bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient characteristics and health system encounters of decedents not marked deceased in the electronic health record
Authors: Sanz Vidorreta Fernando Javier , Dudley Michael T , Walling Anne M , Tseng Chi-Hong , Hogarth Michael , Wenger Neil S
Published: October 2024

Objectives

Health systems are increasingly accountable for patients and require accurate electronic health record (EHR) vital status. We recently demonstrated that 19% of seriously ill primary care patients in one system were not marked dead in the EHR and 80% of these decedents had an encounter or appointment outstanding after death. Herein we describe the mechanism of identifying decedents whose death is not captured at the level of the EHR, characterize these decedents, and describe medications refilled after death.

Materials and Methods

Description of multistep process to identify deceased patients not marked dead in the EHR among a cohort of seriously ill primary care patients including public death file matching, utilization analysis, and chart abstraction. We compared decedents not marked dead in the EHR to known decedents and described pharmacy requests and refills.

Results

Nearly 90% of encounters and appointments occurred because the health system EHR did not record the death although 11% of these encounters contained condolences or death notifications. Decedents not marked dead in the EHR were older and lived in more vulnerable areas than those marked dead. Of 146 refill requests after death, 88 medications were authorized.

Discussion and Conclusion

Matching with a limited public death file is an inadequate solution to inaccurate vital status. Better workflows are needed to capture deaths about which clinicians and staff are aware, but will identify only a fraction of the decedents inaccurately listed as alive. Efforts are needed to connect EHRs with more specific sources of linkable decedent information.
The impact of a primary aldosteronism predictive model in secondary hypertension decision support
Authors: Mack Peter B , Cole Casey , Lee Mintaek , Peterson Lisa , Lundy Matthew , Hegarty Karen , Espinoza William
Published: October 2024

Objectives

To determine whether the addition of a primary aldosteronism (PA) predictive model to a secondary hypertension decision support tool increases screening for PA in a primary care setting.

Materials and Methods

One hundred fifty-three primary care clinics were randomized to receive a secondary hypertension decision support tool with or without an integrated predictive model between August 2023 and April 2024.

Results

For patients with risk scores in the top 1 percentile, 63/2896 (2.2%) patients where the alert was displayed in model clinics had the order set launched, while 12/1210 (1.0%) in no-model clinics had the order set launched (P = .014). Nineteen of 2896 (0.66%) of these highest risk patients in model clinics had an aldosterone-to-renin ratio (ARR) ordered compared to 0/1210 (0.0%) patients in no-model clinics (P = .010). For patients with scores not in the top 1 percentile, 438/20 493 (2.1%) patients in model clinics had the order set launched compared to 273/17 820 (1.5%) in no-model clinics (P < .001). One hundred twenty-four of 20 493 (0.61%) in model clinics had an ARR ordered compared to 34/17 820 (0.19%) in the no-model clinics (P < .001).

Discussion

The addition of a PA predictive model to secondary hypertension alert displays and triggering criteria along with order set displays and order preselection criteria results in a statistically and clinically significant increase in screening for PA, a condition that clinicians insufficiently screen for currently.

Conclusion

Addition of a predictive model for an under-screened condition to traditional clinical decision support may increase screening for these conditions.
Intramuscular fat % in the loin of Australian pork demonstrates a stronger relationship with computed tomography lean and fat % than abattoir measures of P2 and lean %
Authors: Anderson Fiona , Corlett Maddison T , Williams Andrew , Gardner Graham E
Published: October 2024

Intramuscular fat (IMF) % is an important measure of pork eating quality, with reduced IMF % linked to the selection of pigs with low backfat P2 thickness and more muscular genotypes over several decades. This experiment tested the association of IMF % from the M. longissimus thoracis et lumborum of 345 pigs at 3 abattoirs (sites) with computed tomography (CT) determined carcass composition (% lean or fat), accredited abattoir measures of P2 backfat (mm; Hennessy Grading Probe [HGP], AutoFom III, and PorkScan Lite) and the lean % output from abattoir devices (HGP, AutoFom III, and PorkScan Plus). There was a negative relationship between carcass CT lean % with IMF % at all sites (P < 0.05), with the strength of this relationship varying between sites. The strongest relationship was demonstrated at site 1 (R2 0.30, RMSE 0.59), and across a 4 SD range in the carcass lean % at each site, resulted in a decrease in loin IMF % of 1.56, 0.44, and 0.80. There was a positive relationship of carcass CT fat % with IMF %, with similar, albeit slightly stronger relationship to IMF than with CT lean %. In contrast, only one of the 3 sites with an accredited P2 measurement device demonstrated a significant association (P < 0.05) with IMF %. This is the first time the associations of IMF % with carcass CT composition has been assessed alongside that of P2 backfat measurements from commercially deployed abattoir devices. Given P2 backfat is the key industry measure on which carcass value is determined in Australia, this experiment demonstrates the limitations that P2 has in measuring and monitoring the associations of carcass lean and fat % with IMF. Ideally, an independent measure of IMF % would allow for independent selection for lean % and IMF %; however, there is currently no commercial device that can measure pork IMF %.
Dietary full-fat or defatted black soldier fly larvae can replace protein sources with no detrimental effect on growth performance or intestinal health of nursery pigs
Authors: Song Yoon Soo , Ha Dong Uk , Park Kwanho , Kim Beob Gyun
Published: October 2024

