bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of dexamethasone on the microenvironment and efficacy of checkpoint inhibitors in glioblastoma: a systematic review
Authors: Swildens Kyra X , Sillevis Smitt Peter A E , van den Bent Martin J , French Pim J , Geurts Marjolein 
Published: June 2022

Abstract

Background
Checkpoint inhibitor immunotherapy has not proven clinically effective in glioblastoma. This lack of effectiveness may be partially attributable to the frequent administration of dexamethasone in glioblastoma patients. In this systematic review, we assess whether dexamethasone (1) affects the glioblastoma microenvironment and (2) interferes with checkpoint inhibitor immunotherapy efficacy in the treatment of glioblastoma.

Methods
PubMed and Embase were systematically searched for eligible articles published up to September 15, 2021. Both in vitro and in vivo preclinical studies, as well as clinical studies were selected. The following information was extracted from each study: tumor model, corticosteroid treatment, and effects on individual immune components or checkpoint inhibitor immunotherapy.

Results
Twenty-one preclinical studies in cellular glioma models (n = 10), animal glioma models (n = 6), and glioblastoma patient samples (n = 7), and 3 clinical studies were included. Preclinical studies show that dexamethasone decreases the presence of microglia and other macrophages as well as the number of T lymphocytes in both tumor tissue and periphery. Dexamethasone abrogates the antitumor effects of checkpoint inhibitors on T lymphocytes in preclinical studies. Although randomized studies directly addressing our research question are lacking, clinical studies suggest a negative association between corticosteroids and survival outcomes in glioblastoma patients receiving checkpoint inhibitors after adjustment for relevant prognostic factors.

Conclusions
Preclinical research shows that dexamethasone inhibits the antitumor immune response in glioma, thereby promoting a protumorigenic microenvironment. The efficacy of checkpoint inhibitor immunotherapy in glioblastoma patients may therefore be negatively affected by the use of dexamethasone. Future research could investigate the potential of edema-reducing alternatives to dexamethasone.
Efficacy and Safety of Intensified Versus Standard Prophylactic Anticoagulation Therapy in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis
Authors: Wills Nicola K , Nair Nikhil , Patel Kashyap , Sikder Omaike , Adriaanse Marguerite , Eikelboom John , Wasserman Sean 
Published: June 2022

Abstract

Background
Randomized controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in coronavirus disease 2019 (COVID-19). We performed an aggregate data meta-analysis from available trials to quantify effect on nonfatal and fatal outcomes and identify subgroups who may benefit.

Methods
We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) vs prophylactic anticoagulation in adults with laboratory-confirmed COVID-19 through 19 January 2022. We used random-effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events (at end of follow-up or discharge) and performed subgroup analysis for clinical setting and dose of intensified anticoagulation.

Results
Eleven RCTs were included (N = 5873). Intensified vs prophylactic anticoagulation was not associated with a mortality reduction up to 45 days (risk ratio [RR], 0.93 [95% confidence interval {CI}, .79–1.10]). There was a possible signal of mortality reduction for non–intensive care unit (ICU) patients, although with low precision and high heterogeneity (5 studies; RR, 0.84 [95% CI, .49–1.44]; I2 = 75%). Risk of venous thromboembolism was reduced (RR, 0.53 [95% CI, .41–.69]; I2 = 0%), with effect driven by therapeutic rather than intermediate dosing (interaction P = .04). Major bleeding was increased with intensified anticoagulation (RR, 1.73 [95% CI, 1.17–2.56]) with no interaction for dosing and clinical setting.

Conclusions
Intensified anticoagulation has no effect on mortality among hospitalized adults with COVID-19 and is associated with increased bleeding risk. The observed reduction in venous thromboembolism risk and trend toward reduced mortality in non-ICU settings requires exploration in additional RCTs.
Clinical Trials Registration. CRD42021273449 (PROSPERO).
Hypersensitivity-Related Genes HSR201 and HSR203J Are Regulated by Calmodulin-Binding Protein 60-Type Transcription Factors and Required for Pathogen Signal-Induced Salicylic Acid Synthesis
Authors: Takagi Kumiko , Tasaki Kosuke , Komori Hirotomo , Katou Shinpei 
Published: June 2022

