bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape-level variation in spring leaf phenology is driven by precipitation seasonality in the Mexican red oak Quercus castanea
Authors: Ochoa-Alvarez Tamara C , Contreras-Negrete Gonzalo , Lara-De La Cruz Libny Ingrid , González-Rodríguez Antonio
Published: December 2024

Background and Aims

Water availability is one of the essential factors that determine the distribution of plant species, as well as their ecological strategies. The study of leaf phenology, in conjunction with other leaf traits of an ecological nature, such as functional traits, makes it possible to determine the life history strategies of plant species and their variation along environmental gradients, which in turn influences the demographic rates of populations. In the present study, we analyzed the effect of water availability at the landscape scale on spring leaf phenology and foliar traits such as leaf mass per area (LMA) and leaf thickness (LT) in the oak species Quercus castanea from a tropical latitude in central-western Mexico.

Methods

Six sites were selected in the Cuitzeo basin, Michoacán, across a water availability gradient, ranging from 766 mm to 1145 mm of mean annual precipitation. Leaf samples were collected from 10 adult trees at each site and LT and LMA were estimated. Leaf phenology was monitored for each tree every two weeks between March and July for two consecutive years, 2021 and 2022, alongside soil moisture measurements. Temperature and precipitation variables for the two study years were obtained from meteorological stations and long-term bioclimatic variables from the Worldclim database.

Key Results

Significant spatial and temporal variation in leaf phenology was observed. Earlier leaf development and shorter development times were observed with increased soil moisture in March and April, and with higher precipitation in October of the previous year. Also, sites with long-term higher precipitation seasonality and with lower precipitation of the warmest quarter showed longer development times. A positive association between development times and leaf thickness was also observed.

Conclusions

: Quercus castanea shows a brevideciduous leaf phenology but with significant variation among populations, reflecting spatiotemporal mosaics of environmental and genetic variation and in covariation with leaf functional traits such as leaf thickness.
Empirical insights into the legal quicksand: the case of patent illegality in Indian arbitration
Authors: Singh Pratyush , Malipatil Aastha
Published: December 2024

This paper delves into the intriguing evolution of patent illegality in Indian arbitration law, a concept formalized by the Supreme Court in the Saw Pipes case and later refined by the 2015 Amendment to the Arbitration and Conciliation Act, 1996. Analysing 699 cases from 2016 to 2023 reveals a striking 29.38 per cent success rate for arguments based on patent illegality. Despite the Supreme Court’s intent to restrict its scope, lower courts often delve into case merits under this guise. Key rulings like Ssangyong Engineering and Delhi  Airport  Metro  Express highlight the judiciary’s struggle to maintain this balance. The study critiques the inconsistent application of standards under patent illegality, leading to contradictory verdicts and threatening arbitration finality. Overall, this analysis underscores the critical need for clearer judicial guidelines to ensure a balanced approach that respects both the autonomy of arbitral awards and the supervisory role of the judiciary. The findings suggest that current judicial practices may inadvertently expand the scope of patent illegality, thus necessitating reforms to align with the intended legislative framework.
Economic Predictors of Plastic Surgery Expenditures: A 14-Year Analysis of Unemployment, Disposable Income, and Stock Indices
Authors: Fine Keenan S , Bay Caroline C , Wirth Peter J , Shaffrey Ellen C , Edalatpour Armin , Thornton Sarah M , Rao Venkat K
Published: December 2024

Macroeconomic conditions significantly affect consumer spending patterns, including aesthetic surgery expenditures. This study examines the longitudinal relationship between unemployment rates, disposable income, stock indices, and aesthetic surgery spending from 2006 to 2019. Data on aesthetic surgery expenditures were collected from the American Society of Plastic Surgeons, whereas unemployment data were obtained from the US Bureau of Labor Statistics, disposable income from the US Bureau of Economic Analysis, and stock indices from the Federal Reserve Economic Data. Time series correlational analyses and Granger causality tests were used to explore these relationships. Unemployment was inversely related to total aesthetic surgery expenditures and most individual procedures. However, Granger causality tests did not reveal a significant predictive relationship between unemployment and aesthetic procedure spending for most procedures. Disposable income was most strongly associated with expenditures on injection procedures and had nonsignificant relationships with more invasive procedures, including breast augmentation, liposuction, abdominoplasty, and blepharoplasty. The analysis demonstrated a significant positive relationship between the NASDAQ, S&P 500, and Dow Jones with all aesthetic procedures, except rhinoplasty. Granger causality tests revealed significant predictive relationships for several procedures at different lags using disposable income and stock indices as predictive variables. These findings highlight a nuanced relationship between macroeconomic conditions and consumer spending on aesthetic surgery. Overall, this paper provides new insights offering a foundation for further investigation into aesthetic plastic surgery consumption on an individual level, rather than on an aggregate.

