bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Global Health Law: Preparing the Next Generation for Future Challenges
Authors: Gostin Lawrence O. , Bosha Sarah L. , Meier Benjamin Mason
Published: May 2024

Following from sweeping law reforms across the global health landscape, there is a need to prepare the next generation to advance global health law to ensure justice for a healthier world. Educational programs across disciplines have increasingly incorporated the field of global health law, with new courses examining the law and policy frameworks that apply to the new set of public health threats, non-state actors, and regulatory instruments that structure global health. Such interdisciplinary training must be expanded throughout the world to prepare future practitioners to strengthen global health law — ensuring a foundation for global health in legal studies and law and global health studies. Meeting this imperative for global health law teaching — establishing academic courses and textbooks on global legal responses to shared health threats — will be necessary to support students to address the global health challenges of the future.
Battling Environmental Racism in Cancer Alley: A Legislative Approach
Authors: Garofalo Megan Resener
Published: May 2024

This Paper argues that to protect at-risk communities — and all Americans — from the deadly effects of environmental racism, Congress must pass the Environmental Justice for All Act. The Act is intended to “restore, reaffirm, and reconcile environmental justice and civil rights.” It does so by restoring an individual’s right to sue in federal court for discrimination based on race, ethnicity, or national origin regardless of intent under the Civil Rights Act of 1964, strengthening the National Environmental Policy Act, and providing economic incentives focused on environmental justice.
Church Against State: How Industry Groups Lead the Religious Liberty Assault on Civil Rights, Healthcare Policy, and the Administrative State
Authors: Wuest Joanna , Last Briana S.
Published: May 2024

Industry-funded religious liberty legal groups have sought to undermine healthcare policy and law while simultaneously attacking the rights of sexual and gender minorities. Whereas past scholarship has tracked religiously-affiliated healthcare providers’ growing political power and attendant transformations to legal doctrine, our account emphasizes the political donors and visionaries who have leveraged religious providers and the U.S. healthcare system’s delegated structure to transform social policy and bureaucratic agencies more generally.
Enacting Relational Public Health: Federally Qualified Health Centers During the COVID-19 Pandemic
Authors: Pacia Danielle , Crane Johanna , Neuhaus Carolyn , Berlinger Nancy , Fabi Rachel
Published: May 2024

Précis

Federally Qualified Health Centers (FQHCs) proved to be critical points of access for people of color and other underserved populations during the COVID-19 pandemic, administering 61% of their COVID-19 vaccinations to people of color, compared to the 40% rate for the overall United States’ vaccination effort. To better understand the approaches and outcomes of FQHCs in pandemic response, we conducted semi-structured interviews with FQHC health care providers and outreach workers and analyzed them using an inductive qualitative methodology.
Pre-Mortem Interventions for the Purpose of Organ Donation: Legal Approaches to Consent
Authors: Taillieu Renée , Weiss Matthew J. , Harvey Dan , Murphy Nicholas , Weijer Charles , Chandler Jennifer A
Published: May 2024

Précis

The administration of Pre-Mortem Interventions (PMIs) to preserve the opportunity to donate, to assess the eligibility to donate, or to optimize the outcomes of donation and transplantation are controversial as they offer no direct medical benefit and include at least the possibility of harm to the still-living patient. In this article, we describe the legal analysis surrounding consent to PMIs, drawing on existing legal commentary and identifying key legal problems. We provide an overview of the approaches in several jurisdictions that have chosen to explicitly address PMIs within codified law. We then provide, as an example, a detailed exploration of how PMIs are likely to be addressed in one jurisdiction where general medical consent law applies because there is no specific legislation addressing PMIs — the province of Ontario in Canada.
A new post-LOME (Late Ordovician Mass Extinction) recovery brachiopod fauna from South China
Authors: Huang Bing , Candela Yves , Shi Kaiyan , Rong Jiayu
Published: May 2024

