bluuebunny/crossref_metadata_2025 huggingface dataset:
Paravertebral block reduces pain in elderly patients with percutaneous nephrolithotomy
Authors: Deng Jun , Wei Ke , Li Mingliang , Wang Xiaoping , Tang Qianli
Published: December 2020

Objective:

To assess the effectiveness of paravertebral block for the percutaneous nephrolithotomy (PCNL) patients.

Method:

This study will be implemented from May 2021 to March 2022 at Affiliated Hospital of Youjiang Medical University for Nationalities and it was granted through the Research Ethics Committee of Affiliated Hospital of Youjiang Medical University for Nationalities (No.60192038). This study includes a total of 100 patients. The criteria for inclusion of patients involves:

The criteria for exclusion involves:

The visual analogue scores, heart rate, the diastolic and systolic blood pressure, complications, and side effects, the consumption of opioid and extra analgesic needs are recorded in rehabilitation room 1 hour after the surgery and in the first 24 hours of urological service.

Results:

Table 1 shows the postoperative data among 2 groups.

Conclusion:

In comparison with traditional analgesia, the ultrasound-guided paraventric block is an effective analgesic approach in PCNL, and no additional complications are encountered.

Trial registration number:

research registry 6259.
Assessing the impact of a quality improvement program on the quality and timeliness of discharge documents
Authors: Troude Pénélope , Nieto Isabel , Brion Annie , Goudinoux Raphaël , Laganier Jean , Ducasse Valérie , Nizard Rémy , Martinez Fabien , Segouin Christophe
Published: December 2020

Whereas handover of pertinent information between hospital and primary care is necessary to ensure continuity of care and patient safety, both quality of content and timeliness of discharge summary need to be improved. This study aims to assess the impact of a quality improvement program on the quality and timeliness of the discharge summary/letter (DS/DL) in a University hospital with approximatively 40 clinical units using an Electronic medical record (EMR).

A discharge documents (DD) quality improvement program including revision of the EMR, educational program, audit (using scoring of DD) and feedback with a ranking of clinical units, was conducted in our hospital between October 2016 and November 2018. Main outcome measures were the proportion of the DD given to the patient at discharge and the mean of the national score assessing the quality of the discharge documents (QDD score) with 95% confidence interval.

Intermediate evaluation (2017) showed a significant improvement as the proportion of DD given to patients increased from 63% to 85% (P < .001) and mean QDD score rose from 41 (95%CI [36–46]) to 74/100 (95%CI [71–77]). In the final evaluation (2018), the proportion of DD given to the patient has reached 95% and the mean QDD score was 82/100 (95% CI [80–85]). The areas of the data for admission and discharge treatments remained the lowest level of compliance (44%).

The involvement of doctors in the program and the challenge of participating units have fostered the improvement in the quality of the DD. However, the level of appropriation varied widely among clinical units and completeness of important information, such as discharge medications, remains in need of improvement.
Effect of magnetic stimulation of Shenmen point on cognitive function of chronic insomnia
Authors: Yuan Jie , Chen Yimeng , Yu Penglong , Luo Fan , Gao Yongxiang , Chen Jie , Wang Pei , Wang Yuan , Zhao Yuan , Lei Yaling
Published: December 2020

Background:

Chronic insomnia (CI) can lead to cognitive dysfunction and bring great pain to patients’ life. There is no effective intervention for cognitive dysfunction caused by CI. Shenmen (HT7) is the first choice for insomnia treatment. However, the effect and mechanism of this acupoint on cognitive function after insomnia is not clear. Therefore, the purpose of this study is to explore whether magnetic stimulation of HT7 can improve cognitive impairment of CI by regulating prefrontal lobe and its mechanism.

Methods/Design:

This is a randomized controlled clinical trial. Seventy-two subjects aged 18 to 65 years old with primary insomnia and more than 3 months were randomly divided into 2 groups according to the ratio of 1:1, and 36 healthy controls were included. The control group was given sleep hygiene and cognitive therapy in behavioral cognitive therapy technology, while the experimental group was given the behavioral cognitive therapy technology intervention and magnetic stimulation of HT7 acupoint for 30 times (2 times / d, 5 times / wk for 20 days), while the healthy control group had no intervention measures. Before treatment and 20 days after treatment, we evaluated the working memory (1-back test), episodic memory (Complex Figure Test), and problem-solving ability (Hanoi tower test) processed by prefrontal lobe to explore the effect of magnetic stimulation on cognitive function of CI and its possible mechanism. At the same time, insomnia severity index was used to evaluate sleep state, Becker depression scale was used to evaluate depression, and Beck anxiety scale was used to evaluate anxiety. Chi-squared test or rank sum test was used to collect the data of patients. If P value is less than or equal to .05, the difference will be considered statistically significant.

