bluuebunny/crossref_metadata_2025 huggingface dataset:
E-Health-based, trans-sectoral, geriatric health service – Geriatric Network (GerNe)
Authors: Mohr Michael , Büttner Matthias , Deuster Oliver , Heckmann Jochen , Huwer Frank , Krämer Irene , Lippold Cornelia , Siegrist Bettina , Singer Susanne , Veith Marina , Zinke Ariane , Hardt Roland
Published: July 2024

Currently, exchange of information between the geriatric clinic and the attending general practitioner (GP) occurs primarily through the doctor's letter after discharging from the clinic. The aim of our study was to reduce readmissions of multimorbid, geriatric patients to the clinic by establishing a new form of care via an electronic case file (ECF) and a consultation service (CS). The discharging geriatric clinic filled out an online ECF. The patient's GP should document quarterly follow-ups in the ECF. The case file was monitored by the discharging clinic due to a consultation service. The primary efficacy endpoint was the rehospitalization rate within one year. The hospitalization rate for patients managed in the project was 83.1/100 person years (PY), while the control group from insurance data had a rate of 69.0/100 PY. The primary endpoint did not show a statistically significant difference (p = 0.15). A total of 195 contacts were documented via CS for 171 participants, mostly initiated by the clinics. The clinical queries primarily concerned drug therapy. The Covid pandemic had an overall impact on hospitalizations. There are many approaches to reducing hospital readmissions after discharge of older patients. Supporting the transition from inpatient to outpatient care by different professional groups or care systems has been shown to have a positive effect. Furthermore, the utilisation of an ECF can also be beneficial in this regard.
Skeleton density and ellipsoid zone loss are prognostic for progression in Macular Telangiectasia Type 2
Authors: Goerdt Lukas , Berger Moritz , Jungblut Julie , Rodriguez Garcia Jose Luis , Pfau Kristina , Herrmann Philipp , Holz Frank G. , Wintergerst Maximilian W. M.
Published: July 2024

Macular Telangiectasia Type 2 (MacTel) is a chronic, progressive disease of the central retina characterized by vascular and neurodegenerative changes. As there is currently no treatment for non-neovascular MacTel, there is a dearth for biomarkers identifying eyes with an increased risk for disease progression for patient counseling and clinical trial recruitment. Eyes were classified to be stable or progressive, defined by the fundus photography-based grading system by Gass and Blodi. First, structural differences between these two groups were assessed, employing optical coherence tomography (OCT) and OCT-angiography. Univariate regression analyses revealed evidence towards a lower superficial retinal layer (SRL) vessel density (VD), skeleton density (SD) and deep retinal layer (DRL) SD in progressing compared to stable eyes (p = 0.05, p = 0.05, p = 0.07). Second, a multivariable predictive model was employed to examine the predictive value of structural and functional parameters for disease progression. Baseline best corrected visual acuity (BCVA) and SRL SD are prognostic for disease progression (p < 0.001, p = 0.05). The presence of ellipsoid zone (EZ) loss is prognostic for future central retinal thickness (p < 0.01). We propose SRL SD, BCVA, and EZ loss as prognostic biomarkers and as possible outcome measures in future interventional studies in MacTel.
Simulation-based prior knowledge elicitation for parametric Bayesian models
Authors: Bockting Florence , Radev Stefan T. , Bürkner Paul-Christian
Published: July 2024

A central characteristic of Bayesian statistics is the ability to consistently incorporate prior knowledge into various modeling processes. In this paper, we focus on translating domain expert knowledge into corresponding prior distributions over model parameters, a process known as prior elicitation. Expert knowledge can manifest itself in diverse formats, including information about raw data, summary statistics, or model parameters. A major challenge for existing elicitation methods is how to effectively utilize all of these different formats in order to formulate prior distributions that align with the expert’s expectations, regardless of the model structure. To address these challenges, we develop a simulation-based elicitation method that can learn the hyperparameters of potentially any parametric prior distribution from a wide spectrum of expert knowledge using stochastic gradient descent. We validate the effectiveness and robustness of our elicitation method in four representative simulation studies covering linear models, generalized linear models, and hierarchical models. Our results support the claim that our method is largely independent of the underlying model structure and adaptable to various elicitation techniques, including quantile-based, moment-based, and histogram-based methods.
Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria
Authors: van den Biggelaar Robin H. G. A. , Walburg Kimberley V. , van den Eeden Susan J. F. , van Doorn Cassandra L. R. , Meiler Eugenia , de Ries Alex S. , Fusco M. Chiara , Meijer Annemarie H. , Ottenhoff Tom H. M. , Saris Anno
Published: July 2024

