bluuebunny/crossref_metadata_2025 huggingface dataset:
Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s disease pathologies
Authors: Minhas Paras S. , Jones Jeffrey R. , Latif-Hernandez Amira , Sugiura Yuki , Durairaj Aarooran S. , Wang Qian , Mhatre Siddhita D. , Uenaka Takeshi , Crapser Joshua , Conley Travis , Ennerfelt Hannah , Jung Yoo Jin , Liu Ling , Prasad Praveena , Jenkins Brenita C. , Ay Yeonglong Albert , Matrongolo Matthew , Goodman Ryan , Newmeyer Traci , Heard Kelly , Kang Austin , Wilson Edward N. , Yang Tao , Ullian Erik M. , Serrano Geidy E. , Beach Thomas G. , Wernig Marius , Rabinowitz Joshua D. , Suematsu Makoto , Longo Frank M. , McReynolds Melanie R. , Gage Fred H. , Andreasson Katrin I.
Published: August 2024

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer’s disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid β and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor–dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter–dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.
Massively parallel analysis of single-molecule dynamics on next-generation sequencing chips
Authors: Aguirre Rivera J. , Mao G. , Sabantsev A. , Panfilov M. , Hou Q. , Lindell M. , Chanez C. , Ritort F. , Jinek M. , Deindl S.
Published: August 2024

Single-molecule techniques are ideally poised to characterize complex dynamics but are typically limited to investigating a small number of different samples. However, a large sequence or chemical space often needs to be explored to derive a comprehensive understanding of complex biological processes. Here we describe multiplexed single-molecule characterization at the library scale (MUSCLE), a method that combines single-molecule fluorescence microscopy with next-generation sequencing to enable highly multiplexed observations of complex dynamics. We comprehensively profiled the sequence dependence of DNA hairpin properties and Cas9-induced target DNA unwinding-rewinding dynamics. The ability to explore a large sequence space for Cas9 allowed us to identify a number of target sequences with unexpected behaviors. We envision that MUSCLE will enable the mechanistic exploration of many fundamental biological processes.
Use of frozen native feces for fecal microbiota transplantation in recurrent
Clostridioides difficile
infection: a simple way to improve the efficiency of donor feces preparation
Authors: Sintes Rachel , McLellan Paul , Navelli Gabriele , Landman Cécilia , Delage Sandrine , Truong Sandrine , Benech Nicolas , Kapel Nathalie , Moreino Sabater Alicia , Schnuriger Aurélie , Eckert Catherine , Bleibtreu Alexandre , Joly Anne-Christine , Sokol Harry
Published: August 2024

Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent
Clostridioides difficile
infection (rCDI). FFP and FNFP were similarly effective with clinical success rates of 76.7% and 86.7% (
P
= 0.32), respectively. FNFP is an efficient procedure that saves resources while maintaining clinical efficacy in rCDI.
Unraveling the distribution pattern and driving forces of soil microorganisms under geographic barriers
Authors: Rao Gu , Song Wen-Long , Yan Shu-Zhen , Chen Shuang-Lin
Published: August 2024

The Altai Mountains (ALE) and the Greater Khingan Mountains (GKM) in northern China are forest regions dominated by coniferous trees. These geographically isolated regions provide an ideal setting for studying microbial biogeographic patterns. In this study, we employed high-throughput techniques to obtain DNA sequences of soil myxomycetes, bacteria, and fungi and explored the mechanisms underlying the assembly of both local and cross-regional microbial communities in relation to environmental factors. Our investigation revealed that the environmental heterogeneity in ALE and GKM significantly affected the succession and assembly of soil bacterial communities at cross-regional scales. Specifically, the optimal environmental factors affecting bacterial Bray-Curtis similarity were elevation and temperature seasonality. The spatial factors and climate change impact on bacterial communities under the geographical barriers surpassed that of local soil microenvironments. The assembly pattern of bacterial communities transitions from local drift to cross-regional heterogeneous selection. Environmental factors had a relatively weak influence on myxomycetes and fungi. Both soil myxomycetes and fungi faced considerable dispersal limitation at local and cross-regional scales, ultimately leading to weak geographical distribution patterns.

