , Garmsiri Hamid
Published: April 2024

In fractured reservoirs, the fracture network provides the main path for fluid flow. Appropriate estimation of the fracture permeability influences the precise prediction of the reservoir’s future performance. Commonly, for a known geometry of natural or induced fracture, the permeability is estimated by applying local cubic law. One major drawback of this approach is that the fracture surface roughness, which has a significant effect on fracture permeability, is not considered. Moreover, the knowledge about the impact of fracture surface roughness on fracture permeability is not currently sufficient. In this research, the fluid flow in fractures with rough-walled surfaces was studied using computational fluid dynamics. For this purpose, the fluid flow through fractures was simulated by applying appropriate roughness for fracture walls. Furthermore, two correlations, based on response surface methodology and power-law models, were proposed to predict fracture permeability as a function of four independent variables (surface roughness, fracture aperture, angle, and porosity). The results of the two presented correlations were validated, and the statistical analysis indicates that both models are appropriate to predict fracture permeability. The findings of this study will be of great assistance with understanding and characterization of the fluid flow in rough fractures and can be used in future works.
An integrated geomechanical and petrophysical multiparameter approach for gas reservoir evaluation
Authors: Kablan Or Aimon Brou Koffi , Chen Tongjun
Published: April 2024

Integrating petrophysical and geomechanical parameters is an efficient approach to evaluating shale gas reservoir potential. The high cost of corings and their limited number, coupled with time-intensive investigation, led researchers to use this alternative combination approach. In the Jiaoshiba area, from single-pilot well core data and log measurements, petrophysical and geomechanical parameters such as shale volume, total organic carbon, gas content, as well as pore pressure, stress components, and mineral brittleness were first estimated using established methods. In the second phase, based on logging curves, the reservoir electro-facies (EF) classification was performed using the unsupervised multi-resolution graph-based clustering method on a series of twenty wells, identifying five EF with different intrinsic characteristics. Unsupervised analyses were developed using the multilayer artificial neural network while incorporating the K-nearest neighbors and graphical classification algorithms. The results from the first and second phases indicate reservoir richness in organic matter, with the best reservoir exhibited by EF2 and EF3. In addition, effective stress components (SV, SH, and Sh) evaluation shows a normal stress regime with hydraulic fracture systems perpendicular to the minimum horizontal stress at each measured depth of the reservoir (Sv > SH > Sh). This research workflow can efficiently evaluate shale reservoirs with a realistic approach for identifying favorable fracturing positions while reducing errors due to human interference.
Management of surgical diseases of Primary Hyperparathyroidism: indications of the United Italian Society of Endocrine Surgery (SIUEC)
Authors: Del Rio Paolo , Boniardi Marco , De Pasquale Loredana , Docimo Giovanni , Iacobone Maurizio , Materazzi Gabriele , Medas Fabio , Minuto Michele , Mullineris Barbara , Polistena Andrea , Raffaelli Marco , Calò Pietro Giorgio
Published: April 2024

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health‑care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery. The main topics concern diagnostic test and localization studies, mode of admission and waiting time, therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications), hospital discharge and patient information, outpatient care and follow-up, outpatient initial management of patients with pHPT.
Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift
Authors: Lopez-Vince Elliot , Wilhelm Claire , Simon-Yarza Teresa
Published: April 2024

As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use. Several strategies to integrate both tumor and vascular compartments have been developed, but few have been used to assess drug delivery. Permeability, intra/extravasation, and free drug circulation are often evaluated, but imperfectly recapitulate the processes at stake. Indeed, tumor targeting and chemoresistance bypass must be investigated to design promising cancer therapeutics. In vitro models that would help the development of drug delivery systems (DDS) are thus needed. They would allow selecting good candidates before animal studies based on rational criteria such as drug accumulation, diffusion in the tumor, and potency, as well as absence of side damage. In this review, we focus on vascularized tumor models. First, we detail their fabrication, and especially the materials, cell types, and coculture used. Then, the different strategies of vascularization are described along with their classical applications in intra/extravasation or free drug assessment. Finally, current trends in DDS for cancer are discussed with an overview of the current efforts in the domain.

Graphical Abstract
A two-stage bidirectional coevolution algorithm with reverse search for constrained multiobjective optimization
Authors: Liu Cancan , Wang Yujia , Xue Yunfeng
Published: April 2024

Constrained multiobjective optimization problems (CMOPs) are widespread in reality. The presence of constraints complicates the feasible region of the original problem and increases the difficulty of problem solving. There are not only feasible regions, but also large areas of infeasible regions in the objective space of CMOPs. Inspired by this, this paper proposes a bidirectional coevolution method with reverse search (BCRS) combined with a two-stage approach. In the first stage of evolution, constraints are ignored and the population is pushed toward promising regions. In the second stage, evolution is divided into two parts, i.e., the main population evolves toward the constrained Pareto front (CPF) within the feasible region, while the reverse population approaches the CPF from the infeasible region. Then a solution exchange strategy similar to weak cooperation is used between the two populations. The experimental results on benchmark functions and real-world problems show that the proposed algorithm exhibits superior or at least competitive performance compared to other state-of-the-art algorithms. It demonstrates BCRS is an effective algorithm for addressing CMOPs.

Graphical Abstract
The safety, quality evaluation, and lot release of COVID-19 vaccines imported and used in Nigeria from march 2021 to march 2022
Authors: Kanu N. M. , Adeyeye C. M. , Abiola V. O. , Adekunle–Segun O. , Adegoke E. M. , Akapo A. , Okezue M. A.
Published: April 2024

Coronavirus disease (COVID-19) caused by the Severe Acute Respiratory Syndrome Corona 2 Virus (SARS-COV-2 Virus) was a major global health crisis that resulted in severe illness and death around the globe. The swift development of effective vaccines against the disease to mitigate severe illness and death was one of the greatest public health scientific achievements. Most of these vaccines required cold storage and were exported to many developing countries with resource limitations to verify the quality of these products. The National Agency for Food and Drug Administration and Control (NAFDAC) regulates the quality of vaccines imported into Nigeria. This study provides summaries of data collected and QC measures conducted on all the COVID-19 vaccines imported into Nigeria within 2021–2022. Cold-chain parameters and other data requirements for meeting international standards for assessing the quality of vaccines were conducted in ISO17025-accredited laboratories of the Nigerian FDA. QC tests used to assess the safety of the products included tests for sterility, bacterial endotoxin, abnormal toxicity, pH, Physical appearance, extractable volumes, protein tests, and DNA: protein ratios. The products yielded satisfactory compliance, however, there were unsatisfactory sterility and protein test results for two batches of the samples tested. There are additional non-QC regulatory measures employed by NAFDAC to ensure the safety of the COVID-19 vaccines, including supply chain management. Out of ninety-five batches of different COVID-19 vaccines evaluated, 95.5% passed sterility testing. There is a 100% pass of all the vaccines for the Bacteria Endotoxin Test while an 80% pass was observed for the protein content.
Public Health Responses to CBRN Terrorism in the Middle East and North Africa
Authors: Mani Zakaria , Plummer Virginia , Kuhn Lisa , Khorram-Manesh Amir , Tin Derrick , Goniewicz Krzysztof
Published: April 2024

Objective:

Escalating global challenges (such as disasters, conflict, and climate change) underline the importance of addressing Chemical, Biological, Radiological, and Nuclear (CBRN) terrorism for sustainable public health strategies. This study aims to provide a comprehensive epidemiological analysis of CBRN incidents in the Middle East and North Africa (MENA) region, emphasizing the necessity of sustainable responses to safeguard healthcare infrastructures.

Method:

Utilizing a retrospective approach, this research analyzes data from the Global Terrorism Database (GTD) covering the period from 2003 to 2020. The study focuses on examining the frequency, characteristics, and consequences of CBRN incidents in the MENA region to identify patterns and trends that pose significant challenges to public health systems.

Results:

The analysis revealed a significant clustering of CBRN incidents in Iraq and Syria, with a predominant involvement of chemical agents. These findings indicate the extensive impact of CBRN terrorism on healthcare infrastructures, highlighting the challenges in providing immediate health responses and the necessity for long-term recovery strategies.

