bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonreciprocal transport in the superconducting state of the chiral crystal NbGe2
Authors: Liu 刘 Yonglai 永来 , Xu 许 Xitong 锡童 , He 何 Miao 苗 , Zhao 赵 Haitian 海天 , Zeng 曾 Qingqi 庆祺 , Yang 杨 Xingyu 星宇 , Zou 邹 Youming 优鸣 , Du 杜 Haifeng 海峰 , Qu 屈 Zhe 哲
Published: March 2024

Due to the lack of inversion, mirror or other roto-inversion symmetries, chiral crystals possess a well-defined handedness which, when combined with time-reversal symmetry breaking from the application of magnetic fields, can give rise to directional dichroism of the electrical transport phenomena via the magnetochiral anisotropy. In this study, we investigate the nonreciprocal magneto-transport in microdevices of NbGe2, a superconductor with structural chirality. A giant nonreciprocal signal from vortex motions is observed during the superconducting transition, with the ratio of nonreciprocal resistance to the normal resistance γ reaching 6×105 T−1⋅A−1. Interestingly, the intensity can be adjusted and even sign-reversed by varying the current, the temperature, and the crystalline orientation. Our findings illustrate intricate vortex dynamics and offer ways of manipulation on the rectification effect in superconductors with structural chirality.
Cholesterol-induced deformation of the gramicidin-A channel inhibiting potassium ion binding and transport
Authors: Xiao 肖 Pan 盼 , Cao 曹 Yu 宇 , Zhu 朱 Jin 瑾 , Liang 梁 Qing 清
Published: March 2024

Gramicidin A (gA) is a kind of antibiotic peptide produced by bacillus brevis and it can dimerize across lipid bilayers to form a monovalent cation channel. In this work, we investigate the impact of cholesterol in the lipid bilayer on the binding of potassium ions with the gA channel and the transport of the ions across the channel. The results indicate that cholesterol can significantly influence the conformational stability of the gA channel and cause the channel deformation which inhibits the potassium ion binding with the channel and transport across the channel. The work provides some molecular insights into understanding of influence of lipids on the activity of gA channel in both model membranes and plasma membranes of intact cells.
Digitization of Astronomical Photographic Plates of China and Astrometric Measurement of Single-exposure Plates
Authors: Shang 商 Zheng-Jun 正君 , Yu 于 Yong 涌 , Wang 王 Liang-Liang 亮亮 , Yang 杨 Mei-Ting 美婷 , Yang 杨 Jing 静 , Shen 沈 Shi-Yin 世银 , Liu 刘 Min 敏 , Xu 徐 Quan-Feng 权峰 , Cui 崔 Chen-Zhou 辰州 , Fan 樊 Dong-Wei 东卫 , Tang 唐 Zheng-Hong 正宏 , Zhao 赵 Jian-Hai 建海
Published: March 2024

From the mid-19th century to the end of the 20th century, photographic plates served as the primary detectors for astronomical observations. Astronomical photographic observations in China began in 1901, and over a century, a total of approximately 30,000 astronomical photographic plates were captured. These historical plates play an irreplaceable role in conducting long-term, time-domain astronomical research. To preserve and explore these valuable original astronomical observational data, Shanghai Astronomical Observatory has organized the transportation of plates, taken during nighttime observations from various stations across the country, to the Sheshan Plate Archive for centralized preservation. For the first time, plate information statistics were calculated. On this basis, the plates were cleaned and digitally scanned, and finally digitized images were acquired for 29,314 plates. In this study, using Gaia DR2 as the reference star catalog, astrometric processing was carried out successfully on 15,696 single-exposure plates, including object extraction, stellar identification, and plate model computation. As a result, for long focal length telescopes, such as the 40 cm double-tube refractor telescope, the 1.56 m reflector telescope at Shanghai Astronomical Observatory, and the 1m reflecting telescope at Yunnan Astronomical Observatory, the astrometric accuracy obtained for their plates is approximately 0.″1–0.″3. The distribution of astrometric accuracy for medium and short focal length telescopes ranges from 0.″3 to 1.″0. The relevant data of this batch of plates, including digitized images and a stellar catalog of the plates, are archived and released by the National Astronomical Data Center. Users can access and download plate data based on keywords such as station, telescope, observation year, and observed celestial coordinates.
Prospects of the Multi-channel Photometric Survey Telescope in the Cosmological Application of Type Ia Supernovae
Authors: Wang Zhenyu , Zhang Jujia , Er Xinzhong , Bai Jinming
Published: March 2024