The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host–pathogen interface and identified several kinase inhibitors as potential HDTs.
Neurobiological modulation with REAC technology: enhancing pain, depression, anxiety, stress, and quality of life in post-polio syndrome subjects
Authors: André Nogueira Jeyce Adrielly , Souza Bulle Oliveira Acary , Pereira Motta Monalisa , Vieira de Souza Moscardi Alcione Aparecida , Manchim Favaro Vanessa , Munhoz Teixeira Claudete , Orasmo Simcsik Amanda , Patrizi Maria Clara , Conde Maria Salete , Rinaldi Arianna , Fontani Vania , Rinaldi Salvatore
Published: July 2024

Post-polio syndrome (PPS) brings new challenges for polio survivors, including muscle decline, pain, depression, and diminished quality of life. This study explored the potential of REAC neuromodulatory treatments to ease pain, improve mood, and enhance quality of life in PPS patients. 17 individuals with PPS (average age 54.8) received three REAC treatments: Neuro Postural Optimization, Neuro Psycho Physical Optimization, and Neuro Psycho Physical Optimization-Cervico Brachial. Pain, depression, anxiety, stress, and quality of life were assessed before and after using established scales. REAC treatments significantly reduced pain across various dimensions, along with depression, anxiety, and stress levels. Additionally, patients reported improved physical and psychological quality of life. This study suggests REAC neuromodulatory treatments as a promising non-invasive option to improve pain, emotional well-being, and quality of life in individuals with PPS.
Optimal design of fractional-order proportional integral derivative controllers for structural vibration suppression
Authors: Khodadoost Saeed , Saraee Meysam , Talatahari Siamak , Sareh Pooya
Published: July 2024

In designing control systems, it is known that fractional-order proportional integral derivative (FOPID) controllers often provide greater flexibility than conventional proportional integral derivative (PID) controllers. This higher level of flexibility has proven to be extremely valuable for various applications such as vibration suppression in structural engineering. In this paper, we study the optimization of FOPID controllers using twelve well-established algorithms to minimize structural responses under seismic excitations. The algorithms include crystal structure algorithm (CryStAl), stochastic paint optimizer, particle swarm optimization, krill herd, harmony search, ant colony optimization, genetic algorithm, grey wolf optimizer, Harris hawks optimization, sparrow search algorithm, hippopotamus optimization algorithm, and duck swarm algorithm. In addition to highlighting the benefits of fractional calculus in structural control, this study provides a detailed analysis of FOPID controllers as well as a brief description of the algorithms used to optimize them. To evaluate the efficiency of the proposed techniques, two building models with different numbers of stories are examined. FOPID controllers are designed based on oustaloup’s approximation and the El Centro earthquake data. Using five well-known metrics, the performances of the developed methods are evaluated against five earthquake scenarios, including the recent earthquake in Turkey. A non-parametric (Friedman) test is also employed to compare the algorithms based on their corresponding vibration reduction. The findings of this analysis show that CryStAl consistently performs better than the other algorithms for both building models, thus resulting in superior vibration suppression.
Targeting PRMT5 enhances the radiosensitivity of tumor cells grown in vitro and in vivo
Authors: Degorre Charlotte , Lohard Steven , Bobrek Christina N. , Rawal Komal N. , Kuhn Skyler , Tofilon Philip J.
Published: July 2024

PRMT5 is a widely expressed arginine methyltransferase that regulates processes involved in tumor cell proliferation and survival. In the study described here, we investigated whether PRMT5 provides a target for tumor radiosensitization. Knockdown of PRMT5 using siRNA enhanced the radiosensitivity of a panel of cell lines corresponding to tumor types typically treated with radiotherapy. To extend these studies to an experimental therapeutic setting, the PRMT5 inhibitor LLY-283 was used. Exposure of the tumor cell lines to LLY-283 decreased PRMT5 activity and enhanced their radiosensitivity. This increase in radiosensitivity was accompanied by an inhibition of DNA double-strand break repair as determined by γH2AX foci and neutral comet analyses. For a normal fibroblast cell line, although LLY-283 reduced PRMT5 activity, it had no effect on their radiosensitivity. Transcriptome analysis of U251 cells showed that LLY-283 treatment reduced the expression of genes and altered the mRNA splicing pattern of genes involved in the DNA damage response. Subcutaneous xenografts were then used to evaluate the in vivo response to LLY-283 and radiation. Treatment of mice with LLY-283 decreased tumor PRMT5 activity and significantly enhanced the radiation-induced growth delay. These results suggest that PRMT5 is a tumor selective target for radiosensitization.
Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis
Authors: Pollard Samantha , Chan Brandon , Gerrie Alina S. , Raymakers Adam J. N. , Regier Dean A.
Published: July 2024

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491–$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.
Positron unveiling high mobility graphene stack interfaces in Li-ion cathodes
Authors: Zheng Meiying , Kuriplach Jan , Makkonen Ilja , Ferragut Rafael , Di Noto Vito , Pagot Gioele , Laakso Ekaterina , Barbiellini Bernardo
Published: July 2024

