bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of air quality health benefits of medium and heavy-duty electrification policies in New York City
Authors: Naess Brian , Buonocore Jonathan , Southerland Veronica , Khemani Muskaan , Seppanen Catherine , Roy Ananya , Perera Frederica , Coomes Kaitlyn E , Rykowski Rick , Arunachalam Saravanan
Published: December 2024

Increased electrification of the transportation sector promises to both decrease emissions from the largest sector source of greenhouse gases as well as improve health through better air quality. The objective of this study is to evaluate the distribution of air quality health benefits of Medium- and Heavy-Duty Electric Vehicle (MHDEV) policies in New York City (NYC), quantifying differences across neighborhoods (census tracts) and population subgroups (race, ethnicity). We ran an integrated model for a 2040 baseline/business-as-usual scenario and for two policy scenarios simulating different rates of MHDEV adoption, also for 2040. Changes in air quality (fine particulate matter (PM2.5) and nitrogen dioxide (NO2)) and health and economic benefits were calculated for the two policy scenarios. We used a modified version of our previously developed ZIP Code-Level Air Pollution Policy Assessment tool which integrates two reduced form models: the Community Air Quality Tools and the Co-Benefits Risk Assessment Health Impacts Screening and Mapping Tool. Our air quality modeling employed a novel receptor network to capture sharp gradients due to medium- and heavy-duty vehicle (MHDV) emissions in the densely populated NYC region. We find that electrification of MHDVs would have substantial air pollution and health benefits for NYC, with full on-road electrification of MHDVs saving $2.4 billion in health costs in 2040, including the prevention of 248 deaths and 173 childhood asthma emergency departments visits. We find that NO2 benefits contributed between 85% and 97% of the total health benefits, emphasizing its importance for on-road health studies. We find that most health benefits would occur in neighborhoods with the highest percentage of historically marginalized populations, including substantial benefits to Hispanic populations.
The Python-Based Laboratory
Authors: Essick John
Published: December 2024

The Python-Based Laboratory: A Hands-On Guide for Scientists and Engineers provides a learn-by-doing approach to acquiring the Python programming skills needed to implement computer-controlled experimental work. The Python-Based Laboratory leads its readers to mastery of the popular, open-source Python computer language in its role as a powerful laboratory tool by carrying out interesting and relevant projects that explore the acquisition, production, analysis, and presentation of digitized waveforms. Readers, who are assumed to have no prior computer programming or Python background, begin writing meaningful programs in the first few pages. The Python-Based Laboratory can be used as a textbook for science and engineering instructional laboratory students who are being taught up-to-date Python-based experimental skills. The book also works well as a self-study guide for professional laboratory researchers, industrial engineers, hobbyists, and electronics enthusiasts seeking to automate tasks using Python. Topics covered include the control of data-acquisition devices (including multifunction data-acquisition hardware and IEEE 488.2-interfaced stand-alone instruments), data file storage and presentation, digitized data concepts (such as resolution, sampling frequency, and aliasing), data analysis techniques (curve fitting and fast Fourier transform), and building a graphical user interface (GUI) using the Tkinter toolkit that is included as part of the Python Standard Library. As readers work their way through the book, they build several computer-based instruments, including a DC voltmeter, digital oscilloscope, DC voltage source, waveform generator, blinking LED array, digital thermometer, spectrum analyzer, and frequency meter. Each chapter concludes with a Do Yourself project and a Use It! example as well as a healthy selection of homework-style problems, allowing readers to test their understanding and further develop their Python-based experimentation skills.
Python Program Development
Authors: Essick John
Published: December 2024

This chapter focuses on writing a simple Python integer-parity-detector program that tests, and then reports, the parity (i.e., evenness or oddness) of an integer. Central features of Python are presented, including its programming environment (terminal session and IDLE program editor), data types, conditional branching, and exception (error) handling. In addition, Python’s support of object-oriented programming is introduced. A Do It Yourself project explores writing a Python program that accepts two numeric values as input, performs a mathematical calculation, and then outputs the result, while a Use It! example covers how to include comments within Python code as a means of program documentation.
Data Acquisition Using MCC DAQ Device
Authors: Essick John
Published: December 2024

After their Chapter 6 orientation to the MCC DAQ device’s capabilities via DAQami, readers write Python-based data-acquisition and generation programs that call functions from the Universal Library, MCC’s device driver software. These programs execute analog-to-digital and digital-to-analog tasks on the MCC DAQ device in order to realize several computer-based instruments, including a DC voltmeter, digital oscilloscope, DC voltage source, and (for upgraded MCC models) hardware-timed waveform generator. The necessity for placing GUI and DAQ operations on separate execution threads, as well as the need for triggering in an oscilloscope application, are explored. A Do It Yourself project implements the DAQ device’s digital outputs to create a blinking LED array, and a Use It! example demonstrates how a lowpass filter can effectively eliminate aliasing in the waveform-digitization process.
Data Analysis: Curve Fitting
Authors: Essick John
Published: December 2024