The Multi-channel Photometric Survey Telescope (Mephisto) is a real-time, three-color photometric system designed to capture the color evolution of stars and transients accurately. This telescope system can be crucial in cosmological distance measurements of low-redshift (low-z, z ≲0.1) Type Ia supernovae (SNe Ia). To optimize the capabilities of this instrument, we perform a comprehensive simulation study before its official operation is scheduled to start. By considering the impact of atmospheric extinction, weather conditions, and the lunar phase at the observing site involving the instrumental features, we simulate light curves of SNe Ia obtained by Mephisto. The best strategy in the case of SN Ia cosmology is to take the image at an exposure time of 130 s with a cadence of 3 days. In this condition, Mephisto can obtain hundreds of high-quality SNe Ia to achieve a distance measurement better than 4.5%. Given the on-time spectral classification and monitoring of the Lijiang 2.4 m Telescope at the same observatory, Mephisto, in the whole operation, can significantly enrich the well-calibrated sample of supernovae at low-z and improve the calibration accuracy of high-z SNe Ia.
Health benefits to the pediatric population from reduction of ambient particulate matter in Krakow, Poland
Authors: Pac Agnieszka , Majewska Renata , Nidecka Natalia , Sochacka-Tatara Elzbieta , Perera Frederica P
Published: March 2024

There have been few assessments of the health benefits to children of policies aimed at curbing fossil fuel-related air pollution. This has resulted in a lack of awareness regarding their positive impact on the health of this vulnerable population. We estimated the pediatric health benefits of policies targeting coal burning in one of Europe’s most polluted cities, Kraków, Poland. We combined available data on child health outcomes, related concentration-response functions, childhood population counts, and concentrations of PM2.5 and PM10 based on city-wide air monitoring in Kraków. Two exposure reduction scenarios were examined. First, we used the observed decrease in air pollutant concentrations between 2010 and 2019. Second, we hypothesized a reduction to the annual World Health Organization (WHO) air quality guideline values issued in 2005. Between 2010 and 2019, the mean annual air pollution levels in Kraków decreased for both PM2.5 and PM10. Annual average PM2.5 concentrations declined by 39.1%, reaching 23.3 μg m−3; PM10 dropped by 39.2% to 34.6 μg m−3. These reductions in air pollution can be linked to numerous actions undertaken at local and national levels. We estimate that the forgone benefits in 2010 from not having achieved the PM levels observed in 2019 (on an annual basis) included: 505 (35.7%) fewer incident cases of asthma in the 1–14 age group, 81 fewer preterm births (16.8% decrease), 52 fewer cases of low birth weight (12.3% decrease), and 59 avoided asthma hospitalizations in 0–18 year olds. Compliance with the 2005 WHO PM2.5 guidelines in 2010 would have avoided 780 incident asthma cases in the 1–14 age group (54.5% decrease), 138 preterm births (28.3% decrease), and 90 cases of low birth weight (21.2% reduction) and 219 (54.2%) fewer asthma hospitalizations in 0–18 year olds. Large health benefits were also estimated for PM10 in both scenarios. This study estimated substantial health benefits for children in Kraków, which were largely attributable to clean air policies that restrict the use of coal and other solid fuels. Kraków provides a model for other cities in Europe and beyond that are affected by coal pollution and have high rates of preterm birth, low birth weight, and respiratory illness.
Stochastic nested primal-dual method for nonconvex constrained composition optimization
Authors: Jin Lingzi , Wang Xiao
Published: March 2024

In this paper we study the nonconvex constrained composition optimization, in which the objective contains a composition of two expected-value functions whose accurate information is normally expensive to calculate. We propose a STochastic nEsted Primal-dual (STEP) method for such problems. In each iteration, with an auxiliary variable introduced to track the inner layer function values we compute stochastic gradients of the nested function using a subsampling strategy. To alleviate difficulties caused by possibly nonconvex constraints, we construct a stochastic approximation to the linearized augmented Lagrangian function to update the primal variable, which further motivates to update the dual variable in a weighted-average way. Moreover, to better understand the asymptotic dynamics of the update schemes we consider a deterministic continuous-time system from the perspective of ordinary differential equation (ODE). We analyze the Karush-Kuhn-Tucker measure at the output by the STEP method with constant parameters and establish its iteration and sample complexities to find an

ϵ
\epsilon

-stationary point, ensuring that expected stationarity, feasibility as well as complementary slackness are below accuracy

ϵ
\epsilon

. To leverage the benefit of the (near) initial feasibility in the STEP method, we propose a two-stage framework incorporating a feasibility-seeking phase, aiming to locate a nearly feasible initial point. Moreover, to enhance the adaptivity of the STEP algorithm, we propose an adaptive variant by adaptively adjusting its parameters, along with a complexity analysis. Numerical results on a risk-averse portfolio optimization problem and an orthogonal nonnegative matrix decomposition reveal the effectiveness of the proposed algorithms.
Population Characteristics
Authors: Sinner Alejandro , Carreras Cèsar , Houten Pieter
Published: March 2024

Chapter 2 analyses the demographic characteristics of the population of the province under study focusing on key aspects such as fertility, mortality, and life expectancy. The chapter draws on a tradition of demographic studies in Spain and other Roman provinces, and aims to provide a comprehensive understanding of the population characteristics of Hispania Citerior/Tarraconensis. The chapter employs and combines various types of historical and archaeological evidence, including funerary inscriptions, ideal ancient demographic models, and osteological information to surpass the limitations that each of these sources present when studied in isolation. Selected case studies, including the conventus capitals, and anthropological models are used to provide suitable and representative data across the province.
Population and Urbanization in the Late Roman Period
Authors: Sinner Alejandro , Carreras Cèsar , Houten Pieter
Published: March 2024

