bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractPlant 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

ABSTRACT
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

ABSTRACT
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

ABSTRACTAtta 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.