bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription factors CsWRKY53 and CsWRKY40 synergistically regulate l-theanine hydrolysis via the abscisic acid signaling pathway during tea withering
Authors: Cheng Haiyan , Pan Qianhong , Wu Wei , Shen Jimin , Liu Xiaofen , Shi Yuxuan , Yin Xueren , Xu Ping
Published: November 2024

l-Theanine hydrolysis in tea (Camellia sinensis) leaves not only reduces the quality of tea products but also decreases their health benefits. Postharvest dehydration-induced abscisic acid (ABA) contributes to l-theanine hydrolysis, but the specific underlying mechanism has not been explored. Based on transcriptome analysis and gene silencing experiments, CsNCED3a was shown to be a key gene for ABA synthesis in harvested tea leaves, and CsABF7 up-regulated the expression of CsWRKY40, which encodes a transcription factor that directly regulates a l-theanine hydrolysis gene, resulting in the loss of l-theanine. CsWRKY53 and CsWRKY40 activated the expression of CsNCED3a. The CsWRKY53–CsWRKY40 complex exhibited a stronger regulatory effect than the individual transcription factors. These findings reveal an ABA-mediated regulatory pathway for l-theanine hydrolysis, and highlight the pivotal role of ABA in the postharvest metabolism of critical flavor-contributing metabolites in tea leaves.
4D live tracing reveals distinct movement trajectories of meiotic chromosomes
Authors: Xie Peng , Zhu Shiqi , Zhang Jin , Wang Xinrui , Jiang Xu , Xiong Feng , Chen Linjin , Fang Ke , Ji Yuanhui , Zheng Beihong , Da Lincui , Cao Hua , Sun Yan , Luo Zhuojuan , Lin Chengqi
Published: November 2024

Proper chromosome alignment at the spindle equator is a prerequisite for accurate chromosome segregation during cell division. However, the chromosome movement trajectories prior to alignment remain elusive. Here, we established a 4D imaging analysis framework to visualize chromosome dynamics and develop a deep-learning model for chromosome movement trajectory classification. Our data reveal that chromosomes follow at least three distinct movement trajectories (retracing, congressing, and quasi-static) to arrive at the equator. We further revealed the distinct roles of multiple kinesin superfamily proteins (KIFs) in coordinating and maintaining the chromosome movement trajectories. In summary, we have presented an efficient and unbiased approach to studying chromosome dynamics during cell division, thereby uncovering a variety of chromosome movement trajectories that precede alignment.
A simple model for spectroscopic analyses of active stars
Authors: Nordlander T , Baratella M , Spina L , D’Orazi V
Published: November 2024

Spectroscopic analyses of young late-type stars suffer from systematic inaccuracies, typically underestimating metallicities but overestimating abundances of certain elements including oxygen and barium. Effects are stronger in younger and cooler stars, and recent evidence specifically indicates a connection to the level of chromospheric activity. We present here a two-component spectroscopic model representing a non-magnetic baseline plus a magnetic spot, and analyse the resulting synthetic spectra of young solar analogues using a standard spectroscopic technique. For a moderately active star with solar parameters and chromospheric activity index $\log R_\text{HK}^{\prime }= -4.3$ ($\sim 100$ Myr), we predict that $\left[\textrm {Fe/H}\right]$ is underestimated by 0.06 dex while $v_\textrm {mic}$ is overestimated by 0.2 km s$^{-1}$; for higher activity levels we predict effects as large as 0.2 dex and 0.7 km s$^{-1}$. Predictions are in agreement with literature data on solar twins, and indicate that the model is a plausible explanation to the observed effects. The model is simple enough that it can be included in spectroscopic packages with only changes to the underlying spectrum synthesis modules, if a $\log R_\text{HK}^{\prime }$ value is provided.
Spectrophotometry and radial distribution of multiple stellar populations in globular clusters from Gaia XP spectra
Authors: Mehta V J , Milone A P , Casagrande L , Marino A F , Legnardi M V , Cordoni G , Dondoglio E , Jang S , Lionetto S , Ziliotto T , Barbieri M , Bernizzoni M , Bortolan E , Bouras Moreno Sanchez A , Lagioia E P , Mohandasan A , Muratore F
Published: November 2024

Understanding the formation of multiple populations in globular clusters (GCs) represents a challenge for stellar population studies. Nevertheless, the outermost cluster regions, likely to hold clues about the initial configuration of GC stars, remain underexplored. We use synthetic spectra reflecting the chemical compositions of first- and second-population (1P, 2P) stars in 47 Tucanae to identify spectral regions sensitive to these populations. This led us to define new photometric bands that effectively distinguish 1P and 2P giant stars using Gaia XP spectra. Testing these filters, we constructed the pseudo two-colour diagrams dubbed chromosome maps (ChMs) and, for the first time, identified 1P and 2P stars in the cluster’s outermost regions and beyond its tidal radius. We constructed similar diagrams for NGC 3201, NGC 6121, NGC 6752, and NGC 6397, thus exploring GCs with different metallicities. The ChMs effectively distinguished multiple populations in the outer regions of all clusters, except for the metal-poor NGC 6397. Our findings, together with literature results from more-internal regions, show that the 2P stars of 47 Tucanae are more-centrally concentrated than the 1P. A similar pattern is seen for 2P stars with extreme chemical composition of NGC 3201. The multiple populations of NGC 6121, and NGC 6752 share the same radial distributions. These radial behaviours are consistent with the GC formation scenarios where 2P stars originate in the central regions. Noticeably, results on NGC 3201 are in tension with the conclusion from recent work that its 1P is more centrally concentrated than the 2P and might form with more central concentration.
Deciphering the Milky Way disc formation time encrypted in the bar chrono-kinematics
Authors: Zhang Hanyuan , Belokurov Vasily , Evans N Wyn , Li Zhao-Yu , Sanders Jason L , Ardern-Arentsen Anke
Published: November 2024