Carbon-based coatings in Li-ion battery cathodes improve electron conductivity and enable rapid charging. However, the mechanism is not well understood. Here, we address this question by using positrons as non-destructive probes to investigate nano-interfaces within cathodes. We calculate the positron annihilation lifetime in a graphene stack LiCoO2 heterojunction using an ab initio method with a non-local density approximation to accurately describe the electron-positron correlation. This ideal heterostructure represents the standard carbon-based coating performed on cathode nanoparticles to improve the conduction properties of the cathode. We characterize the interface between LiCoO2 and graphene as a p-type Schottky junction and find positron surface states. The intensity of the lifetime component for these positron surface states serves as a descriptor for positive ion ultra-fast mobility. Consequently, optimizing the carbon layer by enhancing this intensity and by analogizing Li-ion adatoms on graphene layers with positrons at surfaces can improve the design of fast-charging channels.
Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial
Authors: Verbout Norah G. , Lorentz Christina U. , Markway Brandon D. , Wallisch Michael , Marbury Thomas C. , Di Cera Enrico , Shatzel Joseph J. , Gruber András , Tucker Erik I.
Published: July 2024

Background

The protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit.

Methods

This phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four.

Results

Here we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002.

Conclusions

As far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations.
Enhancement of tryptophan 2-monooxygenase thermostability by semi-rational enzyme engineering: a strategic design to minimize experimental investigation
Authors: Kongjaroon Sirus , Lawan Narin , Trisrivirat Duangthip , Chaiyen Pimchai
Published: July 2024

A semi-rational and strategic-design approach using in silico tools and site-saturation mutagenesis with minimal experimental effort was used to engineer tryptophan 2-monooxygenase to obtain thermostable variants with the same enzyme activity.
QSPR and q-RASPR predictions of the adsorption capacity of polyethylene, polypropylene and polystyrene microplastics for various organic pollutants in diverse aqueous environments
Authors: Hossain Md Mobarak , Banerjee Arkaprava , Chatterjee Mainak , Roy Kunal , Cronin Mark T. D.
Published: July 2024

In this study, experimental data on the adsorption of organic pollutants onto microplastics in different aqueous environments were used to develop QSPR and q-RASPR models.
Red-light-responsive cucurbit[8]uril based host–guest interaction enabling the construction of a photoswitchable supramolecular polymeric hydrogel
Authors: Yuan Yan-Yan , Hai Yu , Liu Li-Juan , Zhan Tian-Guang , Kong Li-Chun , Zhang Kang-Da
Published: July 2024

A red/blue light induced photoswitchable host–guest system based on CB[8] and water soluble low cytotoxic azo derivatives is constructed, enabling the fabrication of supramolecular polymeric hydrogel with red light-induced gel–sol transformation.
Electrolyte engineering for the mass exfoliation of graphene oxide across wide oxidation degrees
Authors: Ren Huili , Xia Xiaopei , Sun Yingzhi , Zhai Yi , Zhang Zongzheng , Wu Jiahao , Li Jing , Liu Mingjie
Published: July 2024

Herein, we report a two-step electrochemical approach encompassing pre-intercalation and post-exfoliation/oxidation, enabling the mass exfoliation of graphene oxide with customizable oxidation levels on a timescale of minutes.
Layer-structured P3-K0.5Mn0.95W0.05O2 for enhanced potassium-ion batteries by mitigating phase transformation
Authors: Gao Xuan-Wen , Zhao Lu-Kang , Li Qi , Yang Rui , Liu Zhao-meng , Luo Wen-Bin
Published: July 2024

The movement of transition metal layers and the transformation from the P3-type to the O3-type structure were successfully suppressed in the designed P3-type K0.5Mn0.95W0.05O2 cathode for potassium-ion batteries.
Synergistic integration of PdCu alloy on TiO2 for efficient photocatalytic CO2 reduction to CH4 with H2O
Authors: Liu Yang , Sun Shujuan , Ma Meng , Zhong Xinyu , Gao Fengyu , Hai Guangtong , Huang Xiubing
Published: July 2024

The synergistic effect of PdCu alloys on TiO2 nanosheets expands the light-absorption range, improves the adsorption of CO2 and H2O, and accelerates photogenerated electron migration, resulting in an increased CH4 yield with a selectivity of 98.7%.
Multi‐modal video search by examples—A video quality impact analysis
Authors: Wu Guanfeng , Haider Abbas , Tian Xing , Loweimi Erfan , Chan Chi Ho , Qian Mengjie , Muhammad Awan , Spence Ivor , Cooper Rob , Ng Wing W. Y. , Kittler Josef , Gales Mark , Wang Hui
Published: July 2024

