bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Type and Associated Microbiome Influence Chitin's Growth Promotion Effect in Lettuce
Authors: Kaufmann Moritz , Li Leilei , Van Poucke Christof , Rhyner Nicola , De Tender Caroline , Uyttendaele Mieke , Heyndrickx Marc , Zipfel Cyril , Pothier Joël F. , Cottyn Bart
Published: February 2024

Chitin amendment of peat substrate has been proven effective in promoting lettuce growth and increasing phenolic compounds in lettuce seedlings. However, the effect of chitin soil amendment on lettuce growth in mineral soil remains unexplored. The effect of chitin amendment of mineral soil on lettuce growth and metabolite changes was investigated for the first time in the present study in comparison with chitin-amended peat substrate. Our findings showed that chitin addition in peat substrate increased lettuce head weight by approximately 50% at harvest, whereas this increase was 30% when chitin was added to mineral soil. Targeted metabolomics analysis indicated that chitin addition affected the phenolic compounds in lettuce seedlings, but this effect varied between soil types. Moreover, untargeted metabolomics analysis suggested that using peat substrate or mineral soil had a greater influence on produced lettuce metabolites than chitin addition. Rhizobiome analysis showed that specifically Mortierellaceae family members, known for chitin degradation and plant growth promotion, significantly increased in peat substrate upon chitin treatment. In mineral soil, three bacterial genera and five fungi, including known plant-growth-promoting genera, were significantly more abundant upon chitin treatment but Mortierellaceae family members were not. We assume that the observed effects primarily stem from soil characteristics and from chitin-induced alterations in rhizobiome composition, particularly the presence of Mortierellaceae members, leading to promoted lettuce growth. Despite the variability, chitin remains an environmentally friendly alternative to synthetic fertilizers in lettuce production, but its beneficial effects are dependent on rhizobiome composition, which should be considered before chitin application.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Embedding Interprofessional Education in Clinical Settings: Medical and Dental Student Perceptions of a Patient Interview-Storytelling Experience
Authors: Miller Kelsey A. , Keeney Tamra , Singh Tara A. , Tolchin Dorothy W. , Kesselheim Jennifer C. , Farrell Susan E.
Published: February 2024

Problem

Interprofessional education (IPE) is valued but difficult to deliver, given logistical and other barriers. Centering IPE around patients and grounding it in authentic practice settings are challenging within early undergraduate medical education.

Approach

This intervention facilitated student–patient conversations to elicit patient reflections on the health care professionals who keep them healthy and care for them when they are unwell. After being introduced to the Interprofessional Education Collaborative (IPEC) core competencies, first-year medical (n = 127) and dental (n = 34) students conducted a brief semistructured patient interview, using an interview card with guiding questions, during a precepted outpatient clinic session in March–May 2021. Students transcribed patients’ stories and wrote their own reflections on the interview card. These reflections were used as a stimulus for a class IPE discussion. The authors employed a pragmatic qualitative research approach to explore what students learned about interprofessional collaboration from reflecting on patients’ stories.

Outcomes

Of the 161 students, 158 (98%) completed an interview card. Sixteen health professions were represented in patients’ stories. The patients’ stories prompted students to recognize and expand their understanding of the IPEC competencies. Students’ responses reflected synthesis of the competencies into 3 themes: students value patient-centered holistic care as the goal of interprofessional collaboration; students reflect emerging professional and interprofessional identities in relating to patients, teams, and systems; and students appreciate interprofessional care is complex and challenging, requiring sustained effort and commitment.

Next Steps

Next steps include continuing to integrate patient voices through structured conversations across the undergraduate and graduate medical education spectrum and adapting the model to support conversations with other health professionals engaged in shared patient care. These experiences could foster ongoing deliberate reflection by students on their professional and interprofessional identity development but would require investments in student time and faculty development.
Effect of Polypectomy Simulation-Based Mastery Learning on Skill Retention Among Practicing Endoscopists
Authors: Barsuk Jeffrey H. , Cohen Elaine R. , Patel Ronak V. , Keswani Rajesh N. , Aadam Abdul Aziz , Wayne Diane B. , Cameron Kenzie A. , Komanduri Srinadh
Published: February 2024

Purpose

Practicing endoscopists frequently perform and teach screening colonoscopies and polypectomies, but there is no standardized method to train and assess physicians who perform polypectomy procedures. The authors created a polypectomy simulation-based mastery learning (SBML) curriculum and hypothesized that completion of the curriculum would lead to immediate improvement in polypectomy skills and skill retention at 6 and 12 months after training.

Method

The authors performed a pretest-posttest cohort study with endoscopists who completed SBML and were randomized to follow-up at 6 or 12 months from May 2021 to August 2022. Participants underwent SBML training, including a pretest, a video lecture, deliberate practice, and a posttest. All learners were required to meet or exceed a minimum passing standard on a 17-item skills checklist before completing training and were randomized to follow-up at 6 or 12 months. The authors compared simulated polypectomy skills performance on the checklist from pretest to posttest and posttest to 6- or 12-month follow-up test.