Conclusion:

This study explored the effect and mechanism of magnetic stimulation of Shenmen (HT7) on cognitive function of CI, and confirmed that magnetic stimulation of HT7 can be used as an alternative therapy to improve cognitive impairment of CI.

Trial Registration number:

ChiCTR2000034280
Adjunctive therapies in type 1 diabetes mellitus
Authors: Lane Kyrstin , Freeby Matthew
Published: December 2020

Purpose of review

Insulin is the mainstay of treatment in people living with type 1 diabetes mellitus due to an immune-mediated loss of beta cells. Yet despite advances in insulin therapy and other technological advances, glycemic control remains difficult to achieve. Therefore, we aim to highlight risks and benefits of adjunctive therapies that may improve type 1 diabetes care.

Recent findings

We identified studies assessing clinical outcomes of adjunctive therapies that are both Food and Drug Administration (FDA)-approved and off-label in type 1 diabetes. Adjunctive therapies reviewed included metformin, pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors.

Although insulin is required in people living with type 1 diabetes mellitus, adjunctive therapies may positively impact glycemic control, reduce insulin requirements and lead to weight loss. In addition, the risk of hypoglycemia, gastrointestinal side effects and diabetes ketoacidosis may be increased with the use of these adjunctive therapies. Pramlintide is currently the only FDA-approved adjunctive therapy, whereas others require continued research to better understand risk-to-benefit ratio.
Effects of Walking on Fatigue in Cancer Patients
Authors: Wang Pengcheng , Wang Di , Meng Aifeng , Zhi Xiaoxu , Zhu Ping , Lu Lijing , Tang Lin , Pu Yalou , Li Xiaoli
Published: December 2020

Background

Walking is a simple form of exercise that is easily accepted by patients. Exercise is one of the main ways to control cancer-related fatigue (CRF). However, there are conflicting data on the association between walking and severity of CRF.

Objective

The aim of this study was to assess the overall effect of walking on CRF among adult cancer patients.

Methods

Databases including PubMed, CINAHL, EMBASE, and Cochrane Library were systematically reviewed to identify suitable randomized controlled trials from inception to February 29, 2020. Two reviewers independently evaluated the risk of bias and extracted correlated data with Cochrane Handbook of Systematic Reviews on Interventions. The data analysis was performed by Review Manager 5.3.

Results

A total of 12 studies with 1064 patients were identified. Integrated result analysis of walking yielded a statistically significant effect on CRF (standard mean difference [SMD], −0.66; 95% confidence interval [CI], −1.06 to −0.26). Subgroup analysis demonstrated that intervention time longer than 6 weeks (SMD, −0.89; 95% CI, −1.22 to −0.57) had a better effect on fatigue compared with that of less than 6 weeks (SMD, 0.03; 95% CI, −0.39 to 0.45). The study showed walking was statistically more effective than the control intervention in patients undergoing cancer treatment (SMD, −0.79; 95% CI, −1.16 to −0.42). Descriptive analysis also showed that walking was effective for cancer patients who completed treatment.

Conclusions

Walking is effective for CRF during and after cancer therapy.

Implications for Practice

The results provide evidence for a general exercise form to relieve fatigue in cancer patients and facilitate support for future clinical trials and work.
Cervical Cerclage: A Review and Rethinking of Current Practice
Authors: Senarath Sachintha , Ades Alex , Nanayakkara Pavitra
Published: December 2020

Importance

Cervical insufficiency (CI) is a serious complication of pregnancy, which can cause preterm birth. Identifying how to most effectively treat CI has the potential to maximize neonatal survival in this population of women.

Objective

To determine whether transabdominal cervical cerclage should be offered as a first-line treatment option in high-risk women.

Evidence Acquisition

An electronic literature search for relevant studies was conducted using keywords (CI, cervical cerclage) on the MEDLINE database.

Results

Although transabdominal cerclage (TAC) is reserved as a second-line treatment option over transvaginal cerclage (TVC), it has some advantages over TVC: a higher placement of the suture at the level of the cervicoisthmic junction; avoidance of placement of foreign material in the vagina, in turn, reducing risk of infection and inflammation, which can propagate preterm labor; and the option to leave the suture in place for future pregnancies. Systematic review evidence offers TAC as a more effective procedure to TVC in reducing preterm birth and maximizing neonatal survival. Although TAC is a slightly more complex procedure compared with TVC, advances in minimally invasive surgery now allow gynecologists to perform this more effective procedure laparoscopically and therefore without the added morbidity of open surgery but with the same if not better outcomes.

Conclusions

Laparoscopic TAC can provide a more effective treatment option for CI without the added burdens of open abdominal surgery.