This work aimed to determine the effects of dietary full-fat or defatted black soldier fly larvae (BSFL) to replace protein sources on growth performance, blood parameters, intestinal morphology, and intestinal microbiota in nursery pigs and to investigate the effects of dietary defatted BSFL at up to 30% at the expense of protein sources on growth performance in nursery pigs. In Exp. 1, a total of 36 barrows with an initial body weight of 7.0 kg (SD = 0.8) were allotted to three dietary treatments in a randomized complete block design with four replicate pens per treatment and three barrows per pen. A corn-soybean meal (SBM)-whey-based control diet was prepared with soy protein concentrate and fish meal as additional protein supplements. Two additional diets were prepared to include 20% full-fat BSFL or 20% defatted BSFL to replace soy protein concentrate and fish meal to maintain the same energy and nutrient concentrations in all diets. In the 28-d feeding trial, pigs fed the diet containing defatted BSFL tended to consume more feeds (P < 0.10) than other groups during days 14 to 28 and the overall period. On day 28, the serum blood urea nitrogen in pigs fed the control diet was less (P < 0.05) than that fed the full-fat or defatted BSFL, but fecal score and jejunal morphology did not differ among the treatment groups. Relative abundance of Mycoplasma in the ileal digesta was less (P < 0.05) in the pigs fed the diet containing full-fat or defatted BSFL compared with the control group. In Exp. 2, a total of 192 pigs with an initial body weight of 7.8 (SD = 1.2 kg) were randomly allotted to one of four dietary treatments in a randomized complete block design with six replicate pens per treatment and four barrows and four gilts per pen. A control diet was mainly based on corn, SBM, fermented SBM, fish meal, and spray-dried plasma protein (SDPP). Three additional diets were prepared to contain 10%, 20%, and 30% defatted BSFL to replace SBM, fermented SBM, fish meal, and SDPP to maintain for the same energy and nutrient concentrations. Average daily gain, average daily feed intake, gain:feed, and fecal score were not affected by increasing dietary defatted BSFL. Overall, dietary BSFL did not compromise growth performance or intestinal health in nursery pigs. BSFL can be used in nursery pig diets to replace other protein sources without negative effects.
Development and characterization of polymorphic microsatellite markers for Periplaneta americana (Blattodea: Blattidae)
Authors: Lim Li , Ab Majid Abdul Hafiz
Published: October 2024

The American cockroach, Periplaneta americana (Blattodea: Blattidae), is a prevalent urban pest with significant public health implications. This study aimed to develop and validate novel microsatellite markers to understand the genetic diversity and population genetic structure of P. americana. In this study, a total of 397,898 microsatellite markers were developed based on 24.6 million genomic DNA sequences. Twenty microsatellite markers were selected and amplified with varying numbers of alleles ranging from 0 to 35. Seven out of 20 markers were characterized for their polymorphism and amplification efficiency. The polymorphic information content (PIC) values of these markers were high (0.669 to 0.950) implying their effectiveness. These markers also revealed 7 to 35 alleles per locus across tested samples, highlighting their utility in assessing the extensive genetic variation within Periplaneta americana populations. These results provide insightful information that may be applied to the genetic analysis of the American cockroach population using the developed species-specific microsatellite marker.
Published questionnaires and clinical observation surveys on traumatic sheep myiasis: optimizing survey design and the integration of these two survey methods
Authors: Bambaradeniya Tharindu Bandara , Magni Paola Annarosa , Dadour Ian Robert
Published: October 2024

Questionnaires and clinical observations are significant components of human and veterinary epidemiology surveys, providing a comprehensive prognosis of the occurrence and prevalence of diseases. The information compiled by these two survey methods is equally important for establishing an epidemiological surveillance system for disease outbreak management. This review summarizes 57 previous surveys, including questionnaires and clinical observations on sheep myiasis globally from 1976 to 2023, with an emphasis on their methodologies and areas of findings. Overall, this review establishes a baseline understanding of the essential entomological and veterinary aspects required for designing questionnaires and clinical observation surveys on sheep myiasis. Additionally, it provides guidance for implementing future study protocols and proposes a farmer-based approach that integrates these techniques to achieve improved outcomes in mitigating sheep myiasis.
Novel metabolomic predictors of incident colorectal cancer in men and women
Authors: Downie Jonathan M , Joshi Amit D , Geraghty Connor M , Guercio Brendan J , Zeleznik Oana A , Song Mingyang , Bever Alaina M , Drew David A , Tabung Fred K , Zhang Xuehong , Jin Lina , Eliassen A Heather , Willett Walter C , Wu Kana , Kraft Peter , Tamimi Rulla , Clish Clary , Fuchs Charles S , Giovannucci Edward , Meyerhardt Jeffrey A , Chan Andrew T
Published: October 2024

Background

Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.

