bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAP4 kinase regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness
Authors: Sönmez Ece , Yan Shen , Lin Meng-Syuan , Baumgartner Martin 
Published: May 2024

Abstract

De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB.
Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling. Herein, we explored the expression and functional significance of CLSTN1 in MB. We found that CLSTN1 expression is decreased in primary MB tumors compared to tumor-free cerebellum or brain tissues. CLSTN1 is expressed in laboratory-established MB cell lines, where it localized to the plasma membrane, intracellular vesicular structures, and regions of cell-cell contact. The reduction of CLSTN1 expression significantly increased growth factor-driven invasiveness. Pharmacological inhibition of MAP4 kinases caused increased CLSTN1 expression and CLSTN1 accumulation in cell-cell contacts. Co-culture of tumor cells with astrocytes increased CLSTN1 localization in cell-cell contacts, which was further enhanced by MAP4K inhibition.
Our study revealed a repressive function of CLSTN1 in growth-factor-driven invasiveness in MB and its potential implication in homologous and heterologous interactions of the tumor with cells in its microenvironment.
Evaluation of Damage Discrimination in Dopaminergic Neurons Using Dopamine Transporter PET Tracer [18F]FECNT-d4
Authors: Tang Jie , Liu Congjin , Liu Chunyi , Hu Qianyue , Fang Yi , Chen Zhengping 
Published: May 2024

Abstract

Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands， positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson’s disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections.
Results: PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure.
Conclusion: Our findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson’s disease.
Investigation of the synergistic properties of raffinose and hesperidin on growth performance, immune parameters, oxidative status and hematology in juveniles of common carp (Cyprinus carpio)
Authors: Arshadi Ali , Heydarisalkhordeh Mohammadreza , Gisbert Enric 
Published: May 2024

Abstract

The goal of the present research was to assess how two immunomodulators, raffinose and hesperidin alone or in combination, affected the innate immune system and growth performance of common carp. Fish with an initial weight of 33.94 ± 1.45 g were fed the following experimental diets for 56 days: control (without supplementation, T1), 2.0 g kg− 1 raffinose (T2), 150 mg kg− 1 hesperidin (T3), and 2.0 g kg− 1 raffinose + 150 mg kg− 1 hesperidin (T4). Fish growth and feed efficiency, serum immunological parameters and hematological parameters were determined and compared with control after 56 days of feeding. The results of end feeding trial showed, Carp fed in combination with raffinose + hesperidin and control diets had the highest (62.63 ± 2.41) and the lowest (52.88 ± 1.10) final body weight, respectively. The highest growth performance, feed efficiency, total leukocyte counts (WBC), the non-specific humoral (lysozyme, total immunoglobulin, total protein, ACH50 and antioxidant status), and cellular (phagocytic capacity and respiratory burst activity) responses and other hematological parameters were noticed in fish fed mixture raffinose and hesperidin (P < 0.05). Feeding fish with supplemented diets (single or in combination) significantly showed enhanced antioxidant status: catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels in serum, meanwhile, values of antioxidant status enhanced by dietary immunostimulants administration in comparison with the control (P < 0.05). Overall, the combination of 2.0 g kg− 1 raffinose with 150 mg kg− 1 hesperidin is recommended for improving growth performance and immunological responses of Cyprinus carpio.
Cumulative sum analysis for evaluating learning curve of endoscopic lateral neck dissection
Authors: Chen Zhen-Xin , Zhao Xin-Ran , Deng Jie-Min , Cao Ying , Chen Jing-Bao , Pang Feng-Shun , Lin Zhan-Hong , Zhang Xiao-Bo , Xu Bo , Qin You 
Published: May 2024

