bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing patient-nurse verbal communication in building risk identification models: the missing critical data stream in home healthcare
Authors: Zolnoori Maryam , Sridharan Sridevi , Zolnour Ali , Vergez Sasha , McDonald Margaret V , Kostic Zoran , Bowles Kathryn H , Topaz Maxim
Published: October 2023

Background

In the United States, over 12 000 home healthcare agencies annually serve 6+ million patients, mostly aged 65+ years with chronic conditions. One in three of these patients end up visiting emergency department (ED) or being hospitalized. Existing risk identification models based on electronic health record (EHR) data have suboptimal performance in detecting these high-risk patients.

Objectives

To measure the added value of integrating audio-recorded home healthcare patient-nurse verbal communication into a risk identification model built on home healthcare EHR data and clinical notes.

Methods

This pilot study was conducted at one of the largest not-for-profit home healthcare agencies in the United States. We audio-recorded 126 patient-nurse encounters for 47 patients, out of which 8 patients experienced ED visits and hospitalization. The risk model was developed and tested iteratively using: (1) structured data from the Outcome and Assessment Information Set, (2) clinical notes, and (3) verbal communication features. We used various natural language processing methods to model the communication between patients and nurses.

Results

Using a Support Vector Machine classifier, trained on the most informative features from OASIS, clinical notes, and verbal communication, we achieved an AUC-ROC = 99.68 and an F1-score = 94.12. By integrating verbal communication into the risk models, the F-1 score improved by 26%. The analysis revealed patients at high risk tended to interact more with risk-associated cues, exhibit more “sadness” and “anxiety,” and have extended periods of silence during conversation.

Conclusion

This innovative study underscores the immense value of incorporating patient-nurse verbal communication in enhancing risk prediction models for hospitalizations and ED visits, suggesting the need for an evolved clinical workflow that integrates routine patient-nurse verbal communication recording into the medical record.
Using natural language processing to characterize and predict homeopathic product-associated adverse events in consumer reviews: comparison to reports to FDA Adverse Event Reporting System (FAERS)
Authors: Konkel Karen , Oner Nurettin , Ahmed Abdulaziz , Jones S Christopher , Berner Eta S , Zengul Ferhat D
Published: October 2023

Objective

Apply natural language processing (NLP) to Amazon consumer reviews to identify adverse events (AEs) associated with unapproved over the counter (OTC) homeopathic drugs and compare findings with reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Materials and methods

Data were extracted from publicly available Amazon reviews and analyzed using JMP 16 Pro Text Explorer. Topic modeling identified themes. Sentiment analysis (SA) explored consumer perceptions. A machine learning model optimized prediction of AEs in reviews. Reports for the same time interval and product class were obtained from the FAERS public dashboard and analyzed.

Results

Homeopathic cough/cold products were the largest category common to both data sources (Amazon = 616, FAERS = 445) and were analyzed further. Oral symptoms and unpleasant taste were described in both datasets. Amazon reviews describing an AE had lower Amazon ratings (X2 = 224.28, P < .0001). The optimal model for predicting AEs was Neural Boosted 5-fold combining topic modeling and Amazon ratings as predictors (mean AUC = 0.927).

Discussion

Topic modeling and SA of Amazon reviews provided information about consumers’ perceptions and opinions of homeopathic OTC cough and cold products. Amazon ratings appear to be a good indicator of the presence or absence of AEs, and identified events were similar to FAERS.

Conclusion

Amazon reviews may complement traditional data sources to identify AEs associated with unapproved OTC homeopathic products. This study is the first to use NLP in this context and lays the groundwork for future larger scale efforts.
Visualizing machine learning-based predictions of postpartum depression risk for lay audiences
Authors: Desai Pooja M , Harkins Sarah , Rahman Saanjaana , Kumar Shiveen , Hermann Alison , Joly Rochelle , Zhang Yiye , Pathak Jyotishman , Kim Jessica , D’Angelo Deborah , Benda Natalie C , Reading Turchioe Meghan
Published: October 2023

Objectives

To determine if different formats for conveying machine learning (ML)-derived postpartum depression risks impact patient classification of recommended actions (primary outcome) and intention to seek care, perceived risk, trust, and preferences (secondary outcomes).

Materials and methods

We recruited English-speaking females of childbearing age (18-45 years) using an online survey platform. We created 2 exposure variables (presentation format and risk severity), each with 4 levels, manipulated within-subject. Presentation formats consisted of text only, numeric only, gradient number line, and segmented number line. For each format viewed, participants answered questions regarding each outcome.

Results

Five hundred four participants (mean age 31 years) completed the survey. For the risk classification question, performance was high (93%) with no significant differences between presentation formats. There were main effects of risk level (all P < .001) such that participants perceived higher risk, were more likely to agree to treatment, and more trusting in their obstetrics team as the risk level increased, but we found inconsistencies in which presentation format corresponded to the highest perceived risk, trust, or behavioral intention. The gradient number line was the most preferred format (43%).