Methods

We conducted a nested case-control study among women (Nurses’ Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 Nurses’ Health Study, 275 Health Professionals Follow-Up Study) individuals developed CRC and were matched 1:1 to unaffected participants. Liquid chromatography-mass spectrometry identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis was used to identify differential abundance in metabolite classes. The R Weighted Correlation Network Analysis package provided modules of covarying metabolites, which were tested for CRC association.

Results

Metabolite set enrichment analysis identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC diagnosed 2 years after blood draw, myristoleic acid (odds ratio = 1.37 [95% CI = 1.15 to 1.62]; false discovery rate = 0.072) and C60:12 triacylglycerol (odds ratio = 0.75 [95% CI = 0.64 to 0.88]; false discovery rate = 0.072) were associated with CRC risk in women. Weighted correlation network analysis identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women.

Conclusions

We identified prediagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.
Unraveling the influence of essential climatic factors on the number of tones through an extensive database of languages in China
Authors: Wang Shuai , Liang Yuzhu , Wang Tianheng , Huang Wei , Xu Ke , Mitkov Aleksandr , Yuan Shuting , Ding Jun , Wang Lining , Zhou Yongdao , Xia Quansheng , Ran Qibin
Published: October 2024

Recent research has provided supportive evidence for the role of humidity in the evolution of tones. However, there remain numerous challenges in delving deeper into the intricate relationship between the tone system and climatic factors: precisely tracking and identifying potentially relevant climate factors at appropriate temporal and spatial scales, while effectively controlling the potential interference caused by geographical proximity and language inheritance. Based on a substantial database of 1,525 language varieties in China and 41 years of monthly climate data, this study has delved into the correlation between multiple climate factors and number of tones, examined the mediating role of voice quality in this process, and further analyzed the interrelationship between climate factors and pitch variations. The findings reveal that climate factors influencing voice quality and the number of tones are diverse, with specific humidity, precipitation, and average temperature playing pivotal roles. After controlling the influence of language inheritance and geographical proximity, the chain of climate → voice quality → number of tones remains significant in China. Specifically, people living in a humid and warm environment tend to exhibit better voice quality. Meanwhile, regions with higher specific humidity and precipitation tend to have a richer and more diverse range of tone types. These findings enrich the theoretical framework of the interaction between language and the environment and provide robust empirical support for understanding the natural mechanisms of language evolution.
Pilot study of a parent-based intervention for functional somatic symptoms in children
Authors: Etkin Rebecca G , Winograd Sara M , Calhoun Amanda J , Silverman Wendy K , Lebowitz Eli R , Shapiro Eugene D
Published: October 2024

Objective

Functional somatic symptoms are associated with significant distress and impairment for children and their families. Despite the central role that families play in their children’s care, there is little clinical research to guide how parents can support their children with functional somatic symptoms and promote better functioning. To address this gap, we developed a parent-based intervention for functional somatic symptoms in children and obtained preliminary data on acceptability, feasibility, treatment satisfaction, and clinical outcomes.

Method

The intervention was adapted from SPACE (Supportive Parenting for Anxious Childhood Emotions), an evidence-based treatment for anxiety and related disorders in children. The intervention, SPACE-Somatic, was delivered to parents of 16 children (Mage = 14.50 years; 75% girls) with a range of functional somatic symptoms. Parents participated in seven weekly group sessions conducted via telehealth.

Results

We found that SPACE-Somatic was acceptable, feasible, and satisfactory to parents. There were significant improvements in several clinical outcomes from baseline to posttreatment, including children’s level of functional impairment, with some gains maintained at 3-month follow-up. Parents also reported improvements in their own stress and their accommodation of children’s symptoms.

Conclusion

This pilot study provides preliminary evidence that a parent-based intervention is viable and beneficial to children with functional somatic symptoms and their parents.
Determining the prior mean in Bayesian logistic regression with sparse data: a nonarbitrary approach
Authors: Gosho Masahiko , Ishii Ryota , Nagashima Kengo , Noma Hisashi , Maruo Kazushi
Published: October 2024

Logistic regression models lead to a bias of the odds ratio (OR) as estimated using the maximum-likelihood (ML) method, when there are few study participants at the binary outcome and factor levels. Although Bayesian methods are frequently applied to reduce this sparse data bias, the specification of the prior distribution for regression coefficients is the most controversial feature. We propose a nonarbitrary and empirical method to determine the prior mean for regression coefficients in Bayesian logistic regression analysis for sparse data. The proposed prior mean is calculated as the difference between the observed log OR and the quasi-expectation of log OR, and is interpreted as a shrinkage statistic of the ML estimate. Further, for easy and fast inference, the proposed method applies to Bayesian logistic regression with the normal prior and the log-F prior via data augmentation. Simulation results indicate that the OR bias based on the proposed method is consistently smaller than that based on the ML method. The OR bias estimated using the proposed method is generally smaller than that based on the mean prior of zero for the regression coefficient. We apply the proposed methods to 2 real data sets.
Postoperative chylothorax following video-assisted mediastinoscopic lymphadenectomy (VAMLA) for early-stage non-small cell lung carcinoma
Authors: van Dam Kayleigh A M , Vissers Yvonne L J , Hulsewé Karel W E , de Loos Erik R
Published: October 2024

