bluuebunny/crossref_metadata_2025 huggingface dataset:
A two-capillary viscometer for temperatures up to 473 K and pressures up to 100 MPa—operation and verification at low pressure
Authors: Khosravi Bahareh , Austegard Anders , Løvseth Sigurd W , Stang H G Jacob , Jakobsen Jana P
Published: April 2024

In this paper, we described the design and construction of a new two-capillary viscometer with several novel technical solutions for viscosity and density measurements. Our design, which is based on the low-pressure principle, featured numerous improvements in hardware and procedure that allowed the greatly extended range of pressure. The new design adopted a (2 × 2) capillary configuration, utilizing different combinations of four capillaries to enable viscosity measurements with a wide range of flow rates, temperatures, and pressures. The design temperature range is 213 K–473 K, and the pressure range is up to 100 MPa. The viscometer was specifically designed for measuring the viscosity of pure CO2 and CO2-rich mixtures, addressing the scarcity of data in conditions relevant to carbon capture, transport, and storage. Our facility is capable of viscosity measurements in different thermodynamic states; gaseous, liquid, supercritical, and critical regions. A commercial densimeter is integrated to measure density under the same temperatures and pressures. We aimed for a total uncertainty target of better than 0.03%. The performance of the viscometer was validated by measurements with pure CO2 at 298.15 K and zero density. We observed a deviation of less than 0.03% between the reference viscosity of CO2 of this work and accurately calculated data using ab initio quantum mechanics with a standard uncertainty of 0.2%. Our primary focus in this paper was to provide a detailed description of the design and construction of the apparatus, emphasizing improvements and introducing new solutions to other research groups in constructing similar instruments suitable for low- and high-pressure viscosity measurements with high accuracy.
Two-capillary viscometer for temperatures and pressures relevant to CO2 capture, transport, and storage—operation and improved analysis at high pressure
Authors: Khosravi Bahareh , Austegard Anders , Løvseth Sigurd W , Stang H G Jacob , Jakobsen Jana P
Published: April 2024

High-pressure viscosity measurements are crucial for understanding CO2 transport and storage because CO2 is often transported as a supercritical fluid, at a high pressure and temperature above its critical point. In this study, we extended the operational range of our new two-capillary viscometer to handle pressures up to 20 MPa, focusing on the behaviour of CO2 at temperatures around 300 K. The analysis model is based on the low-pressure principle, which relied on virial descriptions of density and viscosity, proved inadequate under these conditions. Therefore, we introduced a modified hydrodynamic model as a function of density that is suitable for viscosity measurements at high pressure and liquid states. The modified model bypasses the need for a density virial correction. We conducted initial viscosity tests on pure CO2 at five isotherms: 280.01 K, 298.15 K, 300.01 K, 323.15 K, and 348.15 K to validate the performance of the new two capillary viscometer and the modified model at high pressures. The experimental viscosities agreed with the model predictions and comparable within the estimated uncertainty of the data. In addition, we thoroughly explained the calibrations and the analysis of uncertainty estimation. The uncertainty analysis showed a maximum extended combined uncertainty of 1.3% (k = 2) within all thermodynamic states—gas, liquid, and close to the critical region.
Asymmetric multi-image encoding and hiding scheme with structured fingerprint phase masks using gyrator transform and phase-shifting digital holography
Authors: Kumar Rao Sonu , Nishchal Naveen K
Published: April 2024

We propose a novel technique for multi-image encryption and hiding schemes under an optical asymmetric framework using structured fingerprint phase masks (SFPMs) in the gyrator transform (GT) domain and three-step phase-shifting digital holography (PSDH). A SFPM contains unique features of fingerprint and structured phases of the optical vortex beam, which provides enhanced security in the cryptosystem. To encrypt multiple images, GT-based phase truncation and phase reservation techniques have been used in the first level of security, whereas three-step PSDH has been used to obtain the final cipher text. The cipher text is embedded in the host image to perform the watermarking process. In this process, the host is further decomposed into three parts in which anyone from the last two parts can be used for watermark embedding, and the first part is stored as the key. The use of polar decomposition in the watermarking process provides an additional layer of security. Numerical simulations and experimental results are presented to support the proposed scheme.
Quantum-enhanced hybrid feature engineering in thoracic CT image analysis for state-of-the-art nodule classification: an advanced lung cancer assessment
Authors: Shivwanshi Resham Raj , Nirala Neelamshobha
Published: April 2024