Results

Twenty-four of 30 eligible participants (80.0%) completed the SBML intervention, and 20 of 24 (83.3%) completed follow-up testing. The minimum passing standard was set at 93% of checklist items correct. The pretest passing rate was 4 of 24 participants (16.7%) compared with 24 of 24 participants (100%) at posttest (P < .001). There were no significant differences in passing rates from posttest to combined 6- and 12-month posttest in which 18 of 20 participants (90.0%) passed.

Conclusions

Before training and despite years of clinical experience, practicing endoscopists demonstrated poor performance of polypectomy skills. SBML was an effective method for practicing endoscopists to acquire and maintain polypectomy skills during a 6- to 12-month period.
Physician Work-Personal Intersection: A Scoping Review of Terms, Definitions, and Measures
Authors: Webber Sarah , Semia Sanaa , Nacht Carrie L. , Garcia Sarahi , Kloster Heidi , Vellardita Lia , Kieren Madeline Q. , Kelly Michelle M.
Published: February 2024

Purpose

A substantial body of evidence describes the multidimensional relationship between the intersection of physicians’ work and personal lives and health care quality and costs, workforce sustainability, and workplace safety culture. However, there is no clear consensus on the terms, definitions, or measures used in physician work-personal intersection (WPI) research. In this scoping review, the authors aimed to describe the terms and definitions used by researchers to describe physician WPI, summarize the measurement tools used, and formulate a conceptual model of WPI that can inform future research.

Method

The authors searched PubMed, CINAHL, Scopus, and Web of Science for studies that investigated U.S. practicing physicians’ WPI and measured WPI as an outcome from January 1990 to March 2022. The authors applied thematic analysis to all WPI terms, definitions, and survey questions or prompts in the included studies to create a conceptual model of physician WPI.

Results

Ultimately, 102 studies were included in the final analysis. The most commonly used WPI terms were work-life balance, work-life integration, and work-home or work-life conflict(s). There was no consistency in the definition of any terms across studies. There was heterogeneity in the way WPI was measured, and only 8 (7.8%) studies used a validated measurement tool. The authors identified 6 key driver domains of WPI: work and personal demands; colleague and institutional support and resources; personal identity, roles, health, and values; work schedule and flexibility; partner and family support; and personal and professional strategies.

Conclusions

The authors found significant variability in the terms, definitions, and measures used to study physician WPI. They offer a conceptual model of the WPI construct that can be used to more consistently study physician WPI in the future. Future work should further investigate the validity of this model and generate consensus around WPI terms, definitions, and measures.
Retrospective Analysis of US Litigations Involving Dermatologists From 2011 to 2022
Authors: Lim Young H. , Saberi Shahin A. , Kamal Kanika , Jalian H. Ray , Avram Mathew
Published: February 2024

BACKGROUND

Physician malpractice lawsuits are climbing, and the reasons underlying litigation against dermatologists are unclear.

OBJECTIVE

To determine the reasons patients pursue litigation against dermatologists or dermatology practices.

MATERIALS AND METHODS

A retrospective analysis of all state and federal cases between 2011 and 2022 was performed after a query using “Dermatology” and “dermatologist” as search terms on 2 national legal data repositories.

RESULTS

The authors identified a total of 48 (37 state and 11 federal) lawsuits in which a practicing dermatologist or dermatology group practice was the defendant. The most common reason for litigation was unexpected harm (26 cases, 54.2%), followed by diagnostic error (e.g. incorrect or delayed diagnoses) (16 cases, 33.3%). Six cases resulted from the dermatologist failing to communicate important information, such as medication side effects or obtaining informed consent. Male dermatologists were sued at a rate 3.1 times higher than female dermatologists.

CONCLUSION

Although lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed diagnoses and ensure critical information is shared with patients to safeguard against easily avoidable litigation.
Association of Interleukin-17 Inhibitors With Hypertension in Patients With Autoimmune Diseases: A Systematic Review and Meta-analysis on Randomized Controlled Trials
Authors: Jiang Kexin , Jia Yuheng , Chen Li , Huang Fangyang , Chen Mao
Published: February 2024

The influence of interleukin (IL)-17 inhibition on blood pressure in patients with autoimmune diseases remains inconclusive. Our objective is to examine the risk of hypertension in patients with autoimmune diseases undergoing IL-17 inhibition therapies through meta-analysis of randomized, placebo-controlled trials. We obtained integrated data from PubMed, Embase, and ClinicalTrials.gov. Incident hypertension rates were calculated, and hazard ratios with 95% confidence intervals were analyzed, along with

statistics to assess heterogeneity. Sequential analysis ensured conclusion reliability. In 30 randomized controlled trials involving 9909 patients with diverse autoimmune diseases treated with anti-IL-17 agents, our meta-analysis revealed a significant increase in hypertension risk (risk ratio 1.69, 95% confidence interval 1.24–2.31, P = 0.001), robustly supported by trial sequential analysis. Among the 4 agents (secukinumab, ixekizumab, bimekizumab, and brodalumab), only secukinumab exhibited a notable association with hypertension. Patients with various primary autoimmune diseases, particularly those with psoriatic arthritis, had a higher likelihood of developing hypertension; in rheumatic arthritis patient cohorts, anti-IL-17 agents did not elevate hypertension risk. Prolonged treatment duration correlated with an increased hypertension risk. Stratifying by sex, studies with a female predominance demonstrated a higher risk ratio for hypertension compared with male-predominant studies. This highlights that anti-IL-17 treatment escalates hypertension risk, emphasizing the need for extra caution when managing patients with autoimmune diseases (Registered by PROSPERO, CRD42016053112).
Immunophenotypes of Newborns From SARS-CoV-2-infected Mothers
Authors: Stracuzzi Marta , Paradiso Laura , Panelli Simona , Amendola Antonella , Tanzi Elisabetta , Fappani Clara , Zuccotti Gianvincenzo , Giacomet Vania
Published: February 2024