We present a novel method to constrain the formation time of the Milky Way disc using the chrono-kinematic signatures of the inner Galaxy. We construct an O-rich Mira variable sample from the Gaia long-period variable catalogue to study the kinematic behaviour of stars with different ages in the inner Galaxy. From the Auriga suite of cosmological zoom-in simulations, we find that the age of the oldest stellar population with imprints of the bar in density and kinematics matches the disc spin-up epoch. This is because stars born before the spin-up show insufficient rotation and are not kinematically cold enough to be efficiently trapped by the bar. We find that the bar kinematic signature disappears for Mira variables with a period shorter than 190 d. Using the period–age relation of Mira variables, we constrain the spin-up epoch of the Milky Way to be younger than $\sim 11{-}12$ Gyr (redshift $\sim 3$). We also discuss and compare our method and result to other evidence of the Milky Way spin-up epoch under the context of a realistic age uncertainty. Age uncertainty leads to an overestimation of the disc formation time when performing backward modelling. Our constrain of the spin-up epoch is independent from previous studies because it relies on the kinematics of the inner Galaxy instead of the solar vicinity.
Latent characterization of the complete BATSE gamma-ray bursts catalogue using Gaussian mixture of factor analysers and model-estimated overlap-based syncytial clustering
Authors: Dai Fan , Maitra Ranjan
Published: November 2024

Characterizing and distinguishing gamma-ray bursts (GRBs) has interested astronomers for many decades. While some authors have found two or three groups of GRBs by analysing only a few parameters, recent work identified five ellipsoidally shaped groups upon considering nine parameters $T_{50}, T_{90}, F_1, F_2, F_3, F_4, P_{64}, P_{256}, P_{1024}$. Yet others suggest subclasses within the two or three groups found earlier. Using a mixture model of Gaussian factor analysers, we analysed 1150 GRBs, that had nine parameters observed, from the current Burst and Transient Source Experiment (BATSE) catalogue, and again established five ellipsoidal-shaped groups to describe the GRBs. These five groups are characterized in terms of their average duration, fluence, and spectrum as shorter-faint-hard, long-intermediate-soft, long-intermediate-intermediate, long-bright-intermediate, and short-faint-hard. The use of factor analysers in describing individual group densities allows for a more thorough group-wise characterization of the parameters in terms of a few latent features. However, given the discrepancy with many other existing studies that advocated for two or three groups, we also performed model-estimated overlap-based syncytial clustering that successively merges poorer separated groups. The five ellipsoidal groups merge into three and then into two groups, one with GRBs of low durations and the other having longer duration GRBs. These groups are also characterized in terms of a few latent factors made up of the nine parameters. Our analysis provides context for all three sets of results, and in doing so, details a multilayered characterization of the BATSE GRBs, while also explaining the structure in their variability.
The impact of astrophysical priors on parameter inference for GW230529
Authors: Chattopadhyay Debatri , Al-Shammari Sama , Antonini Fabio , Fairhurst Stephen , Miles Benjamin , Raymond Vivien
Published: November 2024

We investigate the effects of prior selection on the inferred mass and spin parameters of the neutron star–black hole merger GW230529_181500. Specifically, we explore models motivated by astrophysical considerations, including massive binary and pulsar evolution. We examine mass and spin distributions of neutron stars constrained by radio pulsar observations, alongside black hole spin observations from previous gravitational-wave detections. We show that the inferred mass distribution highly depends upon the spin prior. Specifically, under the most restrictive, binary stellar evolution models, we obtain narrower distributions of masses with a black hole mass of $4.3^{+0.1}_{-0.1}\ {\rm M}_{\odot }$ and neutron star mass of $1.3^{+0.03}_{-0.03}\ {\rm M}_{\odot }$ where, somewhat surprisingly, it is the prior on component spins that has the greatest impact on the inferred mass distributions. Re-weighting using neutron star mass and spin priors from observations of radio pulsars, with black hole spins from observations of gravitational waves, yields the black hole and the neutron star masses to be $3.8^{+0.5}_{-0.6}$ and $1.4^{+0.2}_{-0.1} \ \mathrm{ M}_\odot$, respectively. The sequence of compact object formation – whether the neutron star or the black hole formed first – cannot be determined at the observed signal-to-noise ratio. However, there is no evidence that the black hole was tidally spun up.
Testing ecological function in the carving of anomalodesmatan morphospace (Mollusca: Bivalvia: Anomalodesmata)
Authors: Deng Yue
Published: November 2024