Conclusions:

The study underscores the need for improved healthcare preparedness, robust emergency response systems, and the development of sustainable public health policies. Advocating for international collaboration, the research contributes to the strategic adaptation of healthcare systems to mitigate the impacts of CBRN terrorism, ensuring preparedness for future incidents in the MENA region and beyond.
The role of the cytochrome P450 superfamily in the skin
Authors: Chen Qianqian , Wang Tuan , Wu Xia , Yuan Huipu , Wei Yuan , Xiao Ying
Published: April 2024

In mammals, the skin acts as a barrier to prevent harmful environmental stimuli from entering the circulation. CYP450s are involved in drug biotransformation, exogenous and endogenous substrate metabolism, and maintaining the normal physiological function of the skin, as well as facilitating homeostasis of the internal environment. The expression pattern of CYP450s in the skin is tissue-specific and thus differs from the liver and other organs. The development of skin topical medications, and knowledge of the toxicity and side effects of these medications require a detailed understanding of the expression and function of skin-specific CYP450s. Thus, we summarized the expression of CYP450s in the skin, their function in endogenous metabolic physiology, aberrant CYP450 expression in skin diseases and the influence of environmental variables and medications. This information will serve as a crucial foundation for future studies on the skin, as well as for the design and development of new drugs for skin diseases including topical medications.
Silencing Conversational Silences
Authors: Klieber Anna
Published: April 2024

This paper aims to extend the discussion of silencing beyond the realm of speech and to the domain of conversational silences—that is, silences that have communicative functions in our conversational exchanges. I argue that, insofar as we can use silences to communicate, we can also be prevented from doing things with these silences. Alongside a threefold taxonomy I show the different ways in which this can happen, utilizing and extending Maitra's (2009) account of silencing to illustrate the wrong happening in these cases. This discussion not only highlights a new domain of silencing that has, so far, been underexplored, but also uncovers just how deep linguistic injustices can run.
Leader-contingent sanctions as a cause of violent political conflict
Authors: Mei Yu
Published: April 2024

Economic sanctions are a policy tool that great powers frequently use to interfere with domestic politics of another state. Regime change has been a primary goal of economic sanctions over the past decades. This article studies the relationship between leader-contingent sanctions—sanctions that are designed to impede the flow of revenue to a specific leader—and violent political conflict in target countries. I build a theoretical model to illuminate two mechanisms by which leader-contingent sanctions destabilize a regime—the Depletion Mechanism and the Instigation Mechanism. The Depletion Mechanism works when sanctions mechanically deplete the government's resources so that it becomes unable to buy off domestic opposition even by making the largest possible offer. The Instigation Mechanism implies that as sanctions decrease the benefit of negotiated settlement relative to war, the government may strategically choose to repress rather than buy off the opposition even when it is able to do so. Leader-contingent sanctions lead to bargaining failure by rewarding the opposition for revolt while reducing the government's ability and willingness to appease the opposition.
Leaders but Not Authorities? Gender, Veterans, and Messages about National Security
Authors: CAVERLEY JONATHAN D. , KRUPNIKOV YANNA
Published: April 2024

Politicians’ ability to provide national security to the public is deeply enmeshed in conceptions of the state and of leadership. This article incorporates securitization, feminist, and political communication theories to consider whether gendered and militarized conceptions of national security have different effects for politicians who are women and those who are men. Although scholarship suggests that signaling military bona fides—such as invoking one’s veteran status—can help politicians claim that certain policies are a matter of national security, we consider whether this ability will be gendered. Relying on two national studies, we find results that are contrary to our original predictions. First, we find that military bona fides do help women be seen as leaders. However, we do not find evidence that bona fides increase the “authority” to identify and address national security threats for any politicians.
A Decade after the Arab Revolutions: Reflections on the Evolution of Questions about the SWANA Region
Authors: Dakhli Leyla
Published: April 2024

