bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoglin (CD105) and proliferation index in recurrent glioblastoma treated with anti-angiogenic therapy
Authors: Bastos António G. P. , Carvalho Bruno , Silva Roberto , Leitão Dina , Linhares Paulo , Vaz Rui , Lima Jorge 
Published: September 2022

IntroductionCD105 is an angiogenic biomarker that is useful to determine the microvessel density (MVD) within a tumor, namely, in highly vascularized tumors like glioblastoma (GBM). However, its expression has shown inconsistent associations with the prognosis of GBM patients. The aim of this study was to evaluate the value of MVD-CD105 (microvessel density assessed with anti-CD105 antibody) and Ki-67 (proliferation index marker) as prognostic and therapy response biomarkers, specifically in primary tumors and in recurrent tumoral specimens of a cohort of GBM patients treated with bevacizumab upon recurrence.Materials and methodsWe conducted a retrospective study of 102 consecutive GBM patients treated with bevacizumab upon recurrence at CHUSJ between 2010 and 2017. Demographic, clinical, and survival data of all patients were collected and analyzed. The tissue expression of MVD-CD105 and Ki-67 in primary and recurrent specimens was correlated with progression-free survival after temozolomide (PFS-1), progression-free survival after bevacizumab (PFS-2), and overall survival (OS).ResultsThe immunohistochemical expression score for MVD-CD105 was similar in primary and recurrent tumoral specimens (mean scores of 15 and 16, respectively). Likewise, the mean Ki-67 expression was similar in primary (mean of 31% of tumor cells) and recurrent tumoral specimens (mean of 29% of tumor cells). MVD-CD105 expression in primary tumors had no impact on PFS-1, PFS-2, or OS. At recurrence, patients whose tumors showed increased MVD-CD105 had worse median PFS-2 (2 vs. 8 months, p = 0.045) and OS (17 vs. 26 months, p = 0.007) compared to those whose tumors showed lower MVD-CD105. CD105 tumoral pattern and localization had no impact on prognosis. Ki-67 expression was not associated with differences in survival outcomes.ConclusionIn this study, higher MVD-CD105 expression in recurrent GBM patients seems to be associated with a worse PFS-2 and OS while portending no prognostic significance in the primary tumors. This highlights the importance of keeping track of the molecular evolution of the tumor over the course of the disease.
The immune escape signature predicts the prognosis and immunotherapy sensitivity for pancreatic ductal adenocarcinoma
Authors: Lu Hao , Zheng Li-Yan , Wu Ling-Yan , Chen Jun , Xu Na , Mi Sui-Cai 
Published: September 2022

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide. Immune escape is considered to be a reason for immunotherapy failure in PDAC. In this study, we explored the correlation between immune escape-related genes and the prognosis of PDAC patients.Methods1163 PDAC patients from four public databases, including The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Array-express, and Gene Expression Omnibus (GEO), were included in our study. Cox regression analysis was used to identify the 182 immune genes which were significantly associated with overall survival (OS). And then we established an immune escape-related gene prognosis index (IEGPI) score using several datasets as the training cohort and validated it using the validation cohort. Kaplan-Meier (KM) and Cox regression analysis were used to detect the relationship of IEGPI score with OS. We further explored the relationship between the IEGPI and immune indexes. And the prediction value of response for immunotherapy in Tumor Immune Dysfunction and Exclusion (TIDE) dataset.ResultsWe establish an IEGPI score based on 27 immune escape genes which were significantly related to the prognosis of OS in PDAC patients. Patients in the high-IEGPI group had a significantly worse overall survival rate compared with that in the low-IEGPI groups by KM curves and cox-regression. 5 of the 32 cancer types in TCGA could be significantly distinguished in survival rates through the low- and high-IEGPI groups. Moreover, the correlation between the IEGPI score was negatively correlated with an immune score in several datasets. And higher IEGPI better recurrence-free survival (RFS) and OS in the patients after patients were treated with both PD-1 and CTLA4 in the public datasets (P&lt;0.05). Intriguingly, by using RT-PCR, we verified that the gene of PTPN2, CEP55, and JAK2 were all higher in the BxPC-3 and PANC-1 than HPDE5 cells. Lastly, we found that the IEGPI score was higher in K-rasLSL.G12D/+, p53LSL.R172H/+, Pdx1Cre (KPC) mice model with anti-PD-L1 than that without anti-PD-L1.ConclusionUsing the immune escape-related genes, our study established and validated an IEGPI score in PDAC patients from the public dataset. IEGPI score has the potential to serve as a prognostic marker and as a tool for selecting tumor patients suitable for immunotherapy in clinical practice.
Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs
Authors: Rowlison de Ortiz Avery , Belda Beatriz , Hash Jon , Enomoto Masataka , Robertson James , Lascelles B. Duncan X. 
Published: September 2022

BackgroundAccelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain.MethodsThis was an observational, non-interventional study in healthy dogs and dogs with OA-pain. All dogs were outfitted with the PetPace collar and the Actical monitor simultaneously for 14 days. Output from these devices was compared (correlations), and output from the PetPace device was used to explore differences between groups across the activity and vital sign outputs (including calculated heart rate variability indices).ResultsThere was moderate correlation between the PetPace collar and Actical monitor output (R2= 0.56,p&lt; 0.001). Using data generated by the PetPace collar, OA-pain dogs had lower overall activity counts and spent less time standing than healthy dogs. Healthy dogs spent more time at higher activity levels than OA-pain dogs. Certain heart rate variability indices in OA-pain dogs were lower than in healthy dogs.Conclusions and clinical relevanceThe results of this study suggest that the PetPace collar can detect differences between healthy dogs and those with OA-pain, and that OA-pain negatively impacts overall activity levels in dogs, and especially higher intensity activity.
Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study
Authors: Suzuki Hiromi , Yasuda Saneyuki , Htun Yinmon , Aye Nant San San , Oo Hnin , Oo Thet Paing , Htut Zaw Lin , Koyano Kosuke , Nakamura Shinji , Kusaka Takashi 
Published: September 2022

BackgroundNeonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET).MethodsThis retrospective cohort study was conducted at the Central Women’s Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer’s rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth.ResultsGroups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8–67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively).ConclusionThe management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.
Functional characterization of cannabidiol effect on the serotonergic neurons of the dorsal raphe nucleus in rat brain slices
Authors: Mendiguren Aitziber , Aostri Erik , Alberdi Elena , Pérez-Samartín Alberto , Pineda Joseba 
Published: September 2022

Cannabidiol (CBD), the main non-psychoactive cannabinoid found in the cannabis plant, elicits several pharmacological effects via the 5-HT1A receptor. The dorsal raphe nucleus (DRN) is the main serotonergic cluster in the brain that expresses the 5-HT1A receptor. To date, the effect of CBD on the neuronal activity of DRN 5-HT cells and its interaction with somatodendritic 5-HT1A autoreceptors have not been characterized. Our aim was to study the effect of CBD on the firing activity of DRN 5-HT cells and the 5-HT1A autoreceptor activation by electrophysiological and calcium imaging techniques in male Sprague–Dawley rat brain slices. Perfusion with CBD (30 μM, 10 min) did not significantly change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (50–100 μM, 1 min). However, in the presence of CBD (30 μM, 10 min), the inhibitory effects of 8-OH-DPAT (10 nM) and ipsapirone (100 nM) were reduced by 66% and 53%, respectively. CBD failed to reverse ipsapirone-induced inhibition, whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30 nM) completely restored by 97.05 ± 14.63% the firing activity of 5-HT cells. Administration of AM251 (1 µM), MDL100907 (30 nM), or picrotoxin (20 μM) did not change the blockade produced by CBD (30 μM) on ipsapirone-induced inhibition. Our study also shows that CBD failed to modify the KCl (15 mM, 4 min)-evoked increase in [Ca2+]i or the inhibitory effect of ipsapirone (1 μM, 4 min) on KCl-evoked [Ca2+]i. In conclusion, CBD does not activate 5-HT1A autoreceptors, but it hindered the inhibitory effect produced by selective 5-HT1A receptor agonists on the firing activity of DRN 5-HT cells through a mechanism that does not involve CB1, 5-HT2A, or GABAA receptors. Our data support a negative allosteric modulation of DRN somatodendritic 5-HT1A receptor by CBD.
Self-supervised neural network improves tri-exponential intravoxel incoherent motion model fitting compared to least-squares fitting in non-alcoholic fatty liver disease
Authors: Troelstra Marian A. , Van Dijk Anne-Marieke , Witjes Julia J. , Mak Anne Linde , Zwirs Diona , Runge Jurgen H. , Verheij Joanne , Beuers Ulrich H. , Nieuwdorp Max , Holleboom Adriaan G. , Nederveen Aart J. , Gurney-Champion Oliver J. 
Published: September 2022