As the proliferation of video content continues, and many video archives lack suitable metadata, therefore, video retrieval, particularly through example‐based search, has become increasingly crucial. Existing metadata often fails to meet the needs of specific types of searches, especially when videos contain elements from different modalities, such as visual and audio. Consequently, developing video retrieval methods that can handle multi‐modal content is essential. An innovative Multi‐modal Video Search by Examples (MVSE) framework is introduced, employing state‐of‐the‐art techniques in its various components. In designing MVSE, the authors focused on accuracy, efficiency, interactivity, and extensibility, with key components including advanced data processing and a user‐friendly interface aimed at enhancing search effectiveness and user experience. Furthermore, the framework was comprehensively evaluated, assessing individual components, data quality issues, and overall retrieval performance using high‐quality and low‐quality BBC archive videos. The evaluation reveals that: (1) multi‐modal search yields better results than single‐modal search; (2) the quality of video, both visual and audio, has an impact on the query precision. Compared with image query results, audio quality has a greater impact on the query precision (3) a two‐stage search process (i.e. searching by Hamming distance based on hashing, followed by searching by Cosine similarity based on embedding); is effective but increases time overhead; (4) large‐scale video retrieval is not only feasible but also expected to emerge shortly.
Supermassive Primordial Black Holes for Nano-Hertz Gravitational Waves and High-redshift JWST Galaxies
Authors: Huang Hai-Long , Cai Yong , Jiang Jun-Qian , Zhang Jun , Piao Yun-Song
Published: July 2024

Recently, observational hints for supermassive black holes have been accumulating, prompting the question: Can primordial black holes (PBHs) be supermassive, particularly with masses M ≳ 109
M
⊙? A supercritical bubble, containing an inflating baby universe, that nucleated during inflation can evolve into a PBH in our observable universe. We find that when the inflaton slowly transitions past a neighboring vacuum, the nucleation rate of supercritical bubbles inevitably peaks, leading to a mass distribution of multiverse PBHs with a peak mass up to M ≳ 1011
M
⊙. Thus, our mechanism naturally provides a primordial origin for supermassive black holes.
Tbx-Zn1-x-BDC MOF films synthesized in-situ by the aero-sol-assisted chemical vapor deposition
Authors: Espinoza–Tapia Julio César , Becerril–Landero Luis Alberto , Barrera–Calva Enrique , Vigueras Ramírez Juan Gabriel , González–Reyes Leonardo , Falcony–Guajardo Ciro
Published: July 2024

Tbx-Zn1-x-BDC MOF films were deposited in situ on glass substrates using the aerosol-assisted chemical vapor deposition (AACVD) technique with an ultrasonic spray pyrolysis system, with x ranging from 0 to 1. Various precursors and solvents were used in the precursor solutions, which were precisely nebulized onto the substrate. The resulting films were characterized using techniques such as x-ray diffraction, Raman spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), and Photoluminescence Spectroscopy. The findings revealed the evolution of Zn-BDC and/or Tb-BDC crystalline structures within the films and changes in the physical properties of the Metal Organic Frameworks (MOFs), such as film thickness and roughness. Moreover, these insights offer vital information for the design and control of MOF films with specific properties, highlighting their potential applications in various fields.
Interaction between visual impairment and genetic risk of dementia and psychosis in older adults
Authors: Hamedani Ali G , Ellis Colin A , Ehrlich Joshua R , Willis Allison W
Published: July 2024

Background

Visual impairment (VI) is associated with dementia and other neuropsychiatric outcomes, but previous studies have not considered genetic sources of confounding or effect modification.

Methods

We analysed data from the Health and Retirement Study, an ongoing nationally representative survey of older US adults, a subset of whom underwent genetic testing from 2006 to 2012 (n = 13 465). Using discrete time proportional hazards models and generalised estimating equations, we measured the association between VI and dementia, depression and hallucinations adjusting for demographics and comorbidities, ancestry-specific principal components and polygenic risk scores (PRS) for Alzheimer’s disease, major depressive disorder or schizophrenia. Effect modification was assessed using VI–PRS interaction terms and stratified analyses.

Results

VI was associated with dementia, depression and hallucinations after adjusting polygenic risk and other confounders. There was no VI–PRS interaction for dementia or depression. However, the association between VI and hallucinations varied by genetic risk of schizophrenia. Within the bottom four quintiles of schizophrenia PRS, VI was not associated with hallucinations among White (OR 1.16, 95% CI: 0.87–1.55) or Black participants (OR 0.96, 95% CI: 0.49–1.89). In contrast, VI was strongly associated with hallucinations among White (OR 2.08, 95% CI: 1.17–3.71) and Black (OR 10.63, 95% CI: 1.74–65.03) participants in the top quintile of schizophrenia PRS.