Chapter 6 highlights the deep changes in the population patterns and distribution in Hispania Tarraconensis during the Late Roman period. Some cities were abandoned during the second century ce, whereas the size and importance of most of the surviving ones decreased from the third century onwards. In the past, both factors are linked with the so-called third-century crisis. However, opposing patterns can be observed in the countryside, where luxurious villae were built in the same period, revealing a dynamic self-sufficient territory in constant evolution rather than in decline or crisis. This chapter will therefore tackle the question of whether what can be seen is an overall decline in the Iberian peninsula or rather a shift from urban to rural, with a change in the level of urbanization in the province. One of the major challenges is to quantify the ‘decline’ of an urban community. Again, the use of detailed archaeological reports of well-researched case studies provides insights into the development of the population in the late antique city.
Risk
Authors: Deaves Richard
Published: March 2024

This chapter presents rational risk preference based on expected utility maximization and portfolio theory. Risk neutrality, implying an indifference to risk, and risk seeking, implying a preference for risk, are possible and indeed are sometimes observed. But, most common is risk aversion, whose presence means that most people most of the time require a premium to take on risk. The trade-off between risk and return stemming from portfolio theory is central to many financial decisions. How decision makers might rationally choose the percentage of their savings to be invested in risky assets vs. conservatively investing in a risk-free asset is analyzed.
Risk Takers
Authors: Deaves Richard
Published: March 2024

This chapter focuses on optimal risk-taking over the life cycle and how behavior is sometimes at variance to theory. The stock market participation puzzle is the finding that many people avoid equities contrary to theory. It has been linked to high participation costs, low financial literacy, and lack of trust among other factors. Another puzzle explored is low risk-taking among the young. There is evidence that risk aversion might change after significant experiences of a positive or negative nature, such as increases in one’s wealth, disaster experience (such as living through an earthquake), or being exposed to tough economic times (such as living during the Great Depression).
Strategies to increase the coverage of influenza and pneumonia vaccination in older adults: a systematic review and network meta-analysis
Authors: Du Peipei , Jin Shuyan , Lu Shuya , Wang Li , Ma Xiaofeng , Wang Jie , Huang Runting , Luo Qingyue , Yang Shu , Feng Xixi
Published: March 2024

Background

It is urgent to implement interventions to increase vaccination rates of influenza/pneumonia vaccines in older adults, yet the effectiveness of different intervention strategies has not been thoroughly evaluated.

Objective

We aimed to assess the effectiveness of intervention strategies for increasing the coverage of influenza/pneumonia vaccination in older adults.

Methods

PubMed, Web of Science, Cochrane Library, Embase, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang were searched from 1 January 2000 to 1 October 2022. RCTs that assessed any intervention strategies for increasing influenza/pneumonia vaccination coverage or willingness in older adults were included. A series of random-effects network meta-analysis was conducted by using frequentist frameworks.

Results

Twenty-two RCTs involving 385,182 older participants were eligible for further analysis. Eight types of intervention strategies were evaluated. Compared with routine notification, health education (odds ratio [OR], 1.85 [95%CI, 1.19 to 2.88]), centralised reminder (OR, 1.63 [95%CI, 1.07 to 2.47]), health education + onsite vaccination (OR, 2.89 [95%CI, 1.30 to 6.39]), and health education + centralised reminder + onsite vaccination (OR, 20.76 [95%CI, 7.33 to 58.74]) could effectively improve the vaccination rate. The evidence grade was low or very low due to the substantial heterogeneity among studies.

Conclusions

Our findings suggest that health education + centralised reminder + onsite vaccination may potentially be an effective strategy regardless of cost, but the evidence level was low. More rigorous trials are needed to identify the association between strategies and vaccination rates among older adults and to integrate such evidence into clinical care to improve vaccination rates.
Evaluation of a remote hybrid staffing model for investigational drug service pharmacists
Authors: Miller Travis , Froerer Camryn , Hill Cameron , Schmutz Howard Weston
Published: March 2024

Purpose

This project compared the time to complete investigational prescription drug order verification by investigational drug service (IDS) pharmacists in an onsite vs offsite (hybrid) staffing model, evaluating the impact of remote work on verification time.

Methods

Parenteral IDS drug orders from August 2019 through June 2022 were analyzed. Electronic medical records were timestamped for each order, first verification, second verification, and medication administration. The project was divided into four 6-month time periods to allow for 2 independent comparisons of onsite vs hybrid staffing models. A survey was given retrospectively to IDS pharmacists for the last hybrid timeframe to assess work satisfaction and burnout.

Results

A total of 4,398 orders were evaluated. The time from order entry to first verification was 14 minutes (n = 1,248) during the first onsite time period compared to 13 minutes (n = 1,042) during the first hybrid period (P = 0.003). The time for order verification was similar between the second onsite and hybrid periods (12 minutes [n = 1,041] vs 10 minutes [n = 1,067], respectively; P < 0.0001). The staff satisfaction survey for the hybrid model showed high levels of job satisfaction and no self-reported burnout.