IMPORTANCE

The impact of environmental selection and dispersal on the soil microbial spatial distribution is a key concern in microbial biogeography, particularly in large-scale geographical patterns. However, our current understanding remains limited. Our study found that soil bacteria displayed a distinct cross-regional geographical distribution pattern, primarily influenced by environmental selection. Conversely, the cross-regional geographical distribution patterns of soil myxomycetes and fungi were relatively weak. Their composition exhibited a weak association with the environment at local and cross-regional scales, with assembly primarily driven by dispersal limitation.
Signal recognition particle RNA is critical for genetic competence and virulence of
Streptococcus pneumoniae
Authors: Lin Jingjun , Chong Sook Yin , Oh Myung Whan , Lew Shi Qian , Zhu Luchang , Zhang Xuejin , Witola William H. , Lau Gee W.
Published: August 2024

Streptococcus pneumoniae
(pneumococcus) causes a wide range of important human infectious diseases, including pneumonia, pneumonia-derived sepsis, otitis media, and meningitis. Pneumococcus produces numerous secreted proteins that are critical for normal physiology and pathogenesis. The membrane targeting and translocation of these secreted proteins are partly mediated by the signal recognition particle (SRP) complex, which consists of 4.5S small cytoplasmic RNA (ScRNA), and the Ffh, and FtsY proteins. Here, we report that pneumococcal ∆
scRNA
, ∆
ffh,
and ∆
ftsY
mutants were significantly impaired in competence induction, competence pili production, exogenous DNA uptake, and genetic transformation. Also, the ∆
scRNA
mutant was significantly attenuated in the mouse models of bacteremia and pneumonia. Interestingly, unlike the ∆
scRNA
, both ∆
ffh
and ∆
ftsY
mutants had growth defects on Todd-Hewitt Agar, which were alleviated by the provision of free amino acids or serum. Differences in nutritional requirements between ∆
ffh
and ∆
ftsY
vs ∆
scRNA
suggest that Ffh and FtsY may be partially functional in the absence of ScRNA. Finally, the insertase YidC2, which could functionally rescue some SRP mutations in other streptococcal species, was not essential for pneumococcal genetic transformation. Collectively, these results indicate that ScRNA is crucial for the successful development of genetic competence and virulence in pneumococcus.

IMPORTANCE

Streptococcus pneumoniae
(pneumococcus) causes multiple important infectious diseases in humans. The signal recognition particle (SRP) complex, which comprised 4.5S small cytoplasmic RNA (ScRNA), and the Ffh and FtsY proteins, mediates membrane targeting and translocation of secreted proteins in all organisms. However, the role of SRP and ScRNA has not been characterized during the induction of the competence system for genetic transformation and virulence in pneumococcus. By using a combination of genetic, biochemical, proteomic, and imaging approaches, we demonstrated that the SRP complex plays a significant role in membrane targeting of competence system-regulated effectors important for genetic transformation, virulence during bacteremia and pneumonia infections, and nutritional acquisition.
Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis
Authors: Hsu Tien-Wei , Tsai Chia-Kuang , Kao Yu-Chen , Thompson Trevor , Carvalho Andre F , Yang Fu-Chi , Tseng Ping-Tao , Hsu Chih-Wei , Yu Chia-Ling , Tu Yu-Kang , Liang Chih-Sung
Published: August 2024

Objective

To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding.

Design

Systematic review and Bayesian network meta-analysis.

Data sources

Medline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 12 October 2023.

Eligibility criteria for selecting studies

Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants.

Data extraction and synthesis

The primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials.

Results

Placebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference −3.90 (95% credible interval −7.10 to −0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo.

Conclusions

Of the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small.

Systematic review registration

PROSPERO, CRD42023469014.
Optimising the indications for biliary stent placement during endoscopic retrograde cholangiopancreatography: a quality improvement initiative to enhance patient care and reduce healthcare resource utilisation
Authors: Alhaidari Suliman , Alzahrani Ibrahim , Alhanaee Manar , Decanini Alan , Mohamed Mahmod , Zepeda-Gomez Sergio , Mathura Pamela , Zhang Julie , Sandha Gurpal
Published: August 2024

Background

A retrospective chart audit was performed to review biliary stent utilisation from January 2020 to January 2021. Non-guideline-based stent insertion was identified in 16% of patients with common bile duct (CBD) stones presenting for endoscopic retrograde cholangiopancreatography (ERCP). To improve this knowledge-practice gap, a quality improvement (QI) intervention was devised and trialled.

Aim

To synchronise clinical indications for biliary stent insertion in patients with CBD stones in accordance with published guidelines.

Methods

Using a QI pre–post study design, chart audits were completed and shared with the ERCP team (n=6). Indication for biliary stent insertion was compared to published guidelines assessed by two reviewers independently (kappastatistic calculated). The QI intervention included an education session and quarterly practice audits. An interrupted time series with segmented regression was completed.