Relevance

Our article highlights future directions for study in the area of cervical cerclage and refinement of existing practices.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to identify patients at high risk of CI; describe surgical management techniques for CI; and assess TAC, particularly a laparoscopic approach, as a first-line strategy for management of CI in high-risk groups.
Pseudopuniceibacterium antarcticum sp. nov., isolated from an Antarctic marine sponge
Authors: Liao Li , Su Shi-Yuan , Zhang Yan-Jiao , Liu Huan , Zhang Xi-Ying , Zhang Jin , Wen Jiao , Chen Bo , Yu Yong
Published: December 2020

A Gram-negative, aerobic, rod-shaped, non-motile bacterium, designated strain HQ09T, was isolated from a marine sponge off the coast of Fields Peninsula, West Antarctica. Strain HQ09T grew at 4–35 °C (optimum, 25 °C), pH 5–9 (optimum, pH 7.0), and with 1–10% NaCl (optimum, 2 %). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain HQ09T was affiliated with the genus

Pseudopuniceibacterium

in the family

Rhodobacteraceae

, sharing 99.64 % identity with the type strain of

Pseudopuniceibacterium sediminis

, the only known species in the genus. However, the low digital DNA–DNA hybridization (dDDH) (27.2 %) and average nucleotide identity (ANI) (83.63 %) values between strain HQ09T and the type strain of

Pseudopuniceibacterium sediminis

indicated that they did not belong to the same species. Strain HQ09T could also be differentiated from

Pseudopuniceibacterium sediminis

by many phenotypic characteristics. The major fatty acids (>5 %) of strain HQ09T were summed feature 8 (C18 : 1
 ω7c/C18 : 1 ω6c), 11-methyl C18 : 1
 ω7c, C16 : 0 and C19 : 0 cyclo ω8c. The polar lipids included phosphatidylglycerol, phosphatidylcholine, two unidentified aminolipids and one unidentified phospholipid. The predominant respiratory quinone was ubiquinone 10 (Q-10). The genomic DNA G+C content was 62.63 mol%. Four secondary metabolite biosynthetic gene clusters were detected in the genome, potentially producing ectoine and three types of unknown compounds. On the basis of the polyphasic evidences obtained in this study, strain HQ09T represents a novel species of the genus

Pseudopuniceibacterium

, for which the name Pseudopuniceibacterium antarcticum sp. nov. is proposed, with the type strain being HQ09T (=KCTC 52229T=CGMCC 1.15538T).
Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability
Authors: Ding Bo , Liu Ying , Liu Zhiheng , Zheng Lina , Xu Ping , Chen Zhao , Wu Peiyao , Zhao Ying , Pan Qian , Guo Yu , Wei Wensheng , Wang Wei
Published: December 2020

The majority of the non-coding regions in the human genome do not harbor any annotated element and are even not marked with any epigenomic signal or protein binding. An understudied aspect of these regions is their possible roles in stabilizing the 3D chromatin organization. To illuminate their “structural importance”, we chose to start with the non-coding regions forming many 3D contacts (referred to as hubs) and identified dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact gene expression located distal in the genome. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of the disease-associated genetic variations (GVs). Furthermore, our analyses also suggested a powerful approach to develop “one-drug-multiple-targets” therapeutics targeting the disease-specific non-coding regions.
Engineering clinically-approved drug gated CAR circuits
Authors: Li Hui-Shan , Wong Nicole M. , Tague Elliot , Ngo John T. , Khalil Ahmad S. , Wong Wilson W.
Published: December 2020

Chimeric antigen receptor (CAR) T cell immunotherapy has the potential to revolutionize cancer medicine. However, excessive CAR activation, lack of tumor-specific surface markers, and antigen escape have limited the safety and efficacy of CAR T cell therapy. A multi-antigen targeting CAR system that is regulated by safe,clinically-approvedpharmaceutical agents is urgently needed, yet only a few simple systems have been developed, and even fewer have been evaluated for efficacyin vivo. Here, we present NASCAR (NS3ASsociated CAR), a collection of induc-ible ON and OFF switch CAR circuits engineered with a NS3 protease domain deriving from the Hepatitis C Virus (HCV). We establish their ability to regulate CAR activity using multiple FDA-approved antiviral protease inhibitors, including grazoprevir (GZV), bothin vitroand in a xenograft tumor model. In addition, we have engineered several dual-gated NASCAR circuits, consisting of an AND logic gate CAR, universal ON-OFF CAR, and a switchboard CAR. These engineered receptors enhance control over T cell activity and tumor-targeting specificity. Together, our com-prehensive set of multiplex drug-gated CAR circuits represent a dynamic, tunable, and clinically-ready set of modules for enhancing the safety of CAR T cell therapy.
Epigenetic control of coordinated hematopoietic and cardiovascular development by Rnf2 in zebrafish
Authors: Peng XX , Feng G , Sun YH
Published: December 2020