Conclusion

The remote hybrid staffing model did not result in a meaningful change in the time from order placement to medication administration within the IDS pharmacy. Hybrid staffing also resulted in greater job satisfaction among IDS pharmacists. This study highlights the benefits of implementing remote work practices in the pharmacy practice setting.
Grape cultivars adapted to hotter, drier growing regions exhibit greater photosynthesis in hot conditions despite less drought-resistant leaves
Authors: Sinclair Gabriela , Galarneau Erin R , Hnizdor Josh F , McElrone Andrew J , Walker Michael Andrew , Bartlett Megan K
Published: March 2024

Background and Aims

Many agricultural areas are expected to face hotter, drier conditions from climate change. Understanding the mechanisms that crops use to mitigate these stresses can guide breeding for more tolerant plant material. We tested relationships between traits, physiological function in hot conditions and historical climate associations to evaluate these mechanisms for winegrapes. We expected a more negative leaf osmotic potential at full hydration (πo), which reduces leaf turgor loss during drought, and either a metabolically cheaper or more osmoprotectant leaf chemical composition, to allow cultivars associated with hot, dry regions to maintain greater gas exchange in hot growing conditions.

Methods

We measured πo, gas exchange and leaf chemistry for seven commercially important winegrape cultivars that vary widely in historical climate associations. Vines were grown in common-garden field conditions in a hot wine-growing region (Davis, CA, USA) and measured over the hottest period of the growing season (July–September).

Key Results

The value of πo varied significantly between cultivars, and all cultivars significantly reduced πo (osmotically adjusted) over the study period, although osmotic adjustment did not vary across cultivars. The value of πo was correlated with gas exchange and climate associations, but in the direction opposite to expected. Photosynthesis and πo were higher in the cultivars associated with hotter, less humid regions. Leaf chemical composition varied between cultivars but was not related to climate associations.

Conclusions

These findings suggest that maintenance of leaf turgor is not a primary limitation on grapevine adaptation to hot or atmospherically dry growing conditions. Thus, selecting for a more negative πo or greater osmotic adjustment is not a promising strategy to develop more climate-resilient grape varieties, contrary to findings for other crops. Future work is needed to identify the mechanisms increasing photosynthesis in the cultivars associated with hot, dry regions.
Symbiotic fungi from a wild grass (Celtica gigantea) increase the growth, grain yield and quality of tritordeum under field conditions
Authors: Zabalgogeazcoa Iñigo , Arellano Juan B , Mellado-Ortega Elena , Barro Francisco , Martínez-Castilla Ana , González-Blanco Virginia , Vázquez de Aldana Beatriz R
Published: March 2024

Abstract. Plants function in symbiosis with numerous microorganisms, which might contribute to their adaptation and performance. In this study, we tested whether fungal strains in symbiotic interaction with roots of Celtica gigantea, a wild grass adapted to nutrient-poor soils in semiarid habitats, could improve the field performance of the agricultural cereal tritordeum (Triticum durum × Hordeum chilense). Seedlings of tritordeum were inoculated with 12 different fungal strains isolated from roots of Celtica gigantea that were first proved to promote the growth of tritordeum plants under greenhouse conditions. The inoculated seedlings were transplanted to field plots at two locations belonging to different climatic zones in terms of mean temperatures and precipitation in the Iberian Peninsula. Only one strain, Diaporthe iberica T6, had a significant effect on plant height, number of tillers and grain yield in one location. This result showed a substantial divergence between the results of greenhouse and field tests. In terms of grain nutritional quality, several parameters were differentially affected at both locations: Diaporthe T6, Pleosporales T7, Zygomycota T29 and Zygomycota T80 increased the content of total carotenoids, mainly lutein, in the colder location; whereas gluten proteins increased with several treatments in the warmer location. In conclusion, early inoculation of tritordeum plants with fungal symbionts had substantial beneficial effects on subsequent plant growth and development in the field. Regarding grain nutritional quality, the effect of inoculation was affected by the agroclimatic differences between both field locations.
Phylogenomics and biogeography of the feather lice (Phthiraptera: Ischnocera) of parrots
Authors: Johnson Kevin P , Doña Jorge
Published: March 2024

Avian feather lice (Phthiraptera: Ischnocera) have undergone morphological diversification into ecomorphs based on how they escape host preening defences. Parrot lice are one prominent example of this phenomenon, with wing, body, or head louse ecomorphs occurring on various groups of parrots. Currently defined genera of parrot lice typically correspond to this ecomorphological variation. Here we explore the phylogenetic relationships among parrot feather lice by sequencing whole genomes and assembling a target set of 2395 nuclear protein coding genes. Phylogenetic trees based on concatenated and coalescent analyses of these data reveal highly supported trees with strong agreement between methods of analysis. These trees reveal that parrot feather lice fall into two separate clades that form a grade with respect to the Brueelia-complex. All parrot louse genera sampled by more than one species were recovered as monophyletic. The evolutionary relationships among these lice showed evidence of strong biogeographic signal, which may also be related to the relationships among their hosts.
Mechanoresponsive diacetylenes and polydiacetylenes: novel polymerization and chromatic functions
Authors: Kim Yuna , Iimura Ken-ichi , Tamaoki Nobuyuki
Published: March 2024