A thermistor is a semiconducting device commonly used as a temperature sensor. A physical model for a thermistor’s temperature-dependent resistance is presented and then readers write GUI-equipped Python programs that fit a thermistor’s temperature versus resistance calibration data to various functional forms consistent with the physical model. First, the NumPy library’s polynomial curve-fitting function is used to fit the data to a third-order polynomial. Next, the SciPy library’s more general nonlinear fitting function is used to fit the data to several alternate functions, including the widely used Steinhart–Hart equation. Goodness of the fitted curve is judged via residual plots. For the Do It Yourself project, readers utilize the thermistor’s fitted calibration curve, along with voltage values obtained across a thermistor using a DAQ device, to construct a computer-based digital thermometer. The Use It! example centers on using DAQ-device voltage readings to acquire thermocouple-based temperature measurements.
Control of Stand-Alone Instruments Using VISA
Authors: Essick John
Published: December 2024

Using the Python-based PyVISA and NI-VISA software drivers, control of an IEEE 488.2-interfaced stand-alone instrument over the Universal Serial Bus (USB) as well as the General Purpose Interface Bus (GPIB) is studied. The Agilent 34410A digital multimeter (which has the same command set as digital multimeters from other manufacturers) is used to demonstrate the central concepts of IEEE 488.2 interface-bus communication between a computer and stand-alone instrument, including synchronization (serial poll and service request) methods. Readers write GUI-equipped Python programs to control the instrument’s data-taking functions. In the latter portion of the chapter, reader create an instrument driver for the digital multimeter using the Python dictionary data structure as a lookup table for instrument specifications. A data logger is constructed and the procedure for configuring a LAN/Ethernet interface is described in a Do It Yourself project and Use It! example, respectively.
Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications
Authors: Blythe Eoin N , Barreira Christy , Fink Corby , Brown Arthur , Weaver Lynne C , Dekaban Gregory A
Published: December 2024

Background

Immunomodulatory agents targeting the CD11d/CD18 integrin are in development for the treatment of several pathophysiologies including neurotrauma, sepsis, and atherosclerosis. Murine anti-human CD11d therapeutic antibodies have successfully improved neurological and behavioral recovery in rodent neurotrauma models. Here, we present the progression of CD11d-targeted agents with the development of humanized anti-CD11d monoclonal antibodies.

Methods

Primary human leukocytes and the THP-1 monocytic cell line were used to determine the binding of the CD11d antibodies, determine binding affinities, and assess outside-in signaling induced by CD11d antibody binding. In addition, a rat model of spinal cord injury was employed to demonstrate that the humanized monoclonal antibodies retained their therapeutic function in vivo. These determinations were made using a combination of flow cytometry, western blotting, immunohistochemistry, biochemical assays, and a locomotor behavioral assessment.

Results

Flow cytometric analysis demonstrated that the humanized anti-CD11d clones bind both human monocytes and neutrophils. Using a THP-1 model, the humanized anti-CD11d-2 clone was then determined to bind both the active and inactive CD11d/CD18 conformations without inducing inflammatory cell signaling. Finally, an investigation using anti-CD11d-2 as a detection tool uncovered a mismatch between total and surface-level CD11d and CD18 expression that was not altered by CK2 inhibition.

Conclusions

By developing humanized anti-CD11d monoclonal antibodies, new tools are now available to study CD11d biology and potentially treat inflammation arising from acute neurotrauma via CD11d targeting.
Phytoliths in dicotyledons occurring in Northwest Europe: establishing a baseline
Authors: Hermans Rosalie , Strömberg Caroline A E , Löffelmann Tessi , Vrydaghs Luc , Speleers Lien , Chevalier Alexandre , Nys Karin , Snoeck Christophe
Published: December 2024

Background and Aims

The absence of a modern plant-based ‘dicotyledon’ phytolith reference baseline impedes the accurate interpretation of fossil phytolith records in archaeological and palaeoecological research within Northwest (NW) Europe. This study aims to fill this gap by documenting and analysing the phytolith record from modern dicotyledon taxa occurring in this region.

Methods

Phytoliths were extracted from several plant parts of 117 plant specimens representing 74 species (one or two specimens per species). The study employed light microscopy to examine phytolith production (non-producer, trace, common or abundant) and phytolith assemblage composition. The data were analysed statistically to (1) determine the influence of taxonomy and plant part on phytolith presence (absent/present) using a mixed model, (2) assess phytolith assemblage variation using a permutational multivariate analysis of variance (PerMANOVA) and (3) identify patterns among sample groups including segregation for plant part, life form (forbs vs. shrubs/trees) and order using linear discriminant analyses (LDA).

Key Results

Morphotype analysis revealed diagnostic morphotypes and features for specific plant families, genera and plant parts. LDA effectively segregated plant parts and life forms, though taxonomic groupings showed limited segregation. Phytolith presence (absent/present) was found to vary, influenced by both plant part and taxonomy. For species examined through two specimens, although phytolith production varied considerably, phytolith assemblage composition was consistent.

