bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of multimodal active learning and single-modality procedural simulation for central venous catheter insertion for incoming residents in anesthesiology: a prospective and randomized study
Authors: Blanie Antonia , Shoaleh Cécile , Marquion Fabien , Benhamou Dan
Published: May 2022

Background

Active learning methods, including low-fidelity simulation, are useful but the incremental learning effect of each method is however limited. We designed this study to assess if combining flipped classroom and the modified Peyton’s « 4-steps» method during procedural simulation (intervention group [IG]) would provide better learning results than simulation alone (control group [CG]) in the context of central venous catheter insertion training.

Methods

This prospective, single-center, and randomized study took place in 2017 in a single simulation center. All first year Anesthesiology residents of Ile de France area at the start of their residency were randomly included either in the IG or CG during a seminar aimed at providing initial procedural skills with low-fidelity simulation. A composite learning score which included knowledge MCQ and a questionnaire assessing satisfaction and value of the training session was recorded after training (primary outcome, /100). A randomized sub-group of learners of each group were video-recorded during central venous catheter insertion at the end of training and their skills were evaluated with validated tools, including a specific checklist and a global rating scale (GRS).

Results

Among 89 anesthesiology residents, 48 and 41 learners were randomized in the intervention and control groups respectively. Of the IG residents, 40/48 (83%) had read the learning material prior to the session. There was no significant difference regarding the composite outcome ([IG]= 81.1 vs [CG] = 80.5 /100 (p = 0.68)). Results of the post-session MCQ knowledge questionnaire were also non-significantly different. Residents were similarly satisfied and described a significant improvement of their knowledge and skills after training. Learners highly valued the training session as a mean to improve their future practice. No significant differences regarding checklist and GRS scores were observed.

Conclusions

A multimodal active learning strategy of procedural learning did not provide better learning outcomes when compared to a traditional simulation method. In both groups, satisfaction was high and perception of the acquired theoretical and practical knowledge was improved after training.
Nurses, physicians and patients’ knowledge and attitudes about nurse prescribing
Authors: Haririan Hamidreza , Seresht Deniz Manie , Hassankhani Hadi , Porter Joanne E. , Wytenbroek Lydia
Published: May 2022

Background

One of the roles that nurses have acquired in recent years is the role of prescribing. This study aimed to investigate the knowledge and attitudes of critical care nurses, physicians and patients about nurse prescribing.

Methods

A descriptive cross-sectional study with the participation of 152 nurses, 53 physicians and 75 patients was carried out. Participants were selected by stratified random sampling from the critical care units of six hospitals in Tabriz, Iran. Demographics and participants’ knowledge and attitudes about nurse prescribing questionnaires were used to collect data. The collected data were analyzed using SPSS-22 software.

Results

The mean scores of total knowledge about nurse prescribing in nurses, patients and physicians’ were 15.41 ± 1.85,16.45 ± 2.31, 14.74 ± 1.7 respectively (from a range of 10 -20), and the mean score of knowledge by physicians was significantly higher than others (P = 0.000) and they had more knowledge about nurse prescribing. The mean scores of the attitudes towards nurse prescribing in nurses, physicians and patients were 40.62 ± 3.68, 37.98 ± 5.92 and 39.38 ± 4.39 respectively (from a range of 10 -50). However, the total mean score of attitudes among nurses was significantly higher than others (P = 0.000) and nurses had more positive attitudes toward prescribing.

Conclusion

The results showed that the participants have a good understanding and attitudes toward nurse prescribing. Nurse prescribing as a new duty and authority can be considered in providing more effective care by specialist nurses. The results of this study can also be used in the future planning of health policy for nurses to have the right to prescribe and ultimately improve the quality of patient care.
Accuracy evaluation of combining gastroscopy, multi-slice spiral CT, Her-2, and tumor markers in gastric cancer staging diagnosis
Authors: Zhao Songbo , Bi Yangang , Wang Zhenfang , Zhang Fantao , Zhang Yang , Xu Yongyun
Published: May 2022

Background

To evaluate the diagnostic accuracy of single gastroscopy, multi-slice spiral CT, HER-2 or tumor markers, and their combination in the diagnosis of gastric cancer.