Conclusions

The association between VI and neuropsychiatric outcomes is not explained by shared genetic risk factors, and there is a significant interaction between VI and polygenic risk of hallucinations in older adults.
Cross-sectional description of hospital pharmacy services in Puerto Rico in 2022 using the Practice Advancement Initiative 2030 Self-Assessment Tool
Authors: Rodríguez-Escudero Idaliz , Bonilla-Medina Glorimar , Cabrera-Martínez Janice , Cintrón-Zayas Víctor
Published: July 2024

Purpose

The American Society of Health-System Pharmacists (ASHP) developed the Practice Advancement Initiative 2030 (PAI 2030) to support the continuous improvement of hospital pharmacy services in the United States. Puerto Rico (PR) hospitals’ level of compliance with PAI 2030 recommendations is not currently known. The primary objective of this study was to describe the hospital pharmacy scenario in PR in the 5 areas addressed in PAI 2030 recommendations.

Through a collaboration between the state affiliate, a school of pharmacy, and ASHP, completion of the PAI 2030 Self-Assessment Tool was promoted among hospital pharmacy directors between August 2022 and March 2023. A total of 18 out of 66 hospitals completed the survey. The results were compared with national data provided by ASHP from 163 US hospitals. Areas where PR hospitals rated high were in PAI 2030 domain A (Pharmacy Technician Role, Education, and Training) and domain E (Pharmacist Leadership in Medication Use and Safety). PR hospitals rate their performance lower in domain A (Patient-Centered Care) and domain B (Pharmacist Role, Education, and Training). Specific focus areas for improvement by PR hospitals include pharmacist participation in medication reconciliation, 24/7 access to advanced clinical pharmacy services, expansion of the pharmacist’s scope of practice, and training through the Board of Pharmacy Specialties and residency programs.

Conclusion

This study illustrates how the PAI 2030 Self-Assessment Tool can be used to benchmark pharmacy services at the state level. We suggest that changes are needed to close the gap between hospital pharmacies working towards optimizing the role of pharmacists in healthcare systems and those still struggling with dedicating staff to well-recognized pharmacist roles and responsibilities.
Exploring geography and evolutionary history as drivers of variation in floral scent chemistry in western sessile-flowered Trillium using parsimony-constrained phylogenetics
Authors: Blanco-Moreno Candela , Wayman Kjirsten A , Tomescu Alexandru M F
Published: July 2024

Background and Aims

The sessile-flowered Trillium species from western North America have been challenging to distinguish morphologically owing to overlapping characters and intraspecific variation. Molecular phylogenetic analyses, currently inconclusive for this group, have not sampled multiple populations of the different species to account for this. Here, we query the diversity of floral volatile composition to understand its bearings on the taxonomy, distribution and evolution of this group.

Methods

We explored taxonomic and geographical patterns in average floral volatile composition (105 different compounds) among 42 wild populations of four sessile-flowered Trillium species and the outgroup, Pseudotrillium, in California, Oregon and Washington, by means of parsimony-constrained phylogenetic analyses. To assess the influence of character construction, we coded compound abundance in three different ways for the phylogenetic analyses and compared the results with those of statistical analyses using the same dataset and previously published statistical analyses.

Key Results

Different codings of floral volatile composition generated different phylogenetic topologies with different levels of resolution. The different phylogenies provide similar answers to taxonomic questions but support different evolutionary histories. Monophyly of most populations of each taxon suggests that floral scent composition bears phylogenetic signal in the western sessile-flowered Trillium. Lack of correlation between the distribution of populations and their position in scent-based phylogenies does not support a geographical signal in floral scent composition.

Conclusions

Floral scent composition is a valuable data source for generating phylogenetic hypotheses. The way in which scent composition is coded into characters is important. The phylogenetic patterns supported by floral volatile compounds are incongruent with previously reported phylogenies of the western sessile-flowered Trillium obtained using molecular or morphological data. Combination of floral scent data with gene sequence data and detailed morphological data from multiple populations of each species in future studies is needed for understanding the evolutionary history of western sessile-flowered Trillium.
Marker discovery in the large
Authors: Vieira Mourato Beatriz , Tsers Ivan , Denker Svenja , Klötzl Fabian , Haubold Bernhard
Published: July 2024

Motivation

Markers for diagnostic polymerase chain reactions are routinely constructed by taking regions common to the genomes of a target organism and subtracting the regions found in the targets’ closest relatives, their neighbors. This approach is implemented in the published package Fur, which originally required memory proportional to the number of nucleotides in the neighborhood. This does not scale well.

Results

Here, we describe a new version of Fur that only requires memory proportional to the longest neighbor. In spite of its greater memory efficiency, the new Fur remains fast and is accurate. We demonstrate this by applying it to simulated sequences and comparing it to an efficient alternative. Then we use the new Fur to extract markers from 120 reference bacteria. To make this feasible, we also introduce software for automatically finding target and neighbor genomes and for assessing markers. We pick the best primers from the 10 most sequenced reference bacteria and show their excellent in silico sensitivity and specificity.

