bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Hypo Fractionated Stereotactic Radiosurgery in Facial Nerve Schwannoma: a Single Institution Retrospective Case Series
Authors: Fatima Nida , Dine Anna La , Barnard Zachary R , Ko Katherine , Peng Kevin , Slattery William H , Lekovic Gregory P 
Published: December 2021

Abstract
Background: In the current era of modern neurosurgery, the treatment strategies have been shifted to “nerve-preservation approaches” for achieving a higher facial and hearing function preservation rate following facial nerve tumors.Objective: We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypo fractionated stereotactic radiosurgery (hfSRS).Methods: Retrospective chart review of a prospectively maintained database search was conducted. Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, California., USA) for FNS were included. Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann (HB) and Gardner-Robertson scale, and adverse radiation effects. SPSS 23 was used to perform statistical analysis.Results: With an institutional board review approval, we retrospectively identified 5 patients with FNS [4 intracranial (80%) and 1 extracranial (20%)] treated with hfSRS (2011-2019). Patients received definitive SRS in 3 patients (60.0%) wile adjuvant to surgical resection in 2 patients (40.0%). A median tumor volume of 7.5 cm3 (range, 1.5-19.6 cm3) received a median prescription dose of 23.2 Gy (range, 21-25 Gy) administered in median of 3 fractions (range, 3-5 session). With a median radiographic follow-up of 31.4 months (range, 13.0-71.0 months) and clinical follow-up of 32.6 months (range, 15.1-72.0 months), the local tumor control was 100.0%. At last clinical follow-up, the facial nerve function improved or remained unchanged HB I-II in 80.0% of the patients, while the hearing nerve function improved or remained stable in 100.0% (Gardner-Robertson I-II) of the patients. Temporary clinical toxicity was seen in 3 patients (60.0%) which resolved. None of the patient developed adverse radiation effect.Conclusion: From our case series, hfSRS in FNS seems to be safe and efficacious in terms of local tumor control, and improved facial and hearing nerve function.
Paeoniflorin Ameliorates Cognitive Impairment in Parkinson’s Disease via JNK/p53 Signaling
Authors: He Zhu-qing , Huan Peng-fei , Wang Li , He Jian-cheng 
Published: December 2021

Abstract
Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. It also exhibits neuroprotective effects in Alzheimer’s disease (AD) via the ROS-JNK-p53 pathway. However, it is not clear if it has neuroprotective effects against cognitive impairment in Parkinson’s disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect cognitive impairment in PD. Then, we experimentally validated our findings. The core genes of the PPI network include MAPK8 (JNK), TP53, CASP3 (caspase-3), protein-95 (PSD95), and SYN. Pathway enrichment analysis revealed that genes involved in apoptosis and MAPK signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved MPTP-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating postsynaptic density PSD95 as well as synaptophysin (SYN) protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved cognitive impairment in PD by inhibiting JNK/p53 signaling pathway.
Preferred Offloading Modalities for Management of Diabetic Foot Ulcers in Private Clinical Settings: A Survey of Australian Podiatrists
Authors: Erasmus Adriaan , Melek Michael , Ho Malia 
Published: December 2021

Abstract
Background Diabetic peripheral neuropathy is a common complication of diabetes mellitus. Neuropathy predisposes patients to diabetic foot ulcers (DFU) due to the loss of protective sensation and associated deformities. Management of foot ulcers are multifactorial, but pressure offloading can be considered as one of the most important aspects of management. According to IWGDF Guidelines, non-removable knee-high offloading devices are recommended as the 1st line of treatment for these ulcers. However, this is a very underutilised treatment modality. This study aimed to evaluate the practitioner preferred offloading modalities and reasons for their preference. Methods This project was approved by the university’s human research ethics committee. An online survey was distributed amongst Australian podiatrist via an industry related social media group. The survey collected simple demographical information, management strategies, preferred offloading modalities for the management of diabetic foot ulcers and reasons for their preferred method. Results Sixty-three podiatrists completed the survey with the majority practicing in private clinics. All practitioners treat diabetic foot ulcers regularly with most participants treating up to ten ulcer cases per week and 14% of participants treating more than 20 ulcers per week. Contrary to the IWGDF guidelines, standard therapeutic footwear was the most preferred method of management for the treatment of diabetic foot ulcers, with ease of use reported as the main reason for practitioners using this modality. Non-compliance to the use of non-removable knee-high offloading devices include perceived patient non-compliance and poor tolerance. Conclusion This study shows that practitioners’ offloading strategies do not adhere to the IWGDF guidelines. The reasons for not adhering to the guidelines seems to be a clinical practicality rather than evidence-based practice. Reasons for choosing a management strategy is multi-factorial (not just reducing plantar pressures). Further studies may be required to evaluate the effectiveness of therapeutic footwear in ulcer healing, taking into consideration other factors such as practitioner and patient preference, clinical practicality, and access to support. Based on the findings, this study provides suggestions on how to overcome the barriers that prevent podiatrist from adhering to the recommendations of the IWGDF when selecting offloading devices in general clinical practice.
Association of Aortic Distensibility and Left Ventricular Function in Patients With Stenotic Bicuspid Aortic Valve and Preserved Ejection Fraction: A CMR study
Authors: Pan Yijun , Lin Jiang , Wang Yongshi , Li Jun , Xu Pengju , Zeng Mengsu , Shan Yan 
Published: December 2021