Discussion and conclusion

All formats resulted high accuracy related to the classification outcome (primary), but there were nuanced differences in risk perceptions, behavioral intentions, and trust. Investigators should choose health data visualizations based on the primary goal they want lay audiences to accomplish with the ML risk score.
Virtual reality and augmented reality smartphone applications for upskilling care home workers in hand hygiene: a realist multi-site feasibility, usability, acceptability, and efficacy study
Authors: Gasteiger Norina , van der Veer Sabine N , Wilson Paul , Dowding Dawn
Published: October 2023

Objectives

To assess the feasibility and implementation, usability, acceptability and efficacy of virtual reality (VR), and augmented reality (AR) smartphone applications for upskilling care home workers in hand hygiene and to explore underlying learning mechanisms.

Materials and Methods

Care homes in Northwest England were recruited. We took a mixed-methods and pre-test and post-test approach by analyzing uptake and completion rates of AR, immersive VR or non-immersive VR training, validated and bespoke questionnaires, observations, videos, and interviews. Quantitative data were analyzed descriptively. Qualitative data were analyzed using a combined inductive and deductive approach.

Results

Forty-eight care staff completed AR training (n = 19), immersive VR training (n = 21), or non-immersive VR training (n = 8). The immersive VR and AR training had good usability with System Usability Scale scores of 84.40 and 77.89 (of 100), respectively. They had high acceptability, with 95% of staff supporting further use. The non-immersive VR training had borderline poor usability, scoring 67.19 and only 63% would support further use. There was minimal improved knowledge, with an average of 6% increase to the knowledge questionnaire. Average hand hygiene technique scores increased from 4.77 (of 11) to 7.23 after the training. Repeated practice, task realism, feedback and reminding, and interactivity were important learning mechanisms triggered by AR/VR. Feasibility and implementation considerations included managerial support, physical space, providing support, screen size, lagging Internet, and fitting the headset.

Conclusions

AR and immersive VR apps are feasible, usable, and acceptable for delivering training. Future work should explore whether they are more effective than previous training and ensure equity in training opportunities.
Making the most of it: thinking about educational time with Hägglund and Levinas
Authors: Parker Lana
Published: October 2023

This paper explores the concept of time in education. It argues that the neoliberal capitalist construct of time as a resource to be deployed in service of labour—ever-accelerating—has permeated education, with implications for curriculum, teaching, and learning. To slow the effects of neoliberal capitalism in schools requires a reconsideration of time that permits both different understandings of how time is encountered and different values orienting how one spends one’s time. Using Hägglund’s argument for finitude and Levinas’ idea of time as a gift, the paper articulates the philosophical rationale and pedagogical implications for making the most of one’s educational time.
Early-Life Temperamental Differences as Longitudinal Predictors of Unintentional Injuries
Authors: Ksinan Albert J , Dalecká Andrea , Kukla Lubomír , Pikhart Hynek , Bobák Martin
Published: October 2023

Objective

Unintentional injuries are the leading cause of hospitalization and death among children. Compared to environmental factors, less attention in injury preventive efforts has been paid to how individual characteristics relate to the risk of injury. Using a large prospective cohort, the current study assessed the longitudinal impact of early-life temperament on the cumulative number of injuries until mid-adolescence.

Methods

The data came from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ). Temperament was evaluated by mothers when children were 3 years old (N = 3,545). The main outcome was the pediatrician-reported sum of child’s injuries from age 3 to 15 (seven timepoints). Latent profile analysis (LPA) was used to determine classes based on temperamental dimensions and then extended to a mixture model with a distal count outcome. The covariates included maternal conflict and attachment, sex, family structure, and maternal education.

Results

The LPA determined the existence of three classes: shy children (8.1% of the sample; lowest activity/highest shyness), outgoing children (50.8%; highest activity/lowest shyness), and average: children (41.1%; middle values). Results from a mixture model showed that the outgoing temperament was associated with the highest longitudinal risk for injuries, as both average children (IRR = 0.89 [0.80, 0.99]), and the shy children (IRR = 0.80 [0.68, 0.95]) had lower risk.

Conclusions

Early childhood temperamental differences can have long-term effects on injury risk. Highly active children showed the highest risk for future injuries, suggesting that these characteristics make them more likely to be involved in novel and potentially dangerous situations.
Complementary and Integrative Medicine Prevalence and Utilization in International Military and Veteran Settings and Communities: A Systematic Review
Authors: Bayes Jessica , Palencia John , Wardle Jon
Published: October 2023

Introduction

Active duty military personnel and veterans have unique and complex health needs, with the high demands of military life often leading to chronic physical and mental health conditions. Complementary and integrative medicine (CIM) could be a possible solution to this problem. Some military health systems have started integrating CIM into health care delivery. However, there has been no systematic evaluation of the prevalence and utilization of CIM in military and veteran populations globally.

Materials and Methods

A Preferred Reporting Items For Systematic Reviews and Meta-Analysis Protocols protocol was used to systematically search for original research assessing the prevalence and utilization of CIM among active serving military or veterans. CINAHL, MEDLINE, Scopus, and AMED databases were searched up to February 3, 2023.

Results

A total of 27 studies met the inclusion criteria and were included in this review. The overall quality of evidence was high with a low risk of bias. Utilization of CIM varied. The lowest utilization demonstrated that only 1.9% of services delivered by military health system were CIM. The majority of studies found utilization rates between 30% and 80%, with some studies reporting use as high as 90%. The most commonly used CIM therapies included chiropractic care, massage, mindfulness/meditation, and acupuncture. Utilization of CIM products was high and ranged from 32% to 87%. The most frequently used products were dietary supplements, particularly multivitamins and minerals and protein supplements/amino acids. The use of herbal products was high among veterans ranging from 10% to 79%.

Conclusions

The high demand for CIM by military personnel and veterans has important implications for policy, funding allocation, and integration of these services into clinical practice, particularly by countries not currently doing so. Further research is needed to assess the implementation of CIM into real-world settings to explore barriers and facilitators for their use in clinical practice and, by extension, their integration into the wider health care system.
Training, Deployment Preparation, and Behavioral Health of New York National Guard Personnel Deployed to Assist with COVID-19 Decedent Work
Authors: Riviere Lyndon A , Kim Paul Y , Baker Matthew D , Beymer Matthew R
Published: October 2023

Introduction

A small body of research conducted mostly among civilians has shown that adequate training and preparation can prevent or reduce the development of behavioral health problems in first responders. Several civilian studies have shown that social support is protective against behavioral health problems. However, very few studies have examined the impact of these factors on the behavioral health of military first responders. Military first responders, who serve in the aftermath of natural disasters and disease outbreaks such as the coronavirus disease 2019 (COVID-19) pandemic, are often members of the National Guard (NG). The purpose of this study was to examine the impact of mortuary affairs training/handling human remains, role preparation, equipment preparation, and unit social support provided to families on the behavioral health of New York (NY) NG personnel deployed to assist the NY Office of Chief Medical Examiner with handling the remains of COVID-19 decedents.

Materials and Methods

We invited 410 NYNG personnel who deployed for the Office of Chief Medical Examiner mission to complete an anonymous online questionnaire 3 to 6 months post-mission. Of the 158 participants, we used the data of the 141 participants who provided consent. Standard behavioral health measures (depression, anxiety, post-traumatic stress disorder, alcohol misuse, and insomnia) as well as study-specific items designed to understand the unique dynamics of this deployment were included. Hierarchical logistic regression analysis was used to examine the relationships between mortuary training, role preparation, equipment preparation, and unit support with behavioral health.

Results

Close to two-thirds of the sample reported that they had not been trained in mortuary affairs/handling human remains before the mission. We also found that that lower levels of role preparation and unit support provided to the service members’ families increased the odds of meeting criteria for one or more behavioral health problems, but that training in mortuary affairs and equipment preparation was unrelated to behavioral health.

Conclusions

Our research points to the importance of emotionally and cognitively preparing service members for the specific dynamics of a deployment and the roles that that they are expected to play. Furthermore, it suggests that supporting the families of NG personnel during domestic missions can benefit the behavioral health of the NG personnel. Additional research is needed to corroborate these findings, particularly the impact of unit support provided to family members on service members’ behavioral health.
More Than a Bruise: Two Cases of Morel-Lavallée Lesions in Active Duty Soldiers
Authors: Rodgers David K , Castañeda Philip , Simmons Cecil J , Carius Brandon M
Published: October 2023

Soft tissue injuries are common in the military, generally producing simple hematomas without the need for intensive evaluation and management. In certain situations, a shearing effect between fascial planes whereby a disruption of the vasculature and lymphatic systems creates a “closed degloving injury” is more generally referred to as a Morel-Lavallée Lesion (MLL). With a consistent pool of blood, lymph, and pieces of soft tissue, an M7LL can cause significant poor cosmesis, chronic pain, and risk secondary infection if left undetected and untreated. Proper diagnosis can be made through the effective use of ultrasound and, if detected early enough, through conservative measures to include needle aspiration and compression sleeves. Prior cases describe chronic MLLs existing for extended periods of time, in some cases years, requiring operative intervention, and in some cases poor outcomes. We present two cases of active duty soldiers presenting with seemingly innocuous injuries found on closer evaluation to have MLL, treated in one case with needle aspiration and compression, in the other with operative management.
A Safe Road to Infallibilism?
Authors: Davis Wayne A
Published: October 2023