Conclusions

This study establishes a ‘dicotyledon’ phytolith baseline for NW Europe, showing that the phytolith record can be informative in terms of plant part and life form and that several phytolith morphotypes and/or features are taxonomically diagnostic below ‘dicotyledon’ level. The findings constitute a foundation upon which future research can build, refining and expanding our knowledge of the NW European region.
Purposive Placement: Autonomy Through Self-Lock-Up in Restrictive Housing Units
Authors: Rudes Danielle S , Magnuson Shannon , Ingel Sydney
Published: December 2024

The idea that some prison residents purposively seek placement within restricted housing units (RHUs) within US prisons is perhaps counter-intuitive. Prior scholarship acknowledges that some residents prefer RHUs for safety and solitude; however, scholars to date know very little about how and why RHU placement is purposively secured. The current study presents staff and resident interview data from four prisons within one US state. Findings suggest some residents intentionally seek the RHU for both precautionary and instrumental reasons and, in doing so, often work toward a goal of gaining some (if limited) autonomy. Findings also suggest that to attain RHU placement, residents purposively commit misconducts they know require RHU placement. These findings (1) suggest a need for general population and RHU reform and (2) showcase how residents use their limited autonomy to push back against institutional processes.
Deep learning-based patient stratification for prognostic enrichment of clinical dementia trials
Authors: Birkenbihl Colin , de Jong Johann , Yalchyk Ilya , Fröhlich Holger
Published: December 2024

Dementia probably due to Alzheimer’s disease is a progressive condition that manifests in cognitive decline and impairs patients’ daily life. Affected patients show great heterogeneity in their symptomatic progression, which hampers the identification of efficacious treatments in clinical trials. Using artificial intelligence approaches to enable clinical enrichment trials serves a promising avenue to identify treatments. In this work, we used a deep learning method to cluster the multivariate disease trajectories of 283 early dementia patients along cognitive and functional scores. Two distinct subgroups were identified that separated patients into ‘slow’ and ‘fast’ progressing individuals. These subgroups were externally validated and independently replicated in a dementia cohort comprising 2779 patients. We trained a machine learning model to predict the progression subgroup of a patient from cross-sectional data at their time of dementia diagnosis. The classifier achieved a prediction performance of 0.70 ± 0.01 area under the receiver operating characteristic curve in external validation. By emulating a hypothetical clinical trial conducting patient enrichment using the proposed classifier, we estimate its potential to decrease the required sample size. Furthermore, we balance the achieved enrichment of the trial cohort against the accompanied demand for increased patient screening. Our results show that enrichment trials targeting cognitive outcomes offer improved chances of trial success and are more than 13% cheaper compared with conventional clinical trials. The resources saved could be redirected to accelerate drug development and expand the search for remedies for cognitive impairment.
Improvement in quality of life in patients treated with lebrikizumab monotherapy is mediated by improvement in itch and sleep: Results from two Phase 3 trials in patients with moderate-to-severe atopic dermatitis
Authors: Yosipovitch Gil , de Bruin-Weller Marjolein , Wiseman Marni , Elberling Jesper , Gutermuth Jan , Pierce Evangeline , Montmayeur Sonia , Yang Fan Emily , Ding Yuxin , Bardolet Laia , Chisolm Sarah
Published: December 2024

Pruritus is a hallmark symptom of atopic dermatitis (AD) and is known to worsen patients’ health-related quality of life. Lebrikizumab is a high-affinity monoclonal antibody which binds IL-13, a dominant cytokine implicated in AD. This study includes data from two Phase 3 randomized controlled trials assessing the efficacy and safety of lebrikizumab in patients with moderate-to-severe AD, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). We report a post-hoc analysis to quantify the effect of lebrikizumab vs placebo on the Dermatology Life Quality Index (DLQI) mediated indirectly through its effect on patient-reported outcomes itch and itch interference on sleep. Approximately two-thirds of the improvement in DLQI experienced by lebrikizumab-treated patients vs placebo-treated patients at Week 16 was mediated by improvement in itch and the interference of itch on sleep.
Increased phosphorescence of cyclometalated Ir(III) complex with a planar triarylborane moiety upon fluoride anion binding
Authors: Fukumoto Ryo , Sakuda Eri , Omoto Kenichiro , Horiuchi Shinnosuke , Arikawa Yasuhiro , Umakoshi Keisuke
Published: December 2024

A luminescent Ir(III) complex functionalized with a planar triarylborane moiety was prepared. This complex exhibits unique photophysical properties derived from the electron-withdrawing effect of the triarylborane moiety. A significant change in electron density occurs upon binding of F– to the electron-deficient boron center, resulting in decreased absorption and enhanced emission.
Supervised machine learning including environmental factors to predict in-hospital outcomes in acute heart failure patients
Authors: Sibilia Benjamin , Toupin Solenn , Bouali Nabil , Brette Jean-Baptiste , Ramonatxo Arthur , Schurtz Guillaume , Hamzi Kenza , Trimaille Antonin , Gall Emmanuel , Piliero Nicolas , Unger Alexandre , Andrieu Stéphane , Gonçalves Trecy , Picard Fabien , Roule Vincent , Roubille François , Houssany-Pissot Sonia , Bouchot Océane , Aboyans Victor , Vasram Reza Rossanaly , Bochaton Thomas , Logeart Damien , Solal Alain Cohen , Cartailler Jérôme , Mebazaa Alexandre , Dillinger Jean-Guillaume , Henry Patrick , Pezel Théo
Published: December 2024

Aims

While few traditional scores are available for risk stratification of patients hospitalized for acute heart failure (AHF), the potential benefit of machine learning (ML) is not well established. We aimed to assess the feasibility and accuracy of a supervised ML model including environmental factors to predict in-hospital major adverse events (MAEs) in patients hospitalized for AHF.