Level of Evidence: 5

(Risk)
Comprehensive evaluation and practical guideline of gating methods for high-dimensional cytometry data: manual gating, unsupervised clustering, and auto-gating
Authors: Liu Peng , Pan Yuchen , Chang Hung-Ching , Wang Wenjia , Fang Yusi , Xue Xiangning , Zou Jian , Toothaker Jessica M , Olaloye Oluwabunmi , Santiago Eduardo Gonzalez , McCourt Black , Mitsialis Vanessa , Presicce Pietro , Kallapur Suhas G , Snapper Scott B , Liu Jia-Jun , Tseng George C , Konnikova Liza , Liu Silvia
Published: December 2024

Cytometry is an advanced technique for simultaneously identifying and quantifying many cell surface and intracellular proteins at a single-cell resolution. Analyzing high-dimensional cytometry data involves identifying and quantifying cell populations based on their marker expressions. This study provided a quantitative review and comparison of various ways to phenotype cellular populations within the cytometry data, including manual gating, unsupervised clustering, and supervised auto-gating. Six datasets from diverse species and sample types were included in the study, and manual gating with two hierarchical layers was used as the truth for evaluation. For manual gating, results from five researchers were compared to illustrate the gating consistency among different raters. For unsupervised clustering, 23 tools were quantitatively compared in terms of accuracy with the truth and computing cost. While no method outperformed all others, several tools, including PAC-MAN, CCAST, FlowSOM, flowClust, and DEPECHE, generally demonstrated strong performance. For supervised auto-gating methods, four algorithms were evaluated, where DeepCyTOF and CyTOF Linear Classifier performed the best. We further provided practical recommendations on prioritizing gating methods based on different application scenarios. This study offers comprehensive insights for biologists to understand diverse gating methods and choose the best-suited ones for their applications.
A BLAST from the past: revisiting blastp’s E-value
Authors: Lu Yang Young , Noble William Stafford , Keich Uri
Published: December 2024

Motivation

The Basic Local Alignment Search Tool, BLAST, is an indispensable tool for genomic research. BLAST has established itself as the canonical tool for sequence similarity search in large part thanks to its meaningful statistical analysis. Specifically, BLAST reports the E-value of each reported alignment, which is defined as the expected number of optimal local alignments that will score at least as high as the observed alignment score, assuming that the query and the database sequences are randomly generated.

Results

Here, we critically evaluate the E-values provided by the standard protein BLAST (blastp), showing that they can be at times significantly conservative while at others too liberal. We offer an alternative approach based on generating a small sample from the null distribution of random optimal alignments, and testing whether the observed alignment score is consistent with it. In contrast with blastp, our significance analysis seems valid, in the sense that it did not deliver inflated significance estimates in any of our extensive experiments. Moreover, although our method is slightly conservative, it is often significantly less so than the blastp E-value. Indeed, in cases where blastp’s analysis is valid (i.e., not too liberal), our approach seems to deliver a greater number of correct alignments. One advantage of our approach is that it works with any reasonable choice of substitution matrix and gap penalties, avoiding blastp’s limited options of matrices and penalties. In addition, we can formulate the problem using a canonical family-wise error rate control setup, thereby dispensing with E-values, which can at times be difficult to interpret.

Availability and implementation

The Apache licensed source code is available at https://github.com/batmen-lab/SGPvalue.
Antimicrobial materials based on photothermal action and their application in wound treatment
Authors: Cao Jiangli , Song Zhiyong , Du Ting , Du Xinjun
Published: December 2024

Considering the increasing abundance of antibiotic-resistant bacteria, novel antimicrobial approaches need to be investigated. Photothermal therapy (PTT), an innovative noninvasive therapeutic technique, has demonstrated significant potential in addressing drug-resistant bacteria and bacterial biofilms. However, when used in isolation, PTT requires higher-temperature conditions to effectively eradicate bacteria, thereby potentially harming healthy tissues and inducing new inflammation. This study aims to present a comprehensive review of nanomaterials with intrinsic antimicrobial properties, antimicrobial materials relying on photothermal action, and nanomaterials using drug delivery antimicrobial action, along with their applications in antimicrobials. Additionally, the synergistic mechanisms of these antimicrobial approaches are elucidated. The review provides a reference for developing multifunctional photothermal nanoplatforms for treating bacterially infected wounds.
Modeling, control study, and power management strategy of a hybrid grid-connected AC/DC microgrid with high integration of renewable energies and green hydrogen sources
Authors: El Qouarti Ouassima , Nasser Tamou , Essadki Ahmed , Aboudrar Imad , Nadour Mohamed
Published: December 2024

This first quarter of the 21st century is increasingly marked by population growth, digital and industrial developments, a growing need for electricity supply, and climate change. All these, to name just a few, have made the establishment of a stable, flexible, controlled, well-designed, extensive, and clean power system a necessity. Consequently, distributed microgrid generation based on alternative/renewable energies and/or low-carbon technologies has emerged. In this paper, we study the modeling, the control, and the power management strategy of a grid-connected hybrid alternating/direct current (AC/DC) microgrid based on a wind turbine generation system using a doubly fed induction generator, a photovoltaic generation system, and storage elements including hydrogen storage system and batteries. Adequate modeling is described, and the overall system monitoring is presented and applied to manage appropriate power sharing and to control active and reactive powers, in order to match load and weather fluctuation behavior. Simulations are carried out using a MATLAB/Simulink simulation tool. Simulations reveal convenient results in terms of the bidirectional interlinking converter capabilities regarding power balance establishment between the two subgrids, reactive power compensation to ensure a unity power factor, and DC-bus voltage regulation at 1200 V. In addition, the primary and secondary controls are approved for each distributed generation of the studied system to attain the assigned power references, regardless of whether the subgrid is heavily or lightly loaded throughout the four considered case studies, showing satisfactory tracking and interacting performances, and thus stimulating a stable system implementation.
Opportunities and challenges of large-scale salt cavern hydrogen storage in China coupled with renewable energy sources
Authors: Bai Weizheng , Shi Xilin , Zhu Shijie , Wei Xinxing , Huang Yashuai
Published: December 2024