Methods

A total of 98 patients with gastric cancer were selected as the research subjects. All patients underwent preoperative gastroscopy, MSCT, and the expression levels of HER-2, CEA, CA199, CA724, and CA242 were detected. A control group of 98 normal adults was selected to compare the risk factors for gastric cancer and to analyze the data.

Results

There was statistical significance in the expression of the 5 markers in tumor size (P < 0.05), but no statistical significance in other clinical data (P > 0.05). The tumor marker CEA in gastric mucosal tissue of patients with gastric cancer had the highest positive detection rate for gastric cancer, and the difference was statistically significant (P < 0.05) compared with gastroscopy, MSCT and other markers. The combined diagnosis had higher sensitivity, specificity and accuracy compared with the single diagnosis of gastric cancer staging, and the difference was statistically significant (P < 0.05). Compared with normal adults, patients with gastric cancer had statistically significant differences in diet, body mass index, and family genetic history (P < 0.05), while there was no statistically significant difference in whether they had type A blood (P > 0.05).

Conclusion

The combined diagnosis of gastroscopy, MSCT, immunohistochemical marker Her-2, and tumor markers CEA, CA199, CA724, and CA242 can more accurately determine the clinical staging and lesion invasion depth of patients with gastric cancer and can significantly improve the sensitivity of diagnosis.
Regulatory role of short-chain fatty acids in inflammatory bowel disease
Authors: Zhang Zhilin , Zhang Huan , Chen Tian , Shi Lin , Wang Daorong , Tang Dong
Published: May 2022

Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract. Accumulating evidence shows that the development of IBD is always accompanied by the dysbiosis of the gut microbiota (GM), causing a decrease in prebiotic levels and an increase in harmful metabolite levels. This leads to persistent immune response and inflammation in the intestine, greatly impairing the physiological function of the gastrointestinal tract. Short-chain fatty acids (SCFAs) are produced by probiotic gut bacteria from a fiber-rich diet that cannot be digested directly. SCFAs with significant anti-inflammatory functions regulate immune function and prevent an excessive immune response, thereby delaying the clinical progression of IBD. In this review, we summarize the generation of SCFAs and their potential therapeutic effects on IBD. Furthermore, we suggest that SCFAs may modulate innate immune recognition and cytokine production to intervene in the progression of IBD. Additional randomized controlled trials and prospective cohort studies should also investigate the clinical impact of SCFA.
Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B
Authors: Murcko Robert , Marchi Nicola , Bailey Damian , Janigro Damir
Published: May 2022

Blood biomarkers of neurological diseases are often employed to rule out or confirm the presence of significant intracranial or cerebrovascular pathology or for the differential diagnosis of conditions with similar presentations (e.g., hemorrhagic vs. embolic stroke). More widespread utilization of biomarkers related to brain health is hampered by our incomplete understanding of the kinetic properties, release patterns, and excretion of molecules derived from the brain. This is, in particular, true for S100B, an astrocyte-derived protein released across the blood–brain barrier (BBB). We developed an open-source pharmacokinetic computer model that allows investigations of biomarker’s movement across the body, the sources of biomarker’s release, and its elimination. This model was derived from a general in silico model of drug pharmacokinetics adapted for protein biomarkers. We improved the model’s predictive value by adding realistic blood flow values, organ levels of S100B, lymphatic and glymphatic circulation, and glomerular filtration for excretion in urine. Three key variables control biomarker levels in blood or saliva: blood–brain barrier permeability, the S100B partition into peripheral organs, and the cellular levels of S100B in astrocytes. A small contribution to steady-state levels of glymphatic drainage was also observed; this mechanism also contributed to the uptake of organs of circulating S100B. This open-source model can also mimic the kinetic behavior of other markers, such as GFAP or NF-L. Our results show that S100B, after uptake by various organs from the systemic circulation, can be released back into systemic fluids at levels that do not significantly affect the clinical significance of venous blood or salivary levels after an episode of BBB disruption.
The risk factors for the failure of hook wire localization of ground glass nodules prior to thoracoscopic surgery
Authors: