bluuebunny/crossref_metadata_2025 huggingface dataset:
Does it matter for health if steps are taken during work or leisure? A prospective accelerometer study using register-based long-term sickness absence
Authors: Christensen Marie Raunkjær , Nabe-Nielsen Kirsten , Holtermann Andreas , Gupta Nidhi
Published: June 2023

Background

Walking is known to be good for health. However, it is unknown whether it matters if steps are taken during work or leisure. Therefore, we aimed to examine the prospective association between accelerometer-measured steps taken during work or leisure and register-based long-term sickness absence (LTSA).

Methods

We included 937 blue- and white-collar workers from the PODESA cohort who wore a thigh-based accelerometer over four days to measure number of steps during work and leisure. Steps were divided into domain based on diary data. First event of LTSA was retrieved from a national register with four years’ follow-up. We used Cox proportional hazard models to analyze the association between domain-specific and total daily steps and LTSA, adjusted for age, sex, job type, smoking, and steps in the other domain (e.g., work/leisure).

Results

We found more steps at work to be associated with a higher LTSA risk [Hazard Ratio (HR):1.04; 95% CI: 1.00–1.08 per 1000 steps]. No significant association was found between steps during leisure and LTSA (HR: 0.97; 95% CI: 0.91–1.02), nor between total daily steps and LTSA (HR: 1.01; CI 95% 0.99–1.04).

Conclusions

More steps at work were associated with higher risk of LTSA, while steps during leisure was not clearly associated with LTSA risk. These findings partly support ‘the physical activity paradox’ stating that the association between physical activity and health depends on the domain.
An aerobic exercise intervention to improve metabolic health among people living with HIV with at-risk alcohol use: the ALIVE-Ex research study protocol
Authors: Simon Liz , Primeaux Stefany D. , Levitt Danielle E. , Bourgeois Brianna , Johannsen Neil M. , Peters Adrianna , Ahmed Jameel , Marshall Richard H. , Fairchild Alexandra H. , Ferguson Tekeda F. , Molina Patricia E.
Published: June 2023

Background

Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics.

Methods

The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention is a moderate intensity aerobic exercise protocol implemented 3 days per week for 10 weeks at the Louisiana State University Health Sciences Center-New Orleans. Participants who have a fasting blood glucose level between 94 and 125 mg/dl will be enrolled in the study. Oral glucose tolerance tests, fitness assessments, and skeletal muscle biopsies will be performed pre- and post-exercise intervention. The primary outcome is to determine whether the exercise protocol improves measures of whole-body glucose-insulin dynamics, cardiorespiratory fitness, and skeletal muscle metabolic and bioenergetic function. Secondary outcomes are to determine whether the exercise intervention improves cognitive function and overall quality of life. Results generated will demonstrate the effect of exercise on glycemic measures in PLWH with subclinical dysglycemia and at-risk alcohol use.

Conclusions

The proposed intervention will also have the potential to be scalable to promote lifestyle changes among PLWH, particularly in underserved communities.
Acupuncture combined with moxibustion mitigates spinal cord injury-induced motor dysfunction in mice by NLRP3-IL-18 signaling pathway inhibition
Authors: Zheng Ji-Hui , Yuan Na , Zhang Peng , Liu De-Feng , Lin Wei , Miao Jun
Published: June 2023

Background

Spinal cord injury (SCI), which reportedly induces severe motor dysfunction, imposes a significant social and financial burden on affected individuals, families, communities, and nations. Acupuncture combined with moxibustion (AM) therapy has been widely used for motor dysfunction treatment, but the underlying mechanisms remain unknown. In this work, we aimed to determine whether AM therapy could alleviate motor impairment post-SCI and, if so, the potential mechanism.

Methods

A SCI model was established in mice through impact methods. AM treatment was performed in SCI model mice at Dazhui (GV14) and Jiaji points (T7-T12), Mingmen (GV4), Zusanli (ST36), and Ciliao (BL32) on both sides for 30 min once per day for 28 days. The Basso–Beattie–Bresnahan score was used to assess motor function in mice. A series of experiments including astrocytes activation detected by immunofluorescence, the roles of NOD-like receptor pyrin domain-containing-3 (NLRP3)–IL-18 signaling pathway with the application of astrocyte-specific NLRP3 knockout mice, and western blot were performed to explore the specific mechanism of AM treatment in SCI.

Results

Our data indicated that mice with SCI exposure exhibited motor dysfunction, a significant decrease of neuronal cells, a remarkable activation of astrocytes and microglia, an increase of IL-6, TNF-α, IL-18 expression, and an elevation of IL-18 colocalized with astrocytes, while astrocytes-specific NLRP3 knockout heavily reversed these changes. Besides, AM treatment simulated the neuroprotective effects of astrocyte-specific NLRP3 knockout, whereas an activator of NLRP3 nigericin partially reversed the AM neuroprotective effects.