To expedite China’s pursuit of the “dual-carbon” goal, a gradual transition from traditional fossil energy to renewable energy sources is imperative for the nation’s energy mix. Hydrogen energy, poised to become a pivotal component of the future energy industry, offers myriad advantages, including diverse sources, high efficiency, cleanliness, and high energy density. Salt caverns present distinct benefits for underground storage. This research synthesizes the current development trajectories of renewable energy and hydrogen energy in China, summarizing the advantages, disadvantages, and economic comparisons of various underground hydrogen storage methods, with a particular emphasis on the merits of salt cavern hydrogen storage. Furthermore, it reviews the current state and opportunities for salt cavern hydrogen storage both domestically and internationally, underscoring its substantial potential within China. Ultimately, the research identifies three major scientific and technological challenges associated with hydrogen storage in salt caverns in China and envisions future directions for this technology. The findings of this research are anticipated to contribute to the development of a hydrogen storage strategy in salt caverns that aligns with China’s national conditions.
Catalytic degradation of nitrobenzene derivatives by platinum nanoparticles stabilized in diblock spherical polymer brushes
Authors: Xu Chenming , Hua Chen , Chen Kaimin , Li Ziwei , Yu Liang , Zhang Xueke , Chang Yue
Published: December 2024

A new type of core–shell diblock spherical polymer brushes, poly 2-(methacryloyloxy)ethyl-trimethylammonium chloride-b-poly(N-isopropylacrylamide) diblock polymer brushes with polystyrene cores (PSV@PMETAC-b-PNIPA), was prepared through a surface-initiated photoiniferter-mediated polymerization method. The PSV@PMETAC-b-PNIPA (DSPB) was further used as the nanoreactor to prepare and stabilize platinum nanoparticles in situ (DSPB@Pt). By controlling the reaction temperature, substances with similar structure but different hydrophilicity, i.e. 4-nitrophenol and nitrobenzene, could be catalyzed by DSPB@Pt with different catalytic behaviors.
How citizen science helps to expand the distribution and describe predictors related to a native land snail, while also introducing spatial biases
Authors: Barahona-Segovia Rodrigo M , Gómez Persy , Céspedes-Parada Belén , Soto-Silva Constanza , González-Tobar Matías , Olea-Hernández Christopher , Alfaro Elías
Published: December 2024

Although mollusks represent Earth’s second most diverse invertebrate group, their natural history and ecology are still scarcely known. The compilation of non-traditional data, such as those from citizen science, represents an alternative to fill these gaps, particularly on striking land snail species such as Macrocyclis peruvianus. Based on long-term citizen science, we aimed to update and describe some basic ecological aspects, such as the distribution and protected area types used by M. peruvianus. We performed pairwise comparisons to test potential changes in occurrence and occupancy among administrative regions, forest types, and protected area types using chi-squared tests. The citizen scientists were also asked to provide the number of M. peruvianus individuals observed and the tree species that dominated their habitat. Thus, we tested if the number of land snails found by citizen scientists could be related to forest and protected area types using a generalized linear mixed model. We expanded the northern distributional limit, with Nothofagus, evergreen, and mixed forests far the most frequented by M. peruvianus. Parallelly, the occurrence of M. peruvianus in official protected areas (65.73%) was significantly higher than in privately owned areas. Moreover, we did not find associations between forest and protected area types with the number of M. peruvianus recorded. Although citizen science is a helpful method for obtaining novel information regarding the ecology of neglected species such as M. peruvianus, it also introduces spatial and occurrence biases explained by the access and attractiveness of the officially protected areas compared to privately owned patches of native forest.
Antithrombotic therapy in patients with chronic coronary syndrome: a focus on the 2024 European Society of Cardiology guidelines
Authors: Landi Antonio , Valgimigli Marco
Published: December 2024

Antithrombotic therapy represents the mainstay of the pharmacological treatment in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI). The optimal choice, combination, and duration of antithrombotic therapy represent still a clinical conundrum requiring a critical assessment of patient comorbidities, clinical presentation, and PCI features. The 2024 European Society of Cardiology (ESC) guidelines for the management of patients with CCS have been recently published encompassing new and revised recommendations on antithrombotic therapy. The scope of this manuscript is to provide a focus on the key recommendations on antithrombotic therapy of the 2024 ESC guidelines. Furthermore, we will provide an overview of differences and similarities between the latest ESC recommendations and statements on oral antithrombotic regimens in CCS patients from a recent European expert consensus document.
Neurohormonal response is associated with mortality in women with ST-elevation myocardial infarction
Authors: Kunkel Joakim Bo , Søholm Helle , Holle Sarah L D , Goetze Jens P , Holmvang Lene , Jensen Lisette O , Sheikh Annam P , Møller Jacob E , Hassager Christian , Frydland Martin
Published: December 2024

Aims

Women continue to have a worse prognosis following ST-elevation myocardial infarction (STEMI) compared to men, despite advancements in treatment. This study investigates whether neurohormonal biomarker differences contribute to sex-related disparities in mortality.

Methods and results

A total of 1892 consecutive STEMI patients from two tertiary heart centres were included. Admission neurohormonal activation defined as pro-atrial natriuretic peptide (proANP) and mid-regional pro-adrenomedullin (MR-proADM) was measured in blood drawn prior to acute coronary angiography (CAG). The primary endpoint was 1-year mortality stratified according to sex and biomarker level. Of 1782 (94%) with biomarkers available, 476 (27%) of patients were women. They were older (68 vs. 62 years), had longer symptom-to-angiography delay (211 vs. 181 min), and displayed a higher one-year mortality rate (12% vs. 7.4%, P < 0.001) compared to men. The neurohormonal response was higher in women compared to men [median (interquartile range) proANP 1050 (671–1591) vs. 772 (492–1294) pmol/L, P < 0.001); MR-proADM 0.80 (0.63–1.03) vs. 0.70 (0.58–0.89) nmol/L, P < 0.001]. In women, a level at or above the median was independently associated with a significantly higher mortality risk when adjusting for age, left ventricular ejection fraction, diabetes, heart failure, symptom onset to CAG, left-sided culprit lesion, obesity, renal dysfunction, primary percutaneous intervention, admission systolic blood pressure, and multivessel disease (HR proANP 6.05, 95% CI 1.81–20.3, P = 0.004; HR MR-proADM 3.49, 95% CI 1.42–8.62, P = 0.007). In men, there was an independent prognostic association for proANP but not for MR-proADM (HR proANP 2.38, 95% CI 1.18–4.81, P = 0.015; HR MR-proADM 1.74, 95% CI 0.89–3.40, P = 0.11).

Conclusion

Increased neurohormonal activation (MR-proADM and proANP) is associated with higher mortality in women compared to men. Neurohormonal activation may contribute to the observed sex-related differences in mortality.
Usefulness of dynamic perfusion SPECT with quantitative assessment of myocardial perfusion reserve for the detection of myocardial ischaemia in patients with presumed new left bundle branch block
Authors: Manrique Alain , Guery Clément , Legallois Damien , Richard Pascal , Roule Vincent , Agostini Denis
Published: December 2024

Aims

The aim of this retrospective study was to evaluate the ability of dynamic SPECT with quantitative analysis of myocardial blood flow (MBF) and myocardial flow reserve (MFR) for the detection of coronary artery disease (CAD) in patients with presumed new left bundle branch block (LBBB).

Methods and results

We evaluated the dynamic SPECT results from 174 consecutive patients with LBBB without a history of CAD from a single center. MBF was assessed at rest and during regadenoson (400 μg). Normal MFR was defined as ≥ 2.1. Left ventricular function and segmental perfusion were assessed from conventional gated SPECT. SPECT abnormalities were found in 17/174 (10%) patients including a reversible SPECT defect in 4 patients (2.3%), a fixed defect in 12 patients (7%), and both in 1 patient. Global left ventricular function was normal despite a significant impairment of septal wall motion. Stress and rest MBF was decreased in the septum and the inferior wall compared with other walls (P < 0.0001), resulting in similar MFR. A reduced MFR was associated with a fixed defect (P = 0.04). Only 18 patients (10%) presented with a decreased MFR. They were more often referred to subsequent coronary angiography (8/18, 44%) compared with patients with a normal MFR (9/156, 6%, χ2 = 27.382, P < 0.0001). However, significant coronary lesions were finally found in only 4/174 patients (2%).

Conclusion

Although a decreased MFR was associated with a fixed defect on conventional perfusion imaging, the low rate of CAD finally demonstrated in this study questions the relevance of routine screening for CAD in patients with presumed new LBBB.
The evolution and genetic basis of a functionally critical skull bone, the parasphenoid, among Lake Malawi cichlids
Authors: Conith Andrew J , Pascarella Sarah M , Hope Sylvie A , Albertson R Craig
Published: December 2024

Adaptive radiation, whereby a clade pairs rapid speciation with rapid phenotypic evolution, can result in an uneven distribution of biodiversity across the Metazoan tree. The cichlid fishes of East Africa have undergone multiple adaptive radiations within the major rift lakes. Cichlid radiations are marked by divergence across distinct habitat gradients producing many morphological and behavioural adaptations. Here, we characterize the shape of the parasphenoid, a bone in the neurocranium that dissipates forces generated during feeding. We examine Tropheops, a group that has transitioned between deep and shallow habitats multiple times, to examine habitat-specific differences in parasphenoid shape. We find differences in the depth and length of the parasphenoid between Tropheops residing in each habitat, variation that may impact the ability of the cranium to resist force. We next use a hybrid cross between two cichlid species that differ in parasphenoid shape, Labeotropheus and Tropheops, to examine the genetic basis of these morphological differences. We perform genetic mapping and identify two genomic regions responsible for variation in parasphenoid shape. These regions are implicated in other functional traits including the oral jaws and neurocranium, indicating that the genetic landscape for adaptive evolution may be limited to a few loci with broad effects. Repurposing the same gene(s) for multiple traits via regulatory evolution may be sufficient for selection to drive transitions between habitats important for incipient stages of adaptive radiations.
Contact zones reveal restricted introgression despite frequent hybridization across a recent lizard radiation
Authors: Zozaya Stephen M , Macor Scott A , Schembri Rhiannon , Higgie Megan , Hoskin Conrad J , O’Hara Kate , Lau Ching Ching , Read Wesley J , Moritz Craig
Published: December 2024

Introgression—the exchange of genetic material through hybridization—is now recognized as common among animal species. The extent of introgression, however, can vary considerably even when it occurs: for example, introgression can be geographically restricted or so pervasive that populations merge. Such variation highlights the importance of understanding the factors mediating introgression. Here we used genome-wide SNP data to assess hybridization and introgression at 32 contact zones, comprising 21 phylogenetic independent contrasts across a recent lizard radiation (Heteronotia). We then tested the relationship between the extent of introgression (average admixture at contact zones) and genomic divergence across independent contrasts. Early-generation hybrids were detected at contact zones spanning the range of genomic divergence included here. Despite this, we found that introgression is remarkably rare and, when observed, geographically restricted. Only the two most genomically similar population pairs showed introgression beyond 5 km of the contact zone. Introgression dropped precipitously at only modest levels of genomic divergence, beyond which it was absent or extremely low. Our results contrast with the growing number of studies indicating that introgression is prevalent among animals, suggesting that animal groups will vary considerably in their propensity for introgression.
The proteomic response of Aspergillus fumigatus to amphotericin B (AmB) reveals the involvement of the RTA-like protein RtaA in AmB resistance
Authors: Abou-Kandil Ammar , Tröger-Görler Sophie , Pschibul Annica , Krüger Thomas , Rosin Maira , Schmidt Franziska , Akbarimoghaddam Parastoo , Sarkar Arjun , Cseresnyés Zoltán , Shadkchan Yana , Heinekamp Thorsten , Gräler Markus H , Barber Amelia E , Walther Grit , Figge Marc Thilo , Brakhage Axel A , Osherov Nir , Kniemeyer Olaf
Published: December 2024

The polyene antimycotic amphotericin B (AmB) and its liposomal formulation AmBisome belong to the treatment options of invasive aspergillosis caused by Aspergillus fumigatus. Increasing resistance to AmB in clinical isolates of Aspergillus species is a growing concern, but mechanisms of AmB resistance remain unclear. In this study, we conducted a proteomic analysis of A. fumigatus exposed to sublethal concentrations of AmB and AmBisome. Both antifungals induced significantly increased levels of proteins involved in aromatic acid metabolism, transmembrane transport, and secondary metabolite biosynthesis. One of the most upregulated proteins was RtaA, a member of the RTA-like protein family, which includes conserved fungal membrane proteins with putative functions as transporters or translocases. Accordingly, we found that RtaA is mainly located in the cytoplasmic membrane and to a minor extent in vacuolar-like structures. Deletion of rtaA led to increased polyene sensitivity and its overexpression resulted in modest resistance. Interestingly, rtaA expression was only induced by exposure to the polyenes AmB and nystatin, but not by itraconazole and caspofungin. Orthologues of rtaA were also induced by AmB exposure in A. lentulus and A. terreus. Deletion of rtaA did not significantly change the ergosterol content of A. fumigatus, but decreased fluorescence intensity of the sterol-binding stain filipin. This suggests that RtaA is involved in sterol and lipid trafficking, possibly by transporting the target ergosterol to or from lipid droplets. These findings reveal the contribution of RtaA to polyene resistance in A. fumigatus, and thus provide a new putative target for antifungal drug development.
State drug caps associated with fewer Medicaid-covered prescriptions for opioid use disorder, 2017-2022
Authors: Besaw Robert J , Fry Carrie E
Published: December 2024

The Medicaid program is the largest payer of opioid use disorder (OUD) treatment, including medications for OUD (MOUD). Because of budget neutrality requirements, some Medicaid programs use prescription drug caps to limit the monthly number of prescriptions an enrollee can fill. This study examined the association between Medicaid prescription drug caps and Medicaid-covered prescriptions for 2 forms of MOUD (buprenorphine and naltrexone) from 2017 to 2022 using fee-for-service and managed care data from Medicaid's State Drug Utilization Data. Ten states had monthly prescription drug caps, ranging from 3 to 6 prescriptions. Using multivariate linear regression, we estimated that enrollees in states with monthly drug caps filled 1489.3 fewer MOUD prescriptions per 100 000 enrollees. Further, compared with states with the smallest drug caps (3 drugs), enrollees in states with 4-, 5-, and 6-drug caps filled significantly more prescriptions per state-quarter (907.7, 562.6, and 438.9 more prescriptions, respectively). Our results were robust to sensitivity analyses. Monthly prescription drug caps were significantly associated with a reduction in Medicaid-covered MOUD prescriptions. Medicaid enrollees who need MOUD may be affected by indiscriminate prescription drug cap policies, potentially hindering ongoing efforts to mitigate the opioid crisis.
Deactivating mutations in the catalytic site of a companion serine carboxypeptidase-like acyltransferase enhance catechin galloylation in Camellia plants
Authors: Chen Xiangxiang , Zhang Xue , Zhao Yue , Gao Liping , Wang Zhihui , Su Yanlei , Zhang Lingyun , Xia Tao , Liu Yajun
Published: December 2024