In “How to Be an Infallibilist,” Julien Dutant (2016, 149) presents a simple and seemingly plausible argument that knowledge requires infallible belief—roughly, belief that could not be mistaken. As Dutant recognizes, infallibilism is almost universally dismissed, in large part because it seems to rule out any knowledge of the physical world. He seeks to show how we can be an Infallibilist without being a skeptic, based on the assumption that knowledge has a safety condition. I critically examine each line of Dutant’s argument, showing that the argument is unsound on any plausible interpretation. I also question the idea that knowledge cannot be the conjunction of true belief and a nonfactive condition, that any belief about the physical world could not be false, and that any nonskeptical alternative to infallibilism would have to allow knowledge of chancy outcomes. I briefly suggest that a fallibilist account can be strict enough to satisfy the Infallibilist’s quest for certainty.
How Infallibilists Can Have It All
Authors: Climenhaga Nevin
Published: October 2023

I advance a novel argument for an infallibilist theory of knowledge, according to which we know all and only those propositions that are certain for us. I argue that this theory lets us reconcile major extant theories of knowledge, in the following sense: for any of these theories, if we require that its central condition (evidential support, reliability, safety, etc.) obtains to a maximal degree, we get a theory of knowledge extensionally equivalent to infallibilism. As such, the infallibilist can affirm that, when their conditions are suitably interpreted, most post-Gettier theories of knowledge offer necessary and sufficient conditions for knowledge. The infallibilist can thus reconcile major theories of knowledge, and is in a better position to explain the intuitive appeal of these theories than the fallibilist who only accepts one of them, and rejects the rest.
Gliomatosis cerebri (GC) growth pattern: A single-center analysis of clinical, histological, and molecular characteristics of GC and non-GC glioblastoma
Authors: Divé Iris , Weber Katharina J , Hartung Tabea I , Steidl Eike , Wagner Marlies , Hattingen Elke , Franz Kea , Fokas Emmanouil , Ronellenfitsch Michael W , Herrlinger Ulrich , Harter Patrick N , Steinbach Joachim P
Published: October 2023

Background

The biological understanding of glioblastoma (GB) with gliomatosis cerebri (GC) pattern is poor due to the absence of GC-specific studies. Here, we aimed to identify molecular or clinical parameters that drive GC growth.

Methods

From our methylome database of IDH (isocitrate dehydrogenase)-wildtype GB, we identified 158 non-GC and 65 GC cases. GC cases were subdivided into diffuse-infiltrative (subtype 1), multifocal (subtype 2), or tumors with 1 solid mass (subtype 3). We compared clinical, histological, and molecular parameters and conducted a reference-free tumor deconvolution of DNA methylation data based on latent methylation components (LMC).

Results

GC subtype 1 less frequently showed contrast-enhancing tumors, and more frequently lacked morphological GB criteria despite displaying GB DNA methylation profile. However, the tumor deconvolution did not deliver a specific LMC cluster for either of the GC subtypes. Employing the reference-based analysis MethylCIBERSORT, we did not identify significant differences in tumor cell composition. The majority of both GC and non-GC patients received radiochemotherapy as first-line treatment, but there was a major imbalance for resection. The entire GC cohort had significantly shorter overall survival (OS) and time to treatment failure (TTF) than the non-GC cohort. However, when filtering for cases in which only stereotactic biopsy was performed, the comparison of OS and TTF lost statistical significance.

Conclusions

Our study offers clinically relevant information by demonstrating a similar outcome for GB with GC growth pattern in the surgically matched analysis. The limited number of cases in the GC subgroups encourages the validation of our DNA methylation analysis in larger cohorts.
The Natural Trajectory of Smoking Cessation Among Cancer Patients Who Want to Quit “On Their Own”: A Mixed-Methods, Longitudinal Study
Authors: Borger Tia , Feather Abigayle R , Wakeman Kathleen E , Bowling William , Burris Jessica L
Published: October 2023

Introduction

Many cancer patients who smoke cigarettes want to quit. Unfortunately, many of these cancer patients prefer to quit without the aid of pharmacotherapy or behavioral counseling. The teachable moment of cancer diagnosis might still position these cancer patients to make meaningful changes in their smoking behavior, but no study has documented the trajectory of smoking cessation outcomes among cancer patients who want to quit “on their own.” This study aimed to fill this gap in the literature.

Methods

In this mixed-methods, longitudinal study, 35 cancer patients who declined tobacco treatment because of the desire to quit “on their own” provided data via three surveys and 1–2 semi-structured interviews. The observation period spanned 60 days. Participants were recently diagnosed at and recruited from outpatient cancer clinics.

Results

Participants were mostly female (68.57%), White, non-Hispanic (85.71%), unemployed due to disability (57.14%), and rural residents (54.29%). Across time, 43.76% of participants achieved 50% smoking reduction, 21.88% achieved 3-day floating abstinence, 18.75% achieved 7-day floating abstinence, and 12.50% achieved 30-day point-prevalence abstinence. Key themes that emerged from the interviews centered on intention and confidence to quit and types of tobacco treatment used/received.