Conclusion

AM treatment mitigates SCI-induced motor dysfunction in mice; this protective mechanism may be related to the NLRP3–IL18 signaling pathway inhibition in astrocytes.
“I literally had no support”: barriers and facilitators to supporting the psychosocial wellbeing of young people with mental illness in Tasmania, Australia
Authors: Savaglio Melissa , Yap Marie B. H. , Smith Toni , Vincent Ash , Skouteris Helen
Published: June 2023

Background

There has been limited focus on understanding the barriers and facilitators to meeting the broader psychosocial needs of young people with mental illness from the perspectives of young people. This is required to advance the local evidence base and inform service design and development. The aim of this qualitative study was to explore young people’s (10–25 years) and carers’ experiences of mental health services, focusing on barriers and facilitators to services supporting young people’s psychosocial functioning.

Methods

This study was conducted throughout 2022 in Tasmania, Australia. Young people with lived experience of mental illness were involved in all stages of this research. Semi-structured interviews were conducted with 32 young people aged 10–25 years with experience of mental illness, and 29 carers (n = 12 parent–child dyads). Qualitative analysis was guided by the Social-Ecological Framework to identify barriers and facilitators at the individual (young person/carer level), interpersonal, and service/systemic level.

Results

Young people and carers identified eight barriers and six facilitators across the various levels of the Social-Ecological Framework. Barriers included, at the individual level: (1) the complexity of young people’s psychosocial needs and (2) lack of awareness/knowledge of services available; at the interpersonal level: (3) negative experiences with adults and (4) fragmented communication between services and family; and at the systemic level: (5) lack of services; (6) long waiting periods; (7) limited service accessibility; and (8) the missing middle. Facilitators included, at the individual level: (1) education for carers; at the interpersonal level: (2) positive therapeutic relationships and (3) carer advocacy/support; and at the systemic level: (4) flexible or responsive services, (5) services that address the psychosocial factors; and (6) safe service environments.

Conclusions

This study identified key barriers and facilitators to accessing and utilising mental health services that may inform service design, development, policy and practice. To enhance their psychosocial functioning, young people and carers want lived-experience workers to provide practical wrap-around support, and mental health services that integrate health and social care, and are flexible, responsive and safe. These findings will inform the co-design of a community-based psychosocial service to support young people experiencing severe mental illness.
Regulation of dendritic spine length in corticopontine layer V pyramidal neurons by autism risk gene β3 integrin
Authors: Celora Lucia , Jaudon Fanny , Vitale Carmela , Cingolani Lorenzo A.
Published: June 2023

The relationship between autism spectrum disorder (ASD) and dendritic spine abnormalities is well known, but it is unclear whether the deficits relate to specific neuron types and brain regions most relevant to ASD. Recent genetic studies have identified a convergence of ASD risk genes in deep layer pyramidal neurons of the prefrontal cortex. Here, we use retrograde recombinant adeno-associated viruses to label specifically two major layer V pyramidal neuron types of the medial prefrontal cortex: the commissural neurons, which put the two cerebral hemispheres in direct communication, and the corticopontine neurons, which transmit information outside the cortex. We compare the basal dendritic spines on commissural and corticopontine neurons in WT and KO mice for the ASD risk gene Itgb3, which encodes for the cell adhesion molecule β3 integrin selectively enriched in layer V pyramidal neurons. Regardless of the genotype, corticopontine neurons had a higher ratio of stubby to mushroom spines than commissural neurons. β3 integrin affected selectively spine length in corticopontine neurons. Ablation of β3 integrin resulted in corticopontine neurons lacking long (> 2 μm) thin dendritic spines. These findings suggest that a deficiency in β3 integrin expression compromises specifically immature spines on corticopontine neurons, thereby reducing the cortical territory they can sample. Because corticopontine neurons receive extensive local and long-range excitatory inputs before relaying information outside the cortex, specific alterations in dendritic spines of corticopontine neurons may compromise the computational output of the full cortex, thereby contributing to ASD pathophysiology.
Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
Authors: Ferroni Giulia , Sabeti Soroosh , Abdus-Shakur Tasneem , Scalise Lorenzo , Carter Jodi M. , Fazzio Robert T. , Larson Nicholas B. , Fatemi Mostafa , Alizad Azra
Published: June 2023

Purpose

Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detection of metastatic ALN in vivo.

Experimental design

The proposed ultrasound-based technique, high-definition microvasculature imaging (HDMI) provides superb images of tumor microvasculature at sub-millimeter size scales and enables quantitative analysis of microvessels structures. We evaluated the new HDMI technique on 68 breast cancer patients with ultrasound-identified suspicious ipsilateral axillary lymph nodes recommended for fine needle aspiration biopsy (FNAB). HDMI was conducted before the FNAB and vessel morphological features were extracted, analyzed, and the results were correlated with the histopathology.

Results

Out of 15 evaluated quantitative HDMI biomarkers, 11 were significantly different in metastatic and reactive ALNs (10 with P << 0.01 and one with 0.01 < P < 0.05). We further showed that through analysis of these biomarkers, a predictive model trained on HDMI biomarkers combined with clinical information (i.e., age, node size, cortical thickness, and BI-RADS score) could identify metastatic lymph nodes with an area under the curve of 0.9 (95% CI [0.82,0.98]), sensitivity of 90%, and specificity of 88%.

Conclusions

The promising results of our morphometric analysis of HDMI on ALNs offer a new means of detecting lymph node metastasis when used as a complementary imaging tool to conventional ultrasound. The fact that it does not require injection of contrast agents simplifies its use in routine clinical practice.
Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study
Authors: Tano Sho , Kotani Tomomi , Ushida Takafumi , Yoshihara Masato , Imai Kenji , Nakamura Noriyuki , Iitani Yukako , Moriyama Yoshinori , Emoto Ryo , Kato Sawako , Yoshida Shigeru , Yamashita Mamoru , Kishigami Yasuyuki , Oguchi Hidenori , Matsui Shigeyuki , Kajiyama Hiroaki
Published: June 2023

Background

Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies.

Methods

This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG.

Results

Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02–1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38–0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11–1.73), respectively.

Conclusions

A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.
ATHENA: an independently validated autophagy-related epigenetic prognostic prediction model of head and neck squamous cell carcinoma
Authors: Xu Ziang , Chen Xinlei , Song Xiaomeng , Kong Xinxin , Chen Jiajin , Song Yunjie , Xue Maojie , Qiu Lin , Geng Mingzhu , Xue Changyue , Zhang Wei , Zhang Ruyang
Published: June 2023

The majority of these existing prognostic models of head and neck squamous cell carcinoma (HNSCC) have unsatisfactory prediction accuracy since they solely utilize demographic and clinical information. Leveraged by autophagy-related epigenetic biomarkers, we aim to develop a better prognostic prediction model of HNSCC incorporating CpG probes with either main effects or gene–gene interactions. Based on DNA methylation data from three independent cohorts, we applied a 3-D analysis strategy to develop An independently validated auTophagy-related epigenetic prognostic prediction model of HEad and Neck squamous cell carcinomA (ATHENA). Compared to prediction models with only demographic and clinical information, ATHENA has substantially improved discriminative ability, prediction accuracy and more clinical net benefits, and shows robustness in different subpopulations, as well as external populations. Besides, epigenetic score of ATHENA is significantly associated with tumor immune microenvironment, tumor-infiltrating immune cell abundances, immune checkpoints, somatic mutation and immunity-related drugs. Taken together these results, ATHENA has the demonstrated feasibility and utility of predicting HNSCC survival (http://bigdata.njmu.edu.cn/ATHENA/).
Matrix completion via modified schatten 2/3-norm
Authors: Ha Jincai , Li Chuan , Luo Xiaohu , Wang Zhi
Published: June 2023

Low-rank matrix completion is a hot topic in the field of machine learning. It is widely used in image processing, recommendation systems and subspace clustering. However, the traditional method uses the nuclear norm to approximate the rank function, which leads to only the suboptimal solution. Inspired by the closed-form formulation of $$L_{2/3}$$

L

2
/
3

regularization, we propose a new truncated schatten 2/3-norm to approximate the rank function. Our proposed regularizer takes full account of the prior rank information and achieves a more accurate approximation of the rank function. Based on this regularizer, we propose a new low-rank matrix completion model. Meanwhile, a fast and efficient algorithm are designed to solve the proposed model. In addition, a rigorous mathematical analysis of the convergence of the proposed algorithm is provided. Finally, the superiority of our proposed model and method is investigated on synthetic data and recommender system datasets. All results show that our proposed algorithm is able to achieve comparable recovery performance while being faster and more efficient than state-of-the-art methods.
The relationship between fear of surgery and affecting factors in surgical patients
Authors: Akutay Seda , Ceyhan Özlem
Published: June 2023

Background

This study aimed to explain the fear of surgery in surgical patients, the affecting factors, and their relationship.

Methods

This study was conducted as a descriptive and cross-sectional study. The study population consists of 300 patients undergoing surgical intervention. Data were collected using the “patient information form” and “Surgical Fear Questionnaire.” Parametric and nonparametric tests were used to evaluate the data. The relationship between the fear questionnaire and age, number of previous surgeries, and pre-operative pain was evaluated using Spearman correlation analysis. The relationship with emotional stress was evaluated with multiple linear regression analysis.

Results

In this study, it was determined that the predictors of the surgical fear level of the patients were age, gender, anesthesia type, and pre-operative pain experience. There was a negative correlation between the age of the patients and the fear of surgery score and a positive correlation between the pre-operative pain severity and the fear of surgery score. It was determined that the factors most associated with pre-operative fear levels were the patients’ pre-operative sense of inadequacy (p < 0.001), feeling anxious and unhappy, and confusion about the surgery decision (p < 0.05).

Conclusion

According to the results of this study, it has been determined that the emotional states and fears of the patients before the surgery have significant effects on the fear of surgery. For this, it is recommended to determine the emotional states and fears of the patients before the surgery and to make appropriate interventions, as it will facilitate compliance with the surgical process.
Neighborhood collective efficacy and environmental exposure to firearm homicide among a national sample of adolescents
Authors: Aubel Amanda J. , Bruns Angela , Zhang Xiaoya , Buggs Shani , Kravitz-Wirtz Nicole
Published: June 2023

Background

Living near an incident of firearm violence can negatively impact youth, regardless of whether the violence is experienced firsthand. Inequities in household and neighborhood resources may affect the prevalence and consequences of exposure across racial/ethnic groups.

Findings

Using data from the Future of Families and Child Wellbeing Study and the Gun Violence Archive, we estimate that approximately 1 in 4 adolescents in large US cities lived within 800 m (0.5 miles) of a past-year firearm homicide during 2014–17. Exposure risk decreased as household income and neighborhood collective efficacy increased, though stark racial/ethnic inequities remained. Across racial/ethnic groups, adolescents in poor households in moderate or high collective efficacy neighborhoods had a similar risk of past-year firearm homicide exposure as middle-to-high income adolescents in low collective efficacy neighborhoods.

Conclusions

Empowering communities to build and leverage social ties may be as impactful for reducing firearm violence exposure as income supports. Comprehensive violence prevention efforts should include systems-level strategies that jointly strengthen family and community resources.
Velocity structure above seismological bedrock estimated from earthquake recordings: an application of diffuse wave-field concept to strong motions in Iran
Authors: Ashayeri Iman , Ito Eri , Kawase Hiroshi
Published: June 2023

We present velocity structure inversion for three stations of Iranian Strong Motion Network (ISMN), and one KiK-net station that is used as a benchmark, for the application of diffuse wave-field concept in tectonic and geological setting of the west of Iran. This study compares the results of two existing computer codes for the velocity structure inversion at these sites. The computer codes use different search space parameterization, and error-minimization algorithms. Firstly, the available information on subsurface structure and surface geology from the strong motion stations is introduced. Then, ground motions of MW larger than 4, with PGA of all components less than 50 cm/s2 are used to calculate horizontal-to-vertical spectral ratios of earthquakes (eHVSR) at each station. The observed eHVSR curves are inverted for the velocity structure of the stations, and the results are compared with each other and the information of previous studies. Finally, the eHVSR curves of the mainshock records of the recent MW 7.3 earthquake at two ISMN sites are investigated. The velocity inversion is repeated by considering the shear modulus degradation of several shallow layers. Empirical nonlinear site amplification functions are calculated based on the modified VS structure and the VS structure of the linear ground response for two ISMN stations.

Graphical Abstract
Refractive outcome and lens power calculation after intrascleral intraocular lens fixation: a comparison of three-piece and one-piece intrascleral fixation technique
Authors: Schranz Markus , Reumüller Adrian , Kostolna Klaudia , Novotny Caroline , Schartmüller Daniel , Abela-Formanek Claudette
Published: June 2023

Purpose

To evaluate the refractive prediction error of common intraocular lens (IOL) power calculation formulae in patients who underwent intrascleral IOL fixation using two different techniques.

Methods

This is a prospective, randomized, longitudinal, single-site, single-surgeon study. Patients who underwent intrascleral IOL implantation using the Yamane or the Carlevale technique were followed up for a period of six months postoperatively. Refraction was measured using the best-corrected visual acuity at 4 m (EDTRS chart). Lens decentration, tilt and effective lens position (ELP) were assessed using an anterior segment optical coherence tomography (AS-OCT). The prediction error (PE) and the absolute error (AE) were evaluated for the SRK/T, Hollayday1 and Hoffer Q formula. Subsequently, correlations between the PE and axial length, keratometry, white to white and ELP were assessed.

Results

In total, 53 eyes of 53 patients were included in the study. Twenty-four eyes of 24 patients were in the Yamane group (YG) and 29 eyes of 29 patients were in the Carlevale group (CG). In the YG, the Holladay 1 and Hoffer Q formulae resulted in a hyperopic PE (0.02 ± 0.56 D, and 0.13 ± 0.64 D, respectively) while in the SRK/T formula the PE was slightly myopic (− 0.16 ± 0.56 D). In the CG, SRK/T and Holladay 1 formulae led to a myopic PE (− 0.1 ± 0.80 D and − 0.04 ± 0.74 D, respectively), Hoffer Q to a hyperopic PE (0.04 ± 0.75 D). There was no difference between the PE of the same formulae across both groups (P > 0.05).
In both groups the AE differed significantly from zero in each evaluated formula. The AE error was within ± 0.50 D in 45%–71% and was within ± 1.00 D in 72%–92% of eyes depending on the formula and surgical method used. No significant differences were found between formulae within and across groups (P > 0.05). Intraocular lens tilt was lower in the CG (6.45 ± 2.03°) compared to the YG (7.67 ± 3.70°) (P < 0.001). Lens decentration was higher in the YG (0.57 ± 0.37 mm) than in the CG (0.38 ± 0.21 mm), though the difference was not statistically significant (P = 0.9996).