Galloylated flavan-3-ols are key quality and health-related compounds in tea plants of Camellia section Thea. Camellia ptilophylla and Camellia sinensis are two representative species known for their high levels of galloylated flavan-3-ols. Building on our knowledge of galloyl catechin biosynthesis in C. sinensis, we now focus on the biosynthesis of galloylated phenolics in C. ptilophylla, aiming to elucidate the mechanisms underlying the high accumulation of these compounds in Camellia species. The phenolic compounds in C. ptilophylla were identified and quantified using chromatographic and colorimetric methods. Genes involved in polyphenol galloylation were identified by correlating gene expression with the accumulation of galloylated phenolics across 18 additional Camellia species and 1 related species using Weighted Gene Co-expression Network Analysis. Key findings include the co-expression of SCPL4/2 and SCPL5 subgroup enzymes as crucial for galloylation of catechins, while SCPL3 and SCPL8 showed enzymatic activity related to hydrolyzable tannin synthesis. Variations in the amino acid sequences of SCPL5, particularly in the catalytic triad (T-D-Y vs. S-D-H) observed in C. ptilophylla and C. sinensis, were found to significantly affect enzymatic activity and EGCG production. In conclusion, this research provides important insights into the metabolic pathways of C. ptilophylla, emphasizing the critical role of SCPL enzymes in shaping the phenolic profile within the section Thea. The findings have significant implications for the cultivation and breeding of tea plants with optimized phenolic characteristics.
A comprehensive framework incorporating deep learning for analyzing fishing vessel activity using automatic identification system data
Authors: Han Fangcheng , Liu Yang , Tian Hao , Li Jianchao , Tian Yongjun
Published: December 2024

Automatic Identification System (AIS) has emerged as a crucial and cost-effective tool for monitoring ship behavior, widely employed in various fisheries. However, extracting meaningful insights from extensive AIS data to support fishery research remains challenging. In this study, we developed a framework integrating deep learning for marine fishing activity analysis, leveraging AIS data alongside marine environmental factors. Our approach utilized a transformer-based model with a majority vote for classifying fishing vessel types. The model achieved high accuracy, surpassing 90% in vessel type classification using a small subset of AIS records. Our framework employed the Temporal K-Means algorithm to efficiently identify fishing behavior, leveraging the time-series information of AIS data. Subsequently, it mapped fishing hours onto spatial grids to analyze the relationship between fishing activity and environmental factors. Correlation analysis revealed distinct preferences of different vessel types for environmental conditions, influencing their spatial distributions. Trawlers, for instance, exhibited sensitivity to seafloor bottom temperature, whereas seiners were primarily influenced by sea surface density (SSD) and sea surface temperature and gillnetters by SSD. Through this framework, we have established a coherent process to derive valuable insights about fishery resources from AIS data and guide fisheries management.
A review of nomenclature in minimally invasive coronary artery bypass grafting—the anarchy of terminology
Authors: Görtzen De Qing , Akca Ferdi
Published: December 2024

OBJECTIVES

Since the development of minimally invasive coronary surgery, nomenclature has rapidly grown to distinguish each unique method. The goal of this review was to provide a comprehensive overview of the different terms used for minimally invasive coronary bypass grafting through the years.

METHODS

A literature search was performed in August 2024 using the PubMed electronic database. To extract the best search results: “minimally invasive” and “coronary artery bypass grafting” were used as either keywords or MeSH terms. The term robotic was specifically included for a second search. Eligible articles for this review were articles using an abbreviation to describe minimally invasive coronary artery bypass grafting.

RESULTS

A total of 2118 publications on non-robotic minimally invasive coronary procedures and 392 on robotic-assisted techniques were reviewed, describing 40 unique terms for the procedure. Procedures were grouped based on left internal mammary artery harvest and anastomosis methods: mini-thoracotomy for both harvesting and coronary anastomosis (n = 586), endoscopic harvest with mini-thoracotomy (n = 37), robotic harvest with mini-thoracotomy (n = 144) and closed-chest revascularization (n = 140). Minimally invasive direct coronary artery bypass grafting was the most studied technique (486 publications, non-robotic and robotic), followed by closed-chest totally endoscopic coronary artery bypass (n = 124).

CONCLUSIONS

In conclusion, a wide variety of terms are used within the field of minimally invasive coronary surgery. A total of 40 different terms have been published, each describing certain specifics of the procedure. For anyone involved in the field of minimally invasive surgery, it is important to understand the differences and similarities of these procedures.
Emerging role of rare earth elements in biomolecular functions
Authors: Yang Wenyu , Wu Kaijuan , Chen Hao , Huang Jing , Yu Zheng
Published: December 2024

The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driving research on the biology of rare earth elements. Biomolecules associated with rare earth elements include rare earth element-dependent enzymes (methanol dehydrogenase XoxF, ethanol dehydrogenase ExaF/PedH), rare earth element-binding proteins, and the relevant metallophores. Traditional (chemical) separation methods for rare earth elements harvesting and separation are typically inefficient, while causing environmental problems, whereas bioharvesting, potentially, offers more efficient, more green platforms. Here, we review the current state of research on the biological functions of rare earth element-dependent biomolecules, and the characteristics of the relevant proteins, including the specific amino acids involved in rare earth metal binding. We also provide an outlook at strategies for further understanding of biological processes and the potential applications of rare earth element-dependent enzymes and other biomolecules.
Informatics innovation to provide return of value to participant communities in the All of Us Research Program
Authors: Mapes Brandy M , Peterson Rachele S , Watson Karriem , Basford Melissa , Cohn Elizabeth , Harris Paul A , Denny Joshua C
Published: December 2024

Objectives

The All of Us Research Program harnesses advances in technology, science, and engagement for precision medicine research. We describe informatics innovations which support that goal and return value to the participant cohort and community.