Abstract

Objectives
Endoscopic lateral neck dissection (LND) can be a scarless procedure if a surgeon has performed a sufficient number of operations to become skilled at the techniques involved. Here, we examine the learning curve for a surgeon who performed 53 endoscopic LND procedures via chest approach.
Methods
Surgical outcomes for 53 patients with papillary thyroid carcinoma who underwent endoscopic LND via chest approach between February 2017 and November 2022 were retrospectively reviewed. The surgeon’s learning curve was evaluated using a cumulative sum graphic model (CUSUM).
Results
A CUSUM analysis was applied to 53 patients (10 males, 43 females) with a mean age of 41.4 y who underwent endoscopic LND via chest approach. The best model for the curve was determined to be a third-order polynomial equation as follows: CUSUMOT = − 0.007×patient number3-0.666×patient number2 + 55.721×patient number − 72.964. This equation has a high R2 value of 0.929. The peak operative time (OT) occurred at the 30th case. Consequently, the learning curve model was divided into two phases: phase 1 (1–30 cases) and phase 2 (31–53 cases). OT (307.9 ± 63.8 min vs. 232.4 ± 44.2 min, respectively; p < 0.001), blood loss (50 mL vs. 20 mL, respectively; p = 0.001), and complications (43.3% vs. 13.0%, respectively; p = 0.038) decreased significantly in phase 2 compared to phase 1.
Conclusions
The learning curve of endoscopic LND via chest approach was found to involve 30 cases. With greater experience, the surgery was completed with shorter OT and fewer complications. This approach is an alternative for patients who desire cosmesis. Furthermore, the present data and experience insights regarding endoscopic LND via chest approach may help other surgeons to pass the learning phase more safely.
CDK9 recruits HUWE1 E3 ligase to degrade RARα in a kinase independent manner and offers therapeutic opportunities for cutaneous T-cell lymphoma
Authors: Lu Ying , Luo Chen-Hui , Hu Li-Hong , Liu Jie-Yang , XIA Li , Zhou Li , Sun Ren-Hong , Chen Guoqiang , Yang Meng-Ying , Zhang Xue-Hong , Yang Xiao-Bao 
Published: May 2024

Abstract

Cutaneous T-cell lymphoma (CTCL) is a highly heterogeneous non-Hodgkin lymphoma that originates from the skin and invades the systemic hematopoietic system. Current skin-directed or systemic treatment including chemotherapy, retinoid analogs, interferons, HDAC inhibitors and monoclonal antibodies yielded limited clinical responses with high incidence of side effects, emphasizing urgent clinical need for more effective targeted therapy. Here, through small inhibitors library screening, we identify cyclin dependent kinase 9 (CDK9) as a driver for growth of CTCL. Single-cell RNA-seq data analyses reveal a CDK9high malignant T cell cluster with a unique actively proliferating feature. Pharmacological inhibition, genetic depletion or proteolysis targeting chimera (PROTAC)-medicated degradation of CDK9 significantly inhibit the growth of CTCL cells in vitro and in preclinical murine models. Beyond established kinase-dependent modulation on RNA polymerase II activity, CDK9 protein promotes degradation of retinoid acid receptor α (RARα) at lysine 360 in a kinase-independent manner via recruiting the HECT domain containing E3 ligase HUWE1. Depletion of CDK9 protein thus accumulates RARα and enhances the sensitivity of CTCL cells to all-trans retinoid acid (ATRA) which induces growth arrest and T cell differentiation. Co-administration of CDK9-PROTAC (GT-02897) with ATRA leads to synergistic attenuation of tumor growth in vitro and in xenograft models, providing a potential translational treatment for complete eradication of CTCL.
Incidence and Factors Associated with Immediate Adverse Neonatal Outcomes Among Emergency Obstetric Referrals in Labor at a Tertiary Hospital in Uganda: A Prospective Cohort Study
Authors: Okot Geoffrey , Omara Samuel , Kasujja Musa , Pebalo Francis , Baruti Petrus , Ubarnel Naranjo Almenares 
Published: May 2024