Background:

Little is known about the neonatal immunologic response to a maternal SARS-CoV-2 infection present during childbirth. Here we analyze a cohort of 75 neonates from SARS-CoV-2-infected mothers.

Methods:

The SARS-CoV-2 infection status was laboratory assessed by real-time reverse transcription polymerase chain reaction on nasopharyngeal swabs (NPS) in both mothers during childbirth and neonates within 24 hours of life. Immunophenotypes of peripheral blood mononucleated cells and SARS-CoV-2 antispike IgA, IgM and IgG of the newborns were recorded. Ten (13.3%) of 75 neonates had positive NPS for SARS-CoV-2; 17 of 75 (23%) were SARS-CoV-2-IgG seropositive, of which one with positive NPS. All the newborns resulted seronegative for SARS-CoV-2 IgA and IgM and were asymptomatic. Our cohort of newborns was divided into groups according to IgG seropositivity (IgG+/−) and NPS results (NPS+/−).

Results:

The count and proportion of lymphocyte subsets (evaluated measuring CD3, CD4, CD8 and CD19 markers) and of natural killer cells (evaluated by measuring the CD3−/CD16+/CD56+ subset) were all in the normal range, with no statistical differences among groups. We found a significant expansion of the T cell (CD3+) subset in the IgG+ group interpreted as the result of immune effects triggered by trained immunity in these newborns, but a decrease in CD4+ T cells for NPS+ neonates. It is therefore difficult to conclude that the decrease in CD4 can certainly be caused by an infection.

Conclusions:

A maternal SARS-CoV-2 infection resulted in an expansive effect of CD3+ T cells in IgG+ newborns; nonetheless, it seems not to affect structural and functional development of the newborn immune system.
Risk factors associated with hepatitis D virus infection and preventive strategies in Mongolia
Authors: Su Chien-Wei , Ochirkhuree Bayarmaa , Namdag Bira , Badamnachin Batsukh , Ganbold Sarangua , Gidaagaya Sarantuya , Ganbold Anar , Yang Sien-Sing , Duger Davaadorj , Wu Jaw-Ching
Published: February 2024

Background:

Hepatitis D virus (HDV) infection is highly prevalent in Mongolia. We aimed to identify the risk factors associated with HDV infection, propose preventive strategies, and evaluate the outcomes of a 3-year collaborative project between Taiwan and Mongolia.

Methods:

In 2016 and 2018, we conducted onsite visits to Mongolia. Mongolian investigators collected questionnaires focusing on risk factors, demographic characteristics, and serum samples for acute HDV infections. Furthermore, 19 Mongolian seed teachers participated in a 1-week workshop on infection control in Taiwan. Subsequently, these seed teachers trained more than 400 medical personnel in Mongolia. To assess secular changes in acute HDV infection, we reviewed the registration data from the National Center for Communicable Disease (NCCD) in Mongolia between 2011 and 2021.

Results:

Among the 194 Mongolian patients, 108 had dual infection with hepatitis B virus (HBV) and HDV, while 86 had acute hepatitis B (AHB). Patients with HBV/HDV dual infections were older (28.6 vs 25.5 years, p = 0.030) and had lower rates of positive hepatitis B e antigen in their sera, lower rates of serum HBV DNA exceeding 2000 IU/mL, and higher rates of having received dental treatment (59.4% vs 40.5%, p = 0.014) and injection therapy (64.2% vs 44.0%, p = 0.009) compared with those with AHB. Analysis of NCCD data revealed that new HDV infection cases were more prevalent between 2011 and 2015 (111.20 ± 29.79 cases/y) and decreased to 54.67 ± 27.34 cases/y between 2016 and 2021 (p = 0.010).

Conclusion:

Dental treatment and injections were associated with a higher risk of acute HDV infections in Mongolia. Through collaborative efforts, the incidence rate of HDV infection has declined in recent years.
Racial and Ethnic Minorities With Acute Pancreatitis Live in Neighborhoods With Higher Social Vulnerability Scores
Authors: Sarraf Paya , Agrawal Rohit , Alrashdan Haya , Agarwal Mitali , Boulay Brian , Mutlu Ece R. , Tussing-Humphreys Lisa , Conwell Darwin , Kim Sage , Layden Brian T. , Yazici Cemal
Published: February 2024

Objectives

The primary objective was to determine differences in Social Vulnerability Index (SVI) scores among minorities (African-Americans and Hispanics) with acute pancreatitis (AP) compared with non-Hispanic whites (NHWs) with AP. The secondary objectives were to determine differences in diet, sulfidogenic bacteria gene copy numbers (gcn) and hydrogen sulfide (H2S) levels between the 2 groups.

Materials and Methods

Patients with AP were enrolled during hospitalization (n = 54). Patient residential addresses were geocoded, and the Centers for Disease Control and Prevention’s SVI scores were appended. Dietary intake and serum H2S levels were determined. Microbial DNAs were isolated from stool, and gcn of sulfidogenic bacteria were determined.

Results

Minorities had higher SVI scores compared with NHWs (P = 0.006). They also had lower consumption of beneficial nutrients such as omega-3 fatty acids [stearidonic (P = 0.019), and eicosapentaenoic acid (P = 0.042)], vitamin D (P = 0.025), and protein from seafood (P = 0.031). Lastly, minorities had higher pan-dissimilatory sulfite reductase A (pan-dsrA) gcn (P = 0.033) but no significant differences in H2S levels (P = 0.226).

Conclusion

Minorities with AP have higher SVI compared with NHWs with AP. Higher SVI scores, lower consumption of beneficial nutrients, and increased gcn of pan-dsrA in minorities with AP suggest that neighborhood vulnerability could be contributing to AP inequities.
Treatment of Acute COVID-19 and COVID-19 Exposures in Children and Adolescents
Authors: Daniels Danielle , Conners Gregory P.
Published: February 2024

The landscape of acute COVID-19 therapeutics has dramatically evolved since the onset of the pandemic. The treatment of acute COVID-19 in children and adolescents requires knowledge of risk factors and clinical features to appropriately select antiviral and immunomodulatory therapies. This review article provides updated guidance for emergency physicians in the treatment of acute COVID-19 in children and adolescents.
The Quality Improvement Review Board: An Innovative Approach to Oversight of Projects That Do Not Meet Criteria of Human Subject Research
Authors: Denison Toni L. , Sorensen Kristyn U. , Blanton Michael P. , Johnson Lara , Byrd Theresa , Pass Steven E. , Philips Lacy , Miller Joyce , McMahon Lance R. , Cherry Barbara
Published: February 2024

This article describes the development of an institutional quality improvement review board (QIRB) as an effective and efficient method for reviewing and overseeing institutional quality improvement (QI) initiatives. QI projects involve the systematic collection and analysis of data and the implementation of interventions designed to improve the quality of clinical care and/or educational programs for a distinct population in a specific setting. QI projects are fundamentally distinct from human subjects research (HuSR); however, the differences between them are subtle and highly nuanced. Determining whether a project meets the definition of QI or qualifies as HuSR, thus requiring institutional review board (IRB) review, can be confusing and frustrating. Nevertheless, this distinction is highly consequential due to the heavy regulatory requirements involved in HuSR and IRB oversight. Making the correct determination of a project's regulatory status is essential before the project begins. Project leaders may not realize that their work meets the definition of HuSR and, therefore, might conduct the project without appropriate IRB review. Therefore, best practices dictate that project leaders should not decide which type of institutional review is appropriate for their projects. In addition, when QI project teams attempt to disseminate the results of their work, documentation of formal review and approval is generally required by peer-reviewed journals and professional organizations. However, institutional review mechanisms are rarely available. Projects that do not meet the definition of HuSR fall outside the purview of IRBs and most institutions do not have an alternative review body. This creates frustration for both project leaders and IRB administrators. Apart from IRB review, a separate process for reviewing QI projects offers several benefits. These include (1) relieving the burden on busy IRB staff; (2) promoting scholarly activity; (3) protecting the institution, project leaders, and participants from HuSR conducted outside of appropriate IRB review; and (4) promoting rigorous QI methods.
Decreasing body size is associated with reduced calving probability in critically endangered North Atlantic right whales
Authors: Pirotta Enrico , Tyack Peter L. , Durban John W. , Fearnbach Holly , Hamilton Philip K. , Harris Catriona M. , Knowlton Amy R. , Kraus Scott D. , Miller Carolyn A. , Moore Michael J. , Pettis Heather M. , Photopoulou Theoni , Rolland Rosalind M. , Schick Robert S. , Thomas Len
Published: February 2024

Body size is key to many life-history processes, including reproduction. Across species, climate change and other stressors have caused reductions in the body size to which animals can grow, called asymptotic size, with consequences for demography. A reduction in mean asymptotic length was documented for critically endangered North Atlantic right whales, in parallel with declines in health and vital rates resulting from human activities and environmental changes. Here, we tested whether smaller body size was associated with lower reproductive output, using a state-space model for individual health, survival and reproduction that quantifies the mechanistic links between these processes. Body size (as represented by the cube of length) was strongly associated with a female's calving probability at each reproductive opportunity. This relationship explained 62% of the variation in calving among reproductive females, along with their decreasing health (20%). The effects of decreasing mean body size on reproductive performance are another concerning indication of the worsening prospects for this species and many others affected by environmental change, requiring a focus of conservation and management interventions on improving conditions that affect reproduction as well as reducing mortality.
Aerococcus kribbianus sp. nov., a facultatively anaerobic bacterium isolated from pig faeces
Authors: Bai Lu , Paek Jayoung , Shin Yeseul , Kim Hongik , Kim Si Hyun , Shin Jeong Hwan , Kook Joong-Ki , Chang Young-Hyo
Published: February 2024