Results

A total of 661 patients (337 F), mean age 59±19 years (range 12–98 years), underwent 885 ERCPs during this postintervention period. Of 661 patients, 384 (58%) were referred for CBD stones. A total of 192 biliary stents (105 plastic, 85 metal) were placed during the first ERCP (192/661, 29%), as compared with the preintervention year (223/598, 37%, p=0.2). Furthermore, 13/192 stents (7%) were placed not in accordance with published guidelines (kappa=0.53), compared with 63/223 (28%) in the preintervention year (p<0.0001). A 75% reduction in overall avoidable stent placement was achieved with a direct cost avoidance of $C97 500. For the CBD stone subgroup, there was an 88% reduction in avoidable biliary stent placement compared with the preintervention year (8/384, 2% vs 61/375, 16%, p<0.0001).

Conclusions

Education with audit and feedback supported the closing of a knowledge-to-practice gap for biliary stent insertion during ERCP, especially in patients with CBD stones. This has resulted in a notable reduction of avoidable stent placements and additional follow-up ERCPs and an overall saving of healthcare resources.
Effect of multimorbidity on depressive status in older Chinese adults: evidence from the China Health and Retirement Longitudinal Study (CHARLS)
Authors: Chao Guanqun , Zhang Lan , Zhan Zheli , Bao Yang
Published: August 2024

Objective

This study aims to further explore the relevant influencing factors of depression and explore the correlation between multimorbidity coexistence and depression to find the goals and methods of early intervention of depression in the elderly.

Design

This study adopts a cross-sectional approach.

Setting

The study population of this project came from the China Health and Retirement Longitudinal Study. Depression was grouped according to the 10-item version of Centre for Epidemiological Research Depression Scale. Chronic diseases, height, weight, grip strength, education, marital status, alcohol consumption, exercise and other indicators were included in the analysis.

Participants

2239 adults over 60 years of age were included.

Results

The proportion of women in the depression group was higher (p<0.001). The depression group had a lower grip strength than the control group (p<0.05). The sleep duration was shorter in the depression group (p<0.001). There were differences in education, marital status and alcohol consumption in the depression group (p<0.05). The depression group might have more types of coexisting chronic diseases (p<0.001). The depression group was more likely to have hypertension, dyslipidaemia, chronic lung diseases, heart attack, stroke, stomach disease and memory-related disease. Grip strength was connected with the risk of depression in the elderly (0.971 (95% CI 0.959 to 0.984)). Sleep (0.827 (95% CI 0.785 to 0.872) and education level (0.790 (95% CI 0.662 to 0.942) were related to the risk of depression in the elderly. Concomitant chronic diseases could affect the risk of depression in the elderly (1.455 (95% CI 1.243 to 1.703)).

Conclusion

The coexistence of multiple chronic diseases and depression is very common in the elderly. The coexistence of multiple chronic diseases is more common in older women and older depressed people. With the increase in the number of chronic diseases, the risk of depression in the elderly is significantly increased.
National retrospective registry survey on the epidemiology of sarcoidosis in Finland 2002−2022
Authors: Salonen Johanna , Kaarteenaho Riitta
Published: August 2024

Background

The prevalence of sarcoidosis is known to be high in the Nordic countries. There are no recent research data on the incidence or prevalence of sarcoidosis in Finland. Our aim was to investigate the epidemiology of sarcoidosis in Finland through a retrospective registry-based study.

Methods

We made an information request to the Hilmo database on patients who had been treated in Finnish specialised care with a main diagnosis related to sarcoidosis. Data were requested for the period 1 January−31 December for the years 2002, 2012 and 2022. In addition, we examined the age and gender distribution and regional differences in these variables between the five university hospital districts covering the whole of Finland.

Results

The incidence of sarcoidosis was 17‒19/100 000/year throughout the follow-up period. The prevalence of sarcoidosis in the ≥18-year-old population had risen from 85/100 000 in 2002–106/100 000 in 2022. There were considerable differences between university hospital districts: The highest prevalence rate was 170/100 000 in the Tampere University Hospital district in 2022, which was twice as high as in the Helsinki University Hospital district (84/100 000). The proportion of pulmonary sarcoidosis in all sarcoidosis cases decreased from 62% to 45% while the proportion of multiorgan sarcoidosis (D86.8) increased from 11% to 34%. The incidence of sarcoidosis was 15/100 000 and the prevalence was 82/100 000 in the age groups of ≥60 years in 2002. In 2022, the incidence in this same age group had risen to 20/100 000 and the prevalence to 109/100 000. In the ≥60-year-old population, the proportion of D86.8 increased from 11% to 35%.