Today, the most taxonomically rich bivalve clade is Imparidentia. However, 300 million years ago, Imparidentia's sister clade, Anomalodesmata, was dominant among marine bivalves, while Imparidentia was much less diverse. Both clades are ecologically diverse but infaunal suspension-feeding is the dominant mode of life in each. When taxonomic diversity and morphological disparity are plotted through time for each clade, Imparidentia diversified faster in the Mesozoic than Anomalodesmata until the K/Pg boundary, when the extinction event interrupts the pattern, and both clades then diversified in parallel through the Cenozoic. In this paper, I test the hypothesis that life mode has an effect on morphological disparification and taxonomic diversification, that by ecologically separating themselves from the dominant infaunal suspension-feeding mode, some ‘divergent’ anomalodesmatan lineages may have been able to free themselves from direct competition with imparidents and once more start to rise in morphological and taxonomic diversity. During the Cenozoic, morphological disparity of divergent Anomalodesmata does increase compared to their infaunal suspension-feeding relatives. However, taxonomic diversity does not differ between divergent and infaunal suspension-feeding anomalodesmatan lineages. This suggests that functional partitioning drives morphological disparification, but not taxonomic diversification.
BitterDB: 2024 update on bitter ligands and taste receptors
Authors: Ziaikin Evgenii , David Moran , Uspenskaya Sofya , Niv Masha Y
Published: November 2024

BitterDB (http://bitterdb.agri.huji.ac.il) was introduced in 2012 as a central resource for information on bitter-tasting molecules and their receptors, and was updated in 2019. The information in BitterDB is used for tasks such as exploring the bitter chemical space, choosing suitable ligands for experimental studies, analyzing receptors’ selectivity and promiscuity, and developing machine learning predictors for taste. Here, we describe a major upgrade of the database, including significant increase in content as well as new features. BitterDB now holds over 2200 bitter molecules. For ∼700 molecules, at least one associated bitter taste receptor (TAS2R) is reported. The overall number of ligand-TAS2R associations is now close to 1800. BitterDB is extended to a total of 66 species (including dog, birds, fishes and primates). Following advances in computational structure prediction by AlphaFold and related methods, and the experimental determination of TAS2R structures by cryo-electron microscopy, BitterDB provides links to available structures of TAS2Rs.
MarkerDB 2.0: a comprehensive molecular biomarker database for 2025
Authors: Jackson Hayley , Oler Eponine , Torres-Calzada Claudia , Kruger Ray , Hira Amandeep Singh , López-Hernández Yamilé , Pandit Devanshi , Wang Jiaxuan , Yang Kellie , Fatokun Omolola , Berjanskii Mark , MacKay Scott , Sajed Tanvir , Han Scott , Woudstra Robyn , Sykes Gina , Poelzer Jenna , Sivakumaran Aadhavya , Gautam Vasuk , Wong Gane , Wishart David S
Published: November 2024

MarkerDB (https://markerdb.ca) has become a leading resource for comprehensive information on molecular biomarkers. Over the past 3 years, the database has evolved significantly, reflecting the dynamic landscape of biomarker research and increasing demands from its user community. This year’s update, which is called MarkerDB 2.0, introduces key improvements to enhance the database’s usability, consistency and the range of biomarkers covered. These improvements include (i) the addition of thousands of new biomarkers and associated health conditions, (ii) the inclusion of many new biomarker types and categories, (iii) upgraded searches and data filtering functionalities, (iv) new features for exploring and understanding biomarker panels and (v) significantly expanded and improved descriptions. These upgrades, along with numerous minor improvements in content, interface, layout and overall website performance, have greatly enhanced MarkerDB’s usability and capacity to facilitate biomarker interpretation across various research domains. MarkerDB remains committed to providing a free, publicly accessible platform for consolidated information on a wide range of molecular (protein, genetic, chromosomal and chemical/small molecule) biomarkers, covering diagnostic, prognostic, risk, monitoring, safety and response-related biomarkers. We are confident that these upgrades and updates will improve MarkerDB’s user friendliness, increase its utility and greatly expand its potential applications to many other areas of clinical medicine and biomedical research.
OrthoDB and BUSCO update: annotation of orthologs with wider sampling of genomes
Authors: Tegenfeldt Fredrik , Kuznetsov Dmitry , Manni Mosè , Berkeley Matthew , Zdobnov Evgeny M , Kriventseva Evgenia V
Published: November 2024

