bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources and applications of endothelial seed cells: a review
Authors: Deng Dan , Zhang Yu , Tang Bo , Zhang Zhihui
Published: June 2024

Endothelial cells (ECs) are widely used as donor cells in tissue engineering, organoid vascularization, and in vitro microvascular model development. ECs are invaluable tools for disease modeling and drug screening in fundamental research. When treating ischemic diseases, EC engraftment facilitates the restoration of damaged blood vessels, enhancing therapeutic outcomes. This article presents a comprehensive overview of the current sources of ECs, which encompass stem/progenitor cells, primary ECs, cell lineage conversion, and ECs derived from other cellular sources, provides insights into their characteristics, potential applications, discusses challenges, and explores strategies to mitigate these issues. The primary aim is to serve as a reference for selecting suitable EC sources for preclinical research and promote the translation of basic research into clinical applications.

Graphical abstract
Standardized generation of human iPSC-derived hematopoietic organoids and macrophages utilizing a benchtop bioreactor platform under fully defined conditions
Authors: Ackermann Mania , Saleh Fawaz , Abdin Shifaa M. , Rafiei Hashtchin Anna , Gensch Ingrid , Golgath Julia , Carvalho Oliveira Marco , Nguyen Ariane H. H. , Gaedcke Svenja , Fenske Arno , Jang Mi-Sun , Jirmo Adan C. , Abeln Markus , Hansen Gesine , Lachmann Nico
Published: June 2024

Background

There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac).

Methods

We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks.

Results

The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone.

Conclusions

The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.
Management of pregnant women in tertiary maternity hospitals in the Paris area referred to the intensive care unit for acute hypoxaemic respiratory failure related to SARS-CoV-2: which practices for which outcomes?
Authors: Schortgen Frédérique , Tabra Osorio Cecilia , Demiri Suela , Dzogang Cléo , Jung Camille , Lavenu Audrey , Lecarpentier Edouard ,   for the COVADIS-PREG study group
Published: June 2024

Background

Evidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area.

Methods

We studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation.

Results

One hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded.

Conclusion

In pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women.

Study registration retrospectively registered in ClinicalTrials (NCT05193526).
Frailty assessment in critically ill older adults: a narrative review
Authors: Moïsi L. , Mino J.-C. , Guidet B. , Vallet H.
Published: June 2024

Frailty, a condition that was first defined 20 years ago, is now assessed via multiple different tools. The Frailty Phenotype was initially used to identify a population of “pre-frail” and “frail” older adults, so as to prevent falls, loss of mobility, and hospitalizations. A different definition of frailty, via the Clinical Frailty Scale, is now actively used in critical care situations to evaluate over 65 year-old patients, whether it be for Intensive Care Unit (ICU) admissions, limitation of life-sustaining treatments or prognostication. Confusion remains when mentioning “frailty” in older adults, as to which tools are used, and what the impact or the bias of using these tools might be. In addition, it is essential to clarify which tools are appropriate in medical emergencies. In this review, we clarify various concepts and differences between frailty, functional autonomy and comorbidities; then focus on the current use of frailty scales in critically ill older adults. Finally, we discuss the benefits and risks of using standardized scales to describe patients, and suggest ways to maintain a complex, three-dimensional, patient evaluation, despite time constraints. Frailty in the ICU is common, involving around 40% of patients over 75. The most commonly used scale is the Clinical Frailty Scale (CFS), a rapid substitute for Comprehensive Geriatric Assessment (CGA). Significant associations exist between the CFS-scale and both short and long-term mortality, as well as long-term outcomes, such as loss of functional ability and being discharged home. The CFS became a mainstream tool newly used for triage during the Covid-19 pandemic, in response to the pressure on healthcare systems. It was found to be significantly associated with in-hospital mortality. The improper use of scales may lead to hastened decision-making, especially when there are strains on healthcare resources or time-constraints. Being aware of theses biases is essential to facilitate older adults’ access to equitable decision-making regarding critical care. The aim is to help counteract assessments which may be abridged by time and organisational constraints.
Novel fabrication of macromolecular multi-functional hydrogel encapsulated with HUCB-derived mesenchymal stem cells to effective regeneration of cardiac repair after acute myocardial infarction
Authors: Xue Jun , Gao Yu Ping
Published: June 2024