Early embryogenesis requires the coordinated development of cardiovascular and hematopoietic lineages. However, the underlying cellular and genetic mechanisms are poorly understood. Here, we show that Rnf2, the core enzymatic component of Polycomb repressive complex 1 (PRC1), plays an important role in the control of cardiovascular and hematopoietic development and differentiation via suppressing the master hematoendothelial progenitor genes in zebrafish. In the absence of Rnf2, a group of transcription factor (TF) genes crucial for hematoendothelial specification such asetv2,gata2,lmo2andtal1are significantly up-regulated, which causes an expansion of hematopoietic and endothelial progenitors at the expense of myocardial differentiation, resulting in severe defects in both cardiogenesis and hematopoiesis. Although the number of hematopoietic stem cells (HSCs) is increased, both primitive and definitive waves of hematopoiesis are severely compromised inrnf2mutant embryos, suggesting that Rnf2 is required for differentiation of blood progenitor cells. Combined ChIP-seq and RNA-seq analysis shows that Rnf2 directly binds to key hematoendothelial progenitor genes and represses its expression. We further show that Rnf2-mediated gene repression depends on its H2Aub1 catalytic activity. We propose that PRC1/Rnf2-mediated epigenetic mechanism plays a key role in coordinated development of cardiovascular and hematopoietic lineages by repressing key hematoendothelial progenitor genes.

Highlights

Rnf2 is required for suppressing the expression of key hematoendothelial TF genes in precursors and its differentiated descendants.

Rnf2 mutant zebrafish embryos display defective hematopoiesis and cardiogenesis.

Loss of Rnf2 results in increased HSC numbers and arrested differentiation, hallmarks of leukemia.

Rnf2 suppresses hematoendothelial progenitor genes via depositing H2Aub1.
Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation
Authors: Anand Gautam , Perry Alexandra M. , Cummings Celeste L. , Raymond Emma St. , Clemens Regina A. , Steed Ashley L.
Published: December 2020

SARS-CoV-2, the virus that has caused the COVID-19 pandemic, robustly activates the host immune system in critically ill patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3, TBK1, and MYD88 while that of E is largely MYD88 independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation and pulmonary vasculitis in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation and their potential for therapeutic intervention.

Author Summary

SARS-CoV-2 robustly activates widespread inflammation, but we do not understand mechanistically how the virus engages the immune system. This knowledge will facilitate the development of critically needed therapeutic strategies to promote beneficial immune responses will dampening harmful inflammation. Here we demonstrate that SARS-CoV-2 surface proteins spike and envelope alone activated innate cell function and the interferon signaling pathway. This activation occurred in both immune and epithelial cells, and mechanistic studies demonstrated dependence on known key inflammatory signaling mediators, IRF3, TBK1, and MYD88. In animal studies, we showed that these viral surface proteins induce epithelial cell IFN-dependent lung pathology, reminiscent to acute COVID-19 pulmonary infection. These findings underscore the need for further investigation into the role of SARS-CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation.
Stepwise gating of the Sec61 protein-conducting channel by Sec63 and Sec62
Authors: Itskanov Samuel , Park Eunyong
Published: December 2020

The universally conserved Sec61/SecY channel mediates transport of many newly synthesized polypeptides across membranes, an essential step in protein secretion and membrane protein integration1-5. The channel has two gating mechanisms—a lipid-facing lateral gate, through which hydrophobic signal sequences or transmembrane helices (TMs) are released into the membrane, and a vertical gate, called the plug, which regulates the water-filled pore required for translocation of hydrophilic polypeptide segments6. Currently, how these gates are controlled and how they regulate the translocation process remain poorly understood. Here, by analyzing cryo-electron microscopy (cryo-EM) structures of several variants of the eukaryotic post-translational translocation complex Sec61-Sec62-Sec63, we reveal discrete gating steps of Sec61 and the mechanism by which Sec62 and Sec63 induce these gating events. We show that Sec62 forms a V-shaped structure in front of the lateral gate to fully open both gates of Sec61. Without Sec62, the lateral gate opening narrows, and the vertical pore becomes closed by the plug, rendering the channel inactive. We further show that the lateral gate is opened first by interactions between Sec61 and Sec63 in both cytosolic and luminal domains, a simultaneous disruption of which fully closes the channel. Our study defines the function of Sec62 and illuminates how Sec63 and Sec62 work together in a hierarchical manner to activate the Sec61 channel for post-translational translocation.
Predicting engagement in working memory training for methamphetamine use disorder: indices of motivation, attention, and achievement
Authors: Shorer Eran Frank , Brooks Samantha Jane
Published: December 2020