Abstract

Background
High incidences of adverse neonatal outcomes especially in resource-limited settings are multifactorial and vary from country to country and even within the same country, there are regional and institutional variations. In sub-Saharan Africa, the majority of adverse neonatal outcomes are intrapartum related, and studies in Uganda have shown that referral in labor is a major determinant of adverse neonatal outcomes. This study aimed to assess the incidence and factors associated with immediate adverse neonatal outcomes among emergency obstetric referrals in labor at a tertiary hospital in Eastern Uganda.
Materials and Methods
This was a prospective cohort study involving 265 women referred with obstetric emergencies in labor at Jinja Regional Referral Hospital over 3 months. Consecutive sampling was employed, and interviewer-administered questionnaires were used for data collection. Sociodemographic, referral, and obstetrical factors were recorded, and log-binominal regression analysis was used to establish risk ratios and associations with adverse neonatal outcomes.
Results
Of the 265 emergency obstetric referrals, 40% had adverse neonatal outcomes. Neonatal intensive care admission (27.6%), low Apgar score (23.8%), fresh stillbirth (11.3%), early-onset neonatal infection (6.8%), and early neonatal death (2.3%) were the common neonatal adverse outcomes. Factors significantly associated with adverse neonatal outcomes were; maternal age ≥ 35 years aRR = 1.72, (p = 0.004), APH aRR = 2.48, (p < 0.001) and nonreassuring fetal status aRR = 1.90, ( p < 0.001).
Conclusions
The study revealed a notable incidence of adverse neonatal outcomes, with the most common being admissions to neonatal intensive care units and low Apgar scores. Strong and statistically significant associations with adverse neonatal outcomes were observed for maternal age of 35 years or older, antepartum hemorrhage, and nonreassuring fetal status. Improving obstetric referral protocols is essential to ease the burden on tertiary care centers, enhance the birthing journey, and minimize risks for newborns.
Innate biosignature of treatment failure in human cutaneous leishmaniasis
Authors: Gómez Maria Adelaida , Belew Ashton Trey , Vargas Deninson , Giraldo-Parra Lina , Rebellón-Sanchez David , Alexander Theresa , Sayed Najib El 
Published: May 2024

Abstract

The quality and magnitude of the immune and inflammatory responses determine the clinical outcome of Leishmania infection, and contribute to the efficacy of antileishmanial treatments. However, the precise immune mechanisms involved in healing or in chronic immunopathology of human cutaneous leishmaniasis (CL) are not completely understood. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in CL patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. A composite score derived from the expression of 9 differentially expressed genes (common between Mo, Nφ and Eφ) was predictive of TF in this patient cohort for biomarker discovery. Similarly, machine learning models constructed using data from pre-treatment as well as post-treatment samples, accurately classified treatment outcome between cure and TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.
Caring for the carers: The influence of stress, burnout, and experiences of compassion on educational psychologists’ work-based motivations.
Authors: Sewell Alexandra , Coley Fiona , Gossman Peter , Park Jane 
Published: May 2024

Abstract

This study investigated the constructs of Compassion Satisfaction, Compassion Fatigue, Work-based Stress, and Burnout among EPs, aiming to understand their impact on the motivations (thoughts and actions) toward changes in working practices and contexts. The paper also introduces Compassion Fatigue/Satisfaction to the field of educational psychology, which has been extensively studied in other helping professions but still needs to be explored in the EP field. The multi-dimensional nature of the role of compassion in caring professional practice is explored. A cross-sectional descriptive design study asked 201 EP participants to complete a range of measures relating to the focus variables, capturing working-life contexts, patterns, and work-based motivations. The findings revealed that EPs experience higher levels of Compassion Satisfaction and Burnout, while Compassion Fatigue remains relatively low. Work-based stress was primarily attributed to a lack of control and autonomy rather than workload pressures. Burnout emerged as a significant predictor of motivations to seek a different job/career, explore alternative options, or make changes within the EP role. These findings contribute to understanding EPs' working-life experiences and offer insights into the factors influencing their motivations and well-being, paralleling similar findings in the teaching profession. The results highlight the importance of addressing work-related stress and burnout to support EPs and enhance professional practices and how compassion satisfaction may be harnessed as a mediating variable.
Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft issues
Authors: Paul Arghya , Shamiiya Yasmeen , Chakraborty Aishik , Zahid Alap , Bainbridge Nicholas , Guan Jingyuan , Feng Biao , Pjontek Dominic , Chakrabarti Subrata 
Published: May 2024

Abstract

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers, ability to carry low solubility drugs, and ability to control drug release to the surrounding tissues. Herein, we introduce a visible light-triggered in situ-gelling drug delivery system (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures with a hydrophilic periphery, while the hydrophobic core helps load hydrophobic drugs. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules, such as the amino acids of gelatin, via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with Erythromycin, a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in injectable and sprayable forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics in soft tissues.
Cannabis Hyperemesis Syndrome: Case Study
Authors: Horst Roberta , Marques Lucas , Otani Victor , Sanches Marsal , Uchida Ricardo 
Published: May 2024

Abstract

The rising rates of cannabis abuse have coincided with the recognition of a novel clinical condition known as Cannabinoid Hyperemesis Syndrome (CHS). CHS is characterized by chronic cannabis use, cyclic episodes of nausea and vomiting, and frequent use of hot baths in an attempt to alleviate symptoms. This paper presents a case report of CHS, in which a patient referred to as P.M. was diagnosed with this syndrome. It delves into cannabis consumption as both a substance of abuse and for therapeutic purposes, as well as its connection with Cyclical Vomiting Syndrome. The significance of disseminating general medical knowledge about this syndrome is underscored, especially considering the increasing prevalence of cannabis consumption worldwide. This increase heightens the likelihood of medical professionals from various disciplines encountering cases akin to the one reported here. Thus, it emphasizes the necessity for improved diagnosis and management.
Transcutaneous electrical acupoint stimulation shortens the time to extubation after surgery: a systemic review and meta-analysis
Authors: Zhong Yushan , Zhu Yabing , Wang Yufei , Zhou Xiang , Wang Lu , Tu Qing , Huang Lina 
Published: May 2024

Abstract

Background
The delayed extubation time after often accompany with many adverse events. The purpose of the study was to evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) on the extubation time and adverse events after surgery.
Methods
The randomized controlled trials related to apply TEAS during perioperative period were searched in the database of Cochrane Library, PubMed, Web of Science, Embase, CNKI from the inception to Apil 2024. The main outcome was the extubation time after surgery, and the secondary outcomes were the consumption of analgesics, adverse events during extubation, time of surgery and anesthesia. Data were pooled and analyzed by RevMan 5.3 software.
Results
The study enrolled 9 studies, including 1039 participants. The current results indicated that the application of TEAS effectively shortened the extubation time after surgery (SMD − 0.55 95%-CI [-0.84; -0.26], P = 0.0002), as well as time to recall after surgery (SMD − 0.18 95%-CI [-0.32; -0.03], P = 0.02). TEAS also reduced the consumption of remifentanail during surgery (SMD − 1.15 95%-CI [-1.72, -0.59], P < 0.00001). In addition, TEAS reduced the incidence of PONV (RR 0.49, 95%-CI [0.32, 0.74], P = 0.007), cough (RR 0.53, 95%-CI [0.31, 0.90], P = 0.02) and agitation (RR 0.31, 95%-CI [0.14, 0.67], P = 0.003) during extubation period. While TEAS have no effects on surgical (SMD 0.12, 95%-CI [-0.01, 0.26], P = 0.07) and anesthesia time (SMD 0.15, 95%-CI [-0.15, 0.45], P = 0.32).
Conclusions
The study suggested that application of TEAS effectively shortened the time to extubation and recall after surgery. TEAS also reduce the consumption of analgesics, and adverse events after surgery, but have no effects on surgical and anesthesia time. Which may positively improve the enhanced recovery of patients after surgery.
Trial registration
CRD42018099275
Microfinance Programme Sustainability Analysis Using a Complex System Approach
Authors: Gunawan Indra , Chasanah Nur 
Published: May 2024

Abstract

This study aims to analyse the sustainability of a microfinance programme project in Indonesia via a complex systems approach by using a case study and applied thematic analysis. Data are collected by document review, observation, interviews and focus group discussions. The results reveal some issues that arise as a result of closure of the programme and the actions taken to cope with those issues that led to sustainability of the microfinance institution. The issues are related to project governance, accountability, capital and profitability, competition and empowerment. The analysis shows that the move towards a sustainable project presents characteristics of a complex system, including interconnectedness, adaptation, feedback, self-organisation, and emergence (IAFSE). These findings have implications for microfinance sustainability management and microfinance programme design. Furthermore, a model of sustainable microfinance projects and a framework to sustain microfinance programme (institutions) using a complex system approach are proposed.