Conclusions

This study with cancer patients who desired to quit smoking without assistance found some evidence of quit success, but success waned as criteria grew more stringent. Results showed participants’ initial intention to quit unassisted was quite strong, as few reported tobacco treatment use. Interventions to increase the uptake of evidence-based tobacco treatment among cancer patients are sorely needed.

Implications

The preference to quit smoking without assistance is common among cancer patients, even given lack of evidence supporting its effectiveness. This study is the first to explore the trajectory of smoking cessation outcomes among cancer patients who desire to quit without assistance. These data can be used to develop interventions to increase the uptake of tobacco treatment and increase quit success among cancer patients.
Evaluating Oncologists’ Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study
Authors: Gupta Shilpa , Costantino Halley , Ike Chiemeka , Gupta Shaloo , Bhanegaonkar Abhijeet , Su Cathy , Thakkar Sheena , Mackie deMauri S , Devgan Geeta , Katzenstein Howard M , Liu Frank X
Published: October 2023

Background

The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment.

Materials and Methods

US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing.

Results

Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists’ 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05).

Conclusion

OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians’ decision-making in the real-world setting for la/mUC.
Genome-Wide Analysis of Cotton MYB Transcription Factors and the Functional Validation of GhMYB in Response to Drought Stress
Authors: Su Jiuchang , Zhan Na , Cheng Xiaoru , Song Shanglin , Dong Tianyu , Ge Xiaoyang , Duan Hongying
Published: October 2023

MYB transcription factors play important roles during abiotic stress responses in plants. However, little is known about the accurate systematic analysis of MYB genes in the four cotton species, Gossypium hirsutum, G. barbadense, G. arboreum and G. raimondii. Herein, we performed phylogenetic analysis and showed that cotton MYBs and Arabidopsis MYBs were clustered in the same subfamilies for each species. The identified cotton MYBs were distributed unevenly on chromosomes in various densities for each species, wherein genome-wide tandem and segment duplications were the main driving force of MYB family expansion. Synteny analysis suggested that the abundant collinearity pairs of MYBs were identified between G. hirsutum and the other three species, and that they might have undergone strong purification selection. Characteristics of conserved motifs, along with their consensus sequence, promoter cis elements and gene structure, revealed that MYB proteins might be highly conserved in the same subgroups for each species. Subsequent analysis of differentially expressed genes and expression patterns indicated that most GhMYBs might be involved in response to drought (especially) and salt stress, which was supported by the expression levels of nine GhMYBs using real-time quantitative PCR. Finally, we performed a workflow that combined virus-induced gene silencing and the heterologous transformation of Arabidopsis, which confirmed the positive roles of GhMYBs under drought conditions, as validated by determining the drought-tolerant phenotypes, damage index and/or water loss rate. Collectively, our findings not only expand our understanding of the relationships between evolution and function of MYB genes, but they also provide candidate genes for cotton breeding.
BBX21 Integrates Brassinosteroid Biosynthesis and Signaling in the Inhibition of Hypocotyl Growth under Shade
Authors: Gómez-Ocampo Gabriel , Crocco Carlos D , Cascales Jimena , Oklestkova Jana , Tarkowská Danuše , Strnad Miroslav , Mora-Garcia Santiago , Pruneda-Paz José L , Blazquez Miguel A , Botto Javier F
Published: October 2023

B-Box-containing zinc finger transcription factors (BBX) are involved in light-mediated growth, affecting processes such as hypocotyl elongation in Arabidopsis thaliana. However, the molecular and hormonal framework that regulates plant growth through BBX proteins is incomplete. Here, we demonstrate that BBX21 inhibits the hypocotyl elongation through the brassinosteroid (BR) pathway. BBX21 reduces the sensitivity to 24-epiBL, a synthetic active BR, principally at very low concentrations in simulated shade. The biosynthesis profile of BRs showed that two active BR—brassinolide and 28-homobrassinolide—and 8 of 11 intermediates can be repressed by BBX21 under white light (WL) or simulated shade. Furthermore, BBX21 represses the expression of CYTOCHROME P450 90B1 (DWF4/CYP90B1), BRASSINOSTEROID-6-OXIDASE 1 (BR6OX1, CYP85A1) and BR6OX2 (CYP85A2) genes involved in the BR biosynthesis in WL while specifically promoting DWF4 and PHYB ACTIVATION TAGGED SUPPRESSOR 1 (CYP2B1/BAS1) expression in WL supplemented with far-red (WL + FR), a treatment that simulates shade. In addition, BBX21 represses BR signaling genes, such as PACLOBUTRAZOL RESISTANCE1 (PRE1), PRE3 and ARABIDOPSIS MYB-LIKE 2 (MYBL2), and auxin-related and expansin genes, such as INDOLE-3-ACETIC ACID INDUCIBLE 1 (IAA1), IAA4 and EXPANSIN 11 in short-term shade. By a genetic approach, we found that BBX21 acts genetically upstream of BRASSINAZOLE-RESISTANT 1 (BZR1) for the promotion of DWF4 and BAS1 gene expression in shade. We propose that BBX21 integrates the BR homeostasis and shade-light signaling, allowing the fine-tuning of hypocotyl elongation in Arabidopsis.
Lipidomic and Metabolomic Analyses Reveal Changes of Lipid and Metabolite Profiles in Rapeseed during Nitrogen Deficiency
Authors: Peng Yan , Lou Hongxiang , Tan Zengdong , Ouyang Zhewen , Zhang Yuting , Lu Shaoping , Guo Liang , Yang Bao
Published: October 2023