Abstract
Salicylic acid (SA) plays a key role in plant resistance to pathogens. In Arabidopsis, the isochorismate synthase pathway mainly contributes to pathogen-induced SA synthesis, and the expression of SA synthesis genes is activated by two calmodulin (CaM)-binding protein 60 (CBP60)-type transcription factors, CBP60g and SARD1. In tobacco, the mechanisms underlying SA synthesis remain largely unknown. SA production is induced by wounding in tobacco plants in which the expression of two stress-related mitogen-activated protein kinases is suppressed. Using this phenomenon, we identified genes whose expression is associated with SA synthesis. One of the genes, NtCBP60g, showed 23% amino acid sequence identity with CBP60g. Transient overexpression of NtCBP60g as well as NtSARD1, a tobacco homolog of SARD1, induced SA accumulation in Nicotiana benthamiana leaves. NtCBP60g and NtSARD1 bound CaM, and CaM enhanced SA accumulation induced by NtCBP60g and NtSARD1. Conversely, mutations in NtCBP60g and NtSARD1 that abolished CaM binding reduced their ability to induce SA. Expression profiling and promoter analysis identified two hypersensitivity-related genes, HSR201 and HSR203J as the targets of NtCBP60g and NtSARD1. Virus-induced gene silencing of both NtCBP60g and NtSARD1 homologs compromised SA accumulation and the expression of HSR201 and HSR203J homologs, which were induced by a pathogen-derived elicitor in N. benthamiana leaves. Moreover, elicitor-induced SA accumulation was compromised by silencing of the HSR201 homolog and the HSR203J homolog. These results suggested that HSR201 and HSR203J are regulated by NtCBP60g and NtSARD1 and are required for elicitor-induced SA synthesis.
Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA
Authors: Liu Tianzhen , Zhang Xin , Zhang Huan , Cheng Zhijun , Liu Jun , Zhou Chunlei , Luo Sheng , Luo Weifeng , Li Shuai , Xing Xinxin , Chang Yanqi , Shi Cuilan , Ren Yulong , Zhu Shanshan , Lei Cailin , Guo Xiuping , Wang Jie , Zhao Zhichao , Wang Haiyang , Zhai Huqu , Lin Qibing , Wan Jianmin 
Published: June 2022

Abstract
Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
Multi-omic analysis showsREVEILLEclock genes are involved in carbohydrate metabolism and proteasome function
Authors: Scandola Sabine , Mehta Devang , Li Qiaomu , Rodriguez Gallo Maria Camila , Castillo Brigo , Uhrig Richard Glen 
Published: June 2022

AbstractPlants are able to sense changes in their light environments, such as the onset of day and night, as well as anticipate these changes in order to adapt and survive. Central to this ability is the plant circadian clock, a molecular circuit that precisely orchestrates plant cell processes over the course of a day. REVEILLE (RVE) proteins are recently discovered members of the plant circadian circuitry that activate the evening complex and PSEUDO-RESPONSE REGULATOR genes to maintain regular circadian oscillation. The RVE8 protein and its two homologs, RVE 4 and 6 in Arabidopsis (Arabidopsis thaliana), have been shown to limit the length of the circadian period, with rve 4 6 8 triple-knockout plants possessing an elongated period along with increased leaf surface area, biomass, cell size, and delayed flowering relative to wild-type Col-0 plants. Here, using a multi-omics approach consisting of phenomics, transcriptomics, proteomics, and metabolomics we draw new connections between RVE8-like proteins and a number of core plant cell processes. In particular, we reveal that loss of RVE8-like proteins results in altered carbohydrate, organic acid, and lipid metabolism, including a starch excess phenotype at dawn. We further demonstrate that rve 4 6 8 plants have lower levels of 20S proteasome subunits and possess significantly reduced proteasome activity, potentially explaining the increase in cell-size observed in RVE8-like mutants. Overall, this robust, multi-omic dataset provides substantial insight into the far-reaching impact RVE8-like proteins have on the diel plant cell environment.
Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases
Authors: Wilson Heather , de Natale Edoardo Rosario , Politis Marios 
Published: June 2022

Abstract
Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are progressive disorders for which curative therapy is still lacking. Cell-based therapy aims at replacing dysfunctional cellular populations by repairing damaged tissue and by enriching the microenvironment of selective brain areas, and thus constitutes a promising disease-modifying treatment of neurodegenerative diseases. Scientific research has engineered a wide range of human-derived cellular populations to help overcome some of the logistical, safety, and ethical issues associated with this approach. Open-label studies and clinical trials in human participants have used neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), to assess the success of the transplantation, to evaluate the functional integration of the implanted tissue into the host environment and to understand the pathophysiological changes associated with the therapy. Neuroimaging has constituted an outcome measure of large, randomized clinical trials, and has given answers to clarify the pathophysiology underlying some of the complications linked with this therapy. Novel PET radiotracers and MRI sequences for the staging of neurodegenerative diseases and to study alterations at the molecular level significantly expands the translational potential of neuroimaging to assist pre-clinical and clinical research on cell-based therapy in these disorders. This concise review summarizes the current use of neuroimaging in human studies of cell-based replacement therapy and focuses on the future applications of PET and MRI techniques to evaluate the pathophysiology and treatment efficacy, as well as to aid patient selection and as an outcome measure to improve treatment success.
Normalization of maternal adiponectin in obese pregnant mice prevents programming of impaired glucose metabolism in adult offspring
Authors: Dumolt Jerad , Powell Theresa L. , Jansson Thomas , Rosario Fredrick J. 
Published: June 2022