OrthoDB (https://www.orthodb.org) offers evolutionary and functional annotations of orthologous genes in the widest sampling of eukaryotes, prokaryotes, and viruses, extending experimental gene function knowledge to newly sequenced genomes. We collect gene annotations, delineate hierarchical gene orthology and annotate the orthologous groups (OGs) with functional and evolutionary traits. OrthoDB is the leading resource for species diversity, striving to sample the most diverse and well-researched organisms with the highest quality genomic data. This update expands to include 5827 eukaryotic genomes. We have also added coding DNA sequences (CDSs) and gene loci coordinates. OrthoDB can be browsed, downloaded, or accessed using REST API, SPARQL/RDF and now also via API packages for Python and R Bioconductor. OrthoLoger (https://orthologer.ezlab.org), the tool used for inferring orthologs in OrthoDB, is now available as a Conda package and through BioContainers. ODB-mapper, a component of OrthoLoger, streamlines annotation of genes from newly sequenced genomes with OrthoDB evolutionary and functional descriptors. The benchmarking sets of universal single-copy orthologs (BUSCO), derived from OrthoDB, had correspondingly a major update. The BUSCO tool (https://busco.ezlab.org) has become a standard in genomics, uniquely capable of assessing both eukaryotic and prokaryotic species. It is applicable to gene sets, transcriptomes, genome assemblies and metagenomic bins.
The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial
Authors: Judge Parminder K , Tuttle Katherine R , Staplin Natalie , Hauske Sibylle J , Zhu Doreen , Sardell Rebecca , Cronin Lisa , Green Jennifer B , Agrawal Nikita , Arimoto Ryoki , Mayne Kaitlin J , Sammons Emily , Brueckmann Martina , Shah Shimoli V , Rossing Peter , Nangaku Masaomi , Landray Martin J , Wanner Christoph , Baigent Colin , Haynes Richard , Herrington William G
Published: November 2024

Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi. Together, these observations provide the rationale for trials to assess effects of inhibiting the aldosterone pathway in a broader range of patients with CKD, including those with non-diabetic causes of CKD or low albuminuria. Aldosterone synthase inhibitors (ASi) have emerged as an alternative to MRAs for aldosterone pathway inhibition. Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to-creatinine ratio by ∼40% compared with placebo, with or without concurrent empagliflozin treatment. MRA and ASi increase risk of hyperkalaemia. Combining their use with an SGLT2i may mitigate some of this risk, improving tolerability, and allowing a wider range of patients to be treated (including those with higher levels of blood potassium than in previous trials). The EASi-KIDNEY (NCT06531824) double-blind placebo-controlled trial will test this approach by assessing the safety and cardiorenal efficacy of vicadrostat in combination with empagliflozin in ∼11 000 patients with CKD. It will be sufficiently large to assess effects in patients with and without diabetes separately.
Meningiomas: Sex-Specific Differences and Prognostic Implications of a Chromosome X Loss
Authors: Berghaus Natalie , Hielscher Thomas , Savran Dilan , Schrimpf Daniel , Maas Sybren L N , Preusser Matthias , Weller Michael , Acker Till , Herold-Mende Christel , Wick Wolfgang , von Deimling Andreas , Sahm Felix
Published: November 2024

Background

Meningiomas are the most common primary intracranial tumours in adults. Several studies proposed new stratification systems with a more accurate risk prediction than the WHO grading, e.g. based on methylation and copy number variations (CNVs). Yet, common shortcomings in these analyses are either a lack of stratification by sex of patients or excluding the gonososmes from CNV assessment.

Methods

Within this study, DNA methylation array data from 7,424 meningioma samples as well as targeted sequencing, clinical annotations and morphology subtyping of 796 samples were examined for differences between females and males regarding mutations, methylation classes, copy number variations and histology.

Results

Meningiomas from females accounted for about 53 % of the malignant tumours and present a loss of one X chromosome in 57 % of these malignant cases. In the group of benign tumours, females comprised about 75 % of the patients. Therein, a loss of one X chromosome was detected in only about 10 % of the cases but was associated with a significantly worse progression free survival.

Conclusion

Although genomic instability is a common feature of malignant meningiomas, particularly loss of the X chromosome in tumours of female patients in otherwise histologically and molecularly low-risk tumours confers higher risk. Hence, the gonosomal copy number status can be leveraged for increased diagnostic accuracy.
Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma
Authors: Bazer Danielle A , Wolff Antonio C , Grossman Stuart A
Published: November 2024

Background

Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micro-metastatic disease. While pre-radiation chemotherapy (PRC) use has flourished in systemic cancers, it has not in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma.

Methods

Prospective trials of adults with newly diagnosed systemic and brain cancers treated with PRC published between 1980 and 2023 were identified in PubMed. NCCN guidelines were used to document the standard use of PRC in patients with systemic and brain cancers.

Results

Over 5,000 prospective PRC trials in solid tumors were identified. These accrued >1 million patients and resulted in neoadjuvant therapies being standard-of-care in ~28 systemic cancers. Only 50 similar trials (2,206 patients) were identified in high grade gliomas. In 13 trials containing PRC temozolomide (n=846), radiographic responses ranged from 6-53% with a median survival of ~13 months. Glioblastoma PRC trials were not associated with unexpected toxicities or major negative impacts on survival.