Nitrogen is one of the most essential macronutrients for plant growth and its availability in soil is vital for agricultural sustainability and productivity. However, excessive nitrogen application could reduce the nitrogen use efficiency and produce environmental pollution. Here, we systematically determined the response in lipidome and metabolome in rapeseed during nitrogen starvation. Plant growth was severely retarded during nitrogen deficiency, while the levels of most amino acids were significantly decreased. The level of monogalactosyldiacyglycerol (MGDG) in leaves and roots was significantly decreased, while the level of digalactosyldiacylglycerol (DGDG) was significantly decreased in roots, resulting in a significant reduction of the MGDG/DGDG ratio during nitrogen starvation. Meanwhile, the levels of sulfoquinovosyl diacylglycerol, phosphatidylglycerol and glucuronosyl diacylglycerol were reduced to varying extents. Moreover, the levels of metabolites in the tricarboxylic acid cycle, Calvin cycle and energy metabolism were changed during nitrogen deficiency. These findings show that nitrogen deprivation alters the membrane lipid metabolism and carbon metabolism, and our study provides valuable information to further understand the response of rapeseed to nitrogen deficiency at the metabolism level.
Evolutionary trajectory of organelle-derived nuclear DNAs in the Triticum/Aegilops complex species
Authors: Zhang Zhibin , Zhao Jing , Li Juzuo , Yao Jinyang , Wang Bin , Ma Yiqiao , Li Ning , Wang Hongyan , Wang Tianya , Liu Bao , Gong Lei
Published: October 2023

Organelle-derived nuclear DNAs, nuclear plastid DNAs (NUPTs), and nuclear mitochondrial DNAs (NUMTs) have been identified in plants. Most, if not all, genes residing in NUPTs/NUMTs (NUPGs/NUMGs) are known to be inactivated and pseudogenized. However, the role of epigenetic control in silencing NUPGs/NUMGs and the dynamic evolution of NUPTs/NUMTs with respect to organismal phylogeny remain barely explored. Based on the available nuclear and organellar genomic resources of wheat (genus Triticum) and goat grass (genus Aegilops) within Triticum/Aegilops complex species, we investigated the evolutionary fates of NUPTs/NUMTs in terms of their epigenetic silencing and their dynamic occurrence rates in the nuclear diploid genomes and allopolyploid subgenomes. NUPTs and NUMTs possessed similar genomic atlas, including (i) predominantly located in intergenic regions and preferential integration to gene regulation regions and (ii) generating sequence variations in the nuclear genome. Unlike nuclear indigenous genes, the alien NUPGs/NUMGs were associated with repressive epigenetic signals, namely high levels of DNA methylation and low levels of active histone modifications. Phylogenomic analyses suggested that the species-specific and gradual accumulation of NUPTs/NUMTs accompanied the speciation processes. Moreover, based on further pan-genomic analyses, we found significant subgenomic asymmetry in the NUPT/NUMT occurrence, which accumulated during allopolyploid wheat evolution. Our findings provide insight into the dynamic evolutionary fates of organelle-derived nuclear DNA in plants.
Ethylene and jasmonate signaling converge on gibberellin catabolism during thigmomorphogenesis in Arabidopsis
Authors: Wang Lei , Ma Canrong , Wang Shuanghua , Yang Fei , Sun Yan , Tang Jinxiang , Luo Ji , Wu Jianqiang
Published: October 2023