Acute myocardial infarction (AMI) has been treated via injectable hydrogels and biomaterial patches invented using tissue engineering advancements over the past decade. Yet the curative potential of injectable hydrogels and stem cells is limited. Here, we propose the development of an injectable and conductive hydrogel composed of oxidised macromolecular hyaluronic acid and chitosan-grafted aniline tetramer polymeric components. In an attempt to enhance the therapeutic potential of AMI therapy, mesenchymal stem cells derived from human umbilical cord blood (HUCB-MSC) have been integrated into the formulation of a conductive hydrogel. For reliable connection to the beating hearts, the hydrogel exhibited suitable adhesive properties. Hydrogel’s potent biocompatibility was determined by in vitro investigations of cell viability and proliferation of NRCMs and H9C2 cardiomyocytes. After myocardial injection, longer HUCB-MSCs survival length, cardiac functioning, and histology in SD rat myocardium were demonstrated, greatly associated by up-regulation and downregulation of cardiac-related relative gene expressions of angiogenic factors and inflammatory factors, respectively. The injectable hydrogel that contained HUCB-MSCs substantially enhanced the therapeutic benefits, indicating a potentially beneficial therapeutic approach to AMI therapy.
The CDK9 inhibitor enitociclib overcomes resistance to BTK inhibition and CAR-T therapy in mantle cell lymphoma
Authors: Jiang Vivian , Lee William , Zhang Tianci , Jordan Alexa , Yan Fangfang , Cai Qingsong , McIntosh Joseph , Vargas Jovanny , Liu Yang , Wang Michael
Published: June 2024

Inhibitors of Bruton’s tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes in Dual-R vs. BTKi-R samples. We therefore hypothesized that targeting CDK9 may turn off MYC-driven tumor survival and drug resistance. Enitociclib (formerly VIP152) is a selective CDK9 inhibitor whose potency against MCL has not been assessed. In this study, we found that enitociclib was highly potent in targeting lymphoma cells, with the half-maximal inhibitory concentration (IC50) ranging from 32 to 172 nM in MCL and diffuse large B-cell lymphoma cell lines. It inhibited CDK9 phosphorylation and downstream events including de novo synthesis of the short-lived proteins c-MYC, MCL-1, and cyclin D1, and induced apoptosis in a caspase-3-dependent manner. Enitociclib potently inhibited in vivo tumor growth of cell line-derived and patient-derived xenografts having therapeutic resistance. Our data demonstrate the potency of enitociclib in overcoming therapeutic resistance in MCL models and provide evidence in favor of its clinical investigation.
NMR structure and functional studies of the fourth FAS1 domain of human periostin
Authors: Yun Hyosuk , Seon Jeong-Eun , Ji Kon-Young , Min Hye Jung , Kang Hyung-Sik , Lee Chul Won
Published: June 2024

Periostin is a matricellular protein that consists of several structural and functional domains, including EMILIN-like, four internal repeat fasciclin1 (FAS1) domains, and a carboxyl-terminal variable domain. It is known that periostin is associated with various fundamental biological processes and diseases, such as several types of cancer and chronic inflammatory diseases. Despite its important roles, the biological function of each domain is poorly understood. In this study, we expressed the fourth FAS1 (FAS1 IV) domain of human periostin, which was highly soluble and stable enough for structural and functional studies. The three-dimensional structure of FAS1 IV was determined using 3D NMR spectroscopy. The overall structure of FAS1 IV consists of six α-helices, one 310 helix, and eight β-strands. Two triangular α-helical modules formed by three α-helices each are located on one side of the molecule, while the orthogonal β-sheet sandwich module of FAS1 IV is located on the other side. The isolated FAS1 IV domain exhibited cell invasion, migration, and adhesion activities for cancer cell lines comparable to those of the full FAS1 I–IV domain. In conclusion, we propose that the FAS1 IV domain is functionally active in human periostin and provides valuable information for understanding the biological function of periostin.
Transvaginal resection of a gastrointestinal stromal tumor of the rectum: a case report
Authors: Hatai Sanshiro , Nagai Shuntaro , Yoshida Taiki , Matsuoka Masaru , Shinkawa Tomohiko , Oyama Yasuhiro , Tanabe Yoshitaka , Kitahara Daichi , Tamiya Sadafumi , Amada Satoshi , Nishihara Kazuyoshi , Nakano Toru
Published: June 2024

Background

The most common curative treatment for gastrointestinal stromal tumors (GISTs) is local excision. For rectal GISTs, however, local excision is difficult because of the anatomical features of the rectum. The optimal surgical approach is still under debate, and less invasive methods are desired. We herein report a case of transvaginal resection of a rectal GIST in a young woman.

Case presentation

A 21-year-old woman was diagnosed with a resectable GIST in the anterior rectal wall and underwent transvaginal tumor resection. The posterior vaginal wall was incised, revealing the tumor fully covered by the rectal mucosa. The rectal adventitia and muscular layer were incised, and the tumor was resected en bloc without rupture. The postoperative course was favorable, and the patient was discharged on postoperative day 12. No findings consistent with recurrence were present 6 months postoperatively.