Following the Late Ordovician Mass Extinction event, brachiopod faunas were in a phase of recovery during the late Rhuddanian (early Silurian), documented by a drastic turnover of Ordovician-type to Silurian-type faunas. In this study, we present a recovery brachiopod fauna, from the Niuchang Formation (late Rhuddanian-based graptolite zonation) at the Wanzi section of Zhenxiong in northeastern Yunnan Province, South China. The fossils include 26 species assigned to 25 genera, with a dominance of strophomenides and orthides, but also a diverse suite of atrypides and pentamerides, which exhibit compositional differences compared to the earlier Edgewood–Cathay fauna. The emergence of a more typical Silurian brachiopod fauna suggests a delayed community turnover after the Late Ordovician Mass Extinction event. The shallowing marine environment trend evinced in the brachiopod assemblages in the section indicates a balance between the global transgression and the regional Qianzhong Uplift, which provided a stable environment for the brachiopod recovery. The presence of diverse pentamerides, including the earliest species of the large-shelled genus Sinostricklandiella, suggests early diversification of this clade in South China.
A bidirectional LSTM-based morphological analyzer for Gujarati
Authors: Baxi Jatayu , Bhatt Brijesh
Published: May 2024

Morphological analysis is a crucial preprocessing stage for building the state-of-the-art natural language processing applications. We propose a bidirectional LSTM (long short-term memory)-based approach to develop the morphological analyzer for the Gujarati language. Our morph analyzer predicts a root word and the morphological features for the given inflected word. We have experimented with two different methods for label representation for predicting morphological features: the monolithic representation method and the individual label representation method. We have also created the gold morphological dataset of 16,234 unique words for the Gujarati language. The dataset contains morpheme splitting and grammatical feature information for each inflected word. Due to the change in the label representation technique in the proposed model, the accuracy of the present baseline system is improved by a large margin. The proposed system performs very well across the POS categories without the knowledge of language-specific suffix rules.
An online method for ship trajectory compression using AIS data
Authors: Liu Zhao , Yuan Wensen , Liang Maohan , Zhang Mingyang , Liu Cong , Liu Ryan Wen , Liu Jingxian
Published: May 2024

Vessel trajectories from the Automatic Identification System (AIS) play an important role in maritime traffic management, but a drawback is the huge amount of memory occupation which thus results in a low speed of data acquisition in maritime applications due to a large number of scattered data. This paper proposes a novel online vessel trajectory compression method based on the Improved Open Window (IOPW) algorithm. The proposed method compresses vessel trajectory instantly according to vessel coordinates along with a timestamp driven by the AIS data. In particular, we adopt the weighted Euclidean distance (WED), fusing the perpendicular Euclidean distance (PED) and synchronous Euclidean distance (SED) in IOPW to improve the robustness. The realistic AIS-based vessel trajectories are used to illustrate the proposed model by comparing it with five traditional trajectory compression methods. The experimental results reveal that the proposed method could effectively maintain the important trajectory features and significantly reduce the rate of distance loss during the online compression of vessel trajectories.
THE EXPORT OF CAPITAL TO COLONIES AND THE FALLING RATE OF PROFIT IN ECONOMIC THOUGHT: 1776–1917
Authors: Walke Adam
Published: May 2024

Classical political economists developed several different explanations for what they saw as an inherent tendency for the rate of profit to decline over time. In the second quarter of the nineteenth century, some British advocates of colonization developed a corollary to those theories, suggesting that exporting capital to colonies could help arrest and reverse the decline. That argument was championed by the English political economist and promoter of colonization projects Edward Gibbon Wakefield, and it was systematized by John Stuart Mill. Ironically, the view that capital export and colonization played crucial roles in sustaining the rate of profit in advanced economies was later adopted by some Marxist theorists. Parallels between Karl Marx and J. S. Mill may help explain the remarkable theoretical continuity on this topic between nineteenth-century British advocates of colonization and early twentieth-century Marxist critics of colonialism.
Optimizing insurance risk assessment: a regression model based on a risk-loaded approach
Authors: Landsman Zinoviy , Shushi Tomer
Published: May 2024

Risk measurement and econometrics are the two pillars of actuarial science. Unlike econometrics, risk measurement allows taking into account decision-makers’ risk aversion when analyzing the risks. We propose a hybrid model that captures decision-makers’ regression-based approach to study risks, focusing on explanatory variables while paying attention to risk severity. Our model considers different loss functions that quantify the severity of the losses that are provided by the risk manager or the actuary. We present an explicit formula for the regression estimators for the proposed risk-based regression problem and study the proposed results. Finally, we provide a numerical study of the results using data from the insurance industry.
FINITARY UPPER LOGICISM
Authors: JACINTO BRUNO
Published: May 2024

This paper proposes and partially defends a novel philosophy of arithmetic—finitary upper logicism. According to it, the natural numbers are finite cardinalities—conceived of as properties of properties—and arithmetic is nothing but higher-order modal logic. Finitary upper logicism is furthermore essentially committed to the logicality of finitary plenitude, the principle according to which every finite cardinality could have been instantiated. Among other things, it is proved in the paper that second-order Peano arithmetic is interpretable, on the basis of the finite cardinalities’ conception of the natural numbers, in a weak modal type theory consisting of the modal logic
$\mathsf {K}$
, negative free quantified logic, a contingentist-friendly comprehension principle, and finitary plenitude. By replacing finitary plenitude for the axiom of infinity this result constitutes a significant improvement on Russell and Whitehead’s interpretation of second-order Peano arithmetic, itself based on the finite cardinalities’ conception of the natural numbers.
Translating impartiality into operations from a financial perspective: Uncertainties and solutions
Authors: Wang Yue , Fang Ting
Published: May 2024

Considering the drastic changes in the nature of conflicts, humanitarian organizations (HOs) and donors, investing more attention into impartiality is critical for HOs if they are to survive and improve the quality of their humanitarian activities. As one of the four fundamental humanitarian principles, impartiality has critical implications for humanitarian action in relation to three aspects: its symbolic meaning for humanitarian action, its procedural significance for humanitarian access, and its operational importance for needs assessments. This article analyzes how the practice of impartiality is challenged by the current humanitarian financing model from five angles: funding source, funding amount, funding allocation, financial management and funding categorization. To cope with these obstacles, we focus on the financial perspective and propose three suggestions for international HOs: first, digitally innovating the humanitarian financing model to ensure that overall humanitarian needs are covered; second, strengthening engagement with non-traditional donors such as the Gulf countries and China, with a focus on infrastructure; and third, developing a hybrid financing model, with case studies from UNICEF and the International Committee of the Red Cross.
Evaluation of the b Maps on the Faults of the Major (M > 7) South California Earthquakes
Authors: Convertito V. , Tramelli A. , Godano C.
Published: May 2024

We use the Godano et al. (2022, https://doi.org/10.1029/2021ea002205) method for evaluating the b maps of the faults associated with the largest earthquakes M ≥ 7.0 that occurred in California. The method allows an independent evaluation of the b parameter, avoiding the overlap of the cells and the omission of some earthquakes, while keeping all the available information in the catalog. We analyzed four large earthquakes: Landers, Hector Mine, Baja California, and Searles Valley. The maps obtained confirm that the b value can be considered as a strain meter and allow us to elucidate the presence of barriers, such as obstacles to the propagation of the fracture, on the fault of the analyzed earthquakes. A further estimated parameter is the time window during which aftershocks occur in the cell, Δt. This quantity is very useful for a better definition of the aftershock generation mechanism. It reveals where the stress is released in a short time interval and how the complexity of the faulting process controls the occurrence of aftershocks on the fault, and also the duration of the entire sequence.
Plankton Community Metabolism Variations in Two Temperate Coastal Waters of Contrasting Nutrient Richness
Authors: Mantikci Mustafa , Bentzon‐Tilia Mikkel , Traving Sachia J. , Knudsen‐Leerbeck Helle , Riemann Lasse , Hansen Jørgen L. S. , Markager Stiig
Published: May 2024

Estuarine ecosystems play a crucial role in global carbon cycling. Understanding the factors controlling plankton metabolism in these regions is critical. This study investigates how contrasting nutrient conditions influence plankton metabolism and carbon flow in two Danish estuaries, Roskilde Fjord (RF) (eutrophic) and the Great Belt (GB) (less eutrophic). Despite higher nutrient concentrations in RF, chlorophyll a and biomass only showed a moderate increase compared to the GB. Interestingly, metabolic rates (photosynthesis and respiration) in RF displayed greater temperature sensitivity, suggesting potential nutrient limitation effects in the GB. While both stations exhibited similar annual net primary production, RF's higher net community production highlights the importance of nutrient availability for carbon accumulation within the system. Additionally, the study observed significant seasonal variations in plankton metabolism and its impact on the carbon cycle. Notably, the more dynamic hydrography in the GB weakened correlations between biological and environmental factors.
Modeling the Effects of Artificial Drainage on Agriculture‐Dominated Watersheds Using a Fully Distributed Integrated Hydrology Model
Authors: Rathore Saubhagya S. , Svyatsky Daniil S. , Coon Ethan T. , Son Kyongho , Painter Scott L.
Published: May 2024

In agriculture‐dominated watersheds where natural drainage is poor, agricultural ditches (narrow engineered channels) and tile drains (perforated pipes) are widely employed to enhance surface and subsurface drainage, respectively. Despite their relatively small scale, these features exert substantial control over the hydro‐biogeochemical function of watersheds and their effects need to be represented in the models. We introduce a novel strategy to incorporate the effects of artificial agricultural drainage into a fully distributed basin‐scale integrated surface‐subsurface hydrology models. In our approach, narrow agriculture ditches for surface drainage are resolved efficiently using ditch‐aligned computational meshes that are hydrologically conditioned to ensure connectivity in the stream/ditch network. For tile drainage in the subsurface, we use the physically based Hooghoudt's drainage equation as a subgrid model and route the water drained through tiles to the nearest ditch. Without site‐specific calibration, this model reproduced observed streamflow in the Portage River Watershed (>1,000 km2) as recorded by a USGS gauge with good accuracy (normalized KGE = 0.81) and outperformed a calibrated SWAT model (normalized KGE = 0.68). Numerical experiments confirm that artificial drainage reduces surface inundations and effectively controls the water table. At the watershed scale, artificial drainage increases baseflow but has little effect on watershed discharges above the 90th percentile. The strong physical underpinnings and reduced need for calibration allow us to study the impacts of artificial drainage on distributed hydrological response in terms of fluxes and states and provide a platform for investigating watershed‐scale nutrient transport.
Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets
Authors: Chen Runkai , Zhang Hongrui , Tang Botao , Luo Yukun , Yang Yufei , Zhong Xin , Chen Sifei , Xu Xinjie , Huang Shengkang , Liu Canzhao
Published: May 2024

The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate immune system, macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases, including coronary heart disease, valvular disease, myocarditis, cardiomyopathy, heart failure, atherosclerosis and aneurysm, which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific diseases. Besides, recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity, cell–cell interactions, and downstream mechanisms of therapeutic targets at a higher resolution, which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular diseases. Remarkably, myocardial fibrosis, a prevalent characteristic in most cardiac diseases, remains a formidable clinical challenge, necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac diseases. In this review, we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by single-cell sequencing technologies, with a focus on different causes and characteristics of diseases, especially the relationship between inflammation and fibrosis in cardiac diseases (myocardial infarction, pressure overload, myocarditis, dilated cardiomyopathy, diabetic cardiomyopathy and cardiac aging) and the relationship between inflammation and vascular injury in vascular diseases (atherosclerosis and aneurysm). Finally, we also highlight the preclinical/clinical macrophage targeting strategies and translational implications.
Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy
Authors: Dima Danai , Abdallah Al-Ola , Davis James A. , Awada Hussein , Goel Utkarsh , Rashid Aliya , DeJarnette Shaun , Anwer Faiz , Shune Leyla , Raza Shahzad , Mahmoudjafari Zahra , Williams Louis , Faiman Beth , McGuirk Joseph P. , Sauter Craig S. , Ahmed Nausheen , Khouri Jack , Hashmi Hamza
Published: May 2024

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.
Spatial phenotyping of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma
Authors: Younes Sheren , Subramanian Ajay , Khan Anum , Zhao Shuchun , Binkley Michael , Natkunam Yasodha
Published: May 2024

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.
Peroxiredoxin I and II as novel therapeutic molecular targets in cervical cancer treatment through regulation of endoplasmic reticulum stress induced by bleomycin
Authors: Sun Hu-Nan , Ma Da-Yu , Guo Xiao-Yu , Hao Ying-Ying , Jin Mei-Hua , Han Ying-Hao , Jin Xun , Kwon Taeho
Published: May 2024