Methods and results

In April 2021, a French national prospective multicentre study included all consecutive patients hospitalized in intensive cardiac care unit. Patients admitted for AHF were included in the analyses. A ML model involving automated feature selection by least absolute shrinkage and selection operator (LASSO) and model building with a random forest (RF) algorithm was developed. The primary composite outcome was in-hospital MAE defined by death, resuscitated cardiac arrest, or cardiogenic shock requiring assistance. Among 459 patients included (age 68 ± 14 years, 68% male), 47 experienced in-hospital MAE (10.2%). Seven variables were selected by LASSO for predicting MAE in the training data set (n = 322): mean arterial pressure, ischaemic aetiology, sub-aortic velocity time integral, E/e′, tricuspid annular plane systolic excursion, recreational drug use, and exhaled carbon monoxide level. The RF model showed the best performance compared with other evaluated models [area under the receiver operating curve (AUROC) = 0.82, 95% confidence interval (CI) (0.78–0.86); precision-recall area under the curve = 0.48, 95% CI (0.42–0.5), F1 score = 0.56). Our ML model exhibited a higher AUROC compared with an existing score for the prediction of MAE (AUROC for our ML model: 0.82 vs. ACUTE HF score: 0.57; P < 0.001).

Conclusion

Our ML model including in particular environmental variables exhibited a better performance than traditional statistical methods to predict in-hospital outcomes in patients admitted for AHF.

Study registration

ClinicalTrials.gov identifier: NCT05063097.
Mouse models of type I interferonopathies
Authors: Luca Domnica , Kato Hiroki
Published: December 2024

Type I interferonopathies are severe monogenic diseases caused by mutations that result in chronically upregulated production of type I interferon. They present with a broad variety of symptoms, the mechanisms of which are being extensively studied. Mouse models of type I interferonopathies are an important resource for this purpose, and in this context, we review several key molecular and phenotypic findings that are advancing our understanding of the respective diseases. We focus on genotypes related to nucleic acid metabolism, sensing by cytosolic receptors and downstream signalling.
Feasibility of 4D-flow CMR for haemodynamic characterization in hypertrophic cardiomyopathy after septal myectomy with and without anterior mitral valve leaflet extension
Authors: el Mathari Sulayman , van Ooij Pim , Merton Renske , Schrauben Eric , Hopman Luuk , Nederveen Aart , Götte Marco , Kluin Jolanda
Published: December 2024

OBJECTIVES

The common surgical treatment in patients with obstructive hypertrophic cardiomyopathy is septal myectomy. This involves resection of a segment of the myocardial septum and can be performed with and without concomitant anterior mitral valve leaflet extension (AMVLE). While both approaches have satisfying clinical outcomes, there is a lack of data regarding the added value of concomitant AMVLE. In particular, their impact on postoperative haemodynamics remains unexplored. Therefore, we conducted a study to assess the feasibility of utilizing four-dimensional-flow cardiac magnetic resonance imaging (4D-flow cardiac magnetic resonance imaging (CMR)) to investigate postoperative haemodynamic differences among both surgical approaches.

METHODS

In this feasibility study, nine subjects underwent 4D-flow CMR evaluation, including three patients who underwent isolated myectomy, three patients with myectomy + AMVLE and three healthy controls. Primary end-points were aortic wall shear stress, left ventricular outflow tract (LVOT) peak velocity and peak kinetic energy in the LVOT and ascending aorta.

RESULTS

Results showed that patients who underwent myectomy with concomitant AMVLE exhibited (i) lower aortic wall shear stress (−21.2%), (ii) lower LVOT peak velocity (−6.3%), (iii) higher kinetic energy in the LVOT (+10.8%) and (iv) lower kinetic energy in the ascending aorta (−28.8%) compared to patients who underwent isolated myectomy.

CONCLUSIONS

Patients undergoing additional AMVLE exhibited a better trend towards the haemodynamic reference values from healthy controls compared to patients undergoing isolated myectomy. Our findings underscore the feasibility of 4D-flow CMR to assess postoperative haemodynamic differences in hypertrophic cardiomyopathy patients undergoing different surgical approaches. This highlights the potential of 4D-flow CMR to compare surgical strategies based on postoperative haemodynamics.

Clinical registration number

Dutch National Medical Ethics Committee, registration number 2022.0078
Evaluating Sex Differences in Pneumococcal Disease Burden and Vaccination Effectiveness in Adults: A Population-Based Study
Authors: Forcadell-Peris María José , Vila-Córcoles Ángel , de Diego-Cabanes Cinta , Torras Vives Verònica , Ochoa-Gondar Olga , Satué-Gracia Eva M
Published: December 2024

Background

Information concerning sex differences in pneumococcal vaccine effectiveness in adults is scarce. The main aim of this study is to compare the differences in clinical effectiveness of pneumococcal vaccination between male and female.

Methods

This was a population-based cohort study involving 1 108 634 women and 951 011 men aged ≥50 years in Catalonia, Spain. Baseline characteristics of cohort members were established according to Institutional Research Database and pneumococcal disease-related hospitalizations (PDRH) captured from hospital discharge codes from 68 reference Catalonian hospitals during 2017–2018. Cox regression models were used to estimate PPsV23/PCV13 effectiveness against PDRH by sex.

Results

Across the 2-year follow-up, 4302 PDRH cases (1878 women, 2424 men) were observed, with incidences of 169.4/100 000 and 254.9/100 000 for women and men, respectively. Among women, neither PPsV23 (hazard ratio [HR], 1.04; 95% confidence interval [CI], .92–1.18; P = .540) or PCV13 (HR, 1.24; 95% CI, .91–1.70; P = .171) altered PDRH risk. Among men, PCV13 was associated with significantly increased risk of PDRH (HR, 1.57; 95% CI, 1.07–2.31; P = .021) whereas PPsV23 did not significantly alter this risk (HR, 0.89; 95% CI, .72–1.10; P = .275). No reduced risk of death following PDRH was observed in vaccinated women or men. However, regarding all-cause death, PPsV23 showed slight reduction in risk for women (HR, 0.94; 95% CI, .92–.97; P < .001).

Conclusions

PPsV23/PCV13 vaccinations have not proven effective for either sex in preventing PDRH. PPsV23 appears associated with slight reduction risk of all-cause death in women, which could be related to better or longer-lasting vaccination effects in women compared to men.
Genomic analysis of early ST32 Acinetobacter baumannii strains recovered in US military treatment facilities reveals distinct lineages and links to the origins of the Tn6168 ampC transposon
Authors: Tobin Liam A , Abu Sabah Eradah , Lebreton Francois , Myers Garry S A , McGann Patrick T , Hamidian Mehrad
Published: December 2024

Objectives

To study the population structure and genomic characteristics, including antimicrobial resistance genes, plasmid types and surface polysaccharide type, of the globally distributed Acinetobacter baumannii belonging to ST32 (Institut Pasteur scheme).

Methods

Antibiotic resistance phenotype for 19 antibiotics was determined using Vitek 2. Whole-genome sequencing was performed using the Illumina MiSeq platform. Genomes were assembled using Newbler. Phylogenetic analysis was done by determining the core-genome alignments using Panaroo v1.3, analysed in IQ-Tree2 v2.2.0.3 to construct Maximum Likelihood trees using the RaxML software. Resistance genes and IS were identified using the Abricate programme, and ISFinder databases.

Results

One hundred and thirty-three (n = 133) ST32 A. baumannii isolates were analysed in this study. These genomes originated mainly from US military treatment facilities (n = 113), but also included additional publicly available genomes in GenBank (n = 20) recovered from a broad geographic distribution extending to Asia and South America. Phylogenetic analysis of all 133 genomes revealed at least four clades, with over 80 genomes forming a tightly clustered branch, suggesting they are likely to represent outbreak strains. Analysis of the ampC region showed that ST32 strains played a significant role in the formation of the widely distributed ampC transposon, Tn6168, and supplying DNA segments containing an ISAba1-ampC from ST32s via homologous recombination.

Conclusions

ST32 strains played a significant role in the evolution of antibiotic resistance in several widely distributed sequence types including ST1 (global clone 1) and ST3.
Impact of Fusobacterium nucleatum in the treatment of cancer, including radiotherapy and its future potential in esophageal cancer
Authors: Ohsawa Manato , Nishi Hiromi , Emi Manabu , Yoshikawa Toru , Hamai Yoichi , Ibuki Yuta , Kurokawa Tomoaki , Hirohata Ryosuke , Kitasaki Nao , Kawada-Matsuo Miki , Komatsuzawa Hitoshi , Kawaguchi Hiroyuki , Okada Morihito
Published: December 2024

Despite advances in multimodality therapy, including surgery, chemotherapy, radiation therapy and chemoradiation, the fatality rate for esophageal cancer remains high. Specifically, Fusobacterium nucleatum, due to its aggregation capacity, has shown a tendency to form biofilms. The biofilm-forming capabilities of microbial communities are of utmost importance in the context of cancer treatment, as they have been shown to drive significant losses in the efficaciousness of various cancer treatments. Therefore, elucidating the dynamics of F. nucleatum will be important for the development of effective treatments for esophageal cancer. Therefore, this review summarizes the current knowledge of F. nucleatum, its involvement in cancer and its impact on chemotherapy and radiation therapy. In conclusion, further research on the role of F. nucleatum is essential for the continued advancement of the treatment of esophageal cancer and patient care.
Time-resolved transcriptomics of single Vitis vinifera fruits: membrane transporters as switches of the double sigmoidal growth
Authors: Savoi Stefania , Shi Mengyao , Sarah Gautier , Weber Audrey , Torregrosa Laurent , Romieu Charles
Published: December 2024

Grape berries lose one H+ per accumulated sucrose at the inception of ripening, but the molecular mechanisms associated with this remain unknown. By investigating single fruits, we elucidated the fundamentals of the malate-sugar nexus, previously obscured by asynchrony in population-based models of ripening. The development of individual fruits was explored to capture simultaneous changes in gene expression and metabolic fluxes from flowering to overripening. Dynamics in water, tartrate, malate, hexoses, and K+ fluxes obtained by combining individual single fruit growth and concentration data, allowed us to define eleven sub-phases in fruit development, with defined groups according to RNA sequencing analysis. Co-expression network analysis revealed a range of transcript level-metabolic rate associations. A set of membrane transporters related to vacuolar over-acidification was found specifically expressed during the first growth phase. Unlike in slightly more acidic citrus, vacuolar H+-pyrophosphatase transcripts were predominantly expressed, followed by vacuolar ATPase, clarifying a thermodynamic limit beyond which their replacement by the tonoplast P3A/P3B ATPase complex is essential. Unexpectedly, expression of aluminium-activated malate transporter was low at this stage, possibly replaced by an uncharacterized anion channel. At the onset of ripening, the role of hexose transporter HT6 as a molecular switch in sugar accumulation was confirmed, electroneutralized by malate vacuolar leakage and H+ pumps activation.
A modular toolbox for the optogenetic deactivation of transcription
Authors: Muench Philipp , Fiumara Matteo , Southern Nicholas , Coda Davide , Aschenbrenner Sabine , Correia Bruno , Gräff Johannes , Niopek Dominik , Mathony Jan
Published: December 2024