AbstractInfants born to obese mothers have a greater risk for childhood obesity and insulin resistance. However, the underlying biological mechanism remains elusive, which constitutes a significant roadblock for developing specific prevention strategies. Maternal adiponectin levels are lower in obese pregnant women, which is linked with increased placental nutrient transport and fetal overgrowth. We have previously reported that adiponectin supplementation to obese dams during the last four days of pregnancy prevented the development of obesity, glucose intolerance, muscle insulin resistance, and fatty liver in three months old offspring. In the present study, we tested the hypothesis that 6–9‐month‐old offspring of obese dams show glucose intolerance associated with muscle insulin resistance and mitochondrial dysfunction and that normalization of maternal adiponectin in obese pregnant mice prevents the development of this phenotype in the offspring. Male and female offspring of obese mice exhibited in vivo glucose intolerance and insulin resistance at 6 and 9 months of age. In gastrocnemius muscles ex vivo, male and female offspring of obese dams showed reduced phosphorylation of insulin receptor substrate 1Tyr‐608, AktThr‐308, and decreased Glut4 plasma membrane translocation upon insulin stimulation. These metabolic abnormalities in offspring born to obese mice were largely prevented by normalization of maternal adiponectin levels in late pregnancy. We provide evidence that low circulating maternal adiponectin is a critical mechanistic link between maternal obesity and the development of metabolic disease in offspring. Strategies aimed at improving maternal adiponectin levels may prevent long‐term metabolic dysfunction in offspring of obese mothers.
Academic Faculty Shadowing Their Graduate Nurses
Authors: Mau Kathleen A. , Kavanagh Joan , Burchill Christian N. , Siedlecki Sandra L. 
Published: June 2022

Abstract

AIM
The purpose of this study was to describe insights gained by academic nursing faculty after shadowing one of their new graduate nurses.

BACKGROUND
Shadowing experiences have been successfully used to orient students and new nurses to the role and reality of clinical practice. However, no studies were found on the experience of faculty shadowing a new graduate. This study addressed that gap.

METHOD
A case series design and methodology used both qualitative and quantitative data collection procedures. Qualitative data were derived from faculty during a debriefing session; quantitative data were obtained from a short survey completed by new graduates and faculty.

RESULTS
Faculty identified challenges faced by new graduates and opportunities to modify their nursing programs by addressing patient care delivery, time management, communication, and role ambiguity in more detail.

CONCLUSION
A shadowing experience for academic faculty leaders can help bridge the academic-practice gap and promote collaborative efforts to improve preparation for practice.
Factors Which May Contribute to the Success or Failure of the Use of Mother's Own Milk in a Level IV Neonatal Intensive Care Unit
Authors: D'Ambrosio Mary Ann , Gabrielski Lisbeth , Melara Diane , Pickett Kaci , Pan Zhaoxing , Neu Madalynn 
Published: June 2022

Background:
Benefits of mother's own milk (MOM) for infants in neonatal intensive care units (NICUs) are well known. Many mothers provide for their infant's feedings during their entire hospitalization while others are unable. Knowledge is limited about which infant and maternal factors may contribute most to cessation of MOM feedings.

Purpose:
Study aims were to (1) identify which maternal and infant risk factors or combination of factors are associated with cessation of provision of MOM during hospitalization, (2) develop a lactation risk tool to identify neonatal intensive care unit infants at higher risk of not receiving MOM during hospitalization, and (3) identify when infants stop receiving MOM during hospitalization.

Methods:
A data set of 797 infants admitted into a level IV neonatal intensive care unit before 7 days of age, whose mothers chose to provide MOM, was created from analysis of data from the Children's Hospital Neonatal Database. Maternal and infant factors of 701 dyads who received MOM at discharge were compared with 87 dyads who discontinued use of MOM by discharge using χ2, t tests, and Wilcoxon rank tests. Logistic regression was used to build a risk-scoring model.

Results:
The probability of cessation of MOM increased significantly with the number of maternal–infant risk factors. A Risk Calculator was developed to identify dyads at higher risk for cessation of MOM by discharge.

Implications for Practice:
Identifying mothers at risk for cessation of MOM can enable the healthcare team to provide optimal lactation management and outcomes.

Implications for Research:
Although the Risk Calculator has potential to identify dyads at risk of early MOM cessation, further research is needed to validate these results.
Temporal and Directional Cue Effects on the Cocktail Party Problem for Patients With Listening Difficulties Without Clinical Hearing Loss
Authors: Kawase Tetsuaki , Teraoka Ryo , Obuchi Chie , Sakamoto Shuichi 
Published: June 2022

Objectives:
To evaluate the listening difficulty in a cocktail party environment in the sound field in order to better demonstrate patients’ difficulties listening in noise, and to examine temporal and directional cue effects on the speech intelligibility in patients with listening difficulties in noise in comparison with control subjects.