Cervical cancer, significantly affecting women worldwide, often involves treatment with bleomycin, an anticancer agent targeting breast, ovarian, and cervical cancers by generating reactive oxygen species (ROS) to induce cancer cell death. The Peroxiredoxin (PRDX) family, particularly PRDX1 and 2, plays a vital role in maintaining cellular balance by scavenging ROS, thus mitigating the damaging effects of bleomycin-induced mitochondrial and cellular oxidative stress. This process reduces endoplasmic reticulum (ER) stress and prevents cell apoptosis. However, reducing PRDX1 and 2 levels reverses their protective effect, increasing apoptosis. This research highlights the importance of PRDX1 and 2 in cervical cancer treatments with bleomycin, showing their potential to enhance treatment efficacy by managing ROS and ER stress and suggesting a therapeutic strategy for improving outcomes in cervical cancer treatment.
A theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a spatial suppressor of selection
Authors: Kuo Yang Ping , Nombela-Arrieta César , Carja Oana
Published: May 2024

How the spatial arrangement of a population shapes its evolutionary dynamics has been of long-standing interest in population genetics. Most previous studies assume a small number of demes or symmetrical structures that, most often, act as well-mixed populations. Other studies use network theory to study more heterogeneous spatial structures, however they usually assume small, regular networks, or strong constraints on the strength of selection considered. Here we build network generation algorithms, conduct evolutionary simulations and derive general analytic approximations for probabilities of fixation in populations with complex spatial structure. We build a unifying evolutionary theory across network families and derive the relevant selective parameter, which is a combination of network statistics, predictive of evolutionary dynamics. We also illustrate how to link this theory with novel datasets of spatial organization and use recent imaging data to build the cellular spatial networks of the stem cell niches of the bone marrow. Across a wide variety of parameters, we find these networks to be strong suppressors of selection, delaying mutation accumulation in this tissue. We also find that decreases in stem cell population size also decrease the suppression strength of the tissue spatial structure.
Memristor-based adaptive neuromorphic perception in unstructured environments
Authors: Wang Shengbo , Gao Shuo , Tang Chenyu , Occhipinti Edoardo , Li Cong , Wang Shurui , Wang Jiaqi , Zhao Hubin , Hu Guohua , Nathan Arokia , Dahiya Ravinder , Occhipinti Luigi Giuseppe
Published: May 2024

Efficient operation of control systems in robotics or autonomous driving targeting real-world navigation scenarios requires perception methods that allow them to understand and adapt to unstructured environments with good accuracy, adaptation, and generality, similar to humans. To address this need, we present a memristor-based differential neuromorphic computing, perceptual signal processing, and online adaptation method providing neuromorphic style adaptation to external sensory stimuli. The adaptation ability and generality of this method are confirmed in two application scenarios: object grasping and autonomous driving. In the former, a robot hand realizes safe and stable grasping through fast ( ~ 1 ms) adaptation based on the tactile object features with a single memristor. In the latter, decision-making information of 10 unstructured environments in autonomous driving is extracted with an accuracy of 94% with a 40×25 memristor array. By mimicking human low-level perception mechanisms, the electronic neuromorphic circuit-based method achieves real-time adaptation and high-level reactions to unstructured environments.
Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein
Authors: Mao Xiaobo , Gu Hao , Kim Donghoon , Kimura Yasuyoshi , Wang Ning , Xu Enquan , Kumbhar Ramhari , Ming Xiaotian , Wang Haibo , Chen Chan , Zhang Shengnan , Jia Chunyu , Liu Yuqing , Bian Hetao , Karuppagounder Senthilkumar S. , Akkentli Fatih , Chen Qi , Jia Longgang , Hwang Heehong , Lee Su Hyun , Ke Xiyu , Chang Michael , Li Amanda , Yang Jun , Rastegar Cyrus , Sriparna Manjari , Ge Preston , Brahmachari Saurav , Kim Sangjune , Zhang Shu , Shimoda Yasushi , Saar Martina , Liu Haiqing , Kweon Sin Ho , Ying Mingyao , Workman Creg J. , Vignali Dario A. A. , Muller Ulrike C. , Liu Cong , Ko Han Seok , Dawson Valina L. , Dawson Ted M.
Published: May 2024

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson’s disease and related α-synucleinopathies.
The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation
Authors: Elorette Catherine , Fujimoto Atsushi , Stoll Frederic M. , Fujimoto Satoka H. , Bienkowska Niranjana , London Liza , Fleysher Lazar , Russ Brian E. , Rudebeck Peter H.
Published: May 2024