Conclusions

Sarcoidosis was a more common disease in Finland than in previous studies. Multiorgan sarcoidosis among the elderly has increased over the past 20 years. This might be explained by changes in environmental factors associated with sarcoidosis. Significant regional differences in prevalence might be partly explained by familial clustering.
Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of adults in the PATH Study in 2017–2019 vs 2019–2021
Authors: Brouwer Andrew F , Jeon Jihyoun , Jimenez-Mendoza Evelyn , Land Stephanie R , Holford Theodore R , Friedman Abigail S , Tam Jamie , Mistry Ritesh , Levy David T , Meza Rafael
Published: August 2024

Introduction

The use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the lung injuries outbreak, flavour bans, Tobacco 21 and the COVID-19 pandemic.

Methods

Using the Population Assessment of Tobacco and Health Study, we applied a multistate transition model to 28 061 adults in waves 4–5 (2017–2019) and 24 584 adults in waves 5–6 (2019–2021), estimating transition rates for initiation, cessation and switching products for each period overall and by age group.

Results

Cigarette initiation among adults who never used either product decreased from 2017–2019 to 2019–2021, but ENDS initiation did not significantly change. The persistence of ENDS-only use remained high (75%–80% after 1 year). Cigarette-only use transitions remained similar (88% remaining, 7% to non-current use and 5% to dual or ENDS-only use). In contrast, dual use to ENDS-only transitions increased from 9.5% (95% CI 7.3% to 11.7%) to 20.0% (95% CI 17.4% to 22.6%) per year, decreasing the persistence of dual use. The dual to cigarette-only use transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18–24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use.

Conclusions

The persistence of ENDS use among adults remained high in 2019–2021, but a larger fraction of dual users transitioned to ENDS-only use compared with 2017–2019. Because the fraction of cigarette-only users switching to dual use remained low, especially among older adults, the public health implications of this change are minimal.
Progressive failure of helical anchors in sand under monotonic uplift loading
Authors: Duverneuil Pierre-Yves , Gaudin Christophe , Bienen Britta , Bransby Fraser
Published: August 2024

Helical anchors have been widely used by the onshore industry and are now being considered as anchors for offshore renewable energy infrastructure. As a step towards better understanding of helical anchor behaviour, this paper presents an investigation of the deformation mechanisms observed in centrifuge model tests of a single plate subjected to drained monotonic uplift loading in sand. The particle image velocimetry/digital image correlation technique was used to provide visualisation of soil movements leading to the identification of strain fields around the anchor model for different sand relative densities and plate embedment ratios. Two mechanisms were identified, which govern the volume change and particle displacement in the vicinity of the anchor during uplift.
Gravitational radiation in generalized Brans–Dicke theory: compact binary systems
Authors: Mahmoudi S. , Hendi S. H.
Published: August 2024

This paper investigates the generation and properties of gravitational radiation within the framework of generalized Brans–Dicke (GBD) theory, with a specific emphasis on its manifestation in compact binary systems. The study begins by examining the weak field equations in GBD theory, laying the foundation for subsequent analyses. Solutions to the linearized field equations for point particles are then presented, providing insights into the behavior of gravitational fields in the context of GBD theory. The equation of motion of point mass is explored, shedding light on the dynamics of compact binary systems within the GBD framework. The primary focus of this study lies in the comprehensive exploration of gravitational radiation generated by compact binaries. The energy momentum tensor and the associated gravitational wave (GW) radiation power in GBD theory are investigated, elucidating the relationship between these fundamental concepts. Furthermore, detailed calculations are provided for the GW radiation power originating from both tensor fields and scalar fields. Based on our calculations, both scalar fields contribute to GW radiation by producing dipole radiation. We also study the period derivative of compact binaries in this theory. By comparing with the observational data of the orbital period derivative of the quasicircular white dwarf-neutron star binary PSR J1012+5307, we put bounds on the two parameters of the theory: the Brans–Dicke coupling parameter $$\omega _{0}$$

ω
0

and the mass of geometrical scalar field $$m_f$$

m
f

, resulting in a lower bound $$\omega _{0}>6.09723\times 10^6$$

ω
0

>
6.09723
×

10
6

for a massless BD scalar field and the geometrical field whose mass is smaller than $$10^{-29} \text { GeV}$$