The intricate nature of lung cancer treatment poses considerable challenges upon diagnosis. Early detection plays a pivotal role in mitigating its escalating global mortality rates. Consequently, there are pressing demands for robust and dependable early detection and diagnostic systems. However, the technological limitations and complexity of the disease make it challenging to implement an efficient lung cancer screening system. AI-based CT image analysis techniques are showing significant contributions to the development of computer-assisted detection (CAD) systems for lung cancer screening. Various existing research groups are working on implementing CT image analysis systems for assessing and classifying lung cancer. However, the complexity of different structures inside the CT image is high and comprehension of significant information inherited by them is more complex even after applying advanced feature extraction and feature selection techniques. Traditional and classical feature selection techniques may struggle to capture complex interdependencies between features. They may get stuck in local optima and sometimes require additional exploration strategies. Traditional techniques may also struggle with combinatorial optimization problems when applied to a prominent feature space. This paper proposed a methodology to overcome the existing challenges by applying feature extraction using Vision Transformer (FexViT) and Feature selection using the Quantum Computing based Quadratic unconstrained binary optimization (QC-FSelQUBO) technique. This algorithm shows better performance when compared with other existing techniques. The proposed methodology showed better performance as compared to other existing techniques when evaluated by applying necessary output measures, such as accuracy, Area under roc (receiver operating characteristics) curve, precision, sensitivity, and specificity, obtained as 94.28%, 99.10%, 96.17%, 90.16% and 97.46%. The further advancement of CAD systems is essential to meet the demand for more reliable detection and diagnosis of cancer, which can be addressed by leading the proposed quantum computation and growing AI-based technology ahead.
The Pennsylvania Council of Censors and the Debate on the Guardian of the Constitution in the Early United States
Authors: Brown Angus Harwood
Published: April 2024

In 1776, Pennsylvania established an institution called the Council of Censors, which would be elected every seven years and was tasked with ensuring that the legislative, executive, and judicial branches of government had remained faithful to the constitution. None of the other thirteen colonies would create a similar institution, although Vermont would in 1777. Nor has the Council of Censors enjoyed a positive reputation among historians or constitutional scholars: Gordon Wood, for example, has attacked the institution as ‘a monster [pulled] out of Roman history’. Contemporaries agreed, and the body was abolished in Pennsylvania in 1790 after years of vociferous opposition and was criticized extensively at the Federal Convention in 1787. But the Council of Censors was a remarkably innovative institution, the first designed to enforce a written constitution, created decades before the Supreme Court’s assumption of the power of constitutional judicial review in 1803. This article presents a new history of the origins of the Council of Censors and its reception both in Pennsylvania and across the United States. It challenges prevailing accounts of the origins and purpose of the Council of Censors and argues that it was a product of a new theory of constitutionalism as the codification of popular sovereignty which emerged in the United States in the 1770s in response to the colonists’ fears about legislative overreach. Prior to the nineteenth century, it was only in Pennsylvania that this resulted in the creation of institutions to secure the supremacy of constitutional law over ordinary legislative power. As the final section of this article demonstrates, the idea that the constitution could be enforced against the legislative branch by an independent constitutional guardian—including the Supreme Court—was rejected at the Federal Convention precisely because of its framers’ antipathy to Pennsylvania’s radically democratic constitution.
Túngara frog call-timing decisions arise as internal rhythms interact with fluctuating chorus noise
Authors: Larter Luke C , Ryan Michael J
Published: April 2024