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5–14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.
A zinc oxide resonant nano-accelerometer with ultra-high sensitivity
Authors: Xu Pengfei , Wang Dazhi , He Jianqiao , Cui Yichang , Lu Liangkun , Li Yikang , Chen Xiangji , Liu Chang , Suo Liujia , Ren Tongqun , Wang Tiesheng , Cui Yan
Published: May 2024

Nanoelectromechanical system accelerometers have the potential to be utilized in next-generation consumer electronics, inertial navigation, and seismology due to their low cost, small size, and low power consumption. There is an urgent need to develop resonant accelerometer with high sensitivity, precision and robustness. Here, a zinc oxide resonant nano-accelerometer with high sensitivity has been designed and prototyped using zinc oxide nanowires. Within a device two nanowires were symmetrically placed close to a notched flexure to evaluate acceleration based on differential resonant frequencies. Additionally, microleverages were integrated in the accelerometer to enhance its sensitivity by amplifying the inertial force. High performance of the accelerometer has been demonstrated by the measured absolute sensitivity (16.818 kHz/g), bias instability (13.13 μg at 1.2 s integration time) and bandwidth (from 4.78 to 29.64 kHz), respectively. These results suggest that zinc oxide nanowires could be a candidate to develop future nanoelectromechanical resonant accelerometer potentially used for inertial navigation, tilt measurement, and geophysical measurements.
Fluorescent riboswitch-controlled biosensors for the genome scale analysis of metabolic pathways
Authors: Michaud A. , Garneau D. , Côté J.-P. , Lafontaine D. A.
Published: May 2024

Fluorescent detection in cells has been tremendously developed over the years and now benefits from a large array of reporters that can provide sensitive and specific detection in real time. However, the intracellular monitoring of metabolite levels still poses great challenges due to the often complex nature of detected metabolites. Here, we provide a systematic analysis of thiamin pyrophosphate (TPP) metabolism in Escherichia coli by using a TPP-sensing riboswitch that controls the expression of the fluorescent gfp reporter. By comparing different combinations of reporter fusions and TPP-sensing riboswitches, we determine key elements that are associated with strong TPP-dependent sensing. Furthermore, by using the Keio collection as a proxy for growth conditions differing in TPP levels, we perform a high-throughput screen analysis using high-density solid agar plates. Our study reveals several genes whose deletion leads to increased or decreased TPP levels. The approach developed here could be applicable to other riboswitches and reporter genes, thus representing a framework onto which further development could lead to highly sophisticated detection platforms allowing metabolic screens and identification of orphan riboswitches.
The remarkable potential of machine learning algorithms in estimating water permeability of concrete incorporating nano natural pozzolana
Authors: Alsubai Shtwai , Alqahtani Abdullah , Hashim Muhodir Sabih , Alanazi Abed , Ahmed Mohd , Jasim Dheyaa J. , Palani Sivaprakasam
Published: May 2024

This paper aims to estimate the permeability of concrete by replacing the laboratory tests with robust machine learning (ML)-based models. For this purpose, the potential of twelve well-known ML techniques was investigated in estimating the water penetration depth (WPD) of nano natural pozzolana (NNP)-reinforced concrete based on 840 data points. The preparation of concrete specimens was based on the different combinations of NNP content, water-to-cement (W/C) ratio, median particle size (MPS) of NNP, and curing time (CT). Comparing the results estimated by the ML models with the laboratory results revealed that the hist-gradient boosting regressor (HGBR) and K-nearest neighbors (KNN) algorithms were the most and least robust models to estimate the WPD of NNP-reinforced concrete, respectively. Both laboratory and ML results showed that the WPD of NNP-reinforced concrete decreased with the increase of the NNP content from 1 to 4%, the decrease of the W/C ratio and the MPS, and the increase of the CT. To further aid in the estimation of concrete’s WPD for engineering challenges, a graphical user interface for the ML-based models was developed. Proposing such a model may be effectively employed in the management of concrete quality.
Effective impact of nano-plastic-waste incorporated with nanotitina on the physical, mechanical and microstructural properties of white cement pastes composites for progressing towards sustainability
Authors: Abdelzaher M. A. , Farghali Ahmed A. , Hamouda Asmaa S.
Published: May 2024