Abstract
To determine the relationship between aortic distensibility and left ventricular (LV) remodeling, myocardial strain and blood biomarkers in patients with stenotic bicuspid aortic valve (BAV) and preserved ejection fraction (EF) by cardiovascular magnetic resonance (CMR). 43 stenotic BAV patients were prospectively selected for 3.0T CMR. Patients were divided into LV remodeling group (LV mass /volume ≥ 1.15, n=21) and non-remodeling group (LV mass/volume < 1.15, n=22). Clinical characteristics, biochemical data including cardiac troponin T(cTNT), N-terminal pro-B type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme were noted. Distensibility of middle ascending aorta (mid-AA) and proximal descending aorta, LV structural and functional parameters, global and regional myocardial strain were measured. Compared to non-remodeling group, LV remodeling group had significantly decreased LV global strain (radial: 26.04±8.70 % vs. 32.92±7.81 %, P=0.009; circumferential: -17.20±3.38 % vs. -19.65±2.34 %, P=0.008; longitudinal: -9.13±2.34 % vs. -11.63±1.99 %, P＜0.001), while radial and circumferential strain were significantly reduced at the base (radial: 28.52±9.47 % vs. 39.65±10.33 %, P=0.001; circumferential: -14.45±2.97 % vs. -17.22±2.38 %, P=0.002), longitudinal strain was significantly reduced at all regions (basal: -5.79±3.43 % vs. -8.65±2.42 %, P=0.003; mid: -8.62±2.21 % vs. -11.33±2.58 %, P=0.001; apical : -12.79±2.49 % vs. -15.04±2.20 %, P=0.003). In addition, mid-AA distensibility was independently associated with LV remodeling (β=-0.282, P=0.003), and it was also significantly correlated with LV global strain (radial: r=0.392, P=0.009; circumferential: r=-0.348, P=0.022; longitudinal: r=-0.333, P=0.029), cTNT (r=-0.333, P=0.029) and NT-proBNP (r= -0.440, P=0.003). In this cohort with stenotic BAV and preserved EF, mid-AA distensibility is found significantly associated with LV dysfunction, which may be an important factor for predicting adverse cardiovascular events and a potential therapeutic target to prevent heart failure.
Neurochemical profiles of the anterior temporal lobe predict response of repetitive transcranial magnetic stimulation on semantic processing
Authors: Jung JeYoung , Williams Stephen , Nezhad Faezeh Sanae , Ralph Matthew Lambon 
Published: December 2021

Abstract

The effect of repetitive transcranial magnetic stimulation can vary considerably across individuals, but the reasons for this still remain unclear. Here, we investigated whether the response to continuous theta-burst stimulation (cTBS) – an effective protocol for decreasing cortical excitability – related to individual differences in glutamate and GABA neurotransmission. We applied cTBS over the anterior temporal lobe (ATL), a hub for semantic representation, to explore the relationship between the baseline neurochemical profiles in this region and the response to this stimulation. Our experiments revealed that non-responders (subjects who did not show an inhibitory effect of cTBS on subsequent semantic performance) had higher excitatory-inhibitory balance (glutamate + glutamine/GABA ratio) in the ATL, which led to up-regulated task-induced regional activity as well as increased ATL-connectivity with other semantic regions compared to responders. These results disclose that the baseline neurochemical state of a cortical region can be a significant factor in predicting responses to cTBS.
Barriers and Facilitators to Implementing a Stepped Care Cognitive-Behavioral Therapy for Insomnia in Cancer Patients: A Qualitative Study.
Authors: Savard Josée , Filion Catherine , Gagnon Marie-Pierre , Caplette-Gingras Aude , Bélanger Lynda , Morin Charles M. 
Published: December 2021