Touch induces marked morphological changes in plants, including reduced rosette diameters and delayed flowering, a process called thigmomorphogenesis. Previous studies have revealed that thigmomorphogenesis in Arabidopsis (Arabidopsis thaliana) results from touch-induced accumulation of jasmonic acid (JA) and GIBBERELLIN 2-OXIDASE7 (GA2ox7) transcripts, which encode a gibberellin (GA) catabolism enzyme, leading to reduced levels of active GAs. However, the mechanisms underlying thigmomorphogenesis remain uncharacterized. Here, we showed that touch induces ethylene (ET) production in Arabidopsis. After touch treatment, ET biosynthesis and signaling mutants exhibited even greater thigmomorphogenic changes and more decreased GA4 contents than did wild-type (WT) plants. Biochemical analysis indicated that the transcription factor ETHYLENE INSENSITIVE3 (EIN3) of the ET pathway binds to the promoter of GA2ox8 (encoding another GA 2-oxidase performing the same GA modification as GA2ox7) and represses GA2ox8 transcription. Moreover, MYC2, the master regulator of JA signaling, directly promoted GA2ox7 expression by binding the G-box motif on GA2ox7 promoter. Further genetic analysis suggested that the ET and JA pathways independently control the expression of GA2ox8 and GA2ox7, respectively. This study reveals that the ET pathway is a novel repressor of touch-induced thigmomorphogenesis and highlights that the ET and JA pathways converge on GA catabolism but play opposite roles to fine-tune GA4 content during thigmomorphogenesis.
The effects of multifactorial stress combination on rice and maize
Authors: Sinha Ranjita , Peláez-Vico María Ángeles , Shostak Benjamin , Nguyen Thao Thi , Pascual Lidia S , Ogden Andrew M , Lyu Zhen , Zandalinas Sara I , Joshi Trupti , Fritschi Felix B , Mittler Ron
Published: October 2023

The complexity of environmental factors affecting crops in the field is gradually increasing due to climate change-associated weather events, such as droughts or floods combined with heat waves, coupled with the accumulation of different environmental and agricultural pollutants. The impact of multiple stress conditions on plants was recently termed “multifactorial stress combination” (MFSC) and defined as the occurrence of 3 or more stressors that impact plants simultaneously or sequentially. We recently reported that with the increased number and complexity of different MFSC stressors, the growth and survival of Arabidopsis (Arabidopsis thaliana) seedlings declines, even if the level of each individual stress is low enough to have no significant effect on plants. However, whether MFSC would impact commercial crop cultivars is largely unknown. Here, we reveal that a MFSC of 5 different low-level abiotic stresses (salinity, heat, the herbicide paraquat, phosphorus deficiency, and the heavy metal cadmium), applied in an increasing level of complexity, has a significant negative impact on the growth and biomass of a commercial rice (Oryza sativa) cultivar and a maize (Zea mays) hybrid. Proteomics, element content, and mixOmics analyses of MFSC in rice identified proteins that correlate with the impact of MFSC on rice seedlings, and analysis of 42 different rice genotypes subjected to MFSC revealed substantial genetic variability in responses to this unique state of stress combination. Taken together, our findings reveal that the impacts of MFSC on 2 different crop species are severe and that MFSC may substantially affect agricultural productivity.
Effectiveness, tolerability, and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: a multicenter real-world case-control study
Authors: Gonzalez-Martinez Alicia , Sanz-García Ancor , García-Azorín David , Rodríguez-Vico Jaime , Jaimes Alex , Gómez García Andrea , Casas-Limón Javier , Díaz de Terán Javier , Sastre-Real María , Membrilla Javier , Latorre Germán , Calle de Miguel Carlos , Gil Luque Sendoa , Trevino-Peinado Cristina , Quintas Sonia , Heredia Patricia , Echavarría-Íñiguez Ana , Guerrero-Peral Ángel , Sierra Álvaro , González-García Nuria , Porta-Etessam Jesús , Gago-Veiga Ana Beatriz
Published: October 2023

Objective

To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly.

Design

We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs.

Methods

We included the demographic characteristics, effectiveness—reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates—and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20–24; exploratory 50% response predictors in the elderly were evaluated.

Results

In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66–86); mean age of controls was 42.9 years old(range: 38–49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20–24 weeks, with lower reduction in the MHD at 8–12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20–24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis.

Conclusions

Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.
Applications of genetic code expansion technology in eukaryotes
Authors: Guo Qiao-ru , Cao Yu J
Published: October 2023

Unnatural amino acids (UAAs) have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins. In eukaryotes, genetic code expansion (GCE) enables the incorporation of UAAs and facilitates posttranscriptional modification (PTM), which is not feasible in prokaryotic systems. GCE is also a powerful tool for cell or animal imaging, the monitoring of protein interactions in target cells, drug development, and switch regulation. Therefore, there is keen interest in utilizing GCE in eukaryotic systems. This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.
Leaf trait coordination and variation of blue oak across topo-environmental scales
Authors: Wu Angelica , Anderegg Leander D L , Dawson Todd E , Trugman Anna T
Published: October 2023