10

-
29

GeV

. The obtained bound on $$\omega _0$$

ω
0

is two orders of magnitude stricter than those derived from solar system data. Finally, we find the phase shift that GWs experience in the frequency domain during their propagation. These calculations offer a quantitative understanding of the contributions from different components within the GBD theory, facilitating a deeper comprehension of the overall behavior and characteristics of gravitational radiation.
About this title - Oceanic Gateways: Modern and Ancient Analogues and their Conceptual and Economic Implications
Authors: Hernández-Molina F. J. , Davoli G. , Stirling E. J. , Chiarella D. , Viana A. R.
Published: August 2024

This Special Publication takes a multidisciplinary approach to oceanic gateways and palaeo-gateways, bringing together contributions that are linked to: tectonic controls; oceanographic, palaeoceanographic and sedimentary processes; sedimentary deposits; data integration and multidisciplinary analysis; polar regions; and the implications for energy geosciences.
FAJITA: Stateful Packet Processing at 100 Million pps
Authors: Ghasemirahni Hamid , Farshin Alireza , Scazzariello Mariano , Maguire Gerald Q. , Kostić Dejan , Chiesa Marco
Published: August 2024

Data centers increasingly utilize commodity servers to deploy low-latency Network Functions (NFs). However, the emergence of multi-hundred-gigabit-per-second network interface cards (NICs) has drastically increased the performance expected from commodity servers. Additionally, recently introduced systems that store packet payloads in temporary off-CPU locations (e.g., programmable switches, NICs, and RDMA servers) further increase the load on NF servers, making packet processing even more challenging. This paper demonstrates existing bottlenecks and challenges of state-of-the-art stateful packet processing frameworks and proposes a system, called FAJITA, to tackle these challenges & accelerate stateful packet processing on commodity hardware. FAJITA proposes an optimized processing pipeline for stateful network functions to minimize memory accesses and overcome the overheads of accessing shared data structures while ensuring efficient batch processing at every stage of the pipeline. Furthermore, FAJITA provides a performant architecture to deploy high-performance network functions service chains containing stateful elements with different state granularities. FAJITA improves the throughput and latency of high-speed stateful network functions by ~2.43x compared to the most performant state-of-the-art solutions, enabling commodity hardware to process up to ~178 Million 64-B packets per second (pps) using 16 cores.
SQUID: Faster Analytics via Sampled Quantile Estimation
Authors: Ben Basat Ran , Einziger Gil , Han Wenchen , Tayh Bilal
Published: August 2024

Streaming algorithms are fundamental in the analysis of large and online datasets. A key component of many such analytic tasks is
q
-MAX, which finds the largest
q
values in a number stream. Modern approaches attain a constant runtime by removing small items in bulk and retaining the largest
q
items at all times. Yet, these approaches are bottlenecked by an expensive quantile calculation. This work introduces a quantile-sampling approach called SQUID and shows its benefits in multiple analytic tasks. Using this approach, we design a novel weighted heavy hitters data structure that is faster and more accurate than the existing alternatives. We also show SQUID's practicality for improving network-assisted caching systems with a hardware-based cache prototype that uses SQUID to implement the cache policy. The challenge here is that the switch's dataplane does not allow the general computation required to implement many cache policies, while its CPU is orders of magnitude slower. We overcome this issue by passing just SQUID's samples to the CPU, thus bridging this gap. In software implementations, we show that our method is up to 6.6x faster than the state-of-the-art alternatives when using real workloads. For switch-based caching, SQUID enables a wide spectrum of data-plane-based caching policies and achieves higher hit ratios than the state-of-the-art P4LRU.
A Hierarchical Blockchain supporting Dynamic Locality by Extending Execute-Order-Validate Architecture
Authors: Jo Yongrae , Park Chanik
Published: August 2024

Blockchain scalability is an active area of research. One of the promising approaches is the execute-order-validate (X-O-V) blockchain architecture, which leverages high concurrency. Meanwhile, many transactions exhibit dynamic locality—a workload characteristic with a high degree of locality that changes over time (e.g., due to the mobility of devices). In this paper, we propose DyloChain, a hierarchical blockchain supporting dynamic locality by extending the X-O-V architecture across sharding zones. In DyloChain's hierarchy, higher-level servers (called M-nodes) are responsible for cross-zone communication with a main chain to ensure global consistency and availability, while lower-level servers (called L-nodes) validate local blocks with a local chain. To support dynamic locality, DyloChain suggests an order-execute-order-validate (O-X-O-V) transaction processing model that extends the X-O-V model to accommodate the hierarchical structure. Specifically, the O-X-O-V model optimizes efficiency through speculative local updates on each local chain (O-X) for the early removal of potential conflicts within a zone and enables high parallelism across zones. Subsequently, the model aggregates these local blocks onto the main chain (O-V), ensuring a globally consistent total order across zones. This is facilitated by an extended validation procedure that detects interferences between concurrently dependent transactions across zones. DyloChain resolves interferences using a state synchronization protocol that synchronizes the corresponding main states of the interfered local states into the involved local chains. DyloChain improves locality by employing a state reshard protocol that transfers a user's state ownership between source and destination local chains by atomically committing user-issued reshard requests to the involved chains. We implement and conduct comprehensive performance evaluations of DyloChain under various configurations.
Technology and the Global Economy
Authors: Eaton Jonathan , Kortum Samuel
Published: August 2024