Availability and implementation

Fur is available from github.com/evolbioinf/fur, in the Docker image hub.docker.com/r/beatrizvm/mapro, and in the Code Ocean capsule 10.24433/CO.7955947.v1.
Best practices to evaluate the impact of biomedical research software—metric collection beyond citations
Authors: Afiaz Awan , Ivanov Andrey A , Chamberlin John , Hanauer David , Savonen Candace L , Goldman Mary J , Morgan Martin , Reich Michael , Getka Alexander , Holmes Aaron , Pati Sarthak , Knight Dan , Boutros Paul C , Bakas Spyridon , Caporaso J Gregory , Del Fiol Guilherme , Hochheiser Harry , Haas Brian , Schloss Patrick D , Eddy James A , Albrecht Jake , Fedorov Andrey , Waldron Levi , Hoffman Ava M , Bradshaw Richard L , Leek Jeffrey T , Wright Carrie
Published: July 2024

Motivation

Software is vital for the advancement of biology and medicine. Impact evaluations of scientific software have primarily emphasized traditional citation metrics of associated papers, despite these metrics inadequately capturing the dynamic picture of impact and despite challenges with improper citation.

Results

To understand how software developers evaluate their tools, we conducted a survey of participants in the Informatics Technology for Cancer Research (ITCR) program funded by the National Cancer Institute (NCI). We found that although developers realize the value of more extensive metric collection, they find a lack of funding and time hindering. We also investigated software among this community for how often infrastructure that supports more nontraditional metrics were implemented and how this impacted rates of papers describing usage of the software. We found that infrastructure such as social media presence, more in-depth documentation, the presence of software health metrics, and clear information on how to contact developers seemed to be associated with increased mention rates. Analysing more diverse metrics can enable developers to better understand user engagement, justify continued funding, identify novel use cases, pinpoint improvement areas, and ultimately amplify their software’s impact. Challenges are associated, including distorted or misleading metrics, as well as ethical and security concerns. More attention to nuances involved in capturing impact across the spectrum of biomedical software is needed. For funders and developers, we outline guidance based on experience from our community. By considering how we evaluate software, we can empower developers to create tools that more effectively accelerate biological and medical research progress.

Availability and implementation

More information about the analysis, as well as access to data and code is available at https://github.com/fhdsl/ITCR_Metrics_manuscript_website.
Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells
Authors: Povoleri Giovanni A M , Ridley Michael L , Marrow Rebecca J , Lalnunhlimi Sylvine , Ryan Sarah E , Kelly Audrey , Lavender Paul , Taams Leonie S
Published: July 2024

CD4+ T cells are key players in immune-mediated inflammatory diseases (IMIDs) through the production of inflammatory mediators including tumour necrosis factor (TNF). Anti-TNF therapy has revolutionized the treatment of several IMIDs and we previously demonstrated that in vitro treatment of human CD4+ T cells with anti-TNF promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in CD4+ T cells, isolated from PBMCs of healthy volunteers, stimulated in vitro for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted before performing gene expression profiling and chromatin accessibility analysis. Gene expression analysis of CD45RA-CD4+ T cells showed a distinct anti-TNF specific gene signature of 183 genes (q-value < 0.05). Pathway enrichment analysis of differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22, and CXCL10 were significantly downregulated (q-value < 0.05). Transcription factor motif analysis at the differentially open chromatin regions, after anti-TNF treatment, revealed 58 transcription factor motifs enriched at the IL10 locus. We identified seven transcription factor candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF treatment. Correlation analysis between the expression of these transcription factors and IL10 suggests a role for MAF, PRDM1, and/or EOMES in regulating IL10 expression in CD4+ T cells upon anti-TNF treatment.
Emergent coronary revascularization with percutaneous coronary intervention and coronary artery bypass grafting in patients receiving extracorporeal cardiopulmonary resuscitation
Authors: Fu Hsun-Yi , Chen Yih-Sharng , Yu Hsi-Yu , Chi Nai-Hsin , Wei Ling-Yi , Chen Kevin Po-Hsun , Chou Heng-Wen , Chou Nai-Kuan , Wang Chih-Hsien
Published: July 2024

OBJECTIVES

Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue for refractory cardiac arrest, of which acute coronary syndrome is a common cause. Data on the coronary revascularization strategy in patients receiving ECPR remain limited.

METHODS

The ECPR databases from two referral hospitals were screened for patients who underwent emergent revascularization. The baseline characteristics were matched 1:1 using propensity score between patients who underwent coronary artery bypass grafting (CABG) and those who received percutaneous coronary intervention (PCI). Outcomes, including success rate of weaning from extracorporeal membrane oxygenation (ECMO), hospital survival, and midterm survival in hospital survivors, were compared between CABG and PCI.