Conclusions

PRC in patients with glioblastoma appears safe and feasible. The pre-radiation window is ideally suited to rapidly screen cytotoxic agents for efficacy. It permits radiographic response as a primary outcome, small sample sizes, and initiation of standard therapies a few months after diagnosis. PRC may be most appropriate in patients with glioblastoma who are unlikely to benefit from temozolomide.
TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas
Authors: Liu Yanting , Liu Fang , Li Chuanbao , Zhang Tao , Han Tianyi , Dai Yuting , Huang Ning , Tang Hao , Wang Xiaobin , Lin Shaojian , Xue Li , Wu Zhe Bao
Published: November 2024

Background

Pituitary adenomas (PAs) are common intracranial tumors and the TRIM family plays a crucial role in cell proliferation and therapeutic resistance of tumors. However, the role of the TRIM family in PAs is not well recognized.

Methods

CRISPR screening explored the role of the TRIM family in cell proliferation and drug resistance in PAs. In vitro and in vivo experiments were performed to evaluate the effects of Tripartite Motif Containing 21 (TRIM21). RNA-sequencing, mass spectrometry, immunoprecipitation, and ubiquitination experiments were performed to explore the molecular mechanism. NanoBiT assays were used to screen the drugs reducing TRIM21 expression.

Results

CRISPR-Cas9 screens identified that TRIM21 facilitated cell proliferation and drug resistance in PAs. Mechanistically, TRIM21 interacted with ERK1/2 through PRY-SPRY domain, leading to ERK1/2 K27-linked ubiquitination. The ERK1/2 ubiquitination promotes the interaction between ERK1/2 and MEK1/2, thereby facilitating the phosphorylation of ERK1/2. However, an excess presence of TRIM21 suppressed the phosphorylation of ERK1/2 and cell proliferation via activating ERK1/2 negative feedback pathways. Importantly, TRIM21 was upregulated in dopamine-resistant prolactinomas and cabergoline-resistant MMQ cells. Furthermore, drug screening identified that Fimepinostat and Quisinostat, can reduce the protein levels of TRIM21, inhibit tumor progression, and increase drug sensitivity.

Conclusions

TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.
Bioengineered therapeutic systems for improving antitumor immunity
Authors: Cao Ying , Yan Wenlu , Yi Wenzhe , Yin Qi , Li Yaping
Published: November 2024

Immunotherapy, a monumental advancement in antitumor therapy, still yields limited clinical benefits owing to its unguaranteed efficacy and safety. Therapeutic systems derived from cellular, bacterial and viral sources possess inherent properties that are conducive to antitumor immunotherapy. However, crude biomimetic systems have restricted functionality and may produce undesired toxicity. With advances in biotechnology, various toolkits are available to add or subtract certain properties of living organisms to create flexible therapeutic platforms. This review elaborates on the creation of bioengineered systems, via gene editing, synthetic biology and surface engineering, to enhance immunotherapy. The modifying strategies of the systems are discussed, including equipment for navigation and recognition systems to improve therapeutic precision, the introduction of controllable components to control the duration and intensity of treatment, the addition of immunomodulatory components to amplify immune activation, and the removal of toxicity factors to ensure biosafety. Finally, we summarize the advantages of bioengineered immunotherapeutic systems and possible directions for their clinical translation.
Remote Practice of Infectious Diseases Through Telemedicine: Improving Access for Patients and Appeal for Physicians
Authors: Nabha Linda , Mehta Steinke Seema
Published: November 2024

The specialty of infectious diseases (ID) is facing headwinds in attracting new physicians into training and clinical practice, leading to workforce shortage and rising burnout among existing ID physicians. The distribution of ID physicians across the country is skewed, and many Americans do not have access to ID expertise. Novel care models are needed to ensure the longevity of the ID specialty and patient access to ID care. ID telemedicine provides a new opportunity for ID physicians with the benefits of residing in one's preferred geographic location, eliminating the need to commute, and structuring the workday to improve work-life balance. This viewpoint, which includes personal experiences in transitioning from in-person to remote ID practice, describes the extent of challenges facing the ID specialty and how telemedicine can reduce burnout among ID physicians, attract more physicians into the specialty, and improve access to ID care.
Shaping the Future of Infectious Diseases: The Journey to Promote Value, Opportunity, and Positive Messaging
Authors: Paras Molly L , Chirch Lisa M , Aziz Mariam , Balba Gayle P , Benson Constance , Butt Saira , James Scott H , McCarty Todd P , Razonable Raymund , Reece Rebecca , Shnekendorf Rachel , Swartz Talia H , Viehman J Alex , Luther Vera P ,   For the Infectious Diseases Society of America Fellowship Training Program Directors Community of Practice and Working Group (complete list of contributing authors in the Working Group listed in acknowledgments), Abdoler Emily , Acharya Kartikey , Angarone Michael , Babik Jennifer , Bartash Rachel , Bhanot Nitin , Blackburn Brian , Blumberg Emily , Blyth Dana M , Bourque Daniel , Bran Andres , Burke Victoria , Carey Adrienne L , Cheney Laura L , Chow Brian D , Clough Lisa A , Cunha Cheston , de Sanctis Jorgelina T , Dobrzynski David M , George Ige A , Goebel Melanie , Goshorn Eli S , Gutierrez Ramiro , Herc Erica S , Hillenbrand Molly J , Kaltsas Anna , Khalil Sarwat , Kiley John , Lebron Dora A , Lee Mikyung , Leuck Anne-Marie , Gil Raul Macias , Mapa Christopher , Marcos Luis A , Matt Brionna , Maziarz Eileen K , Melia Michael , Mitra Subhashis , Monday Lea , Montague Brian , Murphy Holly A , Novick Elizabeth E , Nnedu Obinna N , Nori Priya , Ongunti Sharon , Osorio Georgina , Pepe Rosalie , Perez Federico , Pilkington Edward F , Raybould Jillian E , Reid Gail E , Robinson Sara , Sanchez Martha , Schultz Sara , Sellers Christopher , Simon Matthew , Sisco Lauren , Slosar-Cheah Magdalena , Sobhanie Mohammad Mahdee E , Stapleton Ann , Stead Wendy , Streit Judy , Theodore Deborah A , Wald-Dickler Noah , Weber Devin M , Weisenberg Scott A , Witherspoon Kelsey L , Yabes Joseph M , Zuckerman Richard A
Published: November 2024

The field of infectious diseases (ID) offers a rewarding career path and is widely viewed as an essential subspecialty in medicine. However, in recent years, these positive aspects have been overshadowed by concerns surrounding low fellowship match rates, undercompensation, and burnout. The Infectious Diseases Society of America Fellowship Training Program Directors Committee met in 2023, discussed the future of ID as a specialty, and sought to develop strategies to highlight the value and opportunities of ID for future generations, as well as underscore the importance of and provide tools for positive messaging to trainees about the subspecialty. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID training program directors, as well as the wider ID community, in uplifting and shaping the future of the field.
Efficiency of a Long-term Infectious Diseases Consultation and Antimicrobial Stewardship Program at a Japanese Cancer Center: An Interrupted Time-Series Analysis
Authors: Itoh Naoya , Akazawa-Kai Nana , Yamaguchi Makoto , Kawabata Takanori
Published: November 2024

Background

Patients with cancer are particularly susceptible to developing drug-resistant organisms due to the high frequency of infections during cancer treatment and the use of broad-spectrum antimicrobial agents. Therefore, patients with cancer are ideal candidates for an antimicrobial stewardship program (ASP); however, no established ASPs specifically target these patients. In this study, we evaluated the effect of a 46-month ASP intervention and infectious diseases consultation using a unique antimicrobial quality measure.

Methods

Our single-center, retrospective, observational study was conducted from 1 April 2018 to 31 January 2024 and evaluated 2 phases: preintervention (antimicrobial notification by the infection control team) and postintervention (implementation of ASP and establishment of the infectious diseases consultation service).

Results

The days of therapy (DOT) for 3 intravenous carbapenems significantly decreased, and the DOT of narrow-spectrum antimicrobials significantly increased after the intervention. A significant reduction was observed in the length of hospital stay, with no change in the incidence of hospital-acquired resistant microorganisms. All-cause in-hospital mortality rates and the 30-day mortality rate among patients with bacteremia episodes were numerically reduced, although not significantly, compared to the preintervention period. The rate of appropriate use of antimicrobial agents increased significantly during the late postintervention period (1 April 2021 to 31 January 2024).

Conclusions

Our intervention was associated with the promotion of appropriate use of antimicrobial agents and a reduction in the length of hospital stay. These findings can help establish safer cancer treatments and improve patient prognosis.
Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus–Exposed Uninfected Children
Authors: Kelly Matthew S , Cunningham Coleen K , McFarland Elizabeth J , Giganti Mark J , Lindsey Jane C , Perlowski Charlotte , Libous Jennifer L , Jean-Philippe Patrick , Moye Jack , Karron Ruth A , Collins Peter L , Buchholz Ursula J ,   for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1114, 2000, 2011, 2012, 2013, and 2018 Study Teams, Yogev Ram , Chadwick Ellen , Cooper Ellen , Rutstein Richard , Spearman Paul , Camacho-Gonzalez Andres , Karron Ruth , Wiznia Andrew , Dobroszycki Joanna , Aziz Mariam , Patel Nehali , Nachman Sharon , Shearer William , Paul Mary , Deville Jaime , Spector Stephen , McFarland Elizabeth , Cielo Mikhaela
Published: November 2024

Background

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. Human immunodeficiency virus (HIV)–exposed, uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines.

Methods

In a pooled analysis of clinical trials of 7 live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed, uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein immunoglobulin G (IgG) antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season.

Results

Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs 88%) and anti-RSV F IgG (70% vs 89%) titers at 56 days after vaccination.