Trees are arguably the most diverse and complex macro-organisms on Earth. The equally diverse functions of trees directly impact fluxes of carbon, water and energy from the land surface. A number of recent studies have shed light on the substantial within-species variability across plant traits, including aspects of leaf morphology and plant allocation of photosynthates to leaf biomass. Yet, within-tree variability in leaf traits due to microclimatic variations, leaf hydraulic coordination across traits at different physiological scales and variations in leaf traits over a growing season remain poorly studied. This knowledge gap is stymieing the fundamental understanding of what drives trait variation and covariation from tissues to trees to landscapes. Here, we present an extensive dataset measuring within-tree heterogeneity in leaf traits in California’s blue oak (Quercus douglasii) across an edaphic gradient and over the course of a growing season at an oak–grass savanna in Southern CA, USA. We found a high level of within-tree crown leaf area:sapwood area variation that was not attributable to sample height or aspect. We also found a higher level of trait integration at the tree level, rather than branch level, suggesting that trees optimize water use at the organismal level. Despite the large variance in traits within a tree crown and across trees, we did not find strong evidence for adaptive plasticity or acclimation in leaf morphological traits (e.g., changes to phenotype which increased fitness) across temporal and spatial water availability gradients. Collectively, our results highlight strong variation in drought-related physiology, but limited evidence for adaptive trait plasticity over shorter time scales.
Advances in gene therapy for inborn errors of immunity
Authors: Ott de Bruin Lisa M. , Lankester Arjan C. , Staal Frank J.T.
Published: October 2023

Purpose of review

Provide an overview of the landmark accomplishments and state of the art of gene therapy for inborn errors of immunity (IEI).

Recent findings

Three decades after the first clinical application of gene therapy for IEI, there is one market authorized product available, while for several others efficacy has been demonstrated or is currently being tested in ongoing clinical trials. Gene editing approaches using programmable nucleases are being explored preclinically and could be beneficial for genes requiring tightly regulated expression, gain-of-function mutations and dominant-negative mutations.

Gene therapy by modifying autologous hematopoietic stem cells (HSCs) offers an attractive alternative to allogeneic hematopoietic stem cell transplantation (HSCT), the current standard of care to treat severe IEI. This approach does not require availability of a suitable allogeneic donor and eliminates the risk of graft versus host disease (GvHD). Gene therapy can be attempted by using a viral vector to add a copy of the therapeutic gene (viral gene addition) or by using programmable nucleases (gene editing) to precisely correct mutations, disrupt a gene or introduce an entire copy of a gene at a specific locus. However, gene therapy comes with its own challenges such as safety, therapeutic effectiveness and access. For viral gene addition, a major safety concern is vector-related insertional mutagenesis, although this has been greatly reduced with the introduction of safer vectors. For gene editing, the risk of off-site mutagenesis is a main driver behind the ongoing search for modified nucleases. For both approaches, HSCs have to be manipulated ex vivo, and doing this efficiently without losing stemness remains a challenge, especially for gene editing.
Evaluation of Low-dose Buprenorphine Initiation With Buprenorphine Buccal Films in Hospitalized Patients: A Retrospective Cohort Study
Authors: Arnouk Serena , Wunderlich Jeffrey R. , Sidelnik S. Alex
Published: October 2023

Objective

Low-dose buprenorphine initiation (LDBI) strategies to transition patients from full opioid agonists to buprenorphine have previously been described using sublingual films, intravenous solution, transdermal patches, and, more recently, buccal films. The objective of this study was to describe the effectiveness of LDBI using novel titration schedules with buccal films.

Methods

This is a retrospective cohort study of hospitalized patients with opioid use disorder (OUD) or physiologic dependence to opioids who underwent LDBI with buprenorphine buccal films at NYU Langone Health. Two LDBI protocols were evaluated, including a short titration schedule over 4 days and a long schedule over 7 days. The primary outcomes of interest included LDBI completion rates and incidence of opioid withdrawal.

Results

Forty-two patients underwent 46 LDBIs at NYU Langone Health between October 2020 and April 2022. The cohort comprised patients with OUD (57%), chronic pain with OUD (33%), and chronic pain without OUD (10%). Indications for LDBI most commonly included co-occurring pain precluding discontinuation of full opioid agonists (72%), prior history of precipitated withdrawal (30%), and methadone use (23%). The overall completion rate of LDBI was 78%. Withdrawal was encountered in 33% of patients; however, only 2 patients required LDBI discontinuation as a result. On multivariate analysis, a diagnosis of OUD was independently associated with withdrawal during LDBI.

Conclusions

Buprenorphine buccal films can successfully be used off-label to facilitate LDBI in the hospital setting. We present 4- and 7-day titration protocols, which were well-tolerated, and provide practical considerations for use.
Caring to the End
Authors: Gilbert Rachel , Lillekroken Daniela
Published: October 2023

The aim of the current study was to explore the applicability of Swanson's middle-range theory of caring within the context of end-of-life care provided to nursing home residents. A secondary analysis of data collected from 5 individual interviews and 1 focus group with a total of 9 nurses employed at nursing homes was conducted using qualitative deductive content analysis. The findings highlight the influence of nurses' caring attitudes and behaviors on providing end-of-life care, which are described as caring processes. Additionally, the study emphasizes the valuable role of Swanson's theory in guiding end-of-life care practices in nursing homes.