For chorusing males, optimally timing their calls relative to nearby rivals’ calls and fluctuations in background chorus noise is crucial for reproductive success. A caller’s acoustic environment will vary by chorus density and the properties of his chorus-mates’ calls and will fluctuate unpredictably due to chorusing dynamics emerging among his chorus-mates. Thus, callers must continuously monitor moment-to-moment fluctuations in the acoustic scene they perceive at the chorus for advantageous times to call. In live experimental choruses, we investigated the factors influencing túngara frog call-timing responses to chorus-mates’ calls on an interaction-by-interaction basis, revealing that intrinsic and extrinsic factors influenced call-timing decisions. Callers were more likely to overlap calls from smaller chorus-mates and chorus-mates at intermediate distances, as well as calls containing lower frequencies and exhibiting lower final amplitude minima. Consequently, variation among males in call properties led to variation in levels of call-interference received when calling in the same social environment. Additionally, callers were more likely to overlap chorus-mates’ calls after experiencing extended periods of inhibition and were less likely to overlap synchronized chorus-mates’ calls relative to single calls. In chorusing species, female choice is influenced by inter-caller dynamics, selecting for male call-timing strategies which, in turn, constitute the selective environment further refining these same strategies. Thus, understanding the specific factors driving call-timing decisions is essential for understanding how sexual selection operates in chorusing taxa.
Factors defining developmental competence of bovine oocytes collected for in vitro embryo production
Authors: Pytel Aleksandra Teresa , Żyżyńska-Galeńska Krystyna , Gajewski Zdzisław , Papis Krzysztof
Published: April 2024

Despite the currently relatively low effectiveness of producing bovine embryos in vitro, there is a growing interest in applying this laboratory method in the field of reproduction. Many aspects of the procedure need to be improved. One of the main problems is the inferior developmental competence of in vitro matured oocytes that are collected using the ovum pick-up method. The mechanisms of oocyte capacitation and maturation, as well as the in vivo conditions in which they grow and mature, should be carefully analyzed. A deliberate application of the identified mechanisms and beneficial factors affecting the in vitro procedures seems to be essential for achieving higher developmental competence of the oocytes that are subjected to fertilization. The results may be improved by developing and employing a laboratory maturation protocol that corresponds with appropriate preparation of donors before the ovum pick-up, an optimized hormonal treatment program, the appropriate size of ovarian follicles at the time of aspiration, and a fine-tuned coasting period.
Voices of Women Exposed to Honour-Based Violence: On Vulnerability, Needs and Support from Social Services
Authors: Olsson Helén
Published: April 2024

Swedish social services play a pivotal role in preventing men’s violence against women, including honour-based violence. This type of family-based violence is based on norms that disregard human rights. Individuals growing up in an honour context have limited possibilities to choose their own paths in life. The study comprises young women aged eighteen to twenty-five who look back on their vulnerable positions and the circumstances resulting in their seeking help from social services. They also share their experiences of the support that they had received from social services. Semi-structured interviews with ten women were conducted. The data were analysed through a qualitative content analysis. The findings show that the interviewees are not a homogenous group; circumstances, needs and exposure varied considerably between participants. Professional attention is necessary when threats ensue after divorce, for example, in the case of a bride price refund. Child perspectives must be better considered in the event of a divorce. Women or families that reject standards of honour are subject to harassment in public by people aiming to coerce them into adopting honour norms. Leaving the family was facilitated if one’s fears were taken seriously and experiences of being met with understanding and being well cared for.
Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer’s disease and 5XFAD mice
Authors: Barbour Aaron J , Gourmaud Sarah , Lancaster Eunjoo , Li Xiaofan , Stewart David A , Hoag Keegan F , Irwin David J , Talos Delia M , Jensen Frances E
Published: April 2024

Approximately 22% of Alzheimer’s disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in 5XFAD mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages and be further exacerbated by pentylenetetrazol (PTZ) kindling.