This review focuses on recent advancements regarding mechanoresponsive functions of diacetylene (DA) and polydiacetylene (PDA). Their ability to undergo pronounced topochemical polymerization and chromatic behavior variations in response to external stimuli has marked them as a promising platform for chemo- and bio-sensing over the past few decades. Notably, major advances, showcasing selective and highly sensitive mechanoresponses along with their quantitative analysis, have been achieved in recent years. The categorization includes DAs undergoing pressure-controlled crystalline transitions and polymerization, as well as PDAs exhibiting mechanochromic or mechanofluorochromic transitions. Accordingly, this review covers molecular designs allowing mechanical activation for topochemical polymerization, nanostructured or hybridized PDAs for amplifying stimulus-optical response feedback, nanoscopic analytical tools for mechanochromism, and their potential applications in mechanochemical sensing and imaging.
Recurrent immunosuppressive-responsive myocarditis in a patient with desmoplakin cardiomyopathy: a case report
Authors: McColl Hayden , Cordina Rachael , Lal Sean , Parker Matthew , Hunyor Imre , Medi Caroline , Gray Belinda
Published: March 2024

Background

Desmoplakin (DSP) cardiomyopathy is a rare genetic condition characterized by repeated inflammatory myocardial injury and is associated with ventricular arrhythmia and sudden cardiac death. Diagnosis is challenging and requires a combination of genetic testing and advanced imaging techniques.

Case summary

We present the case of a 38-year-old woman with recurrent episodes of subclinical myocarditis. Investigation using cardiac magnetic resonance imaging (cMRI) and genetic testing revealed a diagnosis of DSP cardiomyopathy. Her disease was initially responsive to corticosteroid therapy but quickly relapsed when treatment was tapered. Management of her condition required significant immunosuppression and the subsequent insertion of an implantable cardiac defibrillator due to her risk of sudden cardiac death.

Discussion

Cardiac MRI and genetic testing are key diagnostic techniques in the assessment of patients with recurrent myocarditis and cardiomyopathy. The management of cardiomyopathies with an inflammatory component is not completely understood; however, there is likely a key role for immune suppression therapies. Furthermore, there are several cardiomyopathy genetic variants including DSP which require careful risk stratification due to an increased risk of sudden cardiac death.
Brothers in arms: the value of coalitions in sanctions regimes
Authors: Chowdhry Sonali , Hinz Julian , Kamin Katrin , Wanner Joschka
Published: March 2024

This paper examines the impact of coalitions on the economic costs of the 2012 Iran and 2014 Russia sanctions. By estimating and simulating a quantitative general equilibrium trade model under different coalition setups, we (1) dissect welfare losses for sanctions senders and target; (2) compare prospective coalition partners; (3) investigate ‘optimal’ coalitions that maximize payoff from sanctions; (4) provide bounds for sanctions potential, that is, the maximum welfare change attainable when sanctions are scaled vertically up to an embargo, and horizontally up to a global regime. Relative to unilateral action, we find that coalitions magnify welfare losses imposed while their impact on domestic welfare loss incurred depends on the design and sectoral dimension of sanctions. Hypothetical cooperation of large developing economies such as China additionally raises the deterrent force of coalitions. Additionally, we quantify transfers that equalize welfare losses across coalition members to further demonstrate asymmetries in the relative economic burden of sanctions. In all scenarios, we implement a novel Bayesian bootstrap procedure that generates confidence bands for simulation outcomes.
Facilitating an ecosystem approach through open data and information packaging
Authors: Duplisea Daniel E , Roux Marie-Julie , Plourde Stéphane , Galbraith Peter S , Blais Marjolaine , Benoît Hugues P , Sainte-Marie Bernard , Lavoie Diane , Bourdages Hugo
Published: March 2024

Open data that can be easily incorporated into analyses are essential for developing ecosystem approaches to marine ecological management: a common goal in fisheries policy in many countries. Although it is not always clear what constitutes an ecosystem approach, it always involves scientists working with a large variety of data and information, including data from physical and oceanographic sampling, multispecies surveys, and other sources describing human pressures. This can be problematic for analysts because these data, even when available, are often held in disparate datasets that do not necessarily correspond at appropriate temporal and spatial scales. Data can often only be obtained by specific requests to individuals in governmental agencies who are delivering on an increasing number of data requests as interest grows in practical ecosystem approach implementation. This data access model is not sustainable and hinders the momentum for ecosystem approach development. We describe a data bundling R package that makes data and climate projections available at appropriate scales to facilitate development of an ecosystem approach for the Gulf of St. Lawrence, Canada. This approach integrates closely with the present workflow of most government analysts, academics in fisheries, and scientists in private industry. The approach conforms with open data initiatives and makes data easily available globally while relieving some of the burden of data provision that can fall to some individuals in government laboratories. The structure and approach are generic, adaptable, and transferable to other regions and jurisdictions.
Markov modeling for cost-effectiveness using federated health data network
Authors: Haug Markus , Oja Marek , Pajusalu Maarja , Mooses Kerli , Reisberg Sulev , Vilo Jaak , Giménez Antonio Fernández , Falconer Thomas , Danilović Ana , Maljkovic Filip , Dawoud Dalia , Kolde Raivo
Published: March 2024