RESULTS

After matching, most of the patients (95%) had triple vessel disease. Compared with PCI (n = 40), emergent CABG (n = 40) had better early outcomes, in terms of the rates of successful ECMO weaning (71.1% vs 48.7%, P = 0.05) and hospital survival (56.4% versus 32.4%, P = 0.04). After a mean follow-up of 2 years, both revascularization strategies were associated with favourable midterm survival among hospital survivors (75.3% after CABG vs 88.9% after PCI, P = 0.49), with a trend towards fewer reinterventions in patients who underwent CABG (P = 0.07).

CONCLUSIONS

In patients who received ECPR because of triple vessel disease, the hospital outcomes were better after emergent CABG than after PCI. More evidence is required to determine the optimal revascularization strategy for patients who receive ECPR.
Lung adenocarcinoma manifested as ground-glass nodules in teenagers: characteristics, surgical outcomes and management strategies
Authors: Ma Yi , Fei Xiang , Jiang Chao , Chen Haiming , Wang Ziming , Bao Yi
Published: July 2024

OBJECTIVES

Ground-glass nodules–featured lung cancer have been identified in some teenagers in recent years. This study aims to investigate the characteristics and surgical outcomes of these patients and explore proper management strategy.

METHODS

Patients aged ≤20 with incidentally diagnosed lung cancer were retrospectively reviewed from February 2016 to March 2023. Based on lymph node evaluation status, these patients were divided into non-lymph node evaluation and lymph node evaluation groups. The clinical and pathological characteristics were analysed.

RESULTS

A total of 139 teenage patients were included, with an obviously increased cases observed from 2019, corresponding to the COVID-19 pandemic. The median age of the 139 patients was 18 years (range 12–20). Eighty-five patients had pure ground-glass nodules, while others had mixed ground-glass nodules. The mean diameter of nodules was 8.87 ± 2.20 mm. Most of the patients underwent wedge resection (64%) or segmentectomy (31.7%). Fifty-two patients underwent lymph node sampling or dissection. None of these patients had lymph node metastasis. The majority of lesions were adenocarcinoma in situ (63 cases) and minimally invasive adenocarcinoma (72 cases), while four lesions were invasive adenocarcinoma. The median follow-up time was 2.46 years, and none of these patients experienced recurrence or death during follow-up. The lymph node evaluation group had longer hospital stays (P < 0.001), longer surgery time (P < 0.001), and greater blood loss (P = 0.047) than the non-lymph node evaluation group.

CONCLUSIONS

The COVID-19 pandemic significantly increased the number of teenage patients incidentally diagnosed with lung cancer, presenting as ground-glass nodules on CT scans. These patients have favourable surgical outcomes. We propose a management strategy for teenage patients, and suggest that sub-lobar resection without lymph node dissection may be an acceptable surgical procedure for these patients.
Conversion of notoginsenoside R1 to 3β,12β-dihydroxydammar-(E)-20(22),24-diene-6-O-β-D-xylopyranosyl-(1→2)-β-D-glucopyranoside by Lactiplantibacillus plantarum S165 enhanced protective effects of LPS-induced intestinal epithelial barrier injury in Caco-2 cells
Authors: Wang Penghui , Gao Yansong , Yang Ge , Zhao Lei , Zhao Zijian , Li Shengyu
Published: July 2024

Aims

Microbial transformation to modify saponins and enhance their biological activities has received increasing attention in recent years. This study aimed to screen the strain that can biotransform notoginsenoside R1, identify the product and study its biological activity.

Methods and results

A lactic acid bacteria strain S165 with glycosidase-producing activity was isolated from traditional Chinese fermented foods, which was identified and grouped according to API 50 CHL kit and 16S rDNA sequence analysis. Subsequently, notoginsenoside R1 underwent a 30-day fermentation period by the strain S165, and the resulting products were analyzed using High-performance liquid chromatography (HPLC), Ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS)/MS, and 13C-Nuclear magnetic resonance (NMR) techniques. Employing a model of Lipopolysaccharide (LPS)-induced damage to Caco-2 cells, the damage of Caco-2 cells was detected by Hoechst 33 258 staining, and the activity of notoginsenoside R1 biotransformation product was investigated by CCK-8 and western blotting assay. The strain S165 was identified as Lactiplantibacillus plantarum and was used to biotransform notoginsenoside R1. Through a 30-day biotransformation, L. plantarum S165 predominantly converts notoginsenoside R1 into 3β,12β-dihydroxydammar-(E)-20(22),24-diene-6-O-β-D-xylopyranosyl-(1→2)-β-D-glucopyranoside, temporarily named notoginsenoside T6 (NGT6) according to HPLC, UPLC-MS/MS, and 13C-NMR analysis. Results from CCK-8 and Hoechst 33258 staining indicated that the ability notoginsenoside T6 to alleviate the intestinal injury induced by LPS in the Caco-2 cell was stronger than that of notoginsenoside R1. In addition, Western blotting result showed that notoginsenoside T6 could prevent intestinal injury by protecting tight junction proteins (Claudin-1, Occludin, and ZO-1).