Chylothorax is a rare condition in which chylous fluid accumulates in the pleural cavity, most often due to iatrogenic injury of the thoracic duct. This paper reports a case of a woman in her 50s presenting with chyle leakage after a video-assisted mediastinoscopic lymphadenectomy (VAMLA) for staging of a nodule suspected of non-small cell lung carcinoma. After the VAMLA, a Uniportal Video Assisted Thoracoscopic Surgery lobectomy was scheduled during which the chylothorax was observed. The chyle was evacuated and the planned resection was conducted. The chest drain could be removed after 6 days while the patient followed a medium-chain triglyceride diet for 4 weeks. The purpose of this case report is to raise awareness for this very rare complication after VAMLA and discuss treatment options.
Identification of genes associated with sex expression and sex determination in hemp (Cannabis sativa L.)
Authors: Shi Jiaqi , Toscani Matteo , Dowling Caroline A , Schilling Susanne , Melzer Rainer
Published: October 2024

Dioecy in flowering plants has evolved independently many times, and thus the genetic mechanisms underlying sex determination are diverse. In hemp (Cannabis sativa), sex is controlled by a pair of sex chromosomes (XX for females and XY for males). In an attempt to understand the molecular mechanism responsible for sex expression in hemp plants, we carried out RNA sequencing of male and female plants at different developmental stages. Using a pipeline involving differential gene expression analysis and weighted gene co-expression network analysis, we identified genes important for male and female flower development. We also demonstrate that sex-biased expression is already established at very early vegetative stages, before the onset of reproductive development, and identify several genes encoding transcription factors of the REM, bZIP, and MADS families as candidate sex-determination genes in hemp. Our findings demonstrate that the gene regulatory networks governing male and female development in hemp diverge at a very early stage, leading to profound morphological differences between male and female hemp plants.
Juvenile Spring Eruption: A Report on an Outbreak and 2 Sporadic Cases in French Military Personnel
Authors: Lachaux Jordan , Vuillemin Quentin , Savatier Emilie , Duval Maxime , Colléony Thomas , Schwartzbrod Pierre-Éric
Published: October 2024

Juvenile spring eruption is a sun-related skin eruption primarily affecting boys or young adult males. The pathophysiology is unknown, but there appears to be a link with sun exposure in cold weather. It can cause small outbreaks, particularly in groups of children or young adults. The primary lesions can be pruritic erythema, with or without associated papules, vesicles, or bullae. They are notable for almost exclusively affecting the ears. Spontaneous healing occurs within a few days without leaving scars. We report an outbreak and 2 sporadic cases that occurred at the Valdahon military camp in France between 2021 and 2024 among military personnel.
Psychological Distress and Quality of Life Among Military Trauma Patients
Authors: Al-Ghabeesh Suhair Hussni , Al-Taamraha Gusoon , Abualruz Hasan
Published: October 2024

Introduction

Military trauma has a significant impact on soldiers, affecting many aspects of their lives, with the highest impact on their quality of life and psychological wellness. This study aimed to measure psychological distress and its relationship with the quality of life among Jordanian military trauma patients.

Materials and Methods

A descriptive cross-sectional study was conducted in The Hashemite Protection Departments for military causalities in Amman, Irbid, and Al-Karuk. The authors used the WHO Quality of Life Scale-Brief and Trauma Symptoms Checklist-40 scales for assessing the quality of life and psychological distress among Jordanian military trauma patients. A total of 145 trauma survivors participated in the study and responded to all questionnaires out of 173 distributed. The study was approved by the institutional review board of Al-Zaytoonah University.

Results

The result of this study revealed that military trauma survivors had high levels of psychological distress with a mean of 85.66 (SD = 19.418). The subscale of “Dissociation symptoms” had the highest rating (M = 19.92, SD = 5.096), while the “sleep disorders” subscale had the lowest rating (M = 10.000, SD = 3.501). On the quality of life scale, a moderate level of quality of life resulted among the participants with a mean of 61.620 (SD = 17.190). The “general health” subscale scored the highest among the other domains (M = 18.241, SD = 5.434), while the “physical health” domain scored the lowest (M = 4.910, SD = 2.078). Furthermore, a statistically significant negative relationship between psychological distress and quality of life was reported (r =−0.178, P < .05).