Abstract
BackgroundInsomnia affects between 30 to 60% of cancer patients and tends to become chronic when left untreated. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended first-line treatment for cancer-related insomnia. Yet, this treatment is not readily accessible. A stepped care intervention beginning with a self-administered (web-based) intervention appears to be a promising cost-effective approach to offer CBT-I in routine cancer care as compared to a standard face-to-face therapy. This qualitative study investigated current practices in the assessment and management of insomnia in five hospitals offering cancer care and identified the barriers and facilitators to the implementation of a stepped care CBT-I in these clinical settings.MethodsNine focus groups composed of a total of 43 clinicians (e.g., physicians, nurses, nurse navigators, technologists, psychologists) and administrators, as well as 10 cancer patients were held. The Consolidated Framework for Implementing Research was used to develop the semi-structured interview and analyze the data.ResultsSleep difficulties are not systematically discussed in clinical practice and when a treatment is offered, most often, it is a pharmacological one. Based on the Consolidated Framework for Implementing Research, barriers to the implementation of a stepped care CBT-I included individual characteristics (e.g. lack of knowledge about CBT-I among cancer care providers, patients’ comorbidities and preferences); intervention characteristics (e.g., lack of internet access); inner setting characteristics (e.g., lack of time and resources, resistance to change); and process factors (e.g., need for prior training and engagement of all stakeholders). Facilitators were related to individual characteristics (e.g. strong beliefs in the efficacy of CBT-I); intervention characteristics (e.g. web-based format that increases accessibility at a lower cost, short- and long-term effects of CBT-I); and process factors (e.g. high motivation and commitment to offer a new service to patients).Conclusions﻿This qualitative study confirms the need to better address insomnia in routine cancer care and suggests that, while some barriers were mentioned, the implementation of a stepped care CBT-I is feasible provided that some conditions are met such as prior training and engagement of all stakeholders from the outset.
An Open-Label Clinical Trial of Oral Transmucosal Haloperidol and Olanzapine in the Treatment of Terminal Delirium
Authors: Lyu Xiao Juan , Kan Adrian David , Chong Poh Heng , Lin Keegan , Koh Yung Hua , Yeo Zhi Zheng 
Published: December 2021

Abstract
Background : The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm. Methods : 80 patients with a prognosis of 3 days or less will be recruited for an open-label randomized control trial. The two arms compare oral-transmucosal haloperidol 2.5mg vs olanzapine 5mg over 72 hours. The severity of agitation, delirium and toxicities of treatments will be compared at the 24 th , 48 th and 72 nd hour after drug administration. Discussion : This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures are discussed. Trial registration : ClinicalTrials.gov, NCT04750395. Registered 11 February 2021, https://clinicaltrials.gov/ct2/show/NCT04750395
Association of Sonographic Features of Unifocal Papillary Thyroid Carcinoma With Cervical Lymph Node Metastasis
Authors: Zhou Liuhua , Zhu Qiaodan , Yao Jincao , Yang Chen , Xu Dong 
Published: December 2021

Abstract
Background Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid carcinoma. We aim to evaluate the association of sonographic features of PTC and cervical lymph node metastasis (CLNM) at the initial surgery. Methods Clinical information, ultrasonographic measurements and features for 1335 patients were acquired in data collection. Univariate analysis was performed to test CLNM by 7 independent variables. Receiver operating characteristic (ROC) curve was created to evaluate the diagnostic performance. Results Univariate analysis showed that gland, location, aspect ratio, margin and echogenic foci were independently associated with CLNM metastatic status (P<0.05). Binary linear regression analysis showed that sex, age, tumour maximum diameter and volume, location, margin and echogenic foci were independent correlative factors. The ROC curves were established based on the relevant factors, the AUC of tumour maximum diameter, tumour volume and margin were 0.74, 0.73, and 0.71, respectively. The multiple-variable linear regression model was constructed with AUC of 0.81, specificity of 72.8%, and sensitivity of 75.0%. ANOVA variance analysis for sub-positive groups, tumour maximum diameter, tumour volume, margin and echogenic foci had statistical significance (P<0.05).Conclusion Younger age, male, larger tumour, margin, and echogenic foci were high risk factors for CLNM in PTC. Cross-sectional aspect ratio with value≥1 had higher predictive value for CLNM in patients with larger thyroid tumors.
Aquaporin-4 Expression in the Human Choroid Plexus
Authors: Deffner Felix , Gleiser Corinna , Mattheus Ulrich , Wagner Andreas , Neckel Peter H , Fallier-Becker Petra , Hirt Bernhard , Mack Andreas F 
Published: December 2021