Rationale: Impulsivity and inefficient self-regulation are major deficits in substance use disorder, corresponding to lack of treatment response and low abstinence rates. Prefrontal cortex (PFC) executive functions, such as working memory (WM), enable self-regulation of impulsivity by keeping in mind cognitive strategies for optimal decisions about future action. Training WM may improve self-regulation of impulsivity in various populations, including methamphetamine use disorder (MUD) patients. However, many controversies exist regarding the efficacy of WM training (e.g. near- versus far-transfer effects) and associated improvements to clinical outcomes. Such controversies may relate, as observed in our preliminary study in MUD patients, to variation in WM training engagement. Methods: In this nested examination of n=17 male MUD patient data (age range 20-39 yrs) from a previously published study, the primary aim was to identify variables that may predict a WM training engagement index (EI), and secondarily to determine if EI could predict clinical improvement in MUD patients. The EI consisted of three domains of WM training: motivation, attention/learning and achievement, and we examined the link between self-report measures of impulsivity, self-regulation, anxiety/depression and executive function and EI. Results: Those with higher rates of attention/learning demonstrated greater improvement in attentional impulsivity, and those with higher rates of achievement had a significant improvement in self-reported anxiety, as well as slower time to complete an executive function task after treatment. Discussion: We suggest the EI is a useful measure to detect level of engagement during WM training in patients with MUD, and is predictive of clinical improvements.
Jumping over Baselines with New Methods to Predict Activation Maps from Resting-state fMRI
Authors: Lacosse Eric , Scheffler Klaus , Lohmann Gabriele , Martius Georg
Published: December 2020

Cognitive fMRI research primarily relies on task-averaged responses over many subjects to describe general principles of brain function. Nonetheless, there exists a large variability between subjects that is also reflected in spontaneous brain activity as measured by resting state fMRI (rsfMRI). Leveraging this fact, several recent studies have therefore aimed at predicting task activation from rsfMRI using various machine learning methods within a growing literature on ‘connectome fingerprinting.’ In reviewing these results, we found lack of an evaluation against robust baselines that reliably supports a novelty of predictions for this task. On closer examination to reported methods, we found most underperform against trivial baseline model performances based on massive group averaging when whole-cortex prediction is considered. Here we present a modification to published methods that remedies this problem to large extent. Our proposed modification is based on a single-vertex approach that replaces commonly used brain parcellations. We further provide a summary of this model evaluation by characterizing empirical properties of where prediction for this task appears possible, explaining why some predictions largely fail for certain targets. Finally, with these empirical observations we investigate whether individual prediction scores explain individual behavioral differences in a task.
Predictive modeling of long non-coding RNA chromatin (dis-)association
Authors: Ntini Evgenia , Budach Stefan , Vang Ørom Ulf A , Marsico Annalisa
Published: December 2020

Long non-coding RNAs (lncRNAs) are involved in gene expression regulation incisandtrans. Although enriched in the chromatin cell fraction, to what degree this defines their broad range of functions remains unclear. In addition, the factors that contribute to lncRNA chromatin tethering, as well as the molecular basis of efficient lncRNA chromatin dissociation and its functional impact on enhancer activity and target gene expression, remain to be resolved. Here, we combine pulse-chase metabolic labeling of nascent RNA with chromatin fractionation and transient transcriptome sequencing to follow nascent RNA transcripts from their co-transcriptional state to their release into the nucleoplasm. By incorporating functional and physical characteristics in machine learning models, we find that parameters like co-transcriptional splicing contributes to efficient lncRNA chromatin dissociation. Intriguingly, lncRNAs transcribed from enhancer-like regions display reduced chromatin retention, suggesting that, in addition to splicing, lncRNA chromatin dissociation may contribute to enhancer activity and target gene expression.

Highlights

Chromatin (dis-)association of lncRNAs can be modeled using nascent RNA sequencing from pulse-chase chromatin fractionation

Distinct physical and functional characteristics contribute to lncRNA chromatin (dis-)association

lncRNAs transcribed from enhancers display increased degree of chromatin dissociation

lncRNAs of distinct degrees of chromatin association display differential binding probabilities for RNA-binding proteins (RBPs)
A functional artificial neural network for noninvasive presurgical evaluation of glioblastoma multiforme prognosis and radiosensitivity profiling
Authors: Zander Eric , Ardeleanu Andrew , Singleton Ryan , Bede Barnabas , Wu Yilin , Zheng Shuhua
Published: December 2020

Background and Purpose

Genetic profiling for glioblastoma multiforme (GBM) patients with intracranial biopsy carries a significant risk of permanent morbidity. We previously demonstrated that theCUL2gene, encoding the scaffold cullin2 protein in the cullin2-RING E3 ligase (CRL2), can predict GBM radiosensitivity and prognosis mainly due to the functional involvement of CRL2 in mediating hypoxia-inducible factor 1 (HIF-1) α and epidermal growth factor receptor (EGFR) degradation. BecauseCUL2expression levels are closely regulated with its copy number variations (CNVs), this study aims to develop an artificial neural network (ANN) that can predict GBM prognosis and help optimize personalized GBM treatment planning.

Materials and Methods

Datasets including Ivy-GAP, The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM), the Chinese Glioma Genome Atlas (CGGA) were analyzed. T1 images from corresponding cases were studied using automated segmentation for features of heterogeneity and tumor edge contouring.