Recent literature suggests that tri-exponential models may provide additional information and fit liver intravoxel incoherent motion (IVIM) data more accurately than conventional bi-exponential models. However, voxel-wise fitting of IVIM results in noisy and unreliable parameter maps. For bi-exponential IVIM, neural networks (NN) were able to produce superior parameter maps than conventional least-squares (LSQ) generated images. Hence, to improve parameter map quality of tri-exponential IVIM, we developed an unsupervised physics-informed deep neural network (IVIM3-NET). We assessed its performance in simulations and in patients with non-alcoholic fatty liver disease (NAFLD) and compared outcomes with bi-exponential LSQ and NN fits and tri-exponential LSQ fits. Scanning was performed using a 3.0T free-breathing multi-slice diffusion-weighted single-shot echo-planar imaging sequence with 18 b-values. Images were analysed for visual quality, comparing the bi- and tri-exponential IVIM models for LSQ fits and NN fits using parameter-map signal-to-noise ratios (SNR) and adjusted R2. IVIM parameters were compared to histological fibrosis, disease activity and steatosis grades. Parameter map quality improved with bi- and tri-exponential NN approaches, with a significant increase in average parameter-map SNR from 3.38 to 5.59 and 2.45 to 4.01 for bi- and tri-exponential LSQ and NN models respectively. In 33 out of 36 patients, the tri-exponential model exhibited higher adjusted R2 values than the bi-exponential model. Correlating IVIM data to liver histology showed that the bi- and tri-exponential NN outperformed both LSQ models for the majority of IVIM parameters (10 out of 15 significant correlations). Overall, our results support the use of a tri-exponential IVIM model in NAFLD. We show that the IVIM3-NET can be used to improve image quality compared to a tri-exponential LSQ fit and provides promising correlations with histopathology similar to the bi-exponential neural network fit, while generating potentially complementary additional parameters.
The impact of different exercise protocols on rat soleus muscle reinnervation and recovery following peripheral nerve lesion and regeneration
Authors: Di Palma Michael , Ambrogini Patrizia , Lattanzi Davide , Brocca Lorenza , Bottinelli Roberto , Cuppini Riccardo , Pellegrino Maria A. , Sartini Stefano 
Published: September 2022

Background: Incomplete functional recovery following traumatic peripheral nerve injury is common, mainly because not all axons successfully regenerate and reinnervate target muscles. Exercise can improve functional outcomes increasing the terminal sprouting during the muscle reinnervation. However, exercise is not a panacea per se. Indeed, the type of exercise adopted dramatically impacts the outcomes of rehabilitation therapy. To gain insight into the therapeutic effects of different exercise regimens on reinnervation following traumatic nerve lesion, we evaluated the impact of different clinically transferable exercise protocols (EPs) on metabolic and functional muscle recovery following nerve crush.Methods: The reinnervation of soleus muscle in adult nerve-crushed rats was studied following 6 days of different patterns (continuous or intermittent) and intensities (slow, mid, and fast) of treadmill running EPs. The effects of EPs on muscle fiber multiple innervation, contractile properties, metabolic adaptations, atrophy, and autophagy were assessed using functional and biochemical approaches.Results: Results showed that an intermittent mid-intensity treadmill EP improves soleus muscle reinnervation, whereas a slow continuous running EP worsens the functional outcome. However, the mid-intensity intermittent EP neither enhanced the critical mediators of exercise-induced metabolic adaptations, namely, PGC-1α, nor improved muscle atrophy. Conversely, the autophagy-related marker LC3 increased exclusively in the mid-intensity intermittent EP group.Conclusion: Our results demonstrated that an EP characterized by a mid-intensity intermittent activity enhances the functional muscle recovery upon a nerve crush, thus representing a promising clinically transferable exercise paradigm to improve recovery in humans following peripheral nerve injuries.
Team idiosyncratic deals and team breakthrough innovation: Based on the perspective of input-process-output model
Authors: Fan Zili , Sun Hao , Wang Lijun , Zhu Mengting , Peng Ting 
Published: September 2022

PurposeAs a new human resource management practice, idiosyncratic deals are personalized employment arrangements negotiated between employees and employers and intended to benefit them both. It plays an important role in attracting, retaining and motivating employees to promote breakthrough innovation. Based on the input-process-output (I-P-O) model, this paper examines the relationship between team idiosyncratic deals and team breakthrough innovation, the mediating role of team exploratory-exploitative knowledge sharing, and the moderating roles of team transactive memory systems and team cognitive flexibility.Participants and methodsIn order to reduce the effects of common method biases and causal lag effect, this study is divided into three stages for data collection, with a time interval of 1 month. Eighty teams (406 employees) from six enterprises in Shanghai and Hangzhou were selected as samples, and the hypothesis test was carried out by hierarchical regression analysis, bootstrap, and Johnson-Neyman method.ResultsThe results show that higher team idiosyncratic deals are associated with higher team breakthrough innovation through higher team exploratory-exploitative knowledge sharing, and that team transactive memory systems and team cognitive flexibility positively moderate the mediating effect of team exploratory-exploitative knowledge sharing in the relationship between team idiosyncratic deals and team breakthrough innovation in the first stage and the second stage, respectively. Under the joint effect of high team transactive memory systems and high team cognitive flexibility, the mediating effect of team exploratory-exploitative knowledge sharing is stronger.ConclusionThe research results break through the previous research framework of social exchange theory, and I-P-O model to explore the influence mechanism of team idiosyncratic deals, in order to promote the sustainable growth of team breakthrough innovation through this non-standard work arrangement. It is hoped that this research can inspire modern enterprises to create team idiosyncratic deals for valuable teams engaged in breakthrough innovation, which are more conducive to give full play to their heterogeneous talents, and finally help enterprises break through the industry bottleneck and win the market competition.
Going beyond the DSM in predicting, diagnosing, and treating autism spectrum disorder with covarying alexithymia and OCD: A structural equation model and process-based predictive coding account
Authors: Edwards Darren J. 
Published: September 2022

BackgroundThere is much overlap among the symptomology of autistic spectrum disorders (ASDs), obsessive compulsive disorders (OCDs), and alexithymia, which all typically involve impaired social interactions, repetitive impulsive behaviors, problems with communication, and mental health.AimThis study aimed to identify direct and indirect associations among alexithymia, OCD, cardiac interoception, psychological inflexibility, and self-as-context, with the DV ASD and depression, while controlling for vagal related aging.MethodologyThe data involved electrocardiogram (ECG) heart rate variability (HRV) and questionnaire data. In total, 1,089 participant's data of ECG recordings of healthy resting state HRV were recorded and grouped into age categories. In addition to this, another 224 participants completed an online survey that included the following questionnaires: Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Toronto Alexithymia Scale 20 (TAS-20); Acceptance and Action Questionnaire (AAQII); Depression, Anxiety, and Stress Scale 21 (DAS21); Multi-dimensional Assessment of Interoceptive Awareness Scale (MAIA); and the Self-as-Context Scale (SAC).ResultsHeart rate variability was shown to decrease with age when controlling for BMI and gender. In the two SEMs produced, it was found that OCD and alexithymia were causally associated with autism and depression indirectly through psychological inflexibility, SAC, and ISen interoception.ConclusionThe results are discussed in relation to the limitations of the DSM with its categorical focus of protocols for syndromes and provide support for more flexible ideographic approaches in diagnosing and treating mental health and autism within the Extended Evolutionary Meta-Model (EEMM). Graph theory approaches are discussed in their capacity to depict the processes of change potentially even at the level of the relational frame.
Underuse of recommended treatments among people living with treatment-resistant psychosis
Authors: Lappin Julia M. , Davies Kimberley , O'Donnell Maryanne , Walpola Ishan C. 
Published: September 2022

BackgroundInternational guidelines recommend that individuals with treatment-resistant psychosis must be treated with clozapine. ECT has also been reported to improve symptom profiles. Identification of clozapine and/or ECT use in real-world practice enables understanding of the extent to which this evidence-base is implemented.SettingStatewide public health tertiary referral service, the Tertiary Referral Service for Psychosis (TRSP), NSW, Australia.ObjectivesTo (i) describe clinical characteristics of individuals with treatment-resistant psychosis and to detail the proportion who had received a trial of clozapine or ECT at any point during their illness course; (ii) describe the characteristics of the treatment trials in both those currently on clozapine and those previously on clozapine; (iii) document reasons in relevant individuals why clozapine had never been used.MethodsAll TRSP clients who met the criteria for treatment resistance (TR) were included. A detailed casenote review was conducted to examine whether clozapine and/or ECT had ever been prescribed. Characteristics of clozapine and ECT trials were documented. Tertiary service treatment recommendations are described.FindingsThirty-six of 48 individuals had TR. They had marked clinical and functional impairment. A minority were currently receiving clozapine (n = 14/36). Most had received a clozapine trial at some point (n = 32/36). Most experienced persistent clinical symptoms while on clozapine (n = 29/32). Clozapine plasma levels were very rarely reported (4/32). Augmentation and antipsychotic polypharmacy were common among those currently on clozapine. The median clozapine trial duration was 4.0 (IQR: 3.0–20.3) months in individuals previously prescribed clozapine. Reasons for clozapine discontinuation included intolerable side effects (n = 10/18) and poor adherence (n = 7/18). One-quarter of TR individuals had trialed ECT (n = 9/36). Tertiary service recommendations included routine plasma monitoring to optimize dose among people currently on clozapine; clozapine retrial in those previously treated; and clozapine initiation for those who had never received clozapine. ECT was recommended to augment clozapine and as an alternative where clozapine trial/retrial was not feasible.ConclusionAmong people with TR referred to a tertiary service, clozapine and ECT were underutilized. Clozapine trials are typically terminated without an adequate trial. Strategies to optimize the use of clozapine therapy and ECT in clinical settings are needed to increase the therapeutic effectiveness of evidence-based therapies for treatment-resistant psychosis.