Objective

To introduce 2 R-packages that facilitate conducting health economics research on OMOP-based data networks, aiming to standardize and improve the reproducibility, transparency, and transferability of health economic models.

Materials and Methods

We developed the software tools and demonstrated their utility by replicating a UK-based heart failure data analysis across 5 different international databases from Estonia, Spain, Serbia, and the United States.

Results

We examined treatment trajectories of 47 163 patients. The overall incremental cost-effectiveness ratio (ICER) for telemonitoring relative to standard of care was 57 472 €/QALY. Country-specific ICERs were 60 312 €/QALY in Estonia, 58 096 €/QALY in Spain, 40 372 €/QALY in Serbia, and 90 893 €/QALY in the US, which surpassed the established willingness-to-pay thresholds.

Discussion

Currently, the cost-effectiveness analysis lacks standard tools, is performed in ad-hoc manner, and relies heavily on published information that might not be specific for local circumstances. Published results often exhibit a narrow focus, central to a single site, and provide only partial decision criteria, limiting their generalizability and comprehensive utility.

Conclusion

We created 2 R-packages to pioneer cost-effectiveness analysis in OMOP CDM data networks. The first manages state definitions and database interaction, while the second focuses on Markov model learning and profile synthesis. We demonstrated their utility in a multisite heart failure study, comparing telemonitoring and standard care, finding telemonitoring not cost-effective.
A dual population collaborative harmony search algorithm with adaptive population size for the system reliability-redundancy allocation problems
Authors: Ouyang Haibin , Liang Siqi , Li Steven , Zhou Ziyu , Zhan Zhi-Hui
Published: March 2024

Aiming at the problem that the diversity of the current double population algorithm with dynamic population size reduction cannot be guaranteed in real time in iteration and is easy to fall into local optimum, this study presents a dual population collaborative harmony search algorithm with adaptive population size (DPCHS). Firstly, we propose a dual population algorithm framework for improving the algorithm global search capability. Within this framework, the guidance selection strategy and information interaction mechanism are integrated to strengthen the competition and cooperation among populations, and achieving a good balance between exploration and exploitation. A population state assessment method is designed to monitor population changes in real-time for enhancing population real-time self-regulation. Additionally, population size adjustment approach is designed to adopted to effectively streamline population resources and improve population quality. Comprehensive experiment results demonstrate that DPCHS effectively addresses system reliability-redundancy allocation problems with superior performance and robust convergence compared with other HS variants and algorithms from different categories.
High-efficiency EGFR genotyping using cell-free DNA in bronchial washing fluid
Authors: Murata Yoshihiko , Nakajima Yumi , Sato Yukio , Hizawa Nobuyuki , Yamakawa Daichi , Matsubara Daisuke , Noguchi Masayuki , Minami Yuko
Published: March 2024

Background

EGFR mutation testing is required for treatment of lung adenocarcinoma using epidermal growth factor receptor-tyrosine kinase inhibitor. However, the amounts of tumor tissue or tumor cells obtained by bronchoscopy are often insufficient. Bronchial washing fluid, obtained by lavage with saline after tumor biopsy or brushing, and the supernatant of bronchial washing fluid are thought to contain cell-free DNA that would be potentially applicable for EGFR testing.

Methods

From among patients with suspected adenocarcinoma or non-small cell lung carcinoma diagnosed from biopsy or surgical specimens at the University of Tsukuba Hospital between 2015 and 2019, cell-free DNAs from 80 specimens of supernatant of bronchial washing fluid (50 with EGFR mutation and 30 with wild type EGFR) and 8 blood serum samples were examined for EGFR mutation using droplet digital PCR.

Results

Among the 50 patients harboring EGFR mutation, the rate of positivity for cell-free DNA extracted from supernatant of bronchial washing fluid was 80% (40/50). In nine of the EGFR mutation-positive cases, tumor cells were not detected by either biopsy or cytology, but the mutation was detected in four cases (4/9, 44%). Comparison of the cell-free DNA mutation detection rate between supernatant of bronchial washing fluid and blood serum in six cases showed that mutations were detected from the former in all cases (6/6, 100%), but from the latter in only one case (1/6, 17%).