Light-controlled transcriptional activation is a commonly used optogenetic strategy that allows researchers to regulate gene expression with high spatiotemporal precision. The vast majority of existing tools are, however, limited to light-triggered induction of gene expression. Here, we inverted this mode of action and created optogenetic systems capable of efficiently terminating transcriptional activation in response to blue light. First, we designed highly compact regulators by photo-controlling the VP16 (pcVP16) transactivation peptide. Then, applying a two-hybrid strategy, we engineered LOOMINA (light off-operated modular inductor of transcriptional activation), a versatile transcriptional control platform for mammalian cells that is compatible with various effector proteins. Leveraging the flexibility of CRISPR systems, we combined LOOMINA with dCas9 to control transcription with blue light from endogenous promoters with exceptionally high dynamic ranges in multiple cell lines. Functionally and mechanistically, the versatile LOOMINA platform and the exceptionally compact pcVP16 transactivator represent valuable additions to the optogenetic repertoire for transcriptional regulation.
Impact of resection location on depressive symptoms following glioma surgery
Authors: Belgers Vera , van Genderen Maisa N G , de Schotten Michel Thiebaut , Cakmak Marcus , Douw Linda , Ferles Alexandros , Barkhof Frederik , Klein Martin , Niers Johanna M , Eijgelaar Roelant S , de Witt Hamer Philip C
Published: December 2024

Background

Glioma surgery aims to maximize tumor removal while preserving functional integrity. Functional outcome usually focuses on neurological and neurocognitive functions, but surgery may also affect mood regulation. We determined the occurrence of depressive symptoms after surgery and investigated associated factors, including preoperative depressive symptoms and the location of the resection.

Methods

We included a single-center retrospective cohort of patients with supratentorial diffuse glioma (WHO grade 2-4) who underwent first-time surgical resection between 2009 and 2021 and who completed the Center for Epidemiologic Studies Depression Scale (CES-D) before and one year after surgery. Resection cavities were segmented on postoperative MRI scans. White matter disconnections were computed, the so-called disconnectome, to examine distant effects. Multivariable regression analysis was used to relate patient, tumor, and treatment characteristics to postoperative depression scores and changes after surgery. Lesion symptom mapping was used to relate resection and disconnectome locations to these scores and changes.

Results

We included 83 patients. Before surgery, 25% of patients had depressive symptoms and one year after surgery 34%, which was not statistically different. Resections of gliomas in the right hemisphere were significantly associated with increased depression scores after surgery. A resection involving the left anterior temporal region was significantly associated with low postoperative depression scores. Disconnectome locations were not associated with either postoperative or change in depression scores.

Conclusions

Resection locations affect depressive symptoms in glioma patients. This information may be useful for patient counseling
News about the economy: a literature survey and methodological guidelines
Authors: Garz Marcel
Published: December 2024

This article surveys the economic literature on the role of mass media and social media for the dissemination of news about gross domestic product (GDP), inflation, unemployment and the economy at large. Focusing on studies that use media content data, two key insights emerge. First, identical macroeconomic facts may receive different levels of attention and can be framed in different ways, depending on political and psychological factors. Second, information spread by mass media and on social media may affect economic outcomes independent of the facts on the ground. These and other findings in the literature have helped to refine various theories in behavioral economics, finance, macroeconomics and other fields. The article also identifies untapped research potential and formulates specific recommendations for future studies, especially in terms of underutilized sources of media content data, the application of computational methods (e.g. large language models, image classification, emotion recognition) and econometric designs supporting causal inference.
Prospects for high-throughput estimates of photosynthetic parameters in tropical trees using the Dynamic Assimilation™ Technique
Authors: Braun Emmelia J , Southwick Charles D , Garcia Maquelle N , Taylor Tyeen C , Acebron Kelvin , Rodrigues João Victor F C , Ferreira Marciel J , de Oliveira Jr Raimundo Cosme , Albert Loren P
Published: December 2024