Post-mortem AD temporal cortical tissues from patients with or without seizure history were examined for changes in several markers of E:I balance, including levels of the inhibitory GABAA receptor, the sodium potassium chloride cotransporter 1 (NKCC1) and potassium chloride cotransporter 2 (KCC2) and the excitatory NMDA and AMPA type glutamate receptors. We performed patch-clamp electrophysiological recordings from CA1 neurons in hippocampal slices and examined the same markers of E:I balance in prodromal 5XFAD mice. We next examined 5XFAD mice at chronic stages, after PTZ or control protocols, and in response to chronic mTORC1 inhibitor rapamycin, administered following kindled seizures, for markers of E:I balance.

We found that AD patients with comorbid seizures had worsened cognitive and functional scores and decreased GABAA receptor subunit expression, as well as increased NKCC1/KCC2 ratios, indicative of depolarizing GABA responses. Patch clamp recordings of prodromal 5XFAD CA1 neurons showed increased intrinsic excitability, along with decreased GABAergic inhibitory transmission and altered glutamatergic neurotransmission, indicating that E:I imbalance may occur in early disease stages. Furthermore, seizure induction in prodromal 5XFAD mice led to later dysregulation of NKCC1/KCC2 and a reduction in GluA2 AMPA glutamate receptor subunit expression, indicative of depolarizing GABA receptors and calcium permeable AMPA receptors. Finally, we found that chronic treatment with the mTORC1 inhibitor, rapamycin, at doses we have previously shown to attenuate seizure-induced amyloid-β pathology and cognitive deficits, could also reverse elevations of the NKCC1/KCC2 ratio in these mice.

Our data demonstrate novel mechanisms of interaction between AD and epilepsy and indicate that targeting E:I balance, potentially with US Food and Drug Administration-approved mTOR inhibitors, hold therapeutic promise for AD patients with a seizure history.
Peripherally-derived LGI1-reactive monoclonal antibodies cause epileptic seizures in vivo
Authors: Upadhya Manoj , Kirmann Toni , Wilson Max A , Simon Christian M , Dhangar Divya , Geis Christian , Williams Robyn , Woodhall Gavin , Hallermann Stefan , Irani Sarosh R , Wright Sukhvir K
Published: April 2024

One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures.

We tested this with the molecularly precise monoclonal antibodies directed against LGI1 [LGI1-monoclonal antibodies (mAbs)], derived from patient circulating B cells. These were directed towards both major domains of LGI1, leucine-rich repeat and epitempin repeat, and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied for antibody binding and effects on Kv1.1.

The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield. By comparison to control-Ab injected rats video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events. Memory was not impaired in the novel object recognition test.

Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of direct in vivo epileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation.
A new type of blood–brain barrier aminoacidopathy underlies metabolic microcephaly associated with SLC1A4 mutations
Authors: Odeh Maali , Sajrawi Clara , Majcher Adam , Zubedat Salman , Shaulov Lihi , Radzishevsky Alex , Mizrahi Liron , Chung Wendy K , Avital Avi , Hornemann Thorsten , Liebl Daniel J , Radzishevsky Inna , Wolosker Herman
Published: April 2024

Mutations in the SLC1A4 transporter lead to neurodevelopmental impairments, spastic tetraplegia, thin corpus callosum and microcephaly in children. SLC1A4 catalyses obligatory amino acid exchange between neutral amino acids, but the physiopathology of SLC1A4 disease mutations and progressive microcephaly remain unclear.

Here, we examined the phenotype and metabolic profile of three Slc1a4 mouse models: a constitutive Slc1a4-knockout mouse; a knock-in mouse with the major human Slc1a4 mutation (Slc1a4-K256E); and a selective knockout of Slc1a4 in brain endothelial cells (Slc1a4tie2-cre).