Two cocci-shaped, facultatively anaerobic, Gram-positive bacteria isolated from the faeces of a pig were designated as strains YH-aer221T and YH-aer222. Analysis of the 16S rRNA gene sequences revealed that the isolates were most closely related to Aerococcus suis JCM 18035T with 96.6 % similarity. The multi-locus sequence tree revealed that the isolates formed a sub-cluster adjacent to A. suis JCM 18035T. The average nucleotide identity values for the isolates and their most closely related strains were 71.8 and 71.7 %, respectively; and the digital DNA–DNA hybridization values for the isolates and their most closely related strains were 25.6 and 25.5 %, respectively. The main fatty acids were C18 : 1ω9c, C16 : 0 and C18 : 0. The cell wall contained the meso-diaminopimelic acid-based peptidoglycan. The two isolates shared the same metabolic pathways. Isolates YH-aer221T and YH-aer222 harboured the same CRISPR array with 33 and 46 spacers, respectively. Single-genome vs. metagenome analysis showed that the genomes of the isolates were not found in the available metagenome database. Given their chemotaxonomic, phenotypic and phylogenetic properties, YH-aer221T (= KCTC 25571T=JCM 35699T) and YH-aer222 (=KCTC 25573=JCM 35700) represent a novel taxon. The name Aerococcus kribbianus sp. nov. is proposed.
Directed neural interactions in fMRI: a comparison between Granger Causality and Effective Connectivity
Authors: Allegra Michele , Gilson Matthieu , Brovelli Andrea
Published: February 2024

Understanding how neural populations interact is crucial to understand brain function. Most common approaches to infer neural interactions are based on Granger causality (GC) analyses and effective connectivity (EC) models of neural time series. However, an in-depth investigation of the similarity and complementarity of these approaches is currently lacking. GC and EC are classically thought to provide complementary information about the interdependence between neural signals. Whereas GC quantifies the amount of predictability between time series and it is interpreted as a measure of information flow, EC quantifies the amount and sign of the interaction, and it is often interpreted as the causal influence that a neural unit exert over another. Here, we show that, in the context of functional magnetic resonance imaging (fMRI) data analysis and first-order autoregressive models, GC and EC share common assumptions and are mathematically related. More precisely, by defining a 'corrected' version of GC accounting for unequal noise variances affecting the source and target node, we show that the two measures are linked by an approximately quadratic relation, where positive or negative values of EC are associated with identical values of GC. While the relation is obtained in limit of infinite sampling time, we use simulations to show that it can be observed in finite data samples as classically observed in neuroimaging studies, provided sufficiently long sampling, multiple sessions or group averaging. Finally, we compare the GC and EC analyses on fMRI data from the Human Connectome Project, and obtain results consistent with simulation outcomes. While GC and EC analyses do not provide reliable estimates at the single subject or single connection level, they become stable at the group level (more than approximately 20 subjects), where the predicted relation between GC and EC can be clearly observed from the data. To conclude, our study provides a common mathematical framework to make grounded methodological choices in the reconstruction and analysis of directed brain networks from neuroimaging time series.
Brain preparedness: The cortisol awakening response proacts dynamic organization of large-scale brain networks across emotional and executive functions
Authors: Zeng Yimeng , Xiong Bingsen , Gao Hongyao , Liu Chao , Chen Changming , Wu Jianhui , Qin Shaozheng
Published: February 2024

Emotion and cognition involve an intricate crosstalk of neural and endocrine systems that support allostatic processes for maintenance of dynamic equilibrium and rapid adaptation for upcoming challenges. As a hallmark of human endocrine activity, the cortisol awakening response (CAR) is recognized to play a critical role in modulating emotional and executive functions. Yet, the underlying mechanisms of such effects remain elusive. By leveraging pharmacological neuroimaging technique and Hidden Markov Modeling of brain state dynamics, we show that the CAR proactively modulates rapid reconfigurations (state) of large-scale brain networks across multi-task demands. Behaviorally, suppression of CAR proactively and selectively impaired accuracy for emotional discrimination task but not for working memory (WM). In parallel, suppressed CAR led to a decrease in the occurrence rate of brain state dominant to emotional processing, but an increase in brain state linking to executive control under high WM demand. Further energy-based analyses revealed an increase in transition frequency and sequence complexity along with an increased entropy during emotional tasks when suppressed CAR, suggesting a decreased energy supply. Moreover, an increased transition frequency was observed when shifting from neutral to emotional conditions, but an opposite pattern during WM task, with n decreased transition frequency shifts from low to high-executive demands. Our findings establish a causal link between CAR and dynamic allocation of neural resources for emotional and executive functions, suggesting a cognitive neuroendocrine account for CAR-mediated proactive effects and human allostasis.
A patient-derived amyotrophic lateral sclerosis blood-brain barrier cell model reveals focused ultrasound-mediated anti-TDP-43 antibody delivery
Authors: Wasielewska Joanna M. , Castro Cabral-da-Silva Mauricio , Pecoraro Martina , Nguyen Tam Hong , Bella Vincenzo La , Oikari Lotta E. , Ooi Lezanne , White Anthony R.
Published: February 2024

Background

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development is the non-invasive therapeutic access to the motor cortex currently limited by the presence of the blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS+MB) treatment is an emerging technology that was successfully used in ALS patients to temporarily open the cortical BBB. However, FUS+MB-mediated drug delivery across ALS patients’ BBB has not yet been reported. Similarly, the effects of FUS+MBon human ALS BBB cells remain unexplored.

Methods

Here we established the first FUS+MB-compatible, fully-human ALS patient-cell-derived BBB model based on induced brain endothelial-like cells (iBECs) to study anti-TDP-43 antibody delivery and FUS+MBbioeffectsin vitro.

Results

Generated ALS iBECs recapitulated disease-specific hallmarks of BBB pathology, including changes to BBB integrity, permeability and TDP-43 proteinopathy. Our results also identified differences between sporadic ALS and familial (C9orf72expansion carrying) ALS iBECs reflecting patient heterogeneity associated with disease subgroups. Studies in these models revealed successful ALS iBEC monolayer openingin vitrowith a lack of adverse cellular effects of FUS+MB. This was accompanied by the molecular bioeffects of FUS+MBin ALS iBECs including changes in expression of tight and adherens junction markers, and drug transporter and inflammatory mediators, with sporadic and C9orf72 ALS iBECs generating transient specific responses. Additionally, we demonstrated an effective increase in the delivery of anti-TDP-43 antibody with FUS+MBin C9orf72 (2.7-fold) and sporadic (1.9-fold) ALS iBECs providing the first proof-of-concept evidence that FUS+MBcan be used to enhance the permeability of large molecule therapeutics across the BBB in a human ALSin vitromodel.

Conclusions

Together, our study describes the first characterisation of cellular and molecular responses of ALS iBECs to FUS+MBand provides a fully-human platform for FUS+MB-mediated drug delivery screening on an ALS BBBin vitromodel.
A Multi-Omics Atlas of Sex-Specific Differences in Obstructive Hypertrophic Cardiomyopathy
Authors: Garmany Ramin , Dasari Surendra , Bos J. Martijn , Kim Evelyn T. , Martinez Katherine A. , Tester David J. , Remedios Cristobal dos , Maleszewski Joseph J. , Dearani Joseph A. , Ommen Steve R. , Geske Jeffrey B. , Giudicessi John R. , Ackerman Michael J.
Published: February 2024

ABSTRACT

Background

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease. Women with HCM tend to have a later onset but more severe disease course. However, the underlying pathobiological mechanisms for these differences remain unknown.

Methods

Myectomy samples from 97 patients (53 males/44 females) with symptomatic obstructive HCM and 23 control cardiac tissues were included in this study. RNA-sequencing was performed on all samples. Mass spectrometry-based proteomics and phosphoproteomics was performed on a representative subset of samples.

Results

The transcriptome, proteome, and phosphoproteome was similar between sexes and did not separate on PCA plotting. Overall, there were 482 differentially expressed genes (DEGs) between control females and control males while there were only 53 DEGs between HCM females and HCM males. There were 1963 DEGs between HCM females and control females compared to 1064 DEGs between HCM males and control males. Additionally, there was increased transcriptional downregulation of hypertrophy pathways in HCM females and in HCM males. HCM females had 119 differentially expressed proteins compared to control females while HCM males only had 27 compared to control males. Finally, the phosphoproteome showed females had 341 differentially phosphorylated proteins (DPPs) compared to controls while males only had 184. Interestingly, there was hypophosphorylation and inactivation of hypertrophy pathways in females but hyperphosphorylation and activation in males.

Conclusion

There are subtle, but biologically relevant differences in the multi-omics profile of HCM. This study provides the most comprehensive atlas of sex-specific differences in the transcriptome, proteome, and phosphoproteome present at the time of surgical myectomy for obstructive HCM.
CloVarS: a simulation of single-cell clonal variability
Authors: Faccioni Juliano L. , Buss Julieti H. , Begnini Karine R. , Brunnet Leonardo G. , Oliveira Manuel M. , Lenz Guido
Published: February 2024

High-throughput time-lapse microscopy has allowed researchers to monitor individual cells as they grow into colonies and react to treatments, but a deeper understanding of the data obtained after image analysis is still lacking. This is partly due to the biological and computational challenges related to long-running experiments and single-cell tracking. In this work, we present the Clonal Variability Simulator (CloVarS), a Python tool for generating synthetic data of single-cell lineage trees to model time-lapse microscopy experiments. After colony initialization, each individual cell is simulated for a given number of simulation frames. Over the course of the simulation, cells are able to migrate, enter mitosis (divide), and enter apoptosis (die). These events are determined by distributions of cell division and death times, which can be inferred from and fit to experimental data. Colonies have an adjustable fitness memory, meaning cells are able to inherit their parent cell’s fitness (i.e. their parent’s time to division/death) to a higher or lesser degree. Arbitrary treatments are able to be delivered to colonies at any time point, modifying their division and death distributions, and fitness memory. CloVarS is an important asset for quickly exploring colony fitness dynamics, testing biological hypotheses, bench-marking cell tracking algorithms, and ultimately improving our understanding of single-cell lineage data.
Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures
Authors: Parameshwar Prabu Karthick , Li Chen , Arnauts Kaline , Jiang Junqing , Rostami Sabra , Campbell Benjamin E. , Lu Hongyan , Rosenzweig Derek Hadar , Vaillancourt Cathy , Moraes Christopher
Published: February 2024