Amazônia is a species-rich region of immense importance to Earth’s water and carbon cycling. Photosynthesis drives the global carbon cycle, so understanding photosynthetic differences across diverse landscapes is a key task of ecophysiology and ecosystem science. Unfortunately, due to physiological and logistical constraints, ground-based photosynthesis data in Amazônia remains scarce, and the ‘traditional’ steady-state method (SS) of gas exchange is slow and inefficient. The Dynamic Assimilation™ Technique (DAT; Saathoff and Welles 2021) promises a new way to perform A/Ci curves rapidly without requiring steady-state conditions. Thus far, this technique has only been validated in greenhouse or agricultural-field-grown species and has yet to be tested in forest trees of diverse physiology, morphology, and environmental adaptation. To test the utility of the DAT in a complex tropical forest ecosystem, we compared the DAT to the SS method in 13 Amazonian trees in situ. We found strong agreement between Vcmax from DAT curves and SS curves, while Jmax was underestimated in DAT curves. We conclude that the DAT provides a robust and rapid estimation of Vcmax. We also identified diverse and unexpected DAT curve shapes among some trees, including the presence of an ‘overshoot’ in assimilation beyond model-derived RuBP regeneration limitations. The presence of overshoot may elucidate microclimate and species differences in RuBP regeneration rates and emphasizes the considerable importance of DAT curve protocol specifications, such as the effect of ramp rate and direction on Jmax and TPU. Overall, the DAT saved time relative to the SS method and proved to be an effective and rapid method for quantifying Vcmax in tropical trees.
FAPs orchestrate homeostasis of muscle physiology and pathophysiology
Authors: Yin Kai , Zhang Chengmin , Deng Zihan , Wei Xiaoyu , Xiang Tingwen , Yang Chuan , Chen Can , Chen Yueqi , Luo Fei
Published: December 2024

As a common clinical manifestation, muscle weakness is prevalent in people with mobility disorders. Further studies of muscle weakness have found that patients with muscle weakness present with persistent muscle inflammation, loss of muscle fibers, fat infiltration, and interstitial fibrosis. Therefore, we propose the concept of muscle microenvironment homeostasis, which explains the abnormal pathological changes in muscles through the imbalance of muscle microenvironment homeostasis. And we identified an interstitial progenitor cell FAP during the transition from normal muscle microenvironment homeostasis to muscle microenvironment imbalance caused by muscle damage diseases. As a kind of pluripotent stem cell, FAPs do not participate in myogenic differentiation, but can differentiate into fibroblasts, adipocytes, osteoblasts, and chondrocytes. As a kind of mesenchymal progenitor cell, it is involved in the generation of extracellular matrix, regulate muscle regeneration, and maintain neuromuscular junction. However, the muscle microenvironment is disrupted by the causative factors, and the abnormal activities of FAPs eventually contribute to the complex pathological changes in muscles. Targeting the mechanisms of these muscle pathological changes, we have identified appropriate signaling targets for FAPs to improve and even treat muscle damage diseases. In this review, we propose the construction of muscle microenvironmental homeostasis and find the key cells that cause pathological changes in muscle after homeostasis is broken. By studying the mechanism of abnormal differentiation and apoptosis of FAPs, we found a strategy to inhibit the abnormal pathological changes in muscle damage diseases and improve muscle regeneration.
Right Ventricular Myocardial Infarctions
Authors: Kallash Mohammed , Frishman William
Published: December 2024

Acute isolated right ventricular (RV) myocardial infarctions are relatively uncommon in clinical practice; more frequently, RV infarctions occur in association with inferior ST-segment elevation myocardial infarctions. Recent advances in diagnostic tools and methods have significantly improved our ability to detect RV infarctions in both scenarios. For this reason, it is critical for physicians to understand the pathophysiology, clinical presentation, and diagnostic criteria for RV infarctions to initiate treatment and optimize the outcomes of patients. About half of all patients with an inferior ST-segment elevation myocardial infarction develop RV infarction. In the acute setting, RV infarctions can lead to hemodynamic instability and frank shock, which are responsible for the high morbidity and mortality associated with these episodes. However, when treated properly, the prognosis of RV myocardial infarctions is quite excellent if the patient survives the acute hemodynamic compromise. In addition, RV infarctions are likely a misnomer since these events tend to represent ischemia and stunning of the RV myocardium that results in its short-term dysfunction, but the myocardium remains viable and recovers over time with no signs of an infarct if the patient survives the episode. In fact, patient outcomes in RV ischemia are dependent more on the involvement of the left ventricle than RV involvement, especially since a left ventricular infarct and dysfunction can be difficult to overcome in the long term. It is imperative to understand the various treatments available to target the hemodynamic changes and shock often seen in patients with acute RV ischemia and to implement these treatments accordingly to improve patient survival and prognosis.
Examining the Interactive Associations of Cannabis and Alcohol Outlets With Self-harm Injuries in California: A Spatiotemporal Analysis
Authors: Charris Rafael , Ahern Jennifer , Apollonio Dorie E. , Jent Victoria , Jacobs Laurie M. , Jung Shelley , Schmidt Laura A. , Gruenewald Paul , Matthay Ellicott C.
Published: December 2024

Background:

Cannabis use and alcohol use are associated with self-harm injuries, but little research has assessed links between recreational cannabis outlet openings on rates of self-harm within communities or the interactions of cannabis outlets with the density of alcohol outlets. We estimated the associations of recreational cannabis outlets, alcohol outlets, and their interaction on rates of fatal and nonfatal self-harm injuries in California, 2017–2019.

Methods:

Using California statewide data on recreational cannabis outlets, alcohol outlets, and hospital discharges and deaths due to self-harm injuries, we conducted Bayesian spatiotemporal analyses of quarterly ZIP code-level data over 3 years, accounting for confounders and spatial autocorrelation. Using the model posteriors, we estimated parameters corresponding to hypothetical shifts in outlet densities.