Conclusions

Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.
The FERONIA-RESPONSIVE TO DESICCATION 26 module regulates vascular immunity to Ralstonia solanacearum
Authors: Wang Bingqian , Luo Cailin , Li Xiaoxu , Jimenez Alvaro , Cai Jun , Chen Jia , Li Changsheng , Zhang Chunhui , Ou Lijun , Pu Wenxuan , Peng Yu , Zhang Zhenchen , Cai Yong , Valls Marc , Wu Dousheng , Yu Feng
Published: November 2024

Some pathogens colonize plant leaves, but others invade the roots, including the vasculature, causing severe disease symptoms. Plant innate immunity has been extensively studied in leaf pathosystems; however, the precise regulation of immunity against vascular pathogens remains largely unexplored. We previously demonstrated that loss of function of the receptor kinase FERONIA (FER) increases plant resistance to the typical vascular bacterial pathogen Ralstonia solanacearum. Here, we show that upon infection with R. solanacearum, root xylem cell walls in Arabidopsis thaliana become highly lignified. FER is specifically upregulated in the root xylem in response to R. solanacearum infection, and inhibits lignin biosynthesis and resistance to this pathogen. We determined that FER interacts with and phosphorylates the transcription factor RESPONSIVE TO DESICCATION 26 (RD26), leading to its degradation. Overexpression and knockout of RD26 demonstrated that it positively regulates plant resistance to R. solanacearum by directly activating the expression of lignin-related genes. Tissue-specific expression of RD26 in the root xylem confirmed its role in vascular immunity. We confirmed that the FER–RD26 module regulates lignin biosynthesis and resistance against R. solanacearum in tomato (Solanum lycopersicum). Taken together, our findings unveil that the FER–RD26 cascade governs plant immunity against R. solanacearum in vascular tissues by regulating lignin deposition. This cascade may represent a key defense mechanism against vascular pathogens in plants.
Perceptions of officers’ occupational identity management strategies in police–civilian interactions: does race play a role?
Authors: Chatterjee Deepshikha , Ryan Ann Marie , Den Houter Kate M , Bradburn Jacob
Published: November 2024

When learning about tense police–civilian interactions, observers form perceptions of police officers and their identity management strategies. In an experimental study, how the identity management strategies used by White and Black male officers’ impact others’ ratings of competence, warmth, and appropriateness of actions is assessed. Utilizing a 2 × 2 × 4 design, officer race, civilian race, and the identity management strategy used by an officer were manipulated in a news article discussing policing–civilian interaction. We found that White officers, compared to Black officers, were rated lower on competence when participants were presented with a scenario where a civilian was described as resisting arrest. Black officers were rated as more competent than White officers when the civilian was White, but as similarly competent when the civilian was Black. There are differences in how police officers are viewed in terms of their warmth and competence based on who they police, their own race, and the identity management strategies they choose to engage with civilians. No significant differences were found for perceived appropriateness of actions. The current research offers insight into how officers’ attempts to manage their identities can influence observers’ perceptions of officer competence and warmth.
The screening and management of skin diseases in remote African regions: a narrative review
Authors: Mugisha Nadine , Ghanem Laura , Komi Omar A I , Manoel Agnes Zanotto , Shariff Sanobar , Wojtara Magda , Uwishema Olivier
Published: November 2024

Introduction

Skin diseases in remote African regions are often exacerbated due to a lack of resources and expertise with little current research addressing the challenges that patients and healthcare systems experience. Although skin diseases in remote African regions are prevalent and pose a substantial health burden, they remain neglected and understudied. This review aims to explore current challenges in the diagnosis and management of skin diseases in African regions and focus on the need for enhanced understanding and improved healthcare strategies.

Methods

We reviewed papers that were retrieved from PubMed, Google Scholar, and other relevant academic search sites to analyze the prevalence, screening techniques, as well as management strategies and obstacles associated with dermatological diseases in remote African regions.

Results

Current literature suggests there is indeed a high prevalence of skin diseases where other infections are predominant. Further, different factors, such as socioeconomic status and environmental conditions, make it challenging for optimal screening and treatment of skin diseases in remote African regions. Common screening methods for skin diseases involve clinical examination and laboratory tests, while management includes pharmacotherapy, surgery, and counseling approaches. Overall, access to medications and adequate healthcare services remains limited.

Conclusion

Early diagnosis and management of skin diseases in remote African regions have significant challenges, including a lack of funding for dermatology, education, and research. Future promising strategies such as teledermatology, point-of-care diagnostic technologies, and task shifting show promise in improving access to care. However, there is a need for sustained efforts to address the underlying socioeconomic factors and improve healthcare delivery in remote African regions.
Long-Term Investors, Demand Shifts, and Yields
Authors: Jansen Kristy A E
Published: November 2024

I exploit a Dutch reform in the regulatory discount curve that makes the liabilities of pension funds and insurance companies (P&Is) more sensitive to changes in 20-year interest rates but less so to longer maturity rates. Following the reform, P&Is reduced their longest maturity bond holdings but increased those with 20-year maturities, steepening the long end of the yield curve. Using the reform as a shock to identify price elasticities of demand at the sector level based on holdings across maturity buckets and time, I show that banks are more price elastic than other investors and absorb demand shocks.
Robustness of divergence time estimation despite gene tree estimation error: a case study of fireflies (Coleoptera: Lampyridae)
Authors: Höhna Sebastian , Lower Sarah E , Duchen Pablo , Catalán Ana
Published: November 2024