The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal-fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 marker of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.
Neuronal and behavioral responses to naturalistic texture images in macaque monkeys
Authors: Ziemba Corey M. , Goris Robbe L. T. , Stine Gabriel M. , Perez Richard K. , Simoncelli Eero P. , Movshon J. Anthony
Published: February 2024

The visual world is richly adorned with texture, which can serve to delineate important elements of natural scenes. In anesthetized macaque monkeys, selectivity for the statistical features of natural texture is weak in V1, but substantial in V2, suggesting that neuronal activity in V2 might directly support texture perception. To test this, we investigated the relation between single cell activity in macaque V1 and V2 and simultaneously measured behavioral judgments of texture. We generated stimuli along a continuum between naturalistic texture and phase-randomized noise and trained two macaque monkeys to judge whether a sample texture more closely resembled one or the other extreme. Analysis of responses revealed that individual V1 and V2 neurons carried much less information about texture naturalness than behavioral reports. However, the sensitivity of V2 neurons, especially those preferring naturalistic textures, was significantly closer to that of behavior compared with V1. The firing of both V1 and V2 neurons predicted perceptual choices in response to repeated presentations of the same ambiguous stimulus in one monkey, despite low individual neural sensitivity. However, neither population predicted choice in the second monkey. We conclude that neural responses supporting texture perception likely continue to develop downstream of V2. Further, combined with neural data recorded while the same two monkeys performed an orientation discrimination task, our results demonstrate that choice-correlated neural activity in early sensory cortex is unstable across observers and tasks, untethered from neuronal sensitivity, and thus unlikely to reflect a critical aspect of the formation of perceptual decisions.

Significance statement

As visual signals propagate along the cortical hierarchy, they encode increasingly complex aspects of the sensory environment and likely have a more direct relationship with perceptual experience. We replicate and extend previous results from anesthetized monkeys differentiating the selectivity of neurons along the first step in cortical vision from area V1 to V2. However, our results further complicate efforts to establish neural signatures that reveal the relationship between perception and the neuronal activity of sensory populations. We find that choice-correlated activity in V1 and V2 is unstable across different observers and tasks, and also untethered from neuronal sensitivity and other features of nonsensory response modulation.
Spontaneous pain dynamics characterized by stochasticity in awake human LFP with chronic pain
Authors: Ryu Jihye , Kao Jonathan , Bari Ausaf
Published: February 2024

Chronic pain involves persistent fluctuations lasting seconds to minutes, yet there are limited studies on spontaneous pain fluctuations utilizing high-temporal-resolution electrophysiological signals in humans. This study addresses the gap, capturing data during awake deep brain stimulation (DBS) surgery in five chronic pain patients. Patients continuously reported pain levels using the visual analog scale (VAS), and local field potentials (LFP) from key pain-processing structures (ventral parietal medial of the thalamus, VPM; subgenual cingulate cortex, SCC; periaqueductal gray, PVG) were recorded. Our novel AMI analysis revealed that regular spike-like events in the theta/alpha band was associated with higher pain; and regular events in the gamma band was associated with opioid effects. We demonstrate a novel methodology that successfully characterizes spontaneous pain dynamics with human electrophysiological signals, holding potential for advancing closed-loop DBS treatments for chronic pain.
Stereotyped cell lineage trees support robust development
Authors: Zhang Xiaoyu , Li Zizhang , Chen Jingyu , Yang Wenjing , Wu Peng , Chen Feng , He Xingxing , Chen Xiaoshu , Yang Jian-Rong
Published: February 2024

Multicellular organisms must have robust development to ensure physiological stability in the face of environmental changes or perturbations. While various mechanisms contributing to developmental robustness have been identified at the subcellular level, those at the intercellular and tissue level remain largely unknown. Our study explores this question using an in vitro directed differentiation model of human embryonic stem cells (hESCs) into lung progenitor cells. Integrated analysis of single-cell transcriptomes and high-density cell lineage trees (CLTs) of the same colonies allowed a fine-resolution recapitulation of known cell types, as well as their differentiation hierarchies and developmental trajectories. Most importantly, we observed stable cell type compositions among many sub-CLTs across biological replicates. Systematic comparison among CLTs by a novel computational framework for CLT alignment suggests that stereotypical development extends beyond stable cell type composition to a degree of significant resemblance in sub-CLT topology. The existence of such sub-CLTs resembling each other not only deepens our understanding of developmental robustness by demonstrating the existence of a stereotyped program, but also suggests a novel perspective for the function of specific cell types in the context of stereotyped sub-CLTs.
Thermal acclimation of stem respiration reduces global carbon burden
Authors: Zhang Han , Wang Han , Wright Ian J. , Prentice I. Colin , Harrison Sandy P. , Smith Nicholas G. , Westerband Andrea , Rowland Lucy , Plavcova Lenka , Morris Hugh , Reich Peter B. , Jansen Steven , Keenan Trevor
Published: February 2024