Conclusion

Jordanian injured military persons had a moderate quality of life level and high level of psychological distress. A structured follow-up program is required to be developed to improve those patients’ health and quality of life. Furthermore, additional research is needed to investigate the impact of military trauma and services on soldiers in Jordan and the Middle East.
Dental Emergency Rates at an Expeditionary Medical Facility Supporting Operation Inherent Resolve
Authors: Struthers Michael W , Kosaraju Amar , Vandewalle Kraig S
Published: October 2024

Introduction

A core objective of U.S. medical services is to ensure the medical and dental readiness of military personnel. Oral diseases, resulting in pain, infection, or functional impairment, greatly affect the operational effectiveness of military personnel. This study aimed to compare the current causes of dental emergencies and the rates of dental disease nonbattle injuries in a deployed setting with those documented in previous research. Additionally, the study sought to determine if these rates have decreased because of preventive measures or potential improvements in overall oral health.

Methods

Each soldier reporting to the health facility for dental care was screened by a dentist to determine the presence of a dental emergency. The reason for seeking care was classified into 1 of 7 categories and the rate of dental emergencies per 1,000 military members per calendar year was calculated.

Results

The majority of emergencies (38.60%) were due to tooth fractures and/or caries. The second most common reason for visiting the dental clinic was pain from a tooth requiring endodontic therapy (16.81%). This was followed by musculoskeletal or nonendodontic tooth pain (16.10%), most often associated with stress. Periodontal issues accounted for 14.33% of emergencies. Teeth requiring extraction made up 7.16% of all emergencies, prosthodontic bonding complications accounted for 5.16%, and orthodontic bonding complications affected 1.84% of individuals. The dental disease nonbattle injuries rates determined from the current study were 154 emergencies per 1,000 personnel per year for Air Force members and 264 emergencies per 1,000 personnel per year for Army members, which align with previous research findings.

Conclusions

The results of this study confirm that dental emergencies continue to be a threat to overall readiness in deployed environments. The primary etiologic factor in the current study was as a result of tooth fracture and/or caries.
LnCeCell 2.0: an updated resource for lncRNA-associated ceRNA networks and web tools based on single-cell and spatial transcriptomics sequencing data
Authors: Guo Qiuyan , Liu Qian , He Danni , Xin Mengyu , Dai Yifan , Sun Rui , Li Houxing , Zhang Yujie , Li Jiatong , Kong Congcong , Gao Yue , Zhi Hui , Li Feng , Ning Shangwei , Wang Peng
Published: October 2024

We describe LnCeCell 2.0 (http://bio-bigdata.hrbmu.edu.cn/LnCeCell), an updated resource for lncRNA-associated competing endogenous RNA (ceRNA) networks and web tools based on single-cell and spatial transcriptomics sequencing (stRNA-seq) data. We have updated the LnCeCell 2.0 database with significantly expanded data and improved features, including (i) 257 single-cell RNA sequencing and stRNA-seq datasets across 86 diseases/phenotypes and 80 human normal tissues, (ii) 836 581 cell-specific and spatial spot-specific ceRNA interactions and functional networks for 1 002 988 cells and 367 971 spatial spots, (iii) 15 489 experimentally supported lncRNA biomarkers related to disease pathology, diagnosis and treatment, (iv) detailed annotation of cell type, cell state, subcellular and extracellular locations of ceRNAs through manual curation and (v) ceRNA expression profiles and follow-up clinical information of 20 326 cancer patients. Further, a panel of 24 flexible tools (including 8 comprehensive and 16 mini-analysis tools) was developed to investigate ceRNA-regulated mechanisms at single-cell/spot resolution. The CeCellTraject tool, for example, illustrates the detailed ceRNA distribution of different cell populations and explores the dynamic change of the ceRNA network along the developmental trajectory. LnCeCell 2.0 will facilitate the study of fine-tuned lncRNA-ceRNA networks with single-cell and spatial spot resolution, helping us to understand the regulatory mechanisms behind complex microbial ecosystems.
VDGE: a data repository of variation database for gene-edited animals across multiple species
Authors: Shi Wenwen , Jin Enhui , Fang Lu , Sun Yanling , Fan Zhuojing , Zhu Junwei , Liang Chengzhi , Zhang Ya-Ping , Zhang Yong Q , Wang Guo-Dong , Zhao Wenming
Published: October 2024

Gene-edited animals are crucial for addressing fundamental questions in biology and medicine and hold promise for practical applications. In light of the rapid advancement of gene editing technologies over the past decade, a dramatically increased number of gene-edited animals have been generated. Genome editing at off-target sites can, however, introduce genomic variations, potentially leading to unintended functional consequences in these animals. So, there is an urgent need to systematically collect and collate these variations in gene-edited animals to aid data mining and integrative in-depth analyses. However, existing databases are currently insufficient to meet this need. Here, we present the Variation Database of Gene-Edited animals (VDGE, https://ngdc.cncb.ac.cn/vdge), the first open-access repository to present genomic variations and annotations in gene-edited animals, with a particular focus on larger animals such as monkeys. At present, VDGE houses 151 on-target mutations from 210 samples, and 115,710 variations identified from 107 gene-edited and wild-type animal trios through unified and standardized analysis and concurrently provides comprehensive annotation details for each variation, thus facilitating the assessment of their functional consequences and promoting mechanistic studies and practical applications for gene-edited animals.
HSCGD: a comprehensive database of single-cell whole-genome data and metadata
Authors: Fu Jiye , He Shiyang , Yang Yixuan , Chen Zitong , Qiao Yi , Lu Na , Lu Zuhong , Tu Jing
Published: October 2024

Single-cell whole-genome sequencing is a powerful tool for uncovering mutations in individual cells. In recent times, the generation of vast amounts of data has significantly advanced our understanding of key biological processes, including cell development and tumor progression. This rapid accumulation of data underscores the urgent need for a comprehensive resource platform to manage and utilize this information effectively. To address this need, we introduce HSCGD, the first open-access and comprehensive database dedicated to the collection, integration, analysis, and visualization of single-cell whole-genome data and metadata. The current release of HSCGD includes processed single-cell whole-genome sequencing data and curated metadata of 74 154 human cells derived from 63 public single-cell datasets, involving 23 cell types and 17 major single-cell whole-genome amplification methods. HSCGD is designed to help researchers interested in cellular heterogeneity explore and utilize whole genome data at the single-cell level by providing browsing, searching, visualization, downloading and online tools. The database can be accessed from the following URL: http://www.hscgd.com.
Imaging PD-L1 in the brain—Journey from the lab to the clinic
Authors: Dar Dawoud , Rodak Magdalena , Da Pieve Chiara , Gorczewska Izabela , Sharma Gitanjali , Chmielik Ewa , Niedbala Marcin , Bzowski Pawel , d’Amico Andrea , Bobek-Billewicz Barbara , Nowicka Elzbieta , Tarnawski Rafal , Kaspera Wojciech , Kramer-Marek Gabriela
Published: October 2024

Background

Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy. The aim of this study was to investigate the use of 89Zr-DFO-Atezolizumab to image the spatio-temporal distribution of PD-L1 in preclinical mouse models and in patients with newly diagnosed GBM treated with/without neoadjuvant Pembrolizumab.

Methods

The immunoreactivity, binding affinity, and specificity of 89Zr-DFO-Atezolizumab were confirmed in vitro. Mice-bearing orthotopic GBM tumors or patients with newly diagnosed GBM treated with/without Pembrolizumab were intravenously injected with 89Zr-DFO-Atezolizumab, and PET/CT images were acquired 24, 48, and 72 hours in mice and at 48 and 72 post-injection in patients. Radioconjugate uptake was quantified in the tumor and healthy tissues. Ex vivo immunohistochemistry (IHC) and immunophenotyping were performed on mouse tumor samples or resected human tumors.

Results

89Zr-DFO-Atezolizumab was prepared with high radiochemical purity (RCP > 99%). In vitro cell-associated radioactivity of 89Zr-DFO-Atezolizumab corroborated cell line PD-L1 expression. PD-L1 in mouse GBM tumors was detected with high specificity using 89Zr-DFO-Atezolizumab and radioconjugate uptake correlated with IHC. Patients experienced no 89Zr-DFO-Atezolizumab-related side effects. High 89Zr-DFO-Atezolizumab uptake was observed in patient tumors at 48 hours post-injection, however, the uptake varied between patients treated with/without Pembrolizumab.

Conclusions

89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.
Our clock is truly ticking—a qualitative study on patients’ experiences of tumor treating fields
Authors: Kastbom Lisa , Karlsson Marit , Letter Nina , Degsell Eskil , Malmström Annika
Published: October 2024

Background

TTFields is recommended internationally for the treatment of glioblastoma. In Sweden, TTFields requires a possibly challenging collaboration between the patient, next-of-kin, healthcare, and the private company providing the device, both from an ethical and practical perspective. Little is known about glioblastoma patients’ own experiences of TTFields treatment.

Methods

Semi-structured individual interviews were conducted with 31 patients with glioblastoma who had been offered TTFields by the healthcare. These were analyzed by qualitative content analysis.

Results

Participants described there being multiple actors around them as TTFields users; (1) device prescription from physicians, sometimes providing insufficient information, (2) practical assistance from next-of-kin, necessary to access treatment, (3) home visits from the private company staff for device control, where close bonds between patients and TTFields staff occurred. TTFields treatment created hope and a feeling of control in an otherwise hopeless situation, sometimes evoking worries at the time of planned treatment stop. Some refrained from TTFields or discontinued early due to fear or experience of negative effects on quality of life. Others described finding practical and mental solutions for coping with the treatment in everyday life.

Conclusions

Our study identified a need for better support and information from healthcare providers for TTFields. A solution is necessary for assistance with TTFields for those without support from next-of-kin. The study raises the question of possible advantages of healthcare handling the technical support of the device instead of a private company, thereby avoiding a true or perceived influence on the patient’s decision to continue or stop treatment.
The Effects of Subsidies for Healthy Foods on Food Purchasing Behaviors, Consumption Patterns, and Obesity/Overweight: A Systematic Review
Authors: Comini Luma de Oliveira , Lopes Sílvia Oliveira , Rocha Daniela Mayumi Usuda Prado , Silva Maria Micheliana da Costa , Hermsdorff Helen Hermana Miranda
Published: October 2024

Context

Taxing unhealthy foods and drinks is an essential measure against the double burden of malnutrition that affects every nation worldwide. In turn, subsidizing the consumption of healthy foods can also be a critical measure for changing the population's behavior and improving health indicators.