We show that Slc1a4 is a bona fideL-serine transporter at the blood–brain barrier (BBB) and that acute inhibition or deletion of Slc1a4 leads to a decrease in serine influx into the brain. This results in microcephaly associated with decreased L-serine content in the brain, accumulation of atypical and cytotoxic 1-deoxysphingolipids, neurodegeneration, synaptic and mitochondrial abnormalities and behavioural impairments. Prenatal and early postnatal oral administration of L-serine at levels that replenish the serine pool in the brain rescued the observed biochemical and behavioural changes. Administration of L-serine until the second postnatal week also normalized brain weight in Slc1a4-E256K mice.

Our observations suggest that the transport of ‘non-essential’ amino acids from the blood through the BBB is at least as important as that of essential amino acids for brain metabolism and development. We propose that SLC1A4 mutations cause a BBB aminoacidopathy with deficits in serine import across the BBB, required for optimal brain growth, leading to a metabolic microcephaly, which may be amenable to treatment with L-serine.
Exploring the causal role of immune cells in cerebral aneurysm through single-cell transcriptomics and Mendelian randomization analysis
Authors: Yu Yunhu , Tong Shiao , Liu Tao , Cai Yunpeng , Song Yuanmei , Zhou Hang , Jiang Rongcai
Published: April 2024

Cerebral aneurysm (CA) represents a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudo-time trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064–1.435, P = 0.006), as potential risk factors for CA development, while others, like CD28– CD8br %CD8br (OR: 0.883, 95% CI: 0.789–0.988, P = 0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, and potentially guiding future therapeutic strategies targeting specific immune pathways.
A Comparison of Markov and Mechanistic Models for Soil-Transmitted Helminth Prevalence Projections in the Context of Survey Design
Authors: Eyre Max T , Bulstra Caroline A , Johnson Olatunji , de Vlas Sake J , Diggle Peter J , Fronterrè Claudio , Coffeng Luc E
Published: April 2024

Globally, there are over 1 billion people infected with soil-transmitted helminths (STHs), mostly living in marginalized settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The World Health Organization recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education and the delivery of preventive chemotherapy (PC) to school-age children delivered through schools. Progress of STH control programs is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these 2 methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that, although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not decrease despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other neglected tropical diseases.
An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale
Authors: Touloupou Panayiota , Fronterre Claudio , Cano Jorge , Prada Joaquin M , Smith Morgan , Kontoroupis Periklis , Brown Paul , Rivera Rocio Caja , de Vlas Sake J , Gunawardena Sharmini , Irvine Michael A , Njenga Sammy M , Reimer Lisa , Seife Fikre , Sharma Swarnali , Michael Edwin , Stolk Wilma A , Pulan Rachel , Spencer Simon E F , Hollingsworth T Déirdre
Published: April 2024

Background

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging.

Methods

We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment.

Results

Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively.

Conclusions

While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the “tail” of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.
Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?
Authors: Vasconcelos Andreia , King Jonathan D , Nunes-Alves Cláudio , Anderson Roy , Argaw Daniel , Basáñez Maria-Gloria , Bilal Shakir , Blok David J , Blumberg Seth , Borlase Anna , Brady Oliver J , Browning Raiha , Chitnis Nakul , Coffeng Luc E , Crowley Emily H , Cucunubá Zulma M , Cummings Derek A T , Davis Christopher Neil , Davis Emma Louise , Dixon Matthew , Dobson Andrew , Dyson Louise , French Michael , Fronterre Claudio , Giorgi Emanuele , Huang Ching-I , Jain Saurabh , James Ananthu , Kim Sung Hye , Kura Klodeta , Lucianez Ana , Marks Michael , Mbabazi Pamela Sabina , Medley Graham F , Michael Edwin , Montresor Antonio , Mutono Nyamai , Mwangi Thumbi S , Rock Kat S , Saboyá-Díaz Martha-Idalí , Sasanami Misaki , Schwehm Markus , Spencer Simon E F , Srivathsan Ariktha , Stawski Robert S , Stolk Wilma A , Sutherland Samuel A , Tchuenté Louis-Albert Tchuem , de Vlas Sake J , Walker Martin , Brooker Simon J , Hollingsworth T Déirdre , Solomon Anthony W , Fall Ibrahima Socé
Published: April 2024

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021–2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.
The Hidden Hand of Asymptomatic Infection Hinders Control of Neglected Tropical Diseases: A Modeling Analysis
Authors: Rock Kat S , Chapman Lloyd A C , Dobson Andrew P , Adams Emily R , Hollingsworth T Déirdre
Published: April 2024

Background

Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals.

Methods

We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases.

Results

We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission.

Conclusions

Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.
Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti
Authors: Antony Oliver Mary Chriselda , Graham Matthew , Gass Katherine M , Medley Graham F , Clark Jessica , Davis Emma L , Reimer Lisa J , King Jonathan D , Pouwels Koen B , Hollingsworth T Déirdre
Published: April 2024

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings.

Methods

We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84).

Results

Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000–$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective.

Conclusions

Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.
The Growing Threat of NDM-Producing E. coli With Penicillin-Binding Protein 3 Mutations in the United States—Is There a Potential Role for Durlobactam?
Authors: Aitken Samuel L , Pierce Virginia M , Pogue Jason M , Kline Ellen G , Tverdek Frank P , Shields Ryan K
Published: April 2024

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.
Social inequality in admission chances for prestigious higher education programs in Germany: do application patterns matter?
Authors: Finger Claudia , Solga Heike , Elbers Benjamin
Published: April 2024

Research has shown that admission to prestigious higher education programs varies by students' socio-economic status (SES). Access to these programs is characterized by high competition and often rather complex admission procedures. Thus, access may depend not only on students’ performance and decisions to apply but also on their application patterns: Where and how they apply, which may vary by social background due to differences in educational achievement, aspirations, and constraints. Using applications to highly prestigious medical programs in Germany, we examine whether admission chances are socially selective even among the positively selected group of applicants, and whether this is due to SES differences in application patterns or performance. Based on complete application register data, we identify application patterns through cluster analysis. We then used the resulting cluster model to predict cluster membership in the 2018 applicant cohort, for which we collected survey data with information on applicants’ SES, preferences, and motivations. We find that application patterns vary primarily by applicants’ performance (grades and test scores) and SES-specific geographic constraints. However, our multivariate analyses on admission chances show that application patterns do not mediate SES differences in admission chances. Instead, these differences are entirely due to SES differences in applicants’ performance.
‘The Russians are Coming!’ Entangled Peripheries and Cold War Competition in Motorcycle Speedway
Authors: Mills Richard
Published: April 2024

In its heyday, motorcycle speedway packed stadiums on both sides of the Iron Curtain. Via archival research, oral history, and fieldwork in multiple states this essay argues that speedway is uniquely placed to complicate tired Cold War binaries. Regardless of prevailing political systems, it thrived in provincial settings, as tours, itinerant riders, and machinery ensured regular interactions between speedway’s ‘entangled peripheries’. When small-town Swedes and aspirant Soviets challenged the British Commonwealth’s on-track dominance, this sport born at the imperial margins thrust Muslim riders from the Russian step into the limelight, and Australasian world champions harnessed superior Czechoslovak engineering.
By What Jurisdiction? Law, Settler Colonialism, and the Geographical Assumptions of IR Theory
Authors: Irani Freya
Published: April 2024