On 17 December 2010, the self-immolation of a young street vendor in Sidi Bouzid, a town in inland Tunisia, instigated the uprisings that became known as the Arab Spring or the Arab Revolutions – a wording that I will use here as a translation from the Arabic al-thawrât al-`arabiyya. Observers were shocked at the radical protests arising in these regions, where authoritarian regimes had crushed all serious opposition over the decades. Conflicts governed by geopolitics, in particular the ongoing Israeli–Arab and Israeli–Palestinian hostilities, and the focus on political Islam and jihadism as the only globalized locus of political protest, have arrogated any attention for societies, their transformation, and their mobilization.
Characterisation of the mitochondrial genome and phylogenetic analysis of Toxocara apodemi (Nematoda: Ascarididae)
Authors: Gao Y. , Hu Y. , Xu S. , Liang H. , Lin H. , Yin T. H. , Zhao K.
Published: April 2024

We first sequenced and characterised the complete mitochondrial genome of Toxocara apodeme, then studied the evolutionary relationship of the species within Toxocaridae. The complete mitochondrial genome was amplified using PCR with 14 specific primers. The mitogenome length was 14303 bp in size, including 12 PCGs (encoding 3,423 amino acids), 22 tRNAs, 2 rRNAs, and 2 NCRs, with 68.38% A+T contents. The mt genomes of T. apodemi had relatively compact structures with 11 intergenic spacers and 5 overlaps. Comparative analyses of the nucleotide sequences of complete mt genomes showed that T. apodemi had higher identities with T. canis than other congeners. A sliding window analysis of 12 PCGs among 5 Toxocara species indicated that nad4 had the highest sequence divergence, and cox1 was the least variable gene. Relative synonymous codon usage showed that UUG, ACU, CCU, CGU, and UCU most frequently occurred in the complete genomes of T. apodemi. The Ka/Ks ratio showed that all Toxocara mt genes were subject to purification selection. The largest genetic distance between T. apodemi and the other 4 congeneric species was found in nad2, and the smallest was found in cox2. Phylogenetic analyses based on the concatenated amino acid sequences of 12 PCGs demonstrated that T. apodemi formed a distinct branch and was always a sister taxon to other congeneric species. The present study determined the complete mt genome sequences of T. apodemi, which provide novel genetic markers for further studies of the taxonomy, population genetics, and systematics of the Toxocaridae nematodes.
Extramural English as an individual difference variable in L2 research: Methodology matters
Authors: Sundqvist Pia
Published: April 2024

In light of findings from research on informal foreign/second language (L2) learning, with a focus on English as a target language and using the concept of extramural English (EE), this position paper argues that learners’ engagement in EE (through activities such as watching television or films or playing digital games) constitutes an important individual difference (ID) variable that needs to be included in studies that aim to measure L2 English proficiency or development. In addition, it is suggested that if EE as an ID variable is left out in such studies in the future, the rationale for exclusion should be clearly stated. This position paper also discusses research instruments and methods used in this area of research, the benefits and drawbacks of different methods, and identifies research gaps and under-researched learner groups. Further, it is argued that in some contexts, EE has replaced classroom activities as the starting point for and foundation of learning English.
Live birth derived from a markedly large polar body oocyte: a rare case report
Authors: Liu Yongxiang , Peng Xinliang , Liu Caifeng , Zhang Shuting , Weng Zhiwei , Yu Li , Zhou Shaohu , Huang Xuekun
Published: April 2024

Oocytes with excessively large first polar bodies (PB1) often occur in assisted reproductive procedures. Many times these oocytes are discarded without insemination and, as a result, the application of this portion of oocytes has scarcely been reported to date. Few studies have examined large PB1 oocytes in infertile women and have virtually entirely studied genetic variations for large PB1 oocyte abnormalities. Here, we describe an unusual case of a live birth from a remarkably large PB1 oocyte in a frozen embryo transfer (FET) cycle. This is the first instance of a successful live birth resulting from a PB1 oocyte with an extremely large polar body measuring 80 μM × 40 μM in size. The large PB1 oocyte was performed by an early rescue intracytoplasmic sperm injection (r-ICSI) and was formed into a blastocyst on day 5. Following FET, a healthy boy baby weighing 3100 g was finally delivered by caesarean section at 37 weeks and 5 days after conception. Additionally, there were no complications throughout the antenatal period or the perinatal phase of this following full-term delivery. In this study, it is revealed for the first time that a huge PB1 oocyte can be fertilized, resulting in the growth of a blastocyst, a subsequent pregnancy, and a live birth. This new information prompts us to reconsider the use of large PB1 oocytes. More insightful talks should be given attention to prevent the waste of embryos because not all oocytes with aberrant morphology are unavailable.
Hope and Meaning: Phenomenology in the Thought of Leszek Kołakowski, Józef Tischner, and Václav Havel
Authors: Ciżewska-Martyńska Elżbieta
Published: April 2024