Materials and Methods

Research data from the All of Us Research Program are available to authorized users on the All of Us Researcher Workbench. We describe the technical infrastructure that enables data access and usage for researchers. Participants are considered partners. To ensure return of value, we outline participant access to information.

Results

The All of Us Research Hub allows broad access to data, regardless of background. The innovations described are rooted in the program’s core values: participation is open and reflects the diversity of the United States; participants are partners and have access to their information; transparency, security, and privacy are of the highest importance; data are broadly accessible; and the program promotes positive change. We assess research impact and reflect on how All of Us can increase existing return of value to participant communities through future informatics advancements.

Discussion

The program will continue to support efforts to ensure equitable access to data and return of value to participants. Looking ahead, we invite the community to join us.

Conclusion

All of Us research findings can change clinical care, inform guidelines, and set a new bar for data sharing. The ultimate return of value is better care for all.
Quantification of ∆9-tetrahydrocannabinol, 11-OH-THC, THC-COOH, hexahydrocannabinol, and cannabidiol in human plasma and blood by liquid chromatography–tandem mass spectrometry
Authors: Pavlic Marion , Innerhofer Carolin , Pitterl Florian
Published: December 2024

Ongoing legalization of cannabis for recreational use contributes to increasing numbers not only of incidents of driving under the influence, but within all forensic fields. In addition, newly emerging cannabinoids such as hexahydrocannabinol (HHC) and the increasing use of cannabidiol (CBD) products have to be addressed. The aims of this study were first to extend laboratory analysis capacity for the “established” cannabinoid ∆9-tetrahydrocannabinol (THC) and its metabolites 11-OH-THC and THC-COOH in human plasma/blood, and second to develop analytical procedures concerning HHC and CBD. An LC–MS–MS method based on the available (low-end) instrumentation was used. Samples (250 µl) were prepared by protein precipitation and solid-phase extraction. Chromatographic separation was achieved on a reversed-phase C18 column within 15 min. Detection was performed on a 3200 QTRAP instrument (Sciex) in positive multiple reaction monitoring (MRM) mode. Matrix-matched six-point calibrations were generated applying deuterated internal standards for all analytes except HHC. The method was fully validated according to GTFCh guidelines. Linear ranges were 0.5–25 µg/l for THC, 11-OH-THC, HHC and CBD, and 2.0–100 µg/l for THC-COOH, respectively. Limits of detection and limits of quantification were 0.5 and 1.0 µg/l (THC, 11-OH-THC, HHC, CBD), and 2.0 and 4.0 µg/l (THC-COOH). Applicability of plasma calibrations to blood samples was demonstrated. Acceptance criteria for intra- and inter-day accuracy, precision, extraction efficiency, and matrix effects were met. No interfering signals were detected for 80 exogenous compounds. The presented method is sensitive, specific, easy to handle, and does not require high-end equipment. Since its implementation and accreditation according to ISO 17025, the method has proven to be fit for purpose not only in driving under the influence of drug cases but also within postmortem samples. Furthermore, the design of the method allows for an uncomplicated extension to further cannabinoids if required.
Cystic Neutrophilic Granulomatous Mastitis: Imaging Features With Histopathologic Correlation
Authors: Villavicencio Joseph J , O’Brien Sophia R , Hu Tom , Zuckerman Samantha
Published: December 2024

Cystic neutrophilic granulomatous mastitis (CNGM) is a rare type of granulomatous lobular mastitis (GLM) with a distinct histologic pattern characterized on histopathology by clear lipid vacuoles lined by peripheral neutrophils (“suppurative lipogranulomas”), often containing gram-positive bacilli and strongly associated with Corynebacterial infection (in particular, Corynebacterium kroppenstedtii). Cystic neutrophilic granulomatous mastitis has a distinct histopathologic appearance, but the imaging appearance is less well described and has been limited to case reports and small case series published primarily in pathology literature. Mammographic findings of CNGM include focal asymmetry, skin thickening, and irregular or oval masses. Sonographic findings of CNGM include irregular mass, complex collection/abscess, dilated ducts with intraductal debris, axillary lymphadenopathy, and skin thickening with subcutaneous edema. The imaging features of CNGM are nonspecific, and biopsy is required. Identifying a causative organism, when possible, requires a Gram stain, microbiological culture, and, potentially, molecular analysis. Although therapeutic options exist for CNGM, including antibiotics, steroids, and surgical intervention, there is no current consensus on optimal treatment.
Axillary Lymph Nodes T2 Signal Intensity Characterization in MRI of Patients With Mucinous Breast Cancer: A Pilot Study
Authors: Nissan Noam , Gluskin Jill , Arita Yuki , Ochoa-Albiztegui R Elena , Fruchtman-Brot Hila , Jochelson Maxine S , Sung Janice S
Published: December 2024

Objective

To evaluate the T2 signal intensity (SI) of axillary lymph nodes as a potential functional imaging marker for metastasis in patients with mucinous breast cancer.