Conclusion

Transvaginal tumor resection is a treatment option as a minimally invasive procedure for GISTs in the anterior rectal wall in female patients.
Association of insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme gene (ACE) with Parkinson’s disease and factors risk in eastern Algeria: case–control study
Authors: Meroua Horchi-Mekkaoui , Rayene Achou , Brahim Djoudi , Rania Laouar , Razika Gharzouli , Naima Taghane , Noureddine Abadi , Dalila Satta
Published: June 2024

Background

This study aimed to explore the relationship between Parkinson’s disease and insertion/deletion polymorphism (I/D) of the angiotensin-converting enzyme gene (ACE) and to highlight the related risk factors within Eastern Algerian population. A total of 262 individuals were recruited, including 100 PD patients and 162 controls. Polymerase chain reaction technique was employed to determine the ACE polymorphism genotype of each participant. Logistic regression analysis was conducted to examine factors potentially contributing to Parkinson’s disease.

Results

The mean age of onset of Parkinson’s disease in the patient group was 56.18 $$\pm 12.99$$

±
12.99

. The results revealed that the D allele of the angiotensin-converting enzyme gene and the DD genotype were most prevalent in both patients and controls. However, there were no significant differences in the genotype and allele frequencies of the I/D polymorphism of the angiotensin-converting enzyme gene between patients and healthy subjects. Cardiovascular disease, diabetes and profession were identified as potential risk factors for Parkinson’s disease.

Conclusion

The obtained data indicated no correlation between the angiotensin-converting enzyme I/D gene polymorphism and Parkinson’s disease in our research cohort. Multiple logistic regression analysis revealed that cardiovascular disease, diabetes and profession were possible risk factors for Parkinson’s disease.
Ventricular remodeling and hemodynamic changes in heart failure patients with non-ischemic dilated cardiomyopathy following dapagliflozin initiation
Authors: Hassan Ahmed , Samaan Kerollos , Asfour Ahmed , Baghdady Yasser , Samaan Amir Anwar
Published: June 2024

Background

In heart failure with reduced ejection fraction (HFrEF), sodium–glucose co-transporter inhibitors (SGLT-2i) have persistently shown cardiovascular benefits through different trials. However, their impact on ventricular remodeling and cardiac hemodynamics has not been sufficiently studied. This study aimed to study how SGLT-2i initiation affects invasive hemodynamics and cardiac magnetic resonance imaging (CMR)-derived ventricular volumes, function, and fraction of the extracellular volume (ECV) in HFrEF patients with non-ischemic dilated cardiomyopathy (NIDCM).

Results

In this study, 23 patients with HFrEF and a mean age of 42, including 82.6% males, all have NIDCM and underwent right heart catheterization and CMR at the initiation of dapagliflozin and at 6-month follow-up. The addition of dapagliflozin resulted in significant reductions in the following invasive hemodynamic parameters compared to baseline: left ventricular end-diastolic pressure (23.4 vs 19.7 mmHg, p = 0.003), mean pulmonary artery pressure (31.3 vs 27.7 mmHg, p = 0.03), and systemic vascular resistance (18 vs 15 Wood units, p = 0.047). Among the studied CMR-derived measurements, only the percentage of extracellular volume fraction was significantly less at follow-up (33.7 vs 32.16%, p = 0.001). Additionally, functional class showed significant improvement with a notable reduction of the NT-proBNP level and a considerable decrease in diuretic dose (median: 40 vs 80 mg, p = 0.01).

Conclusion

Adding dapagliflozin to patients with HFrEF due to NIDCM improved invasively measured hemodynamics and significantly reduced left ventricular extracellular volume fraction measured by CMR, with no significant change in ventricular volumes or ejection fraction.
Effect of coffee husk biochar and inorganic NP fertilizer on soil properties, growth and yield of potato (
Solanum tuberosum
L.) on acidic soil of southwest Ethiopia
Authors: Dawerasha Samuel Shaweno , Nebiyu Amsalu , Ahmed Milkiyas , Haile Bewuketu
Published: June 2024