Using an intellectual-history lens, this article offers insights into the spread of phenomenology across Central Europe and its social–political significance in the second half of the twentieth century, particularly its impact on the formation of the Eastern European dissident movement and furnishing it with ideas. Specifically, the article explores the role that phenomenology played in defining one of the core concepts underlying Central European dissidence: the idea of hope. Tracing the story of three public intellectuals—Leszek Kołakowski, Józef Tischner, and Václav Havel—it suggests why the school founded by Edmund Husserl had been embraced by some and rejected by others, and how their particular interpretations of hope had been indebted to phenomenology.
Constitutional Referrals by Ordinary Courts: A Platform for Judicial Dialogue and Another Toolkit for Judicial Resistance?
Authors: Kovalčík Michal
Published: April 2024

Constitutional referrals by ordinary courts – Judicial dialogue between constitutional courts and ordinary courts – Toolkit for judicial resistance – Novel taxonomy of features and functions of constitutional referrals – Separation of powers approach – Democratic decay – Self-defence mechanism – Mix of methodological approaches – Case study on Czechia
Strong Oceanic Forcing on Decadal Surface Temperature Variability Over Global Ocean
Authors: Gu Peng , Liu Zhengyu , Delworth Thomas L.
Published: April 2024

Sea surface temperature (SST) variability on decadal timescales has been associated with global and regional climate variability and impacts. The mechanisms that drive decadal SST variability, however, remain highly uncertain. Many previous studies have examined the role of atmospheric variability in driving decadal SST variations. Here we assess the strength of oceanic forcing in driving decadal SST variability in observations and state‐of‐the‐art climate models by analyzing the relationship between surface heat flux and SST. We find a largely similar pattern of decadal oceanic forcing across all ocean basins, characterized by oceanic forcing about twice the strength of the atmospheric forcing in the mid‐ and high latitude regions, but comparable or weaker than the atmospheric forcing in the subtropics. The decadal oceanic forcing is hypothesized to be associated with the wind‐driven oceanic circulation, which is common across all ocean basins.
The GFDL Variable‐Resolution Global Chemistry‐Climate Model for Research at the Nexus of US Climate and Air Quality Extremes
Authors: Lin Meiyun , Horowitz Larry W. , Zhao Ming , Harris Lucas , Ginoux Paul , Dunne John , Malyshev Sergey , Shevliakova Elena , Ahsan Hamza , Garner Steve , Paulot Fabien , Pouyaei Arman , Smith Steven J. , Xie Yuanyu , Zadeh Niki , Zhou Linjiong
Published: April 2024

We present a variable‐resolution global chemistry‐climate model (AM4VR) developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) for research at the nexus of US climate and air quality extremes. AM4VR has a horizontal resolution of 13 km over the US, allowing it to resolve urban‐to‐rural chemical regimes, mesoscale convective systems, and land‐surface heterogeneity. With the resolution gradually reducing to 100 km over the Indian Ocean, we achieve multi‐decadal simulations driven by observed sea surface temperatures at 50% of the computational cost for a 25‐km uniform‐resolution grid. In contrast with GFDL's AM4.1 contributing to the sixth Coupled Model Intercomparison Project at 100 km resolution, AM4VR features much improved US climate mean patterns and variability. In particular, AM4VR shows improved representation of: precipitation seasonal‐to‐diurnal cycles and extremes, notably reducing the central US dry‐and‐warm bias; western US snowpack and summer drought, with implications for wildfires; and the North American monsoon, affecting dust storms. AM4VR exhibits excellent representation of winter precipitation, summer drought, and air pollution meteorology in California with complex terrain, enabling skillful prediction of both extreme summer ozone pollution and winter haze events in the Central Valley. AM4VR also provides vast improvements in the process‐level representations of biogenic volatile organic compound emissions, interactive dust emissions from land, and removal of air pollutants by terrestrial ecosystems. We highlight the value of increased model resolution in representing climate–air quality interactions through land‐biosphere feedbacks. AM4VR offers a novel opportunity to study global dimensions to US air quality, especially the role of Earth system feedbacks in a changing climate.
Intention-to-treat outcomes utilising a stringent event definition in children and young people treated with tisagenlecleucel for r/r ALL through a national access scheme
Authors: Oporto Espuelas Macarena , Burridge Saskia , Kirkwood Amy A. , Bonney Denise , Watts Kelly , Shenton Geoff , Jalowiec Katarzyna A. , O’Reilly Maeve A. , Roddie Claire , Castleton Anna , Clesham Katherine , Nicholson Emma , Alajangi Rajesh , Prabhu Shilpa , George Lindsay , Uttenthal Ben , Gabelli Maria , Neill Lorna , Besley Caroline , Chaganti Sridhar , Wynn Robert F. , Bartram Jack , Chiesa Robert , Lucchini Giovanna , Pavasovic Vesna , Rao Anupama , Rao Kanchan , Silva Juliana , Samarasinghe Sujith , Vora Ajay , Clark Peter , Cummins Michelle , Marks David I. , Amrolia Persis , Hough Rachael , Ghorashian Sara
Published: April 2024

CAR T-cell therapy has transformed relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukaemia (B-ALL) management and outcomes, but following CAR T infusion, interventions are often needed. In a UK multicentre study, we retrospectively evaluated tisagenlecleucel outcomes in all eligible patients, analysing overall survival (OS) and event-free survival (EFS) with standard and stringent definitions, the latter including measurable residual disease (MRD) emergence and further anti-leukaemic therapy. Both intention-to-treat and infused cohorts were considered. We collected data on feasibility of delivery, manufacture, toxicity, cause of therapy failure and followed patients until death from any cause. Of 142 eligible patients, 125 received tisagenlecleucel, 115/125 (92%) achieved complete remission (CR/CRi). Severe cytokine release syndrome and neurotoxicity occurred in 16/123 (13%) and 10/123 (8.1%), procedural mortality was 3/126 (2.4%). The 2-year intent to treat OS and EFS were 65.2% (95%CI 57.2–74.2%) and 46.5% (95%CI 37.6–57.6%), 2-year intent to treat stringent EFS was 35.6% (95%CI 28.1–44.9%). Median OS was not reached. Sixty-two responding patients experienced CAR T failure by the stringent event definition. Post failure, 1-year OS and standard EFS were 61.2% (95%CI 49.3–75.8) and 55.3% (95%CI 43.6–70.2). Investigation of CAR T-cell therapy for B-ALL delivered on a country-wide basis, including following patients beyond therapy failure, provides clinicians with robust outcome measures. Previously, outcomes post CAR T-cell therapy failure were under-reported. Our data show that patients can be successfully salvaged in this context with good short-term survival.
Identification of a novel form of caspase-independent cell death triggered by BH3-mimetics in diffuse large B-cell lymphoma cell lines
Authors: Yildirim Nahide , Sarojam Lakshmi , Smith Victoria M. , Pieper Nadja M. , Anders Marius , Jackson Ross A. , Fuhrmann Dominik C. , Särchen Vinzenz , Brücher Daniela , Weigert Andreas , Dyer Martin J. S. , Vogler Meike
Published: April 2024

BH3-mimetics represent promising anti-cancer agents in tumors that rely on the anti-apoptotic function of B-Cell Lymphoma 2 (BCL2) proteins, particularly in leukemia and lymphoma cells primed for apoptosis. Mechanistically, BH3-mimetics may displace pro-apoptotic binding partners thus inducing BAX/BAK-mediated mitochondrial permeabilization followed by cytochrome c release, activation of the caspase cascade and apoptosis. Here, we describe a novel mode of caspase-independent cell death (CICD) induced by BH3-mimetics in a subset of diffuse large B-cell lymphoma (DLBCL) cells. Of note, rather than occurring via necroptosis, CICD induced immediately after mitochondrial permeabilization was associated with transcriptional reprogramming mediated by activation of c-Jun N-terminal Kinase (JNK) signaling and Activator Protein 1 (AP1). Thereby, CICD resulted in the JNK/AP1-mediated upregulation of inflammatory chemokines and increased migration of cytotoxic Natural Killer (NK) cells. Taken together, our study describes a novel mode of CICD triggered by BH3-mimetics that may alter the immune response towards dying cells.
Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study
Authors: Engjom Hilde Marie , Ramakrishnan Rema , Vousden Nicola , Bunch Kathryn , Morris Edward , Simpson Nigel , Gale Chris , O’Brien Pat , Quigley Maria , Brocklehurst Peter , Kurinczuk Jennifer J. , Knight Marian
Published: April 2024