Conclusions

Using supernatant of bronchial washing fluid samples, the detection rate of EGFR mutation was high, and EGFR mutations were detectable even when no tumor cells had been detectable by biopsy or cytology. Supernatant of bronchial washing fluid might be an effective sample source for EGFR mutation testing.
Testing SIPA1L2 as a modifier of CMT1A using mouse models
Authors: Murray George C , Hines Timothy J , Tadenev Abigail L D , Xu Isaac , Züchner Stephan , Burgess Robert W
Published: March 2024

Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating peripheral neuropathy caused by the duplication of peripheral myelin protein 22 (PMP22), leading to muscle weakness and loss of sensation in the hands and feet. A recent case-only genome-wide association study of CMT1A patients conducted by the Inherited Neuropathy Consortium identified a strong association between strength of foot dorsiflexion and variants in signal induced proliferation associated 1 like 2 (SIPA1L2), indicating that it may be a genetic modifier of disease. To validate SIPA1L2 as a candidate modifier and to assess its potential as a therapeutic target, we engineered mice with deletion of exon 1 (including the start codon) of the Sipa1l2 gene and crossed them to the C3-PMP22 mouse model of CMT1A. Neuromuscular phenotyping showed that Sipa1l2 deletion in C3-PMP22 mice preserved muscular endurance assayed by inverted wire hang duration and changed femoral nerve axon morphometrics such as myelin thickness. Gene expression changes suggest involvement of Sipa1l2 in cholesterol biosynthesis, a pathway that is also implicated in C3-PMP22 mice. Although Sipa1l2 deletion did impact CMT1A-associated phenotypes, thereby validating a genetic interaction, the overall effect on neuropathy was mild.
Phylogenetically diverse wild plant species use common biochemical strategies to thrive in the Atacama Desert
Authors: Dussarrat Thomas , Nilo-Poyanco Ricardo , Moyano Tomás C , Prigent Sylvain , Jeffers Tim L , Díaz Francisca P , Decros Guillaume , Audi Lauren , Sondervan Veronica M , Shen Bingran , Araus Viviana , Rolin Dominique , Shasha Dennis , Coruzzi Gloria M , Gibon Yves , Latorre Claudio , Pétriacq Pierre , Gutiérrez Rodrigo A
Published: March 2024

The best ideotypes are under mounting pressure due to increased aridity. Understanding the conserved molecular mechanisms that evolve in wild plants adapted to harsh environments is crucial in developing new strategies for agriculture. Yet our knowledge of such mechanisms in wild species is scant. We performed metabolic pathway reconstruction using transcriptome information from 32 Atacama and phylogenetically related species that do not live in Atacama (sister species). We analyzed reaction enrichment to understand the commonalities and differences of Atacama plants. To gain insights into the mechanisms that ensure survival, we compared expressed gene isoform numbers and gene expression patterns between the annotated biochemical reactions from 32 Atacama and sister species. We found biochemical convergences characterized by reactions enriched in at least 50% of the Atacama species, pointing to potential advantages against drought and nitrogen starvation, for instance. These findings suggest that the adaptation in the Atacama Desert may result in part from shared genetic legacies governing the expression of key metabolic pathways to face harsh conditions. Enriched reactions corresponded to ubiquitous compounds common to extreme and agronomic species and were congruent with our previous metabolomic analyses. Convergent adaptive traits offer promising candidates for improving abiotic stress resilience in crop species.
ATRX guards against aberrant differentiation in mesenchymal progenitor cells
Authors: Fang Yan , Barrows Douglas , Dabas Yakshi , Carroll Thomas S , Singer Sam , Tap William D , Nacev Benjamin A
Published: March 2024

Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks. We additionally observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Finally, we demonstrated that loss of ATRX in a mesenchymal malignancy, undifferentiated pleomorphic sarcoma, results in similar epigenetic disruption and de-repression of transposable elements. Together, our results reveal a role for ATRX in maintaining epigenetic states and transcriptional repression in mesenchymal progenitors and tumor cells and in preventing aberrant differentiation in the progenitor context.
Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans
Authors: Kotagama Kasuen , Grimme Acadia L , Braviner Leah , Yang Bing , Sakhawala Rima M , Yu Guoyun , Benner Lars Kristian , Joshua-Tor Leemor , McJunkin Katherine
Published: March 2024

Many microRNA (miRNA)-guided Argonaute proteins can cleave RNA (‘slicing’), even though miRNA-mediated target repression is generally cleavage-independent. Here we use Caenorhabditis elegans to examine the role of catalytic residues of miRNA Argonautes in organismal development. In contrast to previous work, mutations in presumed catalytic residues did not interfere with development when introduced by CRISPR. We find that unwinding and decay of miRNA star strands is weakly defective in the catalytic residue mutants, with the largest effect observed in embryos. Argonaute-Like Gene 2 (ALG-2) is more dependent on catalytic residues for unwinding than ALG-1. The miRNAs that displayed the greatest (albeit minor) dependence on catalytic residues for unwinding tend to form stable duplexes with their star strand, and in some cases, lowering duplex stability alleviates dependence on catalytic residues. While a few miRNA guide strands are reduced in the mutant background, the basis of this is unclear since changes were not dependent on EBAX-1, an effector of Target-Directed miRNA Degradation (TDMD). Overall, this work defines a role for the catalytic residues of miRNA Argonautes in star strand decay; future work should examine whether this role contributes to the selection pressure to conserve catalytic activity of miRNA Argonautes across the metazoan phylogeny.
Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain
Authors: Kumar Nisha Hemandhar , Kluever Verena , Barth Emanuel , Krautwurst Sebastian , Furlan Mattia , Pelizzola Mattia , Marz Manja , Fornasiero Eugenio F
Published: March 2024