Results

We developed a 4-layer neural network that can consistently predict GBM prognosis with 80-85% accuracy with 3 inputs includingCUL2copy number, patient’s age at GBM diagnosis, and surface vs. volume (SvV) ratio.

Conclusion

A functional 4-layer neural network was constructed that can predict GBM prognosis and potential radiosensitivity.
Resting-state functional connectivity and psychopathology in Klinefelter syndrome (47, XXY)
Authors: Whitman Ethan T. , Liu Siyuan , Torres Erin , Warling Allysa , Wilson Kathleen , Nadig Ajay , McDermott Cassidy , Clasen Liv S. , Blumenthal Jonathan D. , Lalonde François M. , Gotts Stephen J. , Martin Alex , Raznahan Armin
Published: December 2020

Klinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collected resting state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males. We implemented a brain-wide screen to identify regions with altered global rsFC in XXY vs. XY males, and then used seed-based analysis to decompose these alterations. We further compared rsFC changes with regional changes in brain volume from voxel-based morphometry and tested for correlations between rsFC and symptom variation within XXY syndrome. We found that XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC), associated with overconnectivity with diverse rsFC networks. Regional rsFC changes were partly coupled to regional volumetric changes in XXY syndrome. Within the precuneus, variation in DLPFC rsFC within XXY syndrome was correlated with the severity of psychopathology in XXY individuals. Our findings provide the first view of altered functional brain connectivity in XXY syndrome and delineate links between these alterations and those relating to both brain anatomy and psychopathology. Taken together, these insights advance biological understanding of XXY syndrome as a disorder in its own right, and as a model of genetic risk for psychopathology more broadly.
A neural crest stem cell-like state drives nongenetic resistance to targeted therapy in melanoma
Authors: Marin-Bejar Oskar , Rogiers Aljosja , Dewaele Michael , Femel Julia , Karras Panagiotis , Pozniak Joanna , Bervoets Greet , Van Raemdonck Nina , Pedri Dennis , Swings Toon , Demeulemeester Jonas , Borght Sara Vander , Bosisio Francesca , van den Oord Joost J. , Bempt Isabelle Vanden , Lambrechts Diether , Voet Thierry , Bechter Oliver , Rizos Helen , Levesque Mitch , Leucci Eleonora , Lund Amanda W. , Rambow Florian , Marine Jean-Christophe
Published: December 2020

The ability to predict the future behaviour of an individual cancer is crucial for precision cancer medicine and, in particular, for the development of strategies that prevent acquisition of resistance to anti-cancer drugs. Therapy resistance, which often develops from a heterogeneous pool of drug-tolerant cells known as minimal residual disease (MRD), is thought to mainly occur through acquisition of genetic alterations. Increasing evidence, however, indicates that drug resistance might also be acquired though nongenetic mechanisms. A key emerging question is therefore whether specific molecular and/or cellular features of the MRD ecosystem determine which of these two distinct resistance trajectories will eventually prevail. We show herein that, in melanoma exposed to MAPK-therapeutics, the presence of a neural crest stem cell (NCSC) subpopulation in MRD concurred with the rapid development of resistance through nongenetic mechanisms. Emergence of this drug-tolerant population in MRD relies on a GDNF-dependent autocrine and paracrine signalling cascade, which activates the AKT survival pathway in a Focal-adhesion kinase-(FAK) dependent manner. Ablation of this subpopulation through inhibition of FAK/SRC-signalling delayed relapse in patient-derived tumour xenografts. Strikingly, all tumours that eventually escaped this treatment exhibited resistance-conferring genetic alterations and increased sensitivity to ERK-inhibition. These findings firmly establish that nongenetic reprogramming events contribute to therapy resistance in melanoma and identify a clinically-compatible approach that abrogates such a trajectory. Importantly, these data demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths and highlight key principles that may permit more effective pre-emptive therapeutic interventions.
Phasertng: directed acyclic graphs for crystallographic phasing
Authors: McCoy Airlie J. , Stockwell Duncan H. , Sammito Massimo D. , Oeffner Robert D. , Hatti Kaushik S. , Croll Tristan I. , Read Randy J.
Published: December 2020

Crystallographic phasing strategies increasingly require the exploration and ranking of many hypotheses about the number, types and positions of atoms, molecules and/or molecular fragments in the unit cell, each with only a small chance of being correct. Accelerating this move has been improvements in phasing methods, which are now able to extract phase information from the placement of very small fragments of structure, from weak experimental phasing signal or from combinations of molecular replacement and experimental phasing information. Describing phasing in terms of a directed acyclic graph allows graph-management software to track and manage the path to structure solution. The crystallographic software supporting the graph data structure must be strictly modular so that nodes in the graph are efficiently generated by the encapsulated functionality. To this end, the development of new software, Phasertng, which uses directed acyclic graphs natively for input/output, has been initiated. In Phasertng, the codebase of Phaser has been rebuilt, with an emphasis on modularity, on scripting, on speed and on continuing algorithm development. As a first application of phasertng, its advantages are demonstrated in the context of phasertng.xtricorder, a tool to analyse and triage merged data in preparation for molecular replacement or experimental phasing. The description of the phasing strategy with directed acyclic graphs is a generalization that extends beyond the functionality of Phasertng, as it can incorporate results from bioinformatics and other crystallographic tools, and will facilitate multifaceted search strategies, dynamic ranking of alternative search pathways and the exploitation of machine learning to further improve phasing strategies.
How aspiring principals applied course-based learning to develop school improvement plans
Authors: Bickmore Dana L. , Roberts Maria M. , Gonzales Miguel M.
Published: December 2020

Purpose

School improvement planning and implementation is one organizational process by which principals may positively impact school and student outcomes. Limited research, however, has explored how principal preparation programs prepare aspiring leaders for this common school leadership activity. This study examined aspiring principals engaged in the school improvement process by evaluating what they included in their school improvement plans (SIPs) that were developed as part of their field experience.

Design/methodology/approach

The authors examined SIPs aspiring principals collaboratively developed as part of their field experience. Using an abductive analysis method, combining both deductive and inductive coding methods, authors examined 77 SIPs in which aspiring principals used school level data in planning.

Findings

Each aspiring principal's SIP was contextually specific. No two plans were identical relative to who was targeted for improvement and how the plan was to be implemented, indicating aspiring principals can apply course-based learning and implement important data-driven decision-making skills in field-based school improvement projects.

Research limitations/implications

Findings are exploratory and limited to SIPs developed by aspiring principals in one university program in one large urban school district context. The findings that specific requirements and program structures affected the aspiring principal's school improvement planning process as did the overall school context adds to current understandings of how course-based learning is applied. However, further investigations are needed.

Practical implications

Findings provide evidence of how school leadership preparation programs may impact leadership development relative to skills associated with school improvement planning. The findings also suggest the importance of detailed analysis of aspiring principals school improvement planning as a program evaluation process.

Originality/value

This study was the first to document the content of aspiring principals' field-based SIPS and how skills in data-driven decision-making were applied in a SIP field-based activity.
Study of Langerhans cells and T lymphocytes in vulvar lichen sclerosus lesions
Authors: Bao Yingqiu , Li Ziyuan , Liu Wan , Fu Yu , Lv Jiaqi , Sun Kailv , Chang Jianmin
Published: December 2020

Background

The aetiology and pathogenesis of vulvar lichen sclerosus (LS), a chronic inflammatory disease, is not completely clear. It has been found that local cellular immune abnormalities play an important role in the immune mechanism of LS, mainly characterised by abnormal numbers of Langerhans cells in the epidermis and abnormal numbers of dermal T lymphocytes.

Objective

To evaluate the densities of Langerhans cells and T‐lymphocyte subpopulations in vulvar LS.

Methods

The density of Langerhans cells in the epidermis, and CD3+, CD4+ and CD8+ T cells in the dermis of seven early‐stage and eight late‐stage cases of vulvar LS were detected with direct immunofluorescence, and compared with 15 normal controls.

Results

The density of Langerhans cells in the late‐stage group was significantly higher than in the normal group (P = 0.001). The densities of CD3+, CD4+ and CD8+ T lymphocytes in both the early‐ and late‐stage (deeper dermis) groups were higher than in the normal group (P < 0.05). The ratio of CD4+/CD8+T lymphocytes in the early‐stage and normal groups showed no significant difference (P = 0.151), while the late‐stage (deeper dermis) groups decreased significantly compared with early‐stage, late‐stage (upper dermis) and normal groups (P < 0.001).

Conclusion

The densities of Langerhans cells, CD3+, CD4+ and CD8+ T cells, and the ratio of CD4+/CD8+T lymphocytes were different in different stages of LS, which supports the important role of cellular immunity in mechanisms of LS.
Microaneurysm density in residual oedema after anti‐vascular endothelial growth factor therapy for diabetic macular oedema
Authors: Yamada Yutaka , Takamura Yoshihiro , Morioka Masakazu , Gozawa Makoto , Matsumura Takehiro , Inatani Masaru
Published: December 2020

Purpose

To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti‐vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO).

Methods

Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography.

Results

We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029).

Conclusion

High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.
Outcomes of a new 3‐D printing‐assisted personalized macular buckle combined with para plana vitrectomy for myopic foveoschisis
Authors: Zou Jing , Tan Wei , Li Fangling , Zhou Gaofeng , Li Liang , Xiong Siqi , Wang Xianggui , Xu Huizhuo
Published: December 2020

Purpose

To describe and evaluate the application of a new 3‐D printing‐assisted personalized macular buckle for patients with myopic foveoschisis (MFS).