Methods

A retrospective review of breast MRIs performed from April 2008 to March 2024 was conducted to identify patients with mucinous breast cancer and adenopathy. Two independent, masked readers qualitatively assessed the T2 SI of tumors and lymph nodes. The T2 SI ratio for adenopathy and contralateral normal lymph nodes was quantitatively measured using the ipsilateral pectoralis muscle as a reference. Comparisons between malignant and nonmalignant lymph nodes were made using the chi-square test for qualitative assessments and the Mann–Whitney U test for quantitative assessments.

Results

Of 17 patients (all female; mean age, 48.4 ± 10.7 years; range: 29-80 years), 12 had malignant nodes, while 5 had benign nodes. Qualitative assessment revealed that the primary mucinous breast cancer was T2 hyperintense in most cases (88.2%-94.1%). No significant difference in qualitative T2 hyperintensity was observed between malignant and nonmalignant nodes (P = .51-.84). Quantitative T2 SI ratio parameters, including the ratio of mean and minimal node T2 SI to mean ipsilateral pectoralis muscle T2 SI, were higher in malignant nodes vs benign and contralateral normal nodes (P <.05).

Conclusion

Metastatic axillary lymph nodes exhibit high T2 SI, which could serve as a functional biomarker beyond traditional morphological assessment. Future studies should prioritize investigating more precise measurements, such as T2 mapping, and confirm these results in larger groups and across mucinous neoplasms in other organs.
Macrophages regulate angiogenesis-osteogenesis coupling induced by mechanical loading through the Piezo1 pathway
Authors: Liu Hongzhi , Zhou Hang , Fan Yuanhao , Li Jiawei , Guo Ziyu , Xu Qiuchi , Liu Yang , Gao Kun , Ait Lahcine Neima , Zhang Jianing , Zhou Jingjing , Guo Fengjin , Liu Chao
Published: December 2024

Bone is a mechanosensitive organ, and its regeneration also depends on the ability of bone cells to perceive and react to mechanical stimuli. Macrophages are indispensable for bone formation, regeneration, and maintenance. Depletion of macrophages resulted in poor bone development due to impaired vessel formation and osteogenesis. However, how mechanical stimulation stimulates macrophages during bone regeneration is unclear. As in many cell types, Piezo1 is part of the mechanotransduction in macrophages and modulates macrophage activity. Here, we utilized conditional KO of Piezo1 in LysM+ myeloid cells and in vivo mechanical loading to investigate the mechanoregulation of macrophages and their contribution to bone repair. We found that mechanical loading increased the ratio of CD206+ macrophages, angiogenesis-osteogenesis coupling, and cell proliferation within the defect region, leading to enhanced bone regeneration. However, all the loading-induced upregulations were blunted by the conditional KO of Piezo1 in macrophages. Furthermore, we implanted WT bone marrow-derived macrophages into the defect area in Piezo1 KO mice. WT macrophages rescued mechanosensitive angiogenesis-osteogenesis coupling and promoted bone regeneration in Piezo1 KO mice. Together, our data showed that Piezo1 in macrophages is indispensable for loading-induced bone regeneration by stimulating macrophage polarization into the CD206+ phenotype, thereby facilitating the angiogenesis-osteogenesis coupling, promoting cell proliferation, and finally resulting in enhanced bone regeneration.
Evaluation of methodology for measuring standard metabolic rates of crayfishes using the red swamp crayfish Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae)
Authors: Iqbal Azeem , Adkins Hannah M , Fogelman Kaelyn J , Stoeckel James A , Kozák Pavel
Published: December 2024

The importance of energy budgets in understanding the ecology, conservation and production of crayfishes has long been recognized. Standard metabolic rate (SMR) estimates the minimum metabolic rate required for basic maintenance of an organism while at rest, and is a critical parameter for investigating energy balance and metabolism. Estimating SMR involves quantifying oxygen uptake under specific conditions. Standard methodology for estimating SMR has been described and evaluated for fishes, but not thoroughly investigated for crayfishes. We adapted a recommended protocol developed for fishes in order to determine appropriate methodologies for measuring SMR in crayfishes. Study animals consisted of 18 individuals of Procambarus clarkii (Girard, 1852) collected in Alabama, USA. Respiration rates were measured using an optical respirometry system (Loligo Systems®; Viborg, Denmark) and intermittent respirometry techniques. Crayfish respiration stabilized the morning after initiation of the trial indicating that a 12 h overnight period was sufficient to acclimate crayfish to respirometry chambers. After 12 h of daylight, respiration of acclimated crayfish typically exhibited a short spike when lights were turned off, indicating data collected within ~2 h following a light change should be excluded from the dataset used to calculate SMR. When calculating SMR, a quantile approach was typically more appropriate than the mean of the lowest normal distribution approach. SMR calculated during the day was only marginally higher than SMR calculated during the night, indicating that SMR can be estimated during either period if shelters are provided in the respiration chambers. Due to the wide diversity of crayfish species and ranges, our recommendations may not be appropriate for every crayfish species or subpopulation. The recommendations can serve, however, as a valuable starting point and the described methodology provides a standardized approach for determining appropriate protocols to measure SMR of crayfish species of interest.