Soil acidity and low soil fertility due to nutrient leaching coupled with low inorganic fertilizer usage is a major cause of low crop yields across Southwest Ethiopia. Recently, biochar potential to improve soil fertility has gained significant attention but there are limited studies on the use of biochar in combination with inorganic fertilizers. A field experiment was, therefore, conducted to investigate the effect of combined application of biochar and inorganic NP nutrient on soil physicochemical properties, growth and yield of potato in Andiracha district, Southwestern Ethiopia. The experiment was laid out in randomized complete block design (RCBD) and replicated three times. The treatment consisted of four levels of biochar rates (0, 2.5, 5 and 7.5 t ha
−1
) and four fertilizer rates of (0, 75,100 and 125% of recommended N P rates). Data were analyzed using SAS version 9.3 Software. Analysis of variance showed that combined application of biochar and inorganic NP fertilizer had highly significant (p < 0.01) effect on days to flowering, stem number, plant height, total leaf area, total dry biomass, marketable tuber number per hill and harvest index and significant (p < 0.05) effect on marketable tuber weight and total tuber weight ha
−1
. Combined application of 7.5 ton ha
−1
biochar with 165 kg N and 60 kg P ha
−1
resulted highest tuber yield (42.64 t ha
−1
), that increased yield by 28.99% compared with recommended NP fertilizer alone (165 kg N ha
−1
and 60 kg P ha
−1
), and by 76.6% compared to the control. The increase was mainly attributed to the improvement in soil physico-chemical properties especially soil pH, CEC, organic matter, total N and available P which is a reflection of increase in soil fertility. Consequently, it was determined that the best course of action for potato production in the area was to apply 7.5 tons of biochar ha
−1
together with 165 kg N and 60 kg P ha
−1
. Therefore, the study recommends adoption of low cost biochar production techniques and capacity building to ensure satisfactory knowledge of biochar use and its adoption by potato growers for soil fertility management and enhanced crop productivity.
The sleep and activity database for the early years (SADEY) study: design and methods
Authors: Cliff Dylan P. , Antczak Devan , Draper Catherine E. , Olds Timothy , Santos Rute , Silva Diego Augusto Santos , Tremblay Mark S. , van Sluijs Esther M.F. , Kemp Byron , Aadland Eivind , Aadland Katrine , Bezerra Thayna Alves , Burley Jade , Carson Valerie , Christian Hayley E. , De Craemer Marieke , Downing Katherine , Hesketh Kylie D. , Jones Rachel A. , Kuzik Nicholas , Lehto Reetta , Martins Clarice , Mota Jorge , Nathan Andrea , Okely Anthony D. , Roos Eva , Sousa-Sá Eduarda , Vale Susana , Wiebe Sandra , Janssen Ian
Published: June 2024

Background

Canada, Australia, the World Health Organization and other countries have released 24-hour movement guidelines for the early years which integrate physical activity, sedentary behaviour, and sleep, focusing on supporting children to achieve a healthy 24-hour day. The guideline evidence synthesis, however, highlighted the dearth of high-quality evidence, particularly from large-scale studies. The Sleep and Activity Database for the Early Years (SADEY) project aims to assemble a large, pooled database of 24-hour movement behaviours and health indicators in young children (birth to 5.99 years), to advance knowledge in these areas. This paper describes the SADEY design and methods.

Methods

Data sets were identified with > 100 children and device-measured (hip-worn ActiGraph accelerometers) physical activity and sedentary behaviour, parent-reported or device-measured sleep, and at least one health outcome: physical (BMI, waist circumference, blood pressure), social-emotional (Strength and Difficulties Questionnaire), cognitive (Early Years Toolbox), or motor development (Test of Gross Motor Development 2). Led by the University of Wollongong co-ordinating centre, the SADEY project collates the datasets to create a pooled database.

Findings

To date, 13 studies from 7 countries have been included in the database. Ethics clearance and data sharing agreements have been secured for all studies and the SADEY 1.0 database is being assembled including ~ 8,000 participants.

Discussion

SADEY will be used to address questions of global importance to public health policy and practice, for example – Is the mix of movement behaviours across the 24-hour day associated with healthy development?, What is the optimal mix of these behaviours?, and; What factors can be targeted to support young children in achieving the optimal mix of 24-hour movement behaviours? Additionally, SADEY seeks to develop and disseminate protocols, develop capacity on the device-based measurement of movement behaviours, and seeks partnerships with stakeholders that promote knowledge translation on movement behaviours to support healthy development among young children.
Incorporating Molecular Data Into Treatment Decision Making in Gastroesophageal and Pancreaticobiliary Cancers: Timing and Strategies
Authors: Hall Andrew , Brown Sarah R. , Mettu Niharika B. , Miller Paul C. , Smyth Elizabeth C. , Nixon Andrew B.
Published: June 2024

Gastroesophageal (GE) and pancreatobiliary (PB) cancers represent a significant clinical challenge. In this context, it is critical to understand the key molecular targets within these malignancies including how they are assayed for as well as the clinical actionability of these targets. Integrating biomarkers into the standard of care presents a critical avenue for refining treatment paradigms. This review aims to explore these complexities, offering insights into the optimal sequencing of chemotherapy and targeted therapies and their utility in the management of GE and PB cancers. The timely integration of promising investigational therapies into clinical practice has broader implications around strategies for future clinical trial designs, which would pave the way for advancements in the management of GE and PB cancers. This review provides guidance in navigating the evolving landscape of GE and PB cancer care, which ultimately will drive forward progress in the field and lead to improved patient outcomes.
CDKN2A deletion and radiation sensitivity in IDH-mutant astrocytomas.
Authors: Muzyka Logan , Kitagawa Yosuke , Nasser Ali Mohamed , Wetzel Ethan A , Miller Julie J. , Wakimoto Hiroaki , Cahill Daniel P.
Published: June 2024