Plastic waste (PW) has received a lot of attention as a possible additional material for industrial and environmental applications, particularly cement and/or concrete production for a more environmentally and economically sound use of raw materials and energy sources. PW has been investigated as an inert and/or active hydraulic filler for cement and/or concrete by numerous scientists. Plastic garbage is cheap, abundant, and takes long period of time to degrade in the eco-system (soil and water). The main goal of the ongoing research is to offer safety and efficacy by partially substituting nano-plastic waste (NPW), incorporated with nano-titania (NT), for the composition of white cement (WC). Blends are built up by substitution of WC with different ratios of NPW incorporated with fixed ratios of nano-titania (1.0 wt.%). Workability, physical, mechanical and microstructural properties have gone through laboratory and instrumental analysis. The results showed improvement in the compressive strength, density and microstructure due to the effective impact of fillers. Consequently, a decrease in total porosity, whiteness reflection (Ry) and early-rapid expansion. Eventually, the outcomes may reduce the pandemic strength, especially in the external environment, and other epidemics.
Activation of SIRT1/Nrf2/HO-1 and Beclin-1/AMPK/mTOR autophagy pathways by eprosartan ameliorates testicular dysfunction induced by testicular torsion in rats
Authors: Abu-Baih Rania H. , Abu-Baih Dalia H. , Abdel-Hafez Sara Mohamed Naguib , Fathy Moustafa
Published: May 2024

Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways.
Painkiller intake and problematic health literacy in sport and music students - A cross-sectional study
Authors: Pöppel Katharina , Kreutz Gunter , Müller Maren , Büsch Dirk
Published: May 2024

Previous works have suggested a high prevalence of painkiller intake (PI) among sport students but also improved health literacy (HL) for sports-active students than for sports-inactive students. Since health-related content also forms part of the sport science curriculum, the study focuses on these seemingly paradoxical results. Music students who are also physically active through their instrumental practice, who act in an area with increased PI and who have no health-related teaching content in their curriculum composed the comparison group. Therefore, this study investigated the prevalence of PI and HL in cohorts of sport (n = 222; 54.5% female) and music students (n = 89; 67.4% female) using a cross-sectional online survey in Lower Saxony, Germany. The hypothesis tests were validated by calculating frequentist and Bayesian statistics. The results show that 50.9% of sport and 28.1% of music students exhibit PI concerning their study programs, often for prophylactical purposes and in the presence of low HL levels. The weak negative correlation between PI and HL was not statistically confirmed and requires further research with improved test power. Regarding the possible health consequences of an inconsiderate PI, target group-specific prevention is indicated to increase general health awareness and HL.
Exergoeconomic analysis and optimization of wind power hybrid energy storage system
Authors: Wen Caifeng , Lyu Yalin , Du Qian , Zhang Boxin , Lian Xuhui , Wang Qiang , Hao Hongliang
Published: May 2024

The hybrid energy storage system of wind power involves the deep coupling of heterogeneous energy such as electricity and heat. Exergy as a dual physical quantity that takes into account both 'quantity' and 'quality, plays an important guiding role in the unification of heterogeneous energy. In this paper, the operation characteristics of the system are related to the energy quality, and the operation strategy of the wind power hybrid energy storage system is proposed based on the exergoeconomics. First, the mathematical model of wind power hybrid energy storage system is established based on exergoeconomics. Then, wind power experiments of three forms of thermal-electric hybrid energy storage are carried out, and RSM is used to analyze the power quality and exergoeconomic characteristics of the system, and the optimal working conditions of the experiment are obtained. Finally, an optimization strategy is proposed by combining experiment and simulation. The system efficiency, unit exergy cost and current harmonic distortion rate are multi-objective optimization functions. The three algorithms evaluate the optimal solution based on standard deviation. The results show that the exergoeconomics can effectively judge the production-storage-use characteristics of the new system of ' wind power + energy storage'. The thermal-electric hybrid energy storage system can absorb the internal exergy loss of the battery, increase the exergy efficiency by 10%, reduce the unit exergy cost by 0.03 yuan/KJ, and reduce the current harmonic distortion rate by 8%. It provides guidance for improving the power quality of wind power system, improving the exergy efficiency of thermal-electric hybrid energy storage wind power system and reducing the unit cost.
Amplification sensing manipulated by a sumanene-based supramolecular polymer as a dynamic allosteric effector
Authors: Mizuno Hiroaki , Nakazawa Hironobu , Miyagawa Akihisa , Yakiyama Yumi , Sakurai Hidehiro , Fukuhara Gaku
Published: May 2024