Design:
This study examined and analyzed 16 control subjects without any complaints of listening difficulties and 16 patients who had visited the outpatient clinic of the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital, with complaints of listening difficulties, especially in background crowded conditions, despite having relatively good hearing on routine audiograms and speech audiometry. Using five loudspeakers located in front of the subject and at 30° and 60° to the left and right from the front, word intelligibility for the target voice (female talker) presented from one of the loudspeakers in random order with four distractor voices (male talker) was assessed under the following cue conditions: (1) “no additional temporal/directional cue (only talker sex as a cue)”; (2) “fixed temporal cue without directional cue” (white noise bursts [cue sounds] were presented from the five loudspeakers just before word presentation at 500-ms intervals); (3) “directional + variable temporal cues” [cue sounds were presented from the loudspeaker where the next target word would be presented with a variable inter-stimulus interval [ISI] of 500, 1000, 1500, or 2000 ms between the cue sound and word presentation); and (4) “directional + fixed temporal cues” (cue sounds were presented from the loudspeaker where the next target word would be presented with a fixed ISI of 500 ms).

Results:
The results indicated the following: (1) word intelligibility under distractors was significantly deteriorated in patients with listening difficulties compared with control subjects, although the clinical speech in noise test using the headphone system did not show any significant differences between the two groups; (2) word intelligibility under distractors for patients with listening difficulties was significantly improved with directional cues presented in advance; and (3) under most cue conditions, individual differences in word intelligibility among patients with listening difficulties were significantly correlated with their dichotic listening ability, which is one of the indicators used to assess auditory selective attention ability.

Conclusions:
The results of this study indicate the usefulness of the presentation of directional cues for speech comprehension in the cocktail party situation in patients with listening difficulties, as well as the importance of evaluating the degree of listening difficulties spatially in the cocktail party situation.
Renal oncocytoma: a challenging diagnosis
Authors: Mirkheshti Nooshin , Farrukh Naveed , Legesse Teklu , Rowe Steven P. , Gordetsky Jennifer , Hussain Arif 
Published: June 2022

Purpose of review
The aim of the review is to provide an update on the current and evolving approaches to diagnosing the challenging clinical entity of renal oncocytoma.

Recent findings
Renal oncocytoma is being increasingly recognized among patients with renal masses, and it can be found in up to 50% of benign small renal masses (SRMs) less than 4 cm. Renal oncocytomas have benign clinical biology but distinguishing them from some of the other renal masses with more malignant potential can be challenging due to overlapping imaging, histologic, and immunophenotypic characteristics. Increasing integration of various imaging modalities, histologic characteristics, cytogenetics, and molecular and metabolic signatures is helping better define and characterize renal masses.

Summary
Evolving and complementary diagnostic approaches, including at the molecular level, are continuing to help refine the classification of renal tumors, with implications on their clinical behavior and ultimately clinical management.
Compliance with the smoke-free policy in hospitals in Spain: the patients’ perspective
Authors: Fu Marcela , Castellano Yolanda , Feliu Ariadna , Saura Judith , Estrada Joan , Galimany-Masclans Jordi , Moreno Carmen , Fernández Esteve , Martínez Cristina 
Published: June 2022

Objective
To explore compliance with the smoke-free policy in hospitals in Catalonia, Spain, by exploring inpatients’ perceptions.

Methods
We conducted a cross-sectional study of a random sample of 1047 inpatients from 13 public hospitals. We collected data about: (a) type of information about the smoke-free policy provided by the hospital, (b) patients’ knowledge about the policy, (c) general appreciation of the compliance with the policy, and (d) specific appreciation of such compliance by noticing any sign of tobacco consumption. We described the data by several patients’ and hospitals’ characteristics and assessed their association with the perceived noncompliance using prevalence ratios (PR) and their 95% confidence intervals (CIs).

Results
Few patients were informed about the smoke-free policy (4.8% orally, 6.1% in writing, and 55.6% through sign postings). About 64% were aware of the regulation and 73.5% believed that it was properly obeyed. While 0.7% had never or rarely observed smoking indoors, 36.2% had seen someone smoking outdoors sometimes or many times. Signs of tobacco consumption were observed indoors and outdoors. Factors associated with the perception of noncompliance were: being less than 45 years old versus being more than 64 years old (adjusted PR, 2.33; 95% CI, 1.09–4.98) and currently smoking versus have never smoked (adjusted PR, 1.84; 95% CI, 1.02–3.34).

Conclusion
Compliance with the smoke-free policy in hospitals according to the patients’ view is notable, although several infringements were reported, mainly outdoors. The smoke-free policy in hospitals should be reinforced by prompting continuous awareness campaigns and the exemplary role of hospital workers.