In this article, I consider critical writings on territory in International Relations, focusing on recent work on U.S. practices of extraterritorial jurisdiction. I suggest that, while such work has importantly traced the multiple ways in which U.S. authority often exceeds the supposed territorial boundaries of the United States, it has nonetheless failed to reckon with the contested and uneven nature of U.S. authority within such supposed boundaries. In particular, IR scholarship has failed to engage with the ways in which U.S. authority has been, and continued to be, contested by Indigenous people and nations. This failure is the product of an assumption that lies at the heart of the discipline—the assumption that Indigenous people are internal to colonizing or settler states. I suggest that the internalization of Indigenous people and Indigenous political organization that is at play in much IR scholarship is not simply a product of a generalized “state-centrism” or a product of histories of settler colonialism, writ large. Rather, at the heart of the territorial assignations and allotments of IR scholarship are assumptions about legal authority or jurisdiction—about who has jurisdiction to define and assign land, about who does not, and what law means at all. Critiquing these assumptions and their political implications, I show the importance of asking: “by what jurisdiction”? That is, what is the legal authority that we implicitly accept and assert when we designate territory in particular ways? The question insists that there are multiple laws (including multiple international laws) at play in global politics and opens up space for critical and postcolonial IR scholars to better take responsibility for their (often implicit) choices between multiple laws.
Detection of drug-resistant malaria in resource-limited settings: efficient and high-throughput surveillance of artemisinin and partner drug resistance
Authors: Fukuda Naoyuki , Yoshida Naoko , Balikagala Betty , Tsuru Ibuki , Ikeda Mie , Hirai Makoto , Anywar Denis A , Odongo-Aginya Emannuel I , Mita Toshihiro
Published: April 2024

Objectives

Artemisinin-resistant Plasmodium falciparum malaria is currently spreading globally, including in Africa. Artemisinin resistance also leads to resistance to partner drugs used in artemisinin-based combination therapies. Sequencing of kelch13, which is associated with artemisinin resistance, culture-based partner drug susceptibility tests, and ELISA-based growth measurement are conventionally used to monitor resistance; however, their application is challenging in resource-limited settings.

Methods

An experimental package for field studies with minimum human/material requirements was developed.

Results

First, qPCR-based SNP assay was applied in artemisinin resistance screening, which can detect mutations within 1 h and facilitate sample selection for subsequent processes. It had 100% sensitivity and specificity compared with DNA sequencing in the detection of the two common artemisinin resistance mutations in Uganda, C469Y and A675V. Moreover, in the partner drug susceptibility test, the cultured samples were dry-preserved on a 96-well filter paper plate and shipped to the central laboratory. Parasite growth was measured by ELISA using redissolved samples. It well reproduced the results of direct ELISA, reducing significant workload in the field (Pearson correlation coefficient: 0.984; 95% CI: 0.975–0.990).

Conclusions

Large-scale and sustainable monitoring is required urgently to track rapidly spreading drug-resistant malaria. In malaria-endemic areas, where research resources are often limited, simplicity and feasibility of the procedure is especially important. Our approach combines a qPCR-based rapid test, which is also applicable to point-of-care diagnosis of artemisinin resistance and centralized analysis of ex vivo culture. The approach could improve efficiency of field experiments and accelerate global drug resistance surveillance.
A detailed analysis of the interpretability of Convolutional Neural Networks for text classification
Authors: Giménez Maite , Fabregat-Hernández Ares , Fabra-Boluda Raül , Palanca Javier , Botti Vicent
Published: April 2024

Convolutional Neural Networks (CNNs) have become ubiquitous in many NLP tasks. However, understanding its process is still an area with much to be done. In this paper, we introduce a method to study the interpretability of CNNs when used for text classification. More specifically, we work on the interpretability of the convolutional filters in the context of sentiment analysis. The framework used in this paper has allowed the understanding of the mechanics of the network when applied to the task of sentiment analysis. The results of the experiments reveal how certain parts of speech (POS) tags are more relevant than others to the classification of a sentence. Furthermore, we also observed a preference for shorter $n$-grams when classifying negative sentiment sequences. Additionally, we detected a certain amount of redundancy among the convolutional filters, thus allowing us to conclude that smaller architectures would have worked for this particular task. This was achieved by computing the relevant metrics to measure the influence of the pertinent property on the desired class. In our case, the concepts treated were POS tags that carry semantic information and properties were related to the convolutional filters.
CD226 promotes renal fibrosis by regulating macrophage activation and migration
Authors: Song Yun , Wang Yazhen , Li Juan , Shen Yuting , Hou Yongli , Fu Zhaoyue , Fang Liang , Jin Boquan , Chen Lihua
Published: April 2024

It has been found that CD226 plays an important role in regulating macrophage function, but its expression and function in macrophages during renal fibrogenesis have not been studied. Our data demonstrated that CD226 expression in macrophages was obviously upregulated in the unilateral ureteral obstruction model, while CD226 deficiency attenuated collagen deposition in renal interstitium along with fewer M1 within renal cortex and renal medulla and a lower level of proinflammatory factors compared to that of control littermates. Further studies demonstrated that Cd226−/− bone marrow–derived macrophages transferring could significantly reduce the tubular injury, collagen deposition, and proinflammatory cytokine secretion compared with that of Cd226+/+ bone marrow–derived macrophages transferring in the unilateral ureteral obstruction model. Mechanistic investigations revealed that CD226 promoted proinflammatory M1 macrophage accumulation in the kidney via suppressing KLF4 expression in macrophages. Therefore, our results uncovered a pathogenic role of CD226 during the development of chronic kidney disease by promoting monocyte infiltration from peripheral blood into the kidney and enhancing macrophage activation toward the inflammatory phenotype by suppressing KLF4 expression.
Growing the global cancer care system: success stories from around the world and lessons for the future
Authors: Dee Edward Christopher , Pramesh C S , Booth Christopher M , Rubagumya Fidel , Mutebi Miriam , Feliciano Erin Jay G , Eala Michelle Ann B , Cerri Giovanni G , Ginsburg Ophira , Gyawali Bishal , Moraes Fabio Ynoe
Published: April 2024

Despite major biomedical advancements in various realms of oncology, the benefits of these developments are not equitably distributed, particularly in underresourced settings. Although much work has described the challenges and systemic barriers in global cancer control, in this article we focus on success stories. This article describes clinical care delivered at Rwanda’s Butaro Cancer Center of Excellence, the cancer research collaborations under India’s National Cancer Grid, and the efforts of Latin America’s Institute of Cancer of São Paulo in advancing cancer care and training. These examples highlight the potential of strategic collaborations and resource allocation strategies in improving cancer care globally. We emphasize the critical role of partnerships between physicians and allied health professionals, funders, and policy makers in enhancing access to treatment and infrastructure, advancing contextualized research and national guidelines, and establishing regional and global collaborations. We also draw attention to challenges faced in diverse global settings and outline benchmarks to measure success in the fight against cancer.
Phenotypic plasticity variations in Phragmites australis under different plant–plant interactions influenced by salinity
Authors: Song Huijia , Guo Xiao , Yang Jingcheng , Liu Lele , Li Mingyan , Wang Jingfeng , Guo Weihua
Published: April 2024

Coastal wetland ecosystems are increasingly threatened by escalating salinity levels, subjecting plants to salinity stress coupled with interactions in the community. Abiotic factors can disrupt the balance between competition and facilitation among plant species. Investigating the effects of different neighboring species and trait plasticity could extend the stress gradient hypothesis and enhance understanding of vegetation distribution and diversity in salt marshes. We conducted a greenhouse experiment and investigated the plastic response of wetland grass Phragmites australis to seven neighboring plants of three functional types (conspecifics, graminoids and forbs) under soil salinity (0 and 10 g/L). Plant height, base diameter, density, leaf thickness, specific leaf area and total and part biomasses were measured. Additionally, the relative interaction index (based on biomass) and the relative distance plasticity index (RDPI) were calculated. Salinity significantly reduced the biomass, height, density and diameter of P. australis. The functional types of neighboring plants also significantly affected these growth parameters. The influence of graminoids on P. australis was negative under 0 g/L, but this negative effect shifted to positive facilitation under 10 g/L. The facilitation effect of forbs was amplified under salinity, both supporting the stress gradient hypothesis. The growth traits of P. australis had a plastic response to salinity and competition, such as increasing belowground biomass to obtain more water and resources. The RDPI was higher under salt conditions than in competitive conditions. The plant–plant interaction response to stress varies with plant functional types and trait plasticity.