The synthesis of signal-amplifying chemosensors induced by various triggers is a major challenge for multidisciplinary sciences. In this study, a signal-amplification system that was flexibly manipulated by a dynamic allosteric effector (trigger) was developed. Herein, the focus was on using the behavior of supramolecular polymerization to control the degree of polymerization by changing the concentration of a functional monomer. It was assumed that this control was facilitated by a gradually changing/dynamic allosteric effector. A curved-π buckybowl sumanene and a sumanene-based chemosensor (SC) were employed as the allosteric effector and the molecular binder, respectively. The hetero-supramolecular polymer, (SC·(sumanene)n), facilitated the manipulation of the degree of signal-amplification; this was accomplished by changing the sumanene monomer concentration, which resulted in up to a 62.5-fold amplification of a steroid. The current results and the concept proposed herein provide an alternate method to conventional chemosensors and signal-amplification systems.
Comparison of the effects of reef and anthropogenic soundscapes on oyster larvae settlement
Authors: Schmidlin Sarah , Parcerisas Clea , Hubert Jeroen , Watson Maryann S. , Mees Jan , Botteldooren Dick , Devos Paul , Debusschere Elisabeth , Hablützel Pascal I.
Published: May 2024

Settlement is a critical period in the life cycle of marine invertebrates with a planktonic larval stage. For reef-building invertebrates such as oysters and corals, settlement rates are predictive for long-term reef survival. Increasing evidence suggests that marine invertebrates use information from ocean soundscapes to inform settlement decisions. Sessile marine invertebrates with a planktonic stage are particularly reliant on environmental cues to direct them to ideal habitats. As gregarious settlers, oysters prefer to settle amongst members of the same species. It has been hypothesized that oyster larvae from species Crassostrea virginica and Ostrea angasi use distinct conspecific oyster reef sounds to navigate to ideal habitats. In controlled laboratory experiments we exposed Pacific Oyster Magallana gigas larvae to anthropogenic sounds from conspecific oyster reefs, vessels, combined reef-vessel sounds as well as off-reef and no speaker controls. Our findings show that sounds recorded at conspecific reefs induced higher percentages of settlement by about 1.44 and 1.64 times compared to off-reef and no speaker controls, respectively. In contrast, the settlement increase compared to the no speaker control was non-significant for vessel sounds (1.21 fold), combined reef-vessel sounds (1.30 fold), and off-reef sounds (1.18 fold). This study serves as a foundational stepping stone for exploring larval sound feature preferences within this species.
Investigation of the myopic outcomes of the newer intraocular lens power calculation formulas in Korean patients with long eyes
Authors: Kim Jinchul , Park Joonsung , Jo Yoonjung
Published: May 2024

This study investigated the underlying causes of the myopic outcomes of the optic-based newer formulas (Barrett Universal II, EVO 2.0, Kane, Hoffer-QST and PEARL-DGS) in long Korean eyes with Alcon TFNT intraocular lens (IOL) implantation. Postoperative data from 3100 randomly selected eyes of 3100 patients were analyzed to compare the reference back-calculated effective lens positions (ELPs) based on the Haigis formula using conventional axial length (AL) and Cooke-modified AL (CMAL) with the predicted ELP of each single- and triple-optimized Haigis formula applied to AL- and CMAL. Contrary to the AL-applied Haigis formula, the predicted ELP curve of the CMAL-applied, single-optimized Haigis formula, simulating the methods of the newer formulas, exhibited a significant upward deviation from the back-calculated ELP in long eyes. The relationship between the AL and anterior chamber depth in our long-eyed population differed from that in the base population of the PEARL-DGS formula. The myopic outcomes in long eyes appeared to stem from the substantial overestimation of the postoperative IOL position with AL modification, leading to the implantation of inappropriately higher-powered IOLs. This discrepancy may be attributed to the ethnic differences in ocular biometrics, particularly the relatively smaller anterior segment in East Asian patients with long AL.