Stem respiration is a key driver of carbon flux from ecosystems to the atmosphere, yet its response to global warming remains poorly constrained. In particular it has been proposed that stem respiration acclimates to changing temperatures, which could have large implications for carbon cycling under climate change, but no theory exists to predict acclimated respiration rates. Here, we hypothesized that stem respiration is physiologically linked to transpiration in order to maintain hydraulic continuity. We then use that linkage, combined with Eco-evolutionary optimality theory, to develop a theoretical prediction of the temperature sensitivity of both acclimated and instantaneous stem respiration. Leveraging an extensive global dataset, we observe temperature sensitivities of stem respiration across geographical and seasonal variations that are consistent with this prediction. Our findings reveal that stem respiration contributes approximately a quarter of the global above-ground auto-trophic respiration, with an estimated annual emission of around 11.20 ± 5.88 Pg C—comparable to total anthropogenic emissions. Importantly, incorporating thermal acclimation of stem respiration into projections significantly reduces predicted land ecosystem carbon emissions by 4.41 and 9.56 Pg C under the SSP126 and SSP585 scenarios, respectively, for the 21st century.
Stimulation Effects Mapping for Optimizing Coil Placement for Transcranial Magnetic Stimulation
Authors: Zhong Gangliang , Jin Fang , Ma Liang , Zhang Baogui , Cao Dan , Li Jin , Zuo Nianming , Fan Lingzhong , Yang Zhengyi , Jiang Tianzi
Published: February 2024

Background: The position and orientation of transcranial magnetic stimulation (TMS) coil, which we collectively refer to as coil placement, significantly affect both the assessment and modulation of cortical excitability. TMS electric field (E-field) simulation can be used to identify optimal coil placement. However, the present E-field simulation required a laborious segmentation and meshing procedure to determine optimal coil placement. Objective: We intended to create a framework that would enable us to offer optimal coil placement without requiring the segmentation and meshing procedure. Methods: We constructed the stimulation effects map (SEM) framework using the CASIA dataset for optimal coil placement. We used leave-one-subject-out cross-validation to evaluate the consistency of the optimal coil placement and the target regions determined by SEM for the 74 target ROIs in MRI data from the CASIA, HCP15 and HCP100 datasets. Additionally, we contrasted the E-norms determined by optimal coil placements using SEM and auxiliary dipole method (ADM) based on the DP and CASIA II datasets. Results: We provided optimal coil placement in 'head-anatomy-based' (HAC) polar coordinates and MNI coordinates for the target region. The results also demonstrated the consistency of the SEM framework for the 74 target ROIs. The normal E-field determined by SEM was more significant than the value received by ADM. Conclusion: We created the SEM framework using the CASIA database to determine optimal coil placement without segmentation or meshing. We provided optimal coil placement in HAC and MNI coordinates for the target region. The validation of several target ROIs from various datasets demonstrated the consistency of the SEM approach. By streamlining the process of finding optimal coil placement, we intended to make TMS assessment and therapy more convenient. Keywords: Transcranial magnetic stimulation; E-field; stimulation effects mapping; coil placement;
Association of Macular Pigment Density with Plasma Macular Carotenoids levels, And lipids in Indian patients with early Age-Related Macular Degeneration
Authors: Srinivasan Senthilkumari , Rajendren Anand , Panneerselvam Bala , Uduman Mohammed Sithiq
Published: February 2024

Purpose

The objective of the present study was to investigate the relationship of macular pigment optical density (MPOD) with plasma carotenoids [(L) and (Z)] and serum lipids in South Indian young healthy volunteers and patients with early AMD.

Methods

Two hundred and fourteen (N= 214) study participants (Healthy control group (N) = 178; Early AMD group (N) = 36) were enrolled after getting their written informed consent. The MPOD of the study participants was assessed using MPS II (Electron Technology, UK) after completing their routine ocular examination. Serum lipids were measured by the standard technique. Plasma levels of L, Z, lycopene and beta-carotene were estimated by HPLC with PDA detector.

Statistical analysis used

Correlations among variables in serum, plasma and the MPOD were established using Spearman’s rho correlation coefficient.

Results

The overall mean MPOD in healthy control group and early AMD group was found to be 0.47 ± 0.16 (N= 178; 317 eyes) and 0.35 ± 0.22 (N=36; 38 eyes) at 1° eccentricity respectively and was found to be significantly low as compared to healthy control group (p<0.001). A strong positive association was found between plasma L, Z and L+Z and MPOD. Serum HDL showed a strong negative association with MPOD and other lipids showed very weak association. MPOD was unaffected by BMI.

Conclusions

MPOD is positively associated with plasma L,Z and L+Z, adding further evidence that additional intake of L/Z may be beneficial in delaying the risk of AMD in our population