2041

Background: IDH-mutant astrocytomas represent the most prevalent primary tumors in younger adults (<45yo). A substantial minority of these tumors exhibit the deletion of CDKN2A (Cyclin-Dependent Kinase Inhibitor Gene 2A). Homozygous deletion of this gene– which encodes the tumor suppressor protein p16 – is associated with a malignant phenotype and poorer prognosis in IDH-mutant astrocytoma. CDKN2A deletions are primarily observed in tumors that have received radiation therapy (RT), suggesting a potential mechanistic relationship between RT and deletion. This observation gives rise to two alternative hypotheses: either RT is causing DNA damage in irradiated cells, leading to the induction of subclonal CDKN2A deletion, or a subset of cells already possesses the CDKN2A deletion and is resistant to RT, resulting in the treatment selecting for the subsequent emergence of these cells. Here, we sought to ascertain the influence of CDKN2A deletion on IDH-mutant astrocytoma cellular response to RT. Methods: The antitumor effect of RT was evaluated in vitro using patient-derived IDH-mutant astrocytoma cells, MGG152. A homozygous CDKN2A deletion was engineered in this parental line, creating a paired line to permit an isogenic comparison between CDKN2A intact versus CDKN2A deleted tumor cells. A photon irradiator was used to deliver a range of clinically-relevant RT doses spanning from 0 to 20 gray (Gy). Differences in cell viability after a predetermined incubation period were examined and relevant statistical comparisons performed. Results: Dose-response curves in response to radiation therapy, comparing CDKN2A intact and deleted cell lines, were generated (Table). Both CDKN2A intact and deleted cell lines exhibited significant reductions in viability following radiation exposure at and above 2Gy (p < 0.001). CDKN2A-deleted cells displayed a small but significantly greater sensitivity than CDKN2A-intact at 1, 2, and 5Gy (Table). Conclusions: Our findings offer evidence indicating that p16 loss does not bestow radioresistance in IDH-mutant astrocytomas. These findings align with a hypothesis that radiotherapy (RT) might promote DNA damage, and consequently, subclonal CDKN2A deletion, in irradiated IDH-mutant tumors. [Table: see text]
Can targeting TSP-1 with gabapentin enhance survival in glioblastoma? A 20-year retrospective cohort study.
Authors: Mehari Mulki , Ambati Vardhaan , Krishna Saritha , Negussie Mikias , Nava Gonzales Cesar , Dada Abraham , Kabir Aymen , Kaur Jasleen , Oten Sena , Sibih Youssef , Daniel Andy , de Groot John Frederick , Odia Yazmin , Hervey-Jumper Shawn L.
Published: June 2024

2048

Background: Molecularly-defined cellular subpopulations of glioblastoma secrete high levels of the synaptogenic protein thrombospondin-1 (TSP-1) which promotes functional integration of tumor into neural circuity. A greater extent of glioma-neuronal crosstalk portends worse survival for patients. In preclinical studies, gabapentin was shown to inhibit TSP-1, in turn disrupting neuronal synaptogenesis and neuronal activity-dependent glioblastoma proliferation; however, clinical survival data is lacking. We aim to determine whether treatment with gabapentin is associated with improved survival and reduced serum TSP-1 in a retrospective cohort of patients with IDH-wildtype glioblastoma. Methods: Newly-diagnosed, IDH-wildtype glioblastoma patients who received care at the UCSF Brain Tumor Center between 1997-2017 were included in this study. Kaplan-Meier curves and multivariate Cox proportional-hazards models, controlled for age, MGMT promoter methylation status, preoperative tumor volume, and extent of resection, were used for survival analyses. Differences in serum TSP-1 measured by ELISA for gabapentin treated patients and matched non-gabapentin treated controls were assessed using unpaired two-tailed student’s t-test. Control samples were matched 2:1 by age, tumor volume, and extent of resection. After 2005, patients were treated with chemoradiation with concurrent and adjuvant temodar. Results: Among 379 adult patients with glioblastoma, 36 (9.5%) were treated with gabapentin. The median daily dose of gabapentin was 600 mg (IQR: 300-900 mg). There were no significant differences between gabapentin treated and non-gabapentin treated patients by age (0.06), sex (p=0.14), or race (p=0.52). Median overall survival for gabapentin treated and non-gabapentin treated patients was 20.8 months (IQR: 11.7 - 32.1) and 14.7 months (IQR: 8.9-23.5), respectively (p= 0.02). On Kaplan-Meier survival analysis, overall survival was longer for gabapentin treated patients compared with non-gabapentin treated patients (p=0.005). In the multivariate Cox proportional-hazards model, gabapentin use was associated with decreased hazard of death (HR 0.67, p=0.030). Mean serum TSP-1 in gabapentin-treated patients was significantly lower than in the matched control group (10181 ng/ml vs 17015 ng/ml, p=0.017). Conclusions: Gabapentin use is associated with a survival benefit for patients with glioblastoma, possibly mediated through a reduction in TSP-1. This promising result lays the foundation for future prospective studies to further evaluate TSP-1 as a circulating prognostic biomarker as well as to explore the therapeutic benefits of gabapentin as a life-prolonging treatment for patients with newly diagnosed glioblastoma.
Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance)
Authors: Nowak Jonathan A. , Twombly Tyler , Ma Chao , Shi Qian , Haruki Koichiro , Fujiyoshi Kenji , Väyrynen Juha , Zhao Melissa , Knight James , Mane Shrikant , Shergill Ardaman , Kumar Pankaj , Couture Felix , Kuebler Philip , Krishnamurthi Smitha , Tan Benjamin , Philip Philip , O'Reilly Eileen M. , Shields Anthony F. , Ogino Shuji , Fuchs Charles S. , Meyerhardt Jeffrey A.
Published: June 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045 ) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( Pinteraction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; Pinteraction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.
Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort
Authors: Sandoval José Luis , Franzoi Maria Alice , di Meglio Antonio , Ferreira Arlindo R. , Viansone Alessandro , André Fabrice , Martin Anne-Laure , Everhard Sibille , Jouannaud Christelle , Fournier Marion , Rouanet Philippe , Vanlemmens Laurence , Dhaini-Merimeche Asma , Sauterey Baptiste , Cottu Paul , Levy Christelle , Stringhini Silvia , Guessous Idris , Vaz-Luis Ines , Menvielle Gwenn
Published: June 2024