Genomic data have become ubiquitous in phylogenomic studies, including divergence time estimation, but provide new challenges. These challenges include, among others, biological gene tree discordance, methodological gene tree estimation error, and computational limitations on performing full Bayesian inference under complex models. In this study, we use a recently published firefly (Coleoptera: Lampyridae) anchored hybrid enrichment data set (AHE; 436 loci for 88 Lampyridae species and 10 outgroup species) as a case study to explore gene tree estimation error and the robustness of divergence time estimation. First, we explored the amount of model violation using posterior predictive simulations because model violations are likely to bias phylogenetic inferences and produce gene tree estimation error. We specifically focused on missing data (either uniformly distributed or systematically) and the distribution of highly variable and conserved sites (either uniformly distributed or clustered). Our assessment of model adequacy showed that standard phylogenetic substitution models are not adequate for any of the 436 AHE loci. We tested if the model violations and alignment errors resulted indeed in gene tree estimation error by comparing the observed gene tree discordance to simulated gene tree discordance under the multispecies coalescent model. Thus, we show that the inferred gene tree discordance is not only due to biological mechanism but primarily due to inference errors. Lastly, we explored if divergence time estimation is robust despite the observed gene tree estimation error. We selected four subsets of the full AHE data set, concatenated each subset and performed a Bayesian relaxed clock divergence estimation in RevBayes. The estimated divergence times overlapped for all nodes that are shared between the topologies. Thus, divergence time estimation is robust using any well selected data subset as long as the topology inference is robust.
The impact of cooling and Moringa supplementation on oxidative stress in serum and milk, including milk cytokines, in heat stressed lactating sows and their litters
Authors: Ogundare Wonders O , Beckett Linda M , Reis Leriana G , Stansberry McKeeley C , Roberts Sydney N , Anele Uchenna Y , Schinckel Allan P , Casey Theresa M , Minor Radiah C
Published: November 2024

Heat stress (HS) poses a significant challenge to the United States swine industry. Sows and their piglets are particularly vulnerable to HS, as the periparturient phase is characterized by heightened metabolism and increased oxidative stress and inflammation. The study examined the effects of using conductive electronic cooling pads (ECP) and dietary supplementation with 4% Moringa (M) leaf powder on controlling oxidative stress and inflammation caused by HS in sows and their piglets. Forty-eight late gestation sows were assigned to four treatment groups: HS-fed corn–soybean meal (HS + CS), ECP-fed corn–soybean meal (ECP + CS), HS + M, and ECP + M. Blood was collected from sows on gestation (G) day 112, and lactation (L) day 14 and L20, and from piglets (2 males and 2 females) in each litter on postnatal (PN) day 1 and PN20. Colostrum was collected within 2h of birth of the first neonate, and mature milk was collected on L14. Piglet fecal samples were collected on PN14 to measure calprotectin concentration as a marker of intestinal inflammation. Biological antioxidant potential (BAP), derivatives of reactive oxygen metabolites (dROMs). and oxidative stress index (OSi) were measured in blood and milk samples using a Free Radical Elective Evaluator. Milk samples pooled by day of lactation and treatment group were analyzed using cytokine array. Levels of inflammatory cytokines in colostrum were affected by Moringa supplementation and cooling, but not mature milk. Notably, the anti-inflammatory cytokines interleukin (IL)-10 and IL-1ra were 2.14 and 1.57 Log2 higher in the colostrum of HS + M compared to other groups. The OSi of colostrum was higher (P = 0.0002) than mature milk. Level of BAP in sow serum was greater in ECP + CS and HS + M (P = 0.0291) compared to other groups. Moringa had an overall effect of increasing dROMs (P = 0.0035) and levels of OSi were lowest in ECP + CS (P = 0.0296) sow serum. Treatments did not affect piglet serum oxidative index (P > 0.05) or calprotectin levels (P > 0.05). Findings support further studies to investigate the efficacy of using ECP and Moringa supplementation to mitigate inflammation and oxidative stress imposed by heat stress conditions in lactating sows.
Identification of novel transcription factors regulated by H3K27 acetylation in myogenic differentiation of porcine skeletal muscle satellite cells
Authors: Zhou Peng , Wang Wenxuan , Li Jingjin , Zheng Zhuqing , Du Xiaoyong , Fu Liangliang , Li Xinyun
Published: November 2024

H3K27 acetylation (H3K27ac) is crucial in muscle development as it regulates gene expression. Dysregulation of H3K27ac level has been linked to muscle‐related diseases such as Duchenne muscular dystrophy, yet the mechanisms through which H3K27ac influences myogenic differentiation are not fully understood. Here, we utilized the SGC‐CBP30 drug, a CBP/p300 bromodomain inhibitor, to reduce H3K27ac level and investigated its effect on myogenic differentiation of porcine skeletal muscle satellite cells. The results demonstrated an increased H3K27ac level during normal muscle satellite cell differentiation. We found that the addition of SGC‐CBP30 resulted in a reduced level of H3K27ac based on ATAC‐seq and CUT&Tag data. Our analysis revealed that a cluster characterized by reduced levels of H3K27ac and increased levels of H3K27me3 was enriched with motifs corresponding to Bach2, MafK, and Fosl2 transcription factors. Furthermore, knockdown of Bach2, MafK, and Fosl2 produced a similar suppression effect on myogenic differentiation. Taken together, our study contributes to a better understanding of how H3K27ac influences myogenic differentiation.