Abstract
The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP using immunofluorescence and qPCR. As previously reported, AQP1 was expressed apically in CP epithelial cells. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain. Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (3 males, 5 females; age 74-91). These results were confirmed by qPCR, and by electron microscopy detecting orthogonal arrays of particles. To find out whether AQP4 expression correlated with the expression pattern of relevant transport-related proteins we also investigated expression of NKCC1, and Na/K-ATPase. Immunostaining with NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Taken together, we provide evidence for AQP4 expression in the CP of the aging brain which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging.
Tumor-B-cell Interactions Promote Isotype Switching to an Immunosuppressive IgG4 Antibody Response Through Upregulation of IL-10 in Triple Negative Breast Cancers
Authors: Toney Nicole J. , Opdenaker Lynn M. , Cicek Kader , Frerichs Lisa , Kennington Christopher Ryan , Oberly Samuel , Archinal Hollis , Somasundaram Rajasekharan , Mourtada Jennifer Sims 
Published: December 2021

Abstract
BackgroundTriple negative breast cancer (TNBC) is an aggressive breast cancer for which there is currently no targeted therapy. Tumor-infiltrating B-cells (TIB) have been observed in tumor tissues of TNBC patients, but their functional role is unclear. IgG4 is one of four antibody subclasses of IgG expressed and secreted by B cells. Unlike other IgG isotypes, IgG4 has an immunosuppressive function and is induced by Th2-type cytokines. In cancers such as melanoma, IgG4 has been linked with advanced disease and poor patient survival. Therefore, we sought to determine the role of IgG4 in TNBC. MethodsWe performed co-culture assays to examine expression of Th2 cytokines by TNBC cells with and without the presence of B cells. We also performed in vitro class switching experiments with peripheral B cells with and without co-culture with TNBC cells in the presence or absence of an IL-10 blocking antibody. We examined expression of CD20 + TIB, IgG4 and Th2 cytokines by immunohistochemistry in 152 TNBC samples. Statistical analysis was done using Log-Rank and Cox-proportional hazards tests. ResultsOur findings indicate that B cells interact with TNBC to drive chronic inflammatory responses through increased expression of inflammatory cytokines including the TH2 cytokines IL-4 and IL-10. In vitro class switching studies show that interactions between TNBC cell lines and B cells drive isotype switching to the IgG4 isotype in an IL-10 dependent manner. In patient tissues, expression of IgG4 correlates with CD20 and tumor expression of IL-10. Both IgG4 and tumor IL-10 are associated to shorter recurrence free survival (RFS) and overall survival (OS) in TNBC. In a multi-variant analysis, IL-10 was associated with poor outcomes indicating that tumor IL-10 may drive immune escape. ConclusionsThese findings indicate that interactions between TIB and TNBC results in activation of chronic inflammatory signals that suppress antibody driven immune responses
Global Analysis of The Signalling Network of Breast Cancer Cells In Response To Progesterone.
Authors: Wright Roni H. G. , Vastolo Viviana , Oliete Javier Quilez , Carbonell-Caballero Jose , Beato Miguel 
Published: December 2021

Abstract
Background: Breast cancer cells enter into the cell cycle following progestin exposure by the activation of signalling cascades involving a plethora of enzymes, transcription factors and co-factors that transmit the external signal from the cell membrane to chromatin, ultimately leading to a change of the gene expression program. Although many of the events within the signalling network have been described in isolation, how they globally team up to generate the final cell response is unclear. Methods: In this study we used antibody microarrays and phosphoproteomics to reveal a dynamic global signalling map that reveals new key regulated proteins and phosphor-sites and links between previously known and novel pathways. T47D breast cancer cells were used, and phosphosites and pathways highlighted were validated using specific antibodies and phenotypic assays. Bioinformatic analysis revealed an enrichment in novel signalling pathways, a coordinated response between cellular compartments and protein complexes. Results: Detailed analysis of the data revealed intriguing changes in protein complexes involved in nuclear structure, epithelial to mesenchyme transition (EMT), cell adhesion, as well as transcription factors previously not associated with breast cancer proliferation. Pathway analysis confirmed the key role of MAPK following progesterone and additional hormone regulated phosphosites were identified. Full network analysis shows the activation of new signalling pathways previously not associated with progesterone signalling in breast cancer cells such as ERBB and TRK. As different post-translational modifications can mediate complex crosstalk mechanisms and massive PARylation is also rapidly induced by progestins, we provide details of important chromatin regulatory complexes containing both phosphorylated and PARylated proteins. Conclusions: This study contributes an important resource for the scientific community, as it identifies novel players and connections meaningful for breast cancer cell biology and potentially relevant for cancer management.