PURPOSE

Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends.

PATIENTS AND METHODS

We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498 ), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment.

RESULTS

Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = –7.6 [–8.9; –6.2], SIIincome = –4.0 [–5.2; –2.8]), SIIeducation = –1.9 [–3.1; –0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment.

CONCLUSION

The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.
Health-related Quality of Life and Problem Behavior After GH Cessation in Adults Born Small for Gestational Age: A 12-Year Follow-up Study
Authors: Dorrepaal Demi Justine , van der Steen Manouk , de Ridder Maria , Goedegebuure Wesley Jim , Hokken-Koelega Anita Charlotte Suzanne
Published: June 2024

Context

Long-term data regarding health-related quality of life (HRQoL) and problem behavior in adults born small for gestational age (SGA) who were treated with GH during childhood are lacking.

Objective

To investigate longitudinal changes in HRQoL and problem behavior in adults born SGA during 12 years after cessation of childhood GH treatment (SGA-GH) and compare these with 3 control groups at age around 30 years.

Participants

One hundred seventy-six SGA-GH adults and 3 untreated age-matched control groups: 50 born SGA with short stature (SGA-S), 77 born SGA with spontaneous catch-up growth to normal height (SGA-CU), and 99 born appropriate-for-gestational-age with normal height (AGA).

Main Outcome Measures

HRQoL and problem behavior were assessed using the TNO-AZL Adults Quality of Life questionnaire and Adolescent Behavior Check List at 6 months and 2, 5, and 12 years after GH cessation. Data at 12 years after GH cessation were compared with 3 control groups.

Results

During 12 years after GH cessation, HRQoL remained similar on 9 subscales in SGA-GH adults but decreased on 3 subscales (gross motor functioning, pain, sleep). Externalizing problem behavior decreased significantly, and internalizing problem behavior tended to decrease. SGA-GH and SGA-S adults had similar HRQoL and problem behavior. SGA-GH adults had, compared to AGA adults, similar HRQoL on 7 subscales, lower HRQoL on 5 subscales, and more internalizing and externalizing problem behavior. All SGA adults had lower HRQoL and more internalizing problem behavior than AGA adults. Adult height associated negatively with externalizing problem behavior, but the influence was small.

Conclusion

During 12 years after GH cessation, HRQoL remained mostly similar and problem behavior decreased in SGA-GH adults. SGA-GH and SGA-S adults had similar HRQoL and problem behavior. All SGA adults had lower HRQoL and more internalizing problem behavior than AGA adults.
Microelectrode Recording During Deep Brain Stimulation Does Not Consistently Represent Lead Trajectory
Authors: Hines Kevin , Sharan Isha , Schaefer Joseph , Fayed Islam , Atik Ahmet , Matias Caio M. , Wu Chengyuan
Published: June 2024

BACKGROUND AND OBJECTIVES:

Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage neurophysiological information to confirm satisfactory trajectory of implanted electrodes. The goal of this study was to evaluate the consistency in which electrodes are placed in sampled microelectrode trajectories.

METHODS:

This is a retrospective study using intraoperative computed tomography to measure final electrode deviation from MER probe placement during the DBS insertion targeting subthalamic nucleus. Fifteen patients had 29 DBS leads placed using MER assistance. Radial distance between the probe and the lead were measured for each patient using intraoperative imaging. In addition, the preoperative target to final lead error was measured in 14 patients undergoing subthalamic nucleus implants without the use of MER and compared with the 15 patients in which MER was used as an adjunct.