Interpreting individual heterogeneity in terms of probability theory has proved powerful in connecting behavior at the individual and aggregate levels. Returning to Ricardo's focus on comparative efficiency as a basis for international trade, much recent quantitative equilibrium modeling of the global economy builds on particular probabilistic assumptions about technology. We review these assumptions and discuss how they deliver a unified framework underlying a wide range of static and dynamic equilibrium models.
Moral Boundaries
Authors: Enke Benjamin
Published: August 2024

This article reviews the growing economics literature that studies the politico-economic impacts of heterogeneity in moral boundaries across individuals and cultures. The so-called universalism-versus-particularism cleavage has emerged as a main organizing principle behind various salient features of contemporary political competition, including individual-level and spatial variation in voting, the realignment of rich liberals and poor conservatives, the internal structure of ideology, and the moral content of political messaging. A recurring theme is that the explanatory power of universalism for left-wing policy views and voting is considerably larger than that of traditional economic variables. Looking at the origins of heterogeneity in universalism, an emerging consensus is that cross-group variation is partly economically functional and reflects that morality evolved to support cooperation in economic production. This insight organizes much work on how kinship systems, market exposure, political institutions, and ecology have shaped universalism through their impacts on the relative benefits of localized and impersonal interactions.
COBRAPRO: An Open-Source Software for the Doyle-Fuller-Newman Model with Co-Simulation Parameter Optimization Framework
Authors: Ha Sara , Onori Simona
Published: August 2024

This paper presents COBRAPRO, a new open-source Doyle-Fuller-Newman (DFN) model software package with an integrated closed-loop parameter optimization routine. A key challenge in DFN model parameterization is that parameters measured from cell tear-down experiments cannot be directly used in simulations, and parameter identification is required to accurately reflect real-world battery dynamics However, existing open-source DFN codes lack the capability to perform parameter identification and operate in open-loop mode. COBRAPRO addresses this gap by implementing a systematic parameterization pipeline to accurately determine parameters using battery current and voltage data. Concepts from structural and practical identifiability are utilized to determine parameters that can be fixed to their experimental values and parameters that are suitable for optimization. In the parameter identification process, particle swarm optimization is used to minimize the error between experimental data and simulation results. Additionally, COBRAPRO incorporates a robust method to determine consistent initial conditions and utilizes a fast numerical solver for improved performance. We demonstrate COBRAPRO’s parameter identification framework on reference performance test data obtained from LG INR21700-M50T cells. The parameterized model is validated against driving cycle data, showing good agreement between the experimental and simulation results.
Optimal Design of a Binder-Free Manganese/Cobalt Bilayer Bifunctional Catalyst for Rechargeable Zinc–Air Batteries
Authors: Kiso Takayuki , Higo Tomoya , Yoshida Wataru , Katayama Yu , Nakayama Masaharu
Published: August 2024

We have developed a bilayer film comprising cobalt oxyhydroxide (CoOOH) underlayer and manganese dioxide (MnO2) upper layer, which are active toward oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), respectively. The bilayer bifunctional catalyst is synthesized by electrodepositing cobalt hydroxide (Co(OH)2) on a porous carbon paper (CP) and subsequently immersing the obtained Co(OH)2/CP in a potassium permanganate (KMnO4) solution without binders or conductive additives. Specifically, electron transfer between the already-deposited Co(OH)2 and MnO4
– proceeded in the solution, yielding MnO2, until all the Co ions become trivalent, after which self-terminates. The proposed method only allows for the construction of the minimum required bifunctional catalyst only at the reaction site of the gas-diffusion electrode, i.e., at the so-called three-phase interface, thus remarkably increasing catalyst utilization while improving reactant and product diffusions. The developed catalyst shows stable MnO2/CoOOH cycles at |20| mA cm–2 with a minimal difference (0.764 V) between the OER and ORR potentials, reflecting the structural advantage of the proposed catalyst. This work proposes efficient bifunctional catalysts having spatially separated OER/ORR reactive sites that can be synthesized via the simple and scalable electrochemical method, which does not require the skill and optimization of binder and electron-conducting additives.
Circulating interleukin-33 levels in obesity and type 2 diabetes: a systematic review and meta-analysis
Authors: Missous Ghalia , Van Panhuys Nicholas
Published: August 2024