Methods

Twelve eyes of 12 patients with MFS were included in this study. Preoperative MRI images were subsequently measured after marker implantation and imported into the MIMICS software for the 3‐D reconstruction of a virtual model of an eyeball and a marker. The virtual eyeball model was designed according to the degree of retinoschisis, which was measured using optical coherence tomography preoperatively. A macular buckle was designed using a titanium stent, assisted by 3‐D printing; furthermore, it was surgically placed in combination with pars plana vitrectomy. Visual acuity, axial length and anatomic outcomes were analysed pre‐ and postoperatively.

Results

Macular schisis in all patients was completely resolved after the surgery without any postoperative complications. The mean postoperative best corrected visual acuity (LogMAR) improved significantly from 1.21 to 0.92 during the 6‐month follow‐up period (p < 0.001) and reached 0.9 (p < 0.001) after 2 years. The axial length was significantly shortened during the 2 years postoperatively follow‐up period (p < 0.01). The average axial lengths in all patients decreased from 30.62 mm preoperatively to 29.81 mm 1 month postoperatively and remained around 30.16 mm from 1 year after the surgery.

Conclusion

The 3‐D printing technique is useful to predict the indentation height and position of the macular buckle. The 3D‐printing‐assisted macular buckle, in combination with vitrectomy, is an effective, safe and accurate treatment modality for MFS.
Mealtime care and dietary intake in older psychiatric hospital inpatient: A multiple case study
Authors: Flint Kate , Matthews‐Rensch Kylie , Flaws Dylan , Mudge Alison , Young Adrienne
Published: December 2020

Aims

To investigate the energy and protein adequacy of meals and dietary intake of older psychiatric inpatients and describe patient and mealtime factors potentially influencing intake.

Design

Multiple case studies.

Methods

Psychiatric inpatients aged 65 years and older, admitted to a single mental health ward during the 6‐week study period (April–May 2019) were eligible for inclusion. Dietary intake was observed for two consecutive days each week (minimum four observation days). Visual plate waste methods were used to estimate patients’ dietary intake at mealtimes, with energy and protein intake calculated using known food composition data and compared with estimated requirements. Medical records were reviewed weekly to collect information on potential factors related to intake and mealtime care. Data from all sources were first summarized in a case record for within‐case analysis using descriptive statistics, followed by cross‐case analysis.

Results

Eight participants (five men, age 67–90 years, two underweight and one overweight, and four requiring some mealtime assistance) had 5–12 days of observation data recorded. Three met their estimated daily energy and protein requirements throughout the study period, while the remaining five participants did not. The main barriers identified as contributing to insufficient energy and protein intake were as follows: missing meals (asleep and treatment); inadequate food provided (insufficiency of the standard hospital menu); and need for increased mealtime assistance.

Conclusion

Poor dietary intake may be common among older psychiatric patients, suggesting that they may also need nursing and multidisciplinary nutrition care interventions shown to effectively prevent and treat malnutrition in other older inpatient groups.

Impact

Older psychiatric patients experience similar nutrition and mealtime issues to other older inpatients. This study highlights the need for nurses and the multidisciplinary team to ensure patients order and receive adequate food, especially when they miss meals and that they receive proactive mealtime assistance.
Opsonization but not pretreatment of equine macrophages with hyperimmune plasma nonspecifically enhances phagocytosis and intracellular killing ofRhodococcus equi
Authors: Harvey Aja B. , Bordin Angela I. , Rocha Joana N. , Bray Jocelyn M. , Cohen Noah D.
Published: December 2020

Background

Evidence regarding the efficacy of equine hyperimmune plasma to prevent pneumonia in foals caused byRhodococcus equiis limited and conflicting.

Hypothesis

Opsonization withR. equi‐specific hyperimmune plasma (HIP) will significantly increase phagocytosis and decrease intracellular replication ofR. equiby alveolar macrophages (AMs) compared to normal plasma (NP).

Animals

Fifteen adult Quarter Horses were used to collect bronchoalveolar lavage cells.

Methods

In the first experiment, AMs from 9 horses were pretreated (incubated) with either HIP, NP, or media only (control) and then infected with nonopsonizedR. equi. In a second experiment, AMs from 6 horses were infected withR. equieither opsonized with HIP or opsonized with NP. For both experiments, AMs were lysed at 0 and 48 hours and the number of viableR. equiquantified by culture were compared among groups using linear mixed‐effects modeling with significance set atP < .05.

Results

Opsonization with either HIP or NP increased phagocytosis by AMs (P < .0001) and decreased intracellular survival of organisms in AMs (P < .0001). Pretreating AMs with either HIP or NP without opsonizingR. equihad no effects on phagocytosis or intracellular replication.

Conclusions and Clinical Importance

OpsonizingR. equiwith either NP or HIP decreases intracellular survival of organisms in AMs, but the effect does not appear to be enhanced by using HIP. Mechanisms other than effects on AMs must explain any clinical benefits of using HIP over NP to decrease the incidence ofR. equipneumonia in foals.