A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.
Viral reprogramming of host transcription initiation
Authors: Ungerleider Nathan A , Roberts Claire , O’Grady Tina M , Nguyen Trang T , Baddoo Melody , Wang Jia , Ishaq Eman , Concha Monica , Lam Meggie , Bass Jordan , Nguyen Truong D , Van Otterloo Nick , Wickramarachchige-Dona Nadeeshika , Wyczechowska Dorota , Morales Maria , Ma Tianfang , Dong Yan , Flemington Erik K
Published: March 2024

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes ‘de novo’ transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.
Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A
Authors: Zheng Xinxing , Su Chenchen , Duan Lei , Jin Mengqi , Sun Yongtao , Zhu Li , Zhang Wenhua
Published: March 2024

In archaea and eukaryotes, the evolutionarily conserved KEOPS is composed of four core subunits―Kae1, Bud32, Cgi121 and Pcc1, and a fifth Gon7/Pcc2 that is found in fungi and metazoa. KEOPS cooperates with Sua5/YRDC to catalyze the biosynthesis of tRNA N6-threonylcarbamoyladenosine (t6A), an essential modification needed for fitness of cellular organisms. Biochemical and structural characterizations of KEOPSs from archaea, yeast and humans have determined a t6A-catalytic role for Kae1 and auxiliary roles for other subunits. However, the precise molecular workings of KEOPSs still remain poorly understood. Here, we investigated the biochemical functions of A. thaliana KEOPS and determined a cryo-EM structure of A. thaliana KEOPS dimer. We show that A. thaliana KEOPS is composed of KAE1, BUD32, CGI121 and PCC1, which adopts a conserved overall arrangement. PCC1 dimerization leads to a KEOPS dimer that is needed for an active t6A-catalytic KEOPS–tRNA assembly. BUD32 participates in direct binding of tRNA to KEOPS and modulates the t6A-catalytic activity of KEOPS via its C-terminal tail and ATP to ADP hydrolysis. CGI121 promotes the binding of tRNA to KEOPS and potentiates the t6A-catalytic activity of KEOPS. These data and findings provide insights into mechanistic understanding of KEOPS machineries.
Clinical impact of the Kidney Failure Risk Equation for vascular access planning
Authors: Hahn Lundström Ulrika , Ramspek Chava L , Dekker Friedo W , van Diepen Merel , Carrero Juan Jesus , Hedin Ulf , Evans Marie
Published: March 2024

Background

Risk-based thresholds for arteriovenous (AV) access creation has been proposed to aid vascular access planning. We aimed to assess the clinical impact of implementing the Kidney Failure Risk Equation (KFRE) for vascular access referral.

Methods

A total of 16 102 nephrology-referred chronic kidney disease (CKD) patients from the Swedish Renal Registry 2008–18 were included. The KFRE was calculated repeatedly, and the timing was identified for when the KFRE risk exceeded several pre-defined thresholds and/or the estimated glomerular filtration rate was <15 mL/min/1.73 m2 (eGFR15). To assess the utility of the KFRE/eGFR thresholds, cumulative incidence curves of kidney replacement therapy (KRT) or death, and decision-curve analyses were computed at 6 and 12 months, and 2 years. The potential impact of using the different thresholds was illustrated by an example from the Swedish access registry.

Results

The 12-month specificity for KRT initiation was highest for KFRE >50% {94.5 [95% confidence interval (CI) 94.3–94.7]} followed by KFRE >40% [90.0 (95% CI 89.7–90.3)], while sensitivity was highest for KFRE >30% [79.3 (95% CI 78.2–80.3)] and eGFR <15 mL/min/1.73 m2 [81.2 (95% CI 80.2–82.2)]. The 2-year positive predictive value was 71.5 (95% CI 70.2–72.8), 61.7 (95% CI 60.4–63.0) and 47.2 (95% CI 46.1–48.3) for KFRE >50%, KFRE >40% and eGFR <15, respectively. Decision curve analyses suggested the largest net benefit for KFRE >40% over 2 years and KFRE >50% over 12 months when it is important to avoid the harm of possibly unnecessary surgery. In Sweden, 54% of nephrology-referred patients started hemodialysis in a central venous catheter (CVC), of whom only 5% had AV access surgery >6 months before initiation. Sixty percent of the CVC patients exceeded KFRE >40% a median of 0.8 years (interquartile range 0.4–1.5) before KRT initiation.

Conclusions

The utility of using KFRE >40% and KFRE >50% is higher compared with the more traditionally used eGFR threshold <15 mL/min/1.73 m2 for vascular access planning.