Our research finds an inconclusive relationship between IL-33 serum levels in individuals with type 2 diabetes (T2D) and nondiabetic individuals with obesity. In addition, we note a potential gender association with IL-33 serum levels. Further studies with larger cohorts are required to assess the significance of serum IL-33 in T2D and obesity. Urgent standardization is needed in IL-33 quantification and reporting methods for reliable comparisons.
Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease
Authors: Gaspar Rafael Calais , Sakuma Ikki , Nasiri Ali , Hubbard Brandon T. , LaMoia Traci E. , Leitner Brooks P. , Tep Samnang , Xi Yannan , Green Eric M. , Ullman Julie C. , Petersen Kitt Falk , Shulman Gerald I.
Published: August 2024

We investigated the effects of small molecule inhibition of glycogen synthase I (GYS1) on glucose metabolism in a mouse model of Pompe disease. GYS1 inhibition reduces abnormal glycogen accumulation and molecular biomarkers associated with Pompe disease while also improving glucose intolerance. Our results collectively demonstrate that the GYS1 inhibitor represents a novel approach to substrate reduction therapy for Pompe disease.
Mammalian copper homeostasis: physiological roles and molecular mechanisms
Authors: Lutsenko Svetlana , Roy Shubhrajit , Tsvetkov Peter
Published: August 2024

In the past decade, evidence for the numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described. Significant progress has been made in the mechanistic studies of two classic disorders of Cu metabolism, Menkes disease and Wilson’s disease, which paved the way for novel approaches to their treatment. The discovery of cuproptosis and the role of Cu in cell metastatic growth have markedly increased interest in targeting Cu homeostatic pathways to treat cancer. In this review, we summarize the established concepts in the field of mammalian Cu physiology and discuss how new discoveries of the past decade expand and modify these concepts. The roles of Cu in brain metabolism and in cell functional speciation and a recently discovered regulated cell death have attracted significant attention and are highlighted in this review.
A Miniaturized High‐Gain Circular Coaxial‐Fed Radiator Filtering Antenna with Configurable Radiation Nulls for Modern 5G Applications
Authors: Verma Ravi Prakash , Gupta Ashish , Sahu Bhagirath
Published: August 2024

In this paper, a low‐profile, high‐gain filtering antenna is proposed and developed for n‐77 (3300–4200 MHz) and n‐78 band (3300−3800 MHz) applications. The suggested filtering antenna is derived from a circular patch antenna. To efficiently reduce the harmonics, in the lower and upper stopbands, a pair of sectoral arcs and rectangular slots is etched out from the driven circular patch. Furthermore, the resultant structure is surrounded by a ring split at three different locations. Simulation studies reveal that this ring with three sectors is coupled with a driven patch and is highly responsible for extending the impedance bandwidth in the passband. This coupling also contributes to an extranull in the upper stopband region. In order to validate the simulated results, a prototype is fabricated, tested, and found that the measured results are consistent with the simulated one. The suggested filtering antenna, with a low profile of 0.0194λ0, demonstrates a wide fractional bandwidth of 10.2% ranging from 3.52 to 3.90 GHz, centred at 3.7 GHz. The maximum peak gain of 7.68 dB is achieved within the passband. Three configurable radiation nulls, first at 3.36 GHz, near the lower band edge; second at 4.04 GHz; and third at 4.24 GHz, near the upper band‐edge frequencies, are generated to achieve fine out‐of‐band suppression levels.
Biological and Physical Characterization of Surface‐Modified Grade V Titanium Alloy
Authors: Kakunje Mahesh , Nambiar Supriya , Isloor Arun M. , Kabekkodu Shamaprasada , Bhat Udaya
Published: August 2024