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years’ active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.
Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Authors: Ke Shizhong , Dang Fabin , Wang Lin , Chen Jia-Yun , Naik Mandar T. , Li Wenxue , Thavamani Abhishek , Kim Nami , Naik Nandita M. , Sui Huaxiu , Tang Wei , Qiu Chenxi , Koikawa Kazuhiro , Batalini Felipe , Stern Gatof Emily , Isaza Daniela Arango , Patel Jaymin M. , Wang Xiaodong , Clohessy John G. , Heng Yujing J. , Lahav Galit , Liu Yansheng , Gray Nathanael S. , Zhou Xiao Zhen , Wei Wenyi , Wulf Gerburg M. , Lu Kun Ping
Published: April 2024

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/CCDH1 mediated by domain-oriented phosphorylation-dependent dual interactions as a fundamental mechanism governing mitotic protein stability and cell-cycle entry. Remarkably, combined PIN1 and cyclin-dependent protein kinases (CDKs) inhibition creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, which force permanent cell-cycle exit and trigger anti-tumor immunity, translating into synergistic efficacy against triple-negative breast cancer.
A widely conserved protein Rof inhibits transcription termination factor Rho and promotes Salmonella virulence program
Authors: Zhang Jing , Zhang Shuo , Zhou Wei , Zhang Xiang , Li Guanjin , Li Ruoxuan , Lin Xingyu , Chen Ziying , Liu Fang , Shen Pan , Zhou Xiaogen , Gao Yue , Chen Zhenguo , Chao Yanjie , Wang Chengyuan
Published: April 2024

Transcription is crucial for the expression of genetic information and its efficient and accurate termination is required for all living organisms. Rho-dependent termination could rapidly terminate unwanted premature RNAs and play important roles in bacterial adaptation to changing environments. Although Rho has been discovered for about five decades, the regulation mechanisms of Rho-dependent termination are still not fully elucidated. Here we report that Rof is a conserved antiterminator and determine the cryogenic electron microscopy structure of Rho-Rof antitermination complex. Rof binds to the open-ring Rho hexamer and inhibits the initiation of Rho-dependent termination. Rof’s N-terminal α-helix undergoes conformational changes upon binding with Rho, and is key in facilitating Rof-Rho interactions. Rof binds to Rho’s primary binding site (PBS) and excludes Rho from binding with PBS ligand RNA at the initiation step. Further in vivo analyses in Salmonella Typhimurium show that Rof is required for virulence gene expression and host cell invasion, unveiling a physiological function of Rof and transcription termination in bacterial pathogenesis.
Tunable stochastic memristors for energy-efficient encryption and computing
Authors: Woo Kyung Seok , Han Janguk , Yi Su-in , Thomas Luke , Park Hyungjun , Kumar Suhas , Hwang Cheol Seong
Published: April 2024

Information security and computing, two critical technological challenges for post-digital computation, pose opposing requirements – security (encryption) requires a source of unpredictability, while computing generally requires predictability. Each of these contrasting requirements presently necessitates distinct conventional Si-based hardware units with power-hungry overheads. This work demonstrates Cu0.3Te0.7/HfO2 (‘CuTeHO’) ion-migration-driven memristors that satisfy the contrasting requirements. Under specific operating biases, CuTeHO memristors generate truly random and physically unclonable functions, while under other biases, they perform universal Boolean logic. Using these computing primitives, this work experimentally demonstrates a single system that performs cryptographic key generation, universal Boolean logic operations, and encryption/decryption. Circuit-based calculations reveal the energy and latency advantages of the CuTeHO memristors in these operations. This work illustrates the functional flexibility of memristors in implementing operations with varying component-level requirements.
Chlorine bridge bond-enabled binuclear copper complex for electrocatalyzing lithium–sulfur reactions
Authors: Yang Qin , Cai Jinyan , Li Guanwu , Gao Runhua , Han Zhiyuan , Han Jingjing , Liu Dong , Song Lixian , Shi Zixiong , Wang Dong , Wang Gongming , Zheng Weitao , Zhou Guangmin , Song Yingze
Published: April 2024

Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium–sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium–sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium–sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm−2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm−2 and electrolyte dosage of 4.8 μL mg−1.
Conjunctive encoding of exploratory intentions and spatial information in the hippocampus
Authors: Zeng Yi-Fan , Yang Ke-Xin , Cui Yilong , Zhu Xiao-Na , Li Rui , Zhang Hanqing , Wu Dong Chuan , Stevens Raymond C. , Hu Ji , Zhou Ning
Published: April 2024

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal’s exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals’ investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.
Continuous and low-carbon production of biomass flash graphene
Authors: Zhu Xiangdong , Lin Litao , Pang Mingyue , Jia Chao , Xia Longlong , Shi Guosheng , Zhang Shicheng , Lu Yuanda , Sun Liming , Yu Fengbo , Gao Jie , He Zhelin , Wu Xuan , Li Aodi , Wang Liang , Wang Meiling , Cao Kai , Fu Weiguo , Chen Huakui , Li Gang , Zhang Jiabao , Wang Yujun , Yang Yi , Zhu Yong-Guan
Published: April 2024

Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g−1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.
Electrocatalytic hydrogenation of acetonitrile to ethylamine in acid
Authors: Tang Chongyang , Wei Cong , Fang Yanyan , Liu Bo , Song Xianyin , Bian Zenan , Yin Xuanwei , Wang Hongbo , Liu Zhaohui , Wang Gongming , Xiao Xiangheng , Duan Xiangfeng
Published: April 2024

Electrochemical hydrogenation of acetonitrile based on well-developed proton exchange membrane electrolyzers holds great promise for practical production of ethylamine. However, the local acidic condition of proton exchange membrane results in severe competitive proton reduction reaction and poor selection toward acetonitrile hydrogenation. Herein, we conduct a systematic study to screen various metallic catalysts and discover Pd/C exhibits a 43.8% ethylamine Faradaic efficiency at the current density of 200 mA cm−2 with a specific production rate of 2912.5 mmol g−1 h−1, which is about an order of magnitude higher than the other screened metal catalysts. Operando characterizations indicate the in-situ formed PdHx is the active centers for catalytic reaction and the adsorption strength of the *MeCH2NH2 intermediate dictates the catalytic selectivity. More importantly, the theoretical analysis reveals a classic d-band mediated volcano curve to describe the relation between the electronic structures of catalysts and activity, which could provide valuable insights for designing more effective catalysts for electrochemical hydrogenation reactions and beyond.
Global meta-analysis reveals overall higher nocturnal than diurnal activity in insect communities
Authors: Wong Mark K. L. , Didham Raphael K.
Published: April 2024

Insects sustain key ecosystem functions, but how their activity varies across the day–night cycle and the underlying drivers are poorly understood. Although entomologists generally expect that more insects are active at night, this notion has not been tested with empirical data at the global scale. Here, we assemble 331 quantitative comparisons of the abundances of insects between day and night periods from 78 studies worldwide and use multi-level meta-analytical models to show that insect activity is on average 31.4% (CI: −6.3%–84.3%) higher at night than in the day. We reveal diel preferences of major insect taxa, and observe higher nocturnal activity in aquatic taxa than in terrestrial ones, as well as in warmer environments. In a separate analysis of the small subset of studies quantifying diel patterns in taxonomic richness (31 comparisons from 13 studies), we detect preliminary evidence of higher nocturnal richness in tropical than temperate communities. The higher overall (but variable) nocturnal activity in insect communities underscores the need to address threats such as light pollution and climate warming that may disproportionately impact nocturnal insects.