Objective

A systematic review was conducted of food subsidies and their potential impact on food purchases, consumption, overweight/obesity, and changes in body mass index (BMI).

Data Sources

The PubMed, Embase, LILAC, Scientific Electronic Library Online, and Google Scholar databases were searched to identify studies investigating the effects of subsidies on the amount of food purchased, food consumption, caloric intake, nutrient intake, and their impact on overweight, obesity, and BMI changes. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.

Data Extraction

Two investigators independently performed data screening, extraction, and quality assessment.

Results

Of the 6135 studies screened, 149 were read in full and 18 were included in this systematic review. Most studies investigated the effects of subsidy scenarios on food purchases and observed increases in fruit and vegetable (F&V) purchases when these were subsidized. In randomized controlled studies, subsidized healthy foods were purchased more often. However, when the subsidy was suspended, F&V consumption decreased. Although quasi-experimental studies have demonstrated increased F&V consumption due to subsidies, some studies showed increased saturated fat and sodium intake. Only 2 studies evaluated the relationship between subsidies and obesity, yielding conflicting results.

Conclusion

Although the subsidies appear to encourage purchase and consumption of healthier foods, enhancing the quality and diversity of dietary choices, the removal of subsidies can lead to a decline in the consumption of healthier foods. Additionally, their impact on obesity and BMI remains uncertain and requires further research.

Systematic Review Registration

PROSPERO registration by the number CRD42023442122.
Lyme Disease Prophylaxis by Single-Dose Doxycycline in the United States, 2010–2020
Authors: Marx Grace E , Beck Alyssa , Corey Cate , Fuller Candace C , Haug Nicole , Ko Jenice S , Martin Dave , Hinckley Alison F
Published: October 2024

Single-dose doxycycline after high-risk tick bites can prevent Lyme disease, which disproportionately affects children. We described single-dose doxycycline dispensings in an outpatient cohort in the United States. During 2010–2020, a total of 427 105 patients received ≥1 dispensing(s); most were aged ≥65 years. Lyme disease postexposure prophylaxis may be underprescribed for some groups, including children.
Retracted: Lethal Disseminated Mucorales Infection With Positive Blood Cultures With Purpura Fulminans Complicating Hemophagocytic Lymphohistiocytosis After Chimeric Antigen Receptor T-Cell Therapy
Authors: Matsuo Takahiro , Wurster Sebastian , Ivan Doina , Hicklen Rachel , McConn Kelly , Bagwell Kelli A , Khawaja Fareed , Chemaly Roy F , Kontoyiannis Dimitrios P
Published: October 2024

This article has been retracted. Please see: https://doi.org/10.1093/ofid/ofae730
Peroxisomal Localization of Benzyl Alcohol O-Benzoyltransferase HSR201 is Mediated by a Non-canonical Peroxisomal Targeting Signal and Required for Salicylic Acid Biosynthesis
Authors: Kotera Yu , Asai Yoshika , Okano Shutaro , Tokutake Yukako , Hosomi Akira , Saito Katsuharu , Yonekura Shinichi , Katou Shinpei
Published: October 2024

The phytohormone salicylic acid (SA) regulates plant responses to various types of environmental stress, particularly pathogen infections. We previously revealed that the benzyl alcohol O-benzoyltransferase HSR201 was required for pathogen signal-induced SA synthesis, and its overexpression together with NtCNL, encoding a cinnamate-coenzyme A ligase, was sufficient for the production of significant amounts of SA in tobacco. We herein examined the subcellular localization of HSR201 and found that it fused to a yellow fluorescent protein localized in peroxisomes. Most peroxisomal matrix proteins possess peroxisomal targeting signal type-1 (PTS1) located at the extreme C-terminus or PTS2 located at the N-terminus; however, a bioinformatics analysis failed to identify similar signals for HSR201. Deletion and mutation analyses of HSR201 identified one essential (extreme C-terminal Leu460) and three important (Ile455, Ile456 and Ala459) amino acid residues for its peroxisomal localization. The virus-induced gene silencing (VIGS) of PEX5, a PTS1 receptor, but not PEX7, a PTS2 receptor, compromised the peroxisomal targeting of HSR201 in Nicotiana benthamiana. When overexpressed with NtCNL, HSR201 mutants with reduced or non-peroxisomal targeting induced lower SA levels than the wild type; however, these mutations did not affect the protein stability or activity of HSR201. VIGS of the HSR201 homolog compromised pathogen signal-induced SA accumulation in N. benthamiana, which was complemented by the HSR201 wild type, but not the mutant with non-peroxisomal targeting. These results suggest that the peroxisomal localization of HSR201 is mediated by a non-canonical PTS1 and required for SA biosynthesis.
Mitogen-activated protein kinase 4 phosphorylates MYC2 transcription factors to regulate jasmonic acid signaling and herbivory responses in maize
Authors: Li Sen , Ma Canrong , Li Shalan , Zhang Mou , Zhang Cuiping , Qi Jinfeng , Wang Lei , Wu Xuna , Li Jing , Wu Jianqiang
Published: October 2024