Surface modification and biomimetic approaches have been widely used to enhance bioinert substances. It is not very clear whether surface alterations and polymer coatings on titanium make it more biologically active and enhance cell adhesion. We tried to focus on the physical and biological characterization of surface‐modified titanium disks. Four different surface modifications were done for the titanium disks, ranging from acid etching, sandblasting, polydopamine coating, and polydopamine‐based chitosan coating, and were compared with disks without any surface modification. The disks were studied for physical characteristics like surface roughness and contact angle. Human gingival fibroblasts were used to investigate the biological effects of surface modification of titanium alloy surfaces. The wettability of chitosan‐coated, acid‐etched, and polydopamine‐coated titanium was much better than that of the sandblasted surface, indicating that surface energy was higher for acid‐etched and coated surfaces than others. The cell seeding with fibroblasts showed increased adhesion to the smoother surfaces as compared to the rougher surfaces. Polydopamine coatings on titanium disks showed the most favorable physical and biological properties compared to others and can be a good surface coating for in vivo implants.
Approach for Identifying the Impact of Local Wind and Spatial Conditions on Wind Turbine Blade Geometry
Authors: Woźniak Agnieszka , Kluczek Aldona , Nycz Paweł D.
Published: August 2024

Efficient wind turbine blade design is crucial, yet current models often fail to fully account for variations in wind inflow due to terrain differences, particularly wind shear. This article aims to verify the theoretical method of designing the geometry of wind turbine blades. The proposed model, which combines the BEM method and the vortex method, was developed to consider the nonuniform inflow caused by wind shear. Model verification employed an explanatory sequential process focusing on two perspectives. First, it examines the correlation between the theoretical terrain roughness coefficient and the blade geometry. Second, it analyzes the relationship between the type of terrain (terrain roughness) and the design of wind turbine blades in two real locations in southeastern Poland. The results highlight the importance of accurate assessment of wind speed and spatial conditions to optimize the use of local wind resources in electricity production. It is suggested that adapting wind turbine blade geometry to the plant’s location will improve resource utilization, providing insight for energy decision‐makers. The findings highlight the importance of considering wind shear when designing blades for varying terrain. The methodology is presented on the example of a wind power plant, and at the end of the article, potential directions of future research in this field are outlined.
Development and Effect of an Interactive Simulated Education Program for Psychological First Aid: A Randomized Controlled Trial
Authors: Choi Eun-Joo , Choi Yun-Jung
Published: August 2024

Background. Considering the importance of psychological first aid, which is the first priority when a disaster occurs, developing a web‐based simulation training program for nurses and confirming its effectiveness is necessary. Aim. This study aimed to develop an interactive simulated education program as a psychological first aid program for nurses and verify its effectiveness. Participants. Nurses working in hospitals and the community who had not participated in psychological first aid training in the last year were recruited. Methods. A web‐based interactive simulated educational program for psychological first aid was developed. To verify its effectiveness, a randomized controlled trial design was used. The experimental group participated in a web‐based educational program, while the control group was provided self‐learning data in the form of e‐books. The program’s effects on disaster response core competencies, problem‐solving abilities, and self‐leadership capacity were measured. We used descriptive statistics to analyze the general characteristics, and independent t‐tests were used to analyze the differences before and after the intervention. Results. The core competencies for disaster response (t = −2.239, p < 0.05, Cohen’s d = 0.59), problem‐solving abilities (t = −2.753, p < 0.01, Cohen’s d = 0.72), and self‐leadership capacity (t = −2.073, p < 0.05, Cohen’s d = 0.54) showed a statistically significant difference between groups. Conclusions. The web‐based simulation education program for psychological first aid training developed in this study effectively enhanced nurses’ ability to respond to disasters and improved their problem‐solving abilities and self‐leadership capacity. Thus, nurses can use the educational program as a tool to learn psychological first aid. This trial is registered with KCT0008965.
Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody–Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Skidmore Lillian K. , Mills David , Kim Ji Young , Knudsen Nick A. , Nelson Jay D. , Pal Manoj , Wang Jianing , GC Kedar , Gray Michael J. , Barkho Wisam , Nagaraja Shastri Prathap , Ramprasad Mysore P. , Tian Feng , O’Connor Daniel , Buechler Ying J. , Zhang Shawn Shao-Hui
Published: August 2024

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard-of-care androgen deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as an mCRPC tumor antigen with overexpression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids into proteins at selected sites, we have developed ARX517, an antibody–drug conjugate composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a noncleavable polyethylene glycol linker and stable oxime conjugation enabled via synthetic amino acid protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice and dose-dependent antitumor activity in both enzalutamide-sensitive and -resistant cell line–derived xenograft and patient-derived xenograft models of prostate cancer. Repeat-dose toxicokinetic studies in nonhuman primates demonstrated that ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a phase I clinical trial (NCT04662580).