Conclusions

Refractive predictability was similar in both groups. IOL tilt was better in the CG, however this did not influence the refractive predictability. Though not significant, Holladay 1 formula seemed to be more probable than the SRK/T and Hoffer Q formulae. However, significant outliers were observed in all three different formulae and therefore remain a challenging task in secondary fixated IOLs.
First-time use of a porcine small intestine submucosal plug device to close an acquired tracheo-esophageal fistula
Authors: Dessard Laura , Deflandre Jacques , Deflandre Justine , Moonen Vincent , Delhougne Nicolas , Goffart Yves
Published: June 2023

Background

Acquired tracheo-esophageal fistula (TEF) is a rare, life-threatening pathology, responsible for severe comorbidities. Its management is a real therapeutic challenge and remains controversial.

Case presentation

We report the first case of endoscopic treatment of TEF by using a porcine small intestine submucosal (SIS) plug device in a young quadriplegic patient after failed surgical closure by cervicotomy. After 1 year of follow-up, oral feeding of the patient was resumed and no clinical signs of fistula recurrence were evident.

Conclusion

To our knowledge, we obtained for the first time, a satisfactory result for TEF closure with the use of a porcine SIS plug.
Naturalistic examination of the anxiolytic effects of medical cannabis and associated gender and age differences in a Canadian cohort
Authors: Minhas Meenu , Lunn Stephanie E.
Published: June 2023

Background

The aim of the current study was to examine patterns of medical cannabis use in those using it to treat anxiety and to investigate if the anxiolytic effects of cannabis were impacted by gender and/or age.

Methods

Patient-reported data (n = 184 participants, 61% female, 34.7 ± 8.0 years) was collected through the Strainprint® app. Tracked sessions were included if the method of administration was inhalation, treatment was for anxiety and the product used was dried flower. The final analyzed dataset encompassed three of the most commonly utilized dried flower products in anxiety sessions. Independent sample t-tests were used. The core analysis examined within subject changes overtime (pre-medication to post-medication) and interactions between time with two candidate moderators [gender (male, female) and age (18–29, 30–39, and 40 + years old)] by using analysis of variance (ANOVA). For significant main effects of interactions, post hoc tests were conducted using a Bonferroni correction. A secondary analysis examined differences in proportion of emotives endorsed as a function of gender or age using chi-square test of independence.

Results

Cannabis consumption resulted in a significant decrease in anxiety scores among both males and females (average efficacy of 50%) and efficacy was similar across the three cultivars. However, gender differences in efficacy were identified in two of the cultivars. All age groups experienced significant reductions in their anxiety post cannabis consumption; however, the 40 + year old group had significantly less efficacy than the other groups. The overall optimal dosing for the entire cohort was 9–11 inhalations for males and 5–7 inhalations for females, with some variation in dosing across the different cultivars, genders and age groups.

Conclusions

We found all three cultivars had significant anxiolytic effects and were well-tolerated. Some limitations of the study are the moderate sample size, self-reported diagnosis of anxiety, unknown comorbidities and experience with cannabis, whether other drugs or cannabis products were used, and restriction to solely inhaled administration. We suggest that the gender and age differences in optimal dosing could support both healthcare practitioners and patients initiate medical cannabis treatment for anxiety.
Development of a portable DNA extraction and cross-priming amplification (CPA) tool for rapid in-situ visual diagnosis of plant diseases
Authors: Li Jie , Du Juan , Li Shengzhican , Dong Jiali , Ying Jiahan , Gu Yuehao , Lu Jie , Zeng Xinyu , Kear Philip , Dou Daolong , Wang Xiaodan
Published: June 2023

Plant pathogens cause severe losses to crop yields and economic returns in agriculture. Despite plant tissue DNA extraction of typically constituting a preliminary step in nucleic acid-based molecular diagnostics, such lab-based methods can be time-consuming and arduous to complete many samples. To mitigate these challenges, we developed an inexpensive portable DNA extraction technique that is lightweight and suitable for deployment in sampling locations, such as fields. It includes a DNA extraction device fabricated with a Steel Microneedle Array (SMA) and a simple high-efficiency DNA extraction buffer. As a result, DNA extraction times can be reduced to within ~ 1 min, and the eluted DNA is demonstrated to be suitable for subsequent molecular biological analyses without requiring additional purification. Cross-priming amplification (CPA) technology was first established to detect Phytophthora infestans, which achieves sensitivity attainment of 10–7 ng/µL. The detection result can be conveniently estimated with naked-eye visual inspection using fluorescent dsDNA binding dye. CPA was demonstrated to be more feasible than PCR-based approaches and performed well in species-specific and practicability tests. This study elucidates a novel integrated pathogen detection technique coupled with SMA-Device extraction and a modified visual CPA assay to establish and verify various field-based samples infected with multiple pathogens. Altogether, the total sample-to-answer time for pathogen detection was reduced to ~ 1.5 h, making field-based analysis affordable and achievable for farmers or extension workers inside and outside the laboratory.
Metabolomics-guided identification of compounds with antibacterial and antioxidant activities from Polygonatum sibiricum-derived endophytic fungi
Authors: Zhao Lingyun , Liu Yu , Sun Huiru , Li Yu , Pachaiyappan Saravana Kumar , Fang Xinyue , Ran Yalan , Qin Yang , Luo Kai , He Meijun
Published: June 2023

Background

Infections caused by multidrug resistant bacterial pathogens have been recognized as major global healthcare threat to medicinal, agricultural and pharmaceutical industries by World Health Organization. In this regard, the present study was aimed to isolate endophytes from medicinal plant Polygonatum sibiricum (P. sibiricum) and to investigate their antibacterial efficacy, radical scavenging ability and chemical fingerprinting using Gas Chromatography–Mass Spectrum (GC–MS) analysis.

Results

Two endophytic fungi Talaromyces assiutensis HJ.14 (T. assiutensis) and Fusarium oxysporum HJ.15 (F. oxysporum) were isolated and identified from the rhizomes of P. sibiricum. Among the extracts screened, ethyl acetate extract of F. oxysporum HJ.15 showed maximum antibacterial activity with the zones of inhibition ranging from 10.98 ± 0.19 to 15.66 ± 1.49 mm and the MIC values ranging from 0.24 to 1.88 µg/mL against the tested bacterial pathogens. In addition, it showed significant antioxidant activity with EC50 values of 6.21–17.97 µg/mL. Further, GC–MS analysis revealed the presence of propanoic acid ethyl ester, hexadecanoic acid methyl ester, hexadecanoic acid ethyl ester, 9-Octadecenoic acid (Z)-methyl ester, 1-Octanol, 2-Undecenal, butanoic acid, 3-hydroxy- and hexanoic acid were the most abundant compounds in the active crude extract which was responsible for the significant antibacterial and antioxidant properties.

Conclusions

In summary, our results clearly suggest that the F. oxysporum HJ.15 will be a promising starting point for the isolation of active antibacterial compounds with antioxidant properties.
Preliminary pharmacokinetic and safety data after a single intravenous infusion of Voyager-V1 (VV1, VSV-IFNβ-NIS) oncolytic virus in patients with relapsed refractory hematologic malignancies.
Authors: Peng Kah Whye , Remick Adam , Bennani Nabila Nora , Cook Joselle , Zhang Lianwen , Witzig Thomas E. , Munoz Javier , Broski Stephen M , Geyer Susan Michelle , Ginos Brenda F. , Russell Luke , Bexon Alice Susannah , Russell Stephen J. , Lacy Martha
Published: June 2023

e14594

Background: Voyager-V1 (VV1) is an oncolytic vesicular stomatitis virus engineered to express interferon beta (IFNβ) to boost cellular antitumor immunity and sodium iodine symporter (NIS). A phase 1 trial investigating a single infusion of VV1 in patients with relapsed refractory multiple myeloma and T-cell lymphoma (TCL) showed promising and durable clinical activity, primarily in patients with TCL. VV1 infects tumor cells and macrophages in the lymph nodes and spleen, resulting in release of tumor antigens and IFNβ that activates and boost cellular antitumor immunity. We present the preliminary pharmacokinetic analysis in patients given one intravenous (IV) dose of VV1. Methods: Patients received 5e9 to 1.7e11 TCID50 (50% tissue culture infective dose) of VV1 given over 30 minutes. We also explored the impact of infusion duration (0.25, 0.5,1 and 3 hours) in 17 patients with solid tumors. The objectives were to determine the impact of viral dose on pharmacokinetics (PK) of VSV and IFNβ. For VSV and IFNβ PK, whole blood was collected in 30 patients on days 1, 2, 3, and 8. Dose levels were 1.7E10, 5E10, and 1.7E11 TCID50. The plasma concentration-time data were estimated with non-compartmental analysis using WinNonlin 8.3. Results: The half-life of VV1 is comparable (10-12h) between dose levels of 1.7e10, 5e10 and 1.7e11. Ideal infusion rate was found to be 30 minutes and provides the highest Cmax and AUC. Most peak concentrations for viremia and IFNβ were achieved between ‘end of infusion’ and 2.5 hours, 4.5 and 24 hours, respectively. Following infusion, a second concentration peak is found in over half the patients leading to highly variable terminal elimination half-life, specifically where the second peak is at 24 hours. There was no second peak for IFNβ levels. Peak plasma concentration and systemic exposure increased in proportion to increased dose, consistent with linear clearance. Conclusions: The 30 minute infusion rate was considered the best as its PK provides the highest Cmax and AUC with no significant CRS differences among other groups. IL-6 and IFNα markers at hour 4 indicate a likely CRS and hour 24 provides a possible prediction of the grade. Cmax and AUC were also highest at 1.7e11 TCID50. This is the recommended dose that will be used in the expansion arm in patients with TCL. Clinical trial information: NCT03017820 , NCT02923466 . [Table: see text]
AOST2031: An in-progress COG phase 3 randomized controlled trial comparing open vs thoracoscopic management of pulmonary metastases in patients with osteosarcoma.
Authors: Doski John J
Published: June 2023

TPS11579

Background: Pulmonary metastasectomy is considered a necessary component of curative therapy in pulmonary metastatic osteosarcoma, however the optimal surgical approach is unknown. Two approaches include open surgery (OSY) including thoracotomy or sternotomy and minimally invasive surgery (MSY) by thoracoscopy. No randomized trial has been completed comparing these approaches in patients with osteosarcoma, however randomized controlled trials in other cancers have not identified superior outcomes in patients undergoing OSY. OSY allows for direct palpation of all lung surfaces and more pulmonary metastatic nodules can be identified during OSY compared to the number predicted by pre-operative imaging. MSY offers the benefit of faster patient recovery, improved quality of life and potential for equivalent surgical control of relevant metastatic disease. Given wide variability in surgical approach and willingness of both surgical oncology and patient advocacy communities to participate in a randomized trial, AOST2031 was developed to address this clinical equipoise. Methods: Eligibility for AOST2031 includes patients < 50 yrs with a histological diagnosis of osteosarcoma and evidence of pulmonary metastases at initial diagnosis or at first recurrence. Patients must have oligometastatic lung metastasis considered resectable by either OSY or MSY, with rapid central review of chest CT images to confirm eligibility. Systemic therapy considered equivalent to methotrexate, cisplatin and doxorubicin is required to be ongoing in newly diagnosed and completed in patients with recurrence. Exclusion criteria include unresectable primary disease, metastatic disease requiring anatomic lung resection, pleural or mediastinal lesions or pleural effusions, progression while receiving initial therapy, extra-pulmonary metastases and prior chest surgery for pulmonary metastases. Patients are randomized 1:1 to either OSY or MSY, with randomization stratified by disease status and risk. The primary outcome is thoracic event free survival, defined as intrathoracic tumor recurrence or death that results from the procedure or a complication related to the procedure. Two-hundred and twenty-five eligible patients are anticipated to answer the primary objective. Secondary objectives include event free, overall survival and . Exploratory objectives include surgical complication rates, patterns of recurrence, use of surgical localization techniques, comparison of CT findings to pathology of resected specimens, and patient reported outcomes. Biologic objectives include the collection of metastatic tissues to facilitate the study of metastatic disease and serial blood samples for future tumor profiling, germline and circulating tumor DNA studies. AOST2031 opened to enrollment at NCTN sites in February 2022. Clinical trial information: NCT05235165 .
Massive Biochemically Silent Pheochromocytoma Masquerading as Nonfunctioning Adrenocortical Cancer
Authors: Kumar Shejil , Wu Katherine , Rodrigo Natassia , Glover Anthony
Published: June 2023

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine excess. Clinically and biochemically silent pheochromocytoma without adrenergic symptoms or elevated catecholamine concentrations are rare. A 71-year-old female presented with acute right flank pain with abdominal computed tomography (CT) scan revealing a hemorrhagic right adrenal mass. She had no preceding adrenergic symptoms, and normal serum electrolytes, on a background of well-controlled hypertension on amlodipine monotherapy. After conservative management and discharge, an outpatient CT adrenal scan confirmed an 88 × 64 mm right adrenal mass demonstrating intense avidity (maximum standardized uptake value, 20.2) on fluorodeoxyglucose F 18-positron emission tomography (FDG-PET)/CT scan. Biochemical screening supported a nonfunctional adrenal lesion with normal-range plasma normetanephrines and metanephrines. She underwent a right adrenalectomy for presumed nonfunctioning adrenocortical cancer; however, histopathology demonstrated a 120-mm pheochromocytoma. Succinate dehydrogenase subunit B (SDHB) and fumarate hydratase (FH) staining were retained; however, weakly positive 2SC staining raised concerns for FH-deficient pheochromocytoma. Germline DNA sequencing was negative for pathogenic RET, VHL, SDHB, SDHD, or FH variants. Tumor cells stained positive for tyrosine hydroxylase and negative for dopamine β hydroxylase. Four months postoperatively, progress FDG-PET/CT scan demonstrated no focal avidity. Massive biochemically silent pheochromocytomas are exceedingly rare, and we discuss various mechanisms that may predispose patients to this phenomenon.
Unique Presentation and Perioperative Management of a Giant Pheochromocytoma
Authors: Villarraga Nicolas , Palani Gurunanthan , Risk Michael , Sibley Shalamar
Published: June 2023

Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10 cm, and their incidence and presentation is not well known. We present a case of a 62-year-old female with a giant 15.9 cm cystic pheochromocytoma. The patient was medically managed with oral phenoxybenzamine solution dose 4 times greater than average and was treated with a radical left nephrectomy and adrenalectomy. This case offers insight into the clinical presentation of giant pheochromocytomas and the unique challenges they present both medically and surgically.
Chapter Three: Romancing Landscape and Human Animal
Authors: Wang Ban
Published: June 2023

Sensitive to modernity's estrangement of human bonds to nature and the rural lifeworld, Shen Congwen affirms an ecological understanding of writing and life. The writing self sinks its roots into nature and enmeshes with nonhuman worlds. Animistic language immerses bodily sensations, pleasure, and feelings in organic environs, connecting humans to the millennial entwinement of the archaic ways of living with the soil, landscape, and the earth. Targeting the modern city's erosion of rural simplicity, authenticity, and vitality, Shen's ecological writing evinces a deep appreciation of unconventional sexuality, affirming the biological and ecological union between inner and outer nature.
A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation
Authors: Keegan Sophie E. , Haskins Julie , Simmonds Andrew J. , Hughes Sarah C.
Published: June 2023

Coordinated spatio-temporal regulation of the determination and differentiation of neural stem cells is essential for brain development. Failure to integrate multiple factors leads to defective brain structures or tumour formation. Previous studies suggest changes of chromatin state are needed to direct neural stem cell differentiation, but the mechanisms are unclear. Analysis of Snr1, the Drosophila orthologue of SMARCB1, an ATP-dependent chromatin remodelling protein, identified a key role in regulating the transition of neuroepithelial cells into neural stem cells and subsequent differentiation of neural stem cells into the cells needed to build the brain. Loss of Snr1 in neuroepithelial cells leads to premature neural stem cell formation. Additionally, loss of Snr1 in neural stem cells results in inappropriate perdurance of neural stem cells into adulthood. Snr1 reduction in neuroepithelial or neural stem cells leads to the differential expression of target genes. We find that Snr1 is associated with the actively transcribed chromatin region of these target genes. Thus, Snr1 likely regulates the chromatin state in neuroepithelial cells and maintains chromatin state in neural stem cells for proper brain development.
Multiplatform modeling of atrial fibrillation identifies phospholamban as a central regulator of cardiac rhythm
Authors: Kervadec Anaïs , Kezos James , Ni Haibo , Yu Michael , Marchant James , Spiering Sean , Kannan Suraj , Kwon Chulan , Andersen Peter , Bodmer Rolf , Grandi Eleonora , Ocorr Karen , Colas Alexandre R.
Published: June 2023

Atrial fibrillation (AF) is a common and genetically inheritable form of cardiac arrhythmia; however, it is currently not known how these genetic predispositions contribute to the initiation and/or maintenance of AF-associated phenotypes. One major barrier to progress is the lack of experimental systems to investigate the effects of gene function on rhythm parameters in models with human atrial and whole-organ relevance. Here, we assembled a multi-model platform enabling high-throughput characterization of the effects of gene function on action potential duration and rhythm parameters using human induced pluripotent stem cell-derived atrial-like cardiomyocytes and a Drosophila heart model, and validation of the findings using computational models of human adult atrial myocytes and tissue. As proof of concept, we screened 20 AF-associated genes and identified phospholamban loss of function as a top conserved hit that shortens action potential duration and increases the incidence of arrhythmia phenotypes upon stress. Mechanistically, our study reveals that phospholamban regulates rhythm homeostasis by functionally interacting with L-type Ca2+ channels and NCX. In summary, our study illustrates how a multi-model system approach paves the way for the discovery and molecular delineation of gene regulatory networks controlling atrial rhythm with application to AF.
Strong positive allometry of bite force in leaf-cutter ants increases the range of cuttable plant tissues
Authors: Püffel Frederik , Roces Flavio , Labonte David
Published: June 2023

Atta leaf-cutter ants are the prime herbivore in the Neotropics: differently sized foragers harvest plant material to grow a fungus as a crop. Efficient foraging involves complex interactions between worker size, task preferences and plant–fungus suitability; it is, however, ultimately constrained by the ability of differently sized workers to generate forces large enough to cut vegetation. In order to quantify this ability, we measured bite forces of Atta vollenweideri leaf-cutter ants spanning more than one order of magnitude in body mass. Maximum bite force scaled almost in direct proportion to mass; the largest workers generated peak bite forces 2.5 times higher than expected from isometry. This remarkable positive allometry can be explained via a biomechanical model that links bite forces with substantial size-specific changes in the morphology of the musculoskeletal bite apparatus. In addition to these morphological changes, we show that bite forces of smaller ants peak at larger mandibular opening angles, suggesting a size-dependent physiological adaptation, probably reflecting the need to cut leaves with a thickness that corresponds to a larger fraction of the maximum possible gape. Via direct comparison of maximum bite forces with leaf mechanical properties, we demonstrate (i) that bite forces in leaf-cutter ants need to be exceptionally large compared with body mass to enable them to cut leaves; and (ii), that the positive allometry enables colonies to forage on a wider range of plant species without the need for extreme investment in even larger workers. Our results thus provide strong quantitative arguments for the adaptive value of a positively allometric bite force.