Regulation of responses induced by herbivory and jasmonic acid (JA) remains poorly understood in the important staple crop maize (Zea mays). MYC2 is the key transcription factor regulating many aspects of JA signaling, while mitogen-activated protein kinases (MAPKs or MPKs) play important roles in various plant physiological processes. Using a combination of reverse genetics, transcriptome analysis, and biochemical assays, we elucidated the important role of mitogen-activated protein kinase 4 (MPK4) in maize resistance to insects and in JA signaling. Silencing MPK4 increased the JA and jasmonoyl-isoleucine levels elicited by wounding or simulated herbivory but decreased maize resistance to armyworm (Mythimna separata) larvae. We showed that MPK4 is required for transcriptional regulation of many genes responsive to methyl jasmonate, indicating the important role of maize MPK4 in JA signaling. Biochemical analyses indicated that MPK4 directly phosphorylates MYC2s at Thr115 of MYC2a and Thr112 of MYC2b. Compared with nonphosphorylated MYC2s, phosphorylated MYC2s were more prone to degradation and exhibited enhanced transactivation activity against the promoters of several benzoxazinoid biosynthesis genes, which are important for maize defense against insects. This study reveals the essential role of maize MPK4 in JA signaling and provides insights into the functions of MAPKs in maize.
Death and survival of gut CD4 T cells following HIV-1 infection ex vivo
Authors: Mickens Kaylee L , Dillon Stephanie M , Guo Kejun , Thompson Ashley N , Barrett Bradley S , Wood Cheyret , Kechris Katerina , Santiago Mario L , Wilson Cara C
Published: October 2024

The gastrointestinal tract is ground zero for the massive and sustained CD4 T cell depletion during acute HIV-1 infection. To date, the molecular mechanisms governing this fundamental pathogenic process remain unclear. HIV-1 infection in the gastrointestinal tract is associated with chronic inflammation due to a disrupted epithelial barrier that results in microbial translocation. Here, we utilized the lamina propria aggregate culture model to demonstrate that the profound induction of granzyme B by bacteria in primary gut CD4 T cells ex vivo significantly contributes to HIV-1-mediated CD4 T cell death. Counterintuitively, a substantial fraction of gut granzyme B+ CD4 T cells harboring high levels of HIV-1 infection survive via a pathway linked to CD120b/TNFR2. Our findings underscore previously undescribed mechanisms governing the death and survival of gut CD4 T cells during HIV-1 infection that could inform strategies to counter HIV-1 pathogenesis and persistence in this critical tissue compartment.
Cell-microsphere based living microhybrids for osteogenesis regulating to boosting biomineralization
Authors: Hu Zhaofan , Zhang Yunyang , Zhang Jingjing , Zheng Ran , Yang Yang , Kong Fei , Li Haoran , Yang Xinyan , Yang Shuhui , Kong Xiangdong , Zhao Ruibo
Published: October 2024

Biomineralization-based cell-material living composites ex vivo showed great potential for living materials construction and cell regulation. However, cells in scaffolds with unconnected pores usually induce confined nutrient transfer and cell–cell communications, affecting the transformation of osteoblasts into osteocytes and the mineralization process. Herein, the osteoblast-materials living hybrids were constructed with porous PLLA microspheres using a rational design, in which cell-based living materials presented an improved osteoblast differentiation and mineralization model using rationally designed cell-microsphere composites. The results indicated that the microfluidic-based technique provided an efficient and highly controllable approach for producing on-demand PLLA microspheres with tiny pores (<5 μm), medium pores (5–15 μm) and large pores (>15 μm), as well as further drug delivery. Furthermore, the simvastatin (SIM)-loaded porous PLLA microsphere with ε-polylysine (ε-PL) modification was used for osteoblast (MC3T3-E1) implantation, achieving the cell-material living microhybrids, and the results demonstrated the ε-PL surface modification and SIM could improve osteoblast behavior regulation, including cell adhesion, proliferation, as well as the antibacterial effects. Both in vitro and in vivo results significantly demonstrated further cell proliferation, differentiation and cascade mineralization regulation. Then, the quantitative polymerase chain reaction or histological staining of typical markers, including collagen type I, alkaline phosphatase, runt-related transcription factor 2 and bone morphogenetic protein 2, as well as the calcium mineral deposition staining in situ, reconfirmed the transformation of osteoblasts into osteocytes. These achievements revealed a promising boost in osteogenesis toward mineralization at the microtissue level by cell-microsphere integration, suggesting an alternative strategy for materials-based ex vivo tissue construction and cell regulation, further demonstrating excellent application prospects in the field of biomineralization-based tissue regeneration.