Conclusion

Notoginsenoside R1 was biotransformed into the notoginsenoside T6 by L. plantarum S165, and the biotransformed product showed an enhanced intestinal protective effect in vitro.
Continuous variation in the shell colour of the snail Cepaea nemoralis is associated with the colour locus of the supergene
Authors: Chowdhury Mehrab , Johansen Margrethe , Davison Angus
Published: July 2024

While the shell of the land snail Cepaea nemoralis is typically classed as yellow, pink, or brown, the reality is that colour variation is continuously distributed. To further understand the origin of the continuous variation, we used crosses of C. nemoralis to compare quantitative measures of the colour with the inferred genotype of the underlying supergene locus. We also used a recently developed linkage map to find quantitative trait loci that may influence colour. The results show that the colour locus of the supergene—at around 31.385 cM on linkage group 11—is involved in determining the quantitative chromatic differences that are perceptible to human vision. We also found some evidence that variation within colour classes may be due to allelic variation at or around the supergene. There are likely other unlinked loci involved in determining colour within classes, but confirmation will require greater statistical power. Although not investigated here, environmental factors, including diet, may also impact upon variation within colour types.
Evolutionary insights of interferon lambda genes in tetrapods
Authors: Gautam Devika , Sindhu Anil , Vats Ashutosh , Rajput Shiveeli , Rana Chanchal , De Sachinandan
Published: July 2024

Type III interferon (IFN), also known as IFN-λ, is an innate antiviral protein. We retrieved the sequences of IFN-λ and their receptors from 42 tetrapod species and conducted a computational evolutionary analysis to understand the diversity of these genes. The copy number variation (CNV) of IFN-λ was determined through qPCR in Indian cattle and buffalo. The tetrapod species feature intron-containing type III IFN genes. Some reptiles and placental mammals have 2 IFN-λ loci, while marsupials, monotremes, and birds have a single IFN-λ locus. Some placental mammals and amphibians exhibit multiple IFN-λ genes, including both intron-less and intron-containing forms. Placental mammals typically possess 3–4 functional IFN-λ genes, some of them lack signal peptides. IFN-λ of these tetrapod species formed 3 major clades. Mammalian IFN-λ4 appears as an ancestral form, with syntenic conservation in most mammalian species. The intron-less IFN-λ1 and both type III IFN receptors have conserved synteny in tetrapod. Purifying selection was noted in their evolutionary analysis that plays a crucial role in minimizing genetic diversity and maintaining the integrity of biological function. This indicates that these proteins have successfully retained their biological function and indispensability, even in the presence of the type I IFNs. The expansion of IFN-λ genes in amphibians and camels have led to the evolution of multiple IFN-λ. The CNV can arise from gene duplication and conversion events. The qPCR-based absolute quantification revealed that IFN-λ3 and IFN-λ4 have more than 1 copy in buffalo (Murrah) and 6 cattle breeds (Sahiwal, Tharparkar, Kankrej, Red Sindhi, Jersey, and Holstein Friesian). Overall, these findings highlight the evolutionary diversity and functional significance of IFN-λ in tetrapod species.
Transient composition of the thrips species (Thysanoptera: Thripidae) infesting mulberry in southern India: first report of two, including the dominating invasive pestThrips parvispinus
Authors: Sreerama Kumar Prakya , Rachana Rajan Remani , Amarendra Bellapu , Sheela Nanjundaiah
Published: July 2024

Alerted by the steady upsurge of thrips infestation that led to drastic leaf-yield losses in mulberry, we investigated the composition of thrips species damaging the crop in the south Indian states of Andhra Pradesh, Karnataka, and Tamil Nadu from 2017 to 2023. The 5 species recorded included 3 previously recognized mulberry pests—Bathrips melanicornis, Pseudodendrothrips darci, and Scirtothrips dorsalis—and 2 newly encountered pests, namely Thrips palmi and Thrips parvispinus. At Handenahalli village in Anekal taluk of Bengaluru Urban district in Karnataka, where multiple thrips species simultaneously infested mulberry, the typical downward curling of leaves was ascribed to T. parvispinus. This was in contrast to the upward curling caused by the sole infestation of P. darci, the most common species infesting mulberry across the 3 states. Diagnostic characters of all the reported species are presented here along with the identification keys and photomicrographs. Thrips parvispinus as a new pest of mulberry warrants special attention given the economic loss caused by this highly polyphagous invasive species in chili in southern India during the latter half of 2021. Its presence in the transient composition of mulberry-infesting thrips species signals the possibility of it becoming a regular pest in the future with serious repercussions for the moriculture and sericulture sectors.