Results:

If recreational cannabis outlets had never opened, we estimated that nonfatal self-harm injuries would have been −0.35 per 100,000 lower (95% credible interval [CI]: −1.25, 0.51), while fatal self-harm injuries would have been −0.004 per 100,000 lower (95% CI: −0.26, 0.25). These associations did not depend on alcohol outlet density, but a hypothetical 20% reduction in alcohol outlet densities was associated with fewer self-harm injuries (risk difference per 100,000, nonfatal: −1.59; 95% CI: −2.60, −0.59; fatal: −0.10; 95% CI: −0.37, 0.16). Associations for nonfatal incidents were strongest for people aged 15–34 years, and White and Hispanic people.

Conclusion:

We did not find evidence that the introduction of recreational cannabis outlets was associated with self-harm injuries or that cannabis and alcohol outlet densities interact, but alcohol outlet density had a strong association with nonfatal self-harm injuries.
Integrating network pharmacology and in vivo pharmacological investigation for deciphering the mechanism of Simiao Yong’an decoction in alleviating rheumatoid arthritis
Authors: Jie Shanshan , Gao Yan , Sun Huijuan , Zhao Hongyan , Zhao Yukun , Chen Chen , Zeng Hui , Ma Yaluan
Published: December 2024

Objective:

To investigate the mechanism of Simiao Yong’an Decoction in alleviating the damage of rheumatoid arthritis (RA), and accordingly provide pharmacological evidence and further experimental support for the application of Simiao Yong’an Decoction, as well as provide a reference direction for the development of new drugs for RA treatments.

Materials and methods:

Arthritis was induced in Balb/c mice. The animals were randomly divided into 4 groups: control, model, methotrexate (MTX), and Simiao Yong’an Decoction group (n = 6). The Simiao Yong’an Decoction group was orally administered 4.5 g·kg−1 of Simiao Yong’an Decoction every day, and the MTX group received a single intraperitoneal injection of 2 mg·kg−1 of MTX. The arthritis symptoms of joints were scored every day after injecting a cocktail antibody. The histopathology injuries and bone destruction of joints were measured by hematoxylin and eosin staining, Safranin-O fast green staining, tartrate-resistant acid phosphatase staining, and micro–computed tomography. The regulation of Simiao Yong’an Decoction on leukocytes was analyzed by flow cytometry. The expression of inflammatory cytokines, chemokines, and matrix metalloproteinases in joints was detected by quantitative real-time polymerase chain reaction. In the network pharmacology analysis, drug targets of Simiao Yong’an Decoction were obtained from Swiss Target Prediction. Disease targets of RA were obtained from the Therapeutic Target Database and Disgenet. The ingredients-targets network, protein-protein interaction network, and gene ontology function enrichment were performed and visualized by Cytoscape software.

Results:

In the collagen antibody-induced arthritis (CAIA) murine model, Simiao Yong’an Decoction effectively improved arthritis symptoms, decreased the expression of inflammatory cytokines, and reduced joint pathologic damage and bone destruction. In the network pharmacology analysis, multiple active ingredients of Simiao Yong’an Decoction were found to regulate genes related to inflammation, chemotaxis, and collagen degradation in RA, and reduce RA damage by regulating biological processes including leukocyte migration, myeloid cell homeostasis, and collagen degradation metabolism. We further verified that Simiao Yong’an Decoction effectively regulated the number of myeloid cells in CAIA mice. Moreover, Simiao Yong’an Decoction suppressed the expression of myeloid cell-associated chemokines and matrix metalloproteinases in inflamed joints of CAIA mice.

Conclusion:

Simiao Yong’an Decoction effectively reduces RA damage by regulating myeloid cells and reducing collagen degradation.
Guidelines for clinical application of Chinese patent medicine in the treatment of influenza in children (2024)
Authors: Hu Ziteng , Liang Ning , Ming Xi , Yan Lijiao , Zhang Xuefei , Zhang Yujing , Chen Yaxin , Yang Yijiu , Wang Xuefeng , Wang Lining , Wu Liqun , Zhang Baoqing , Chang Ke , Chen Hua , Feng Xiaochun , Gao Jian , Gao Xiuan , Li Jijun , Li Min , Li Xinmin , Qin Yanhong , Ren Xianqing , Sang Gao , Sun Liping , Sun Yuanling , Wang Bo , Wang Mengqing , Wang Sumei , Wang Xiao , Wang Youpeng , Wu Li , Wu Zhenqi , Xue Zheng , Yu Jianer , Zhang Xiuying , Zhang Xia , Zhao Xia , Wang Yanping , Ma Rong , Xiong Lei , Shi Nannan
Published: December 2024

Children are highly susceptible to influenza and are at high risk for severe cases. Chinese patent medicine (CPM) offers advantages in treating pediatric influenza, but the issue of its improper use is increasingly prevalent in clinical practice. To address this, we adopted a dual leadership approach involving clinical and methodological experts, guided by evidence-based and clinical practice principles. We referred to existing guidelines, consensus statements, and treatment protocols, and designed relevant clinical questions based on the “3 specific” principles: specific CPM, specific disease stages, and specific outcomes. This allowed us to conduct evidence-based evaluations of the efficacy and application of CPMs specifically designed for children or with pediatric dosages. Using the “Checklist for Reporting Clinical Practice Guidelines for Chinese Patent Medicines V1.0” developed by our research team, we formulated recommendations for CPM. Ultimately, 13 CPMs were recommended, providing clinicians with references on “how to select medication” and “how to use medication.”