RESULTS:

There was no significant difference in the mean radial target error (1.2 vs 1.0 mm, P = .156) when comparing the leads placed with or without MER assistance, respectively. The mean difference in final position of microelectrode compared with DBS lead was 0.9 ± 0.1 (range 0.4-2.0 mm). Of all MER-assisted electrodes placed, 44.8% (13) of electrode final positions radially deviated 1.0 mm or more from the MER probe.

CONCLUSION:

Electrode placement may deviate significantly from MER trajectories. Given the concern that physiological data may not be representative of the final electrode trajectory, surgeons should consider using intraoperative imaging or other adjunctive techniques during DBS to confirm accuracy and satisfactory trajectory of DBS leads.
Microvascular Decompression Using the Gelatin Sponge Insertion Technique for Trigeminal Neuralgia: A Retrospective Cohort Study
Authors: Zhang Zhongding , Zhao Hua , Tang Yinda , Wang Baimiao , Yuan Qing , Wang Haopeng , Cai Xiaomin , Zhu Wanchun , Li Shiting
Published: June 2024

BACKGROUND AND OBJECTIVES:

Microvascular decompression (MVD) is the primary surgical intervention for trigeminal neuralgia (TN), with Teflon being the most conventional decompressing material. However, Teflon has been associated with adhesion and granulomas after MVD, which closely correlated with the recurrence of TN. Therefore, we developed a new technique to prevent direct contact between Teflon and nerve. The purpose of this study is to compare the efficacy of MVD using the gelatin sponge (GS) insertion technique with that of Teflon inserted alone in treating primary TN.

METHODS:

We retrospectively analyzed the medical records and the follow-up data of 734 patients with unilateral primary TN who underwent MVD at our center from January 2014 to December 2019. After exclusions, we identified 313 cases of GS-inserted MVD and 347 cases of traditional MVD. The follow-up exceeded 3 years.

RESULTS:

The operating time of the GS-inserted group was longer than that of the Teflon group (109.38 ± 14.77 vs 103.53 ± 16.02 minutes, P < .001). There was no difference between 2 groups in immediate surgical outcomes and postoperative complications. The yearly recurrence rate for GS-inserted MVD was lower at first (1.0%), second (1.2%), and third (1.2%) years after surgery, compared with its counterpart of Teflon group (3.7%, 2.9%, and 1.7% respectively). The first-year recurrence rate (P = .031) and total recurrence rate in 3 years (P = .013) was significantly lower in the GS-inserted group than Teflon group. Kaplan–Meier survival analysis demonstrated better outcomes in GS-inserted MVD groups (P = .020).

CONCLUSION:

The application of the GS insertion technique in MVD reduced first-year postoperative recurrence of TN, with similar complications rates compared with traditional MVD.
PERSONAL BRANDING
Authors: Patzlaff Airton Carlos , Patzlaff Priscila Maria Gregolin
Published: June 2024

O presente artigo efetua uma análise acerca das contribuições da psicologia e da sociologia no gerenciamento de marcas pessoais, buscando preencher algumas lacunas teóricas referentes à incipiente difusão do Personal Branding no meio acadêmico. Em uma perspectiva dialética, os autores discutidos nesta revisão de literatura inferem que, na mesma medida em que as empresas anseiam consolidar sua imagem corporativa, igualmente as pessoas almejam evidenciar sua identidade única e reforçar suas vantagens competitivas. Em face da crescente demanda pela diferenciação no mercado e da constante busca pelo autoconhecimento, os resultados desta pesquisa bibliográfica indicam que o Personal Branding vem ocupando um espaço importante enquanto ciência capaz de interpretar as singularidades pessoais e convertê-las em ativos mercadológicos. Entre as ferramentas capazes de otimizar os trabalhos em Personal Branding, destacam-se os estudos emanados da Psicologia Analítica e da Psicologia Social, tendo Jung e Goffman como expoentes teóricos de grande relevância nesta seara. Destarte, o arcabouço científico desses autores será apreciado no decorrer do artigo, evidenciando o protagonismo do inconsciente e do interacionismo simbólico na construção de personalidades autênticas e marcas duradouras.
Ιστορική αναδρομή στις παθήσεις των βλεφάρων και στη χειρουργική τους αποκατάσταση
Authors: Λάγιου Ευσταθία
Published: June 2024

Το βλέφαρο ως μία εξωτερική ανατομική δομή του ανθρωπίνου σώματος υποβαλλόταν σε χειρουργικές επεμβάσεις από την Ελληνική αρχαιότητα. Σύμφωνα με την αρχαία Ελληνική γραμματεία θεωρήθηκε ως ο προστάτης του οφθαλμού ο οποίος συμμετέχει στην όραση, τον ύπνο, την ασθένεια και τη προβολή του χαρακτήρα. Οι χειρουργικές επεμβάσεις ήταν αρχικά απλές τομές που ακολουθούσαν τις πτυχές του δέρματος και αργότερα την τάση του ταρσού. Ο 19ος αιώνας αποτέλεσε την απαρχή της σύγχρονης χειρουργικής των βλεφάρων αν και ακόμη ήταν δύσκολος ο διαχωρισμός των όγκων σε καλοήθεις και κακοήθεις, ενώ οι επεμβάσεις περιγράφονταν συνοπτικά και σε μερικές περιπτώσεις με κενά. Στην αυγή όμως του 20ου αιώνα τα κείμενα έγιναν σαφή, οι ανατομικές δομές περιεγράφηκαν με ακρίβεια, εισήχθη η διαφορική διάγνωση για τους όγκους και η χειρουργικές τεχνικές εξελίχθηκαν. Οι δύο παγκόσμιοι πόλεμοι συνετέλεσαν περαιτέρω στην ανάπτυξη της χειρουργικής των βλεφάρων. Οι τεχνικές απομακρύνθηκαν από τις τομές σε δέρμα, μύες και ταρσό και οδηγήθηκαν σε μετατροπές του λίπους της περιοχής, σε χρήση κρημνών και σε μικροχειρουργική μυών και απονευρώσεων. Η παρούσα διδακτορική διατριβή διαπραγματεύεται το θέμα της εξέλιξης της χειρουργικής των βλεφάρων με τη μέθοδο της βιβλιογραφικής ανασκόπησης (documentary research). Με τη χρήση λέξεων κλειδιά α) βλέφαρο, β) χειρουργική, γ) πλαστική, δ) βλεφαροπλαστική ε) ιστορία και στ) οφθαλμός και συνδυασμούς και παράγωγα στην Ελληνική, Γαλλική και Αγγλική γλώσσες πραγματοποιήθηκαν α) αποδελτίωση της ηλεκτρονικής βάσης της αρχαίας Ελληνικής και Ρωμαϊκής γραμματείας Thesaurus Linguae Graecae (TLG), β) έρευνα και αποθησαυρισμός του ηλεκτρονικού αποθετηρίου γραπτών έργων Google Books, γ) έρευνα και ανασκόπηση των άρθρων στην ηλεκτρονική βάση δεδομένων PubMed/MedLine και δ) on hand documentary research στη Βιβλιοθήκη Επιστημών Υγείας (Αθήνα). Η βιβλιογραφική ανασκόπηση επιχειρεί να καταγράψει την ιστορία της χειρουργικής των βλεφάρων ανά τους αιώνες και να παρουσιάσει τις σημαντικότερες προσωπικότητες που συνετέλεσαν στην εξέλιξη της. Λέξεις κλειδιά: πλαστική, επανορθωτική χειρουργική, οφθαλμολογία, ιστορία της ιατρικής.
Research on intelligent auxiliary assembly technology based on deep learning
Authors: Yan Wang , Wei Wei , Baitao Tang
Published: June 2024

Background Auxiliary assembly refers to guiding and prompting the assembly process to help operators complete complex assembly operations. Due to the complex structure of products, the similar shape of parts and human factors, the misassembly and missing assembly of parts still occur in the process of product assembly, so it is of great significance to detect the assembly correctness of complex products. Methods Aiming at the problem that manual inspection is inefficient and depends heavily on the level of inspectors in the process of complex product assembly inspection, this paper proposes an assembly correctness detection method based on deep learning. Through the three steps of view transformation, semantic segmentation and template matching, the automatic judgment of assembly errors such as wrong assembly, missing assembly and redundancy is realized, and the method is verified by the computer motherboard. Results Taking the computer motherboard as the verification object to test the correctness of assembly, the experimental re sults show that the perspective adjustment of the image after homography transformation is very obvious. The evaluation index of the semantic segmentation network detection object is calculated, and each accuracy meets the requirements of assembly correctness detection. A visualization module is also used to visually display the results of assembly correctness detection based on template matching. Conclusions The assembly correctness detection method can provide a guarantee for the manual assembly process and reduce the error rate of assembly. The machine vision detection technology can be used for automatic detection of assembly quality to improve the efficiency and automation level of detection.
A class of double phase problem without Ambrosetti-Rabinowitz-type growth condition: infinitely many solutions
Authors: Ge Bin , Han Yuhang , Cao Qinghai , Ren Haixin
Published: June 2024

This paper concerns with a class of double phase problem without
Ambrosetti-Rabinowitz-type growth condition.
Under reasonable hypotheses, we establish the existence of infinitely many solutions by using the
variant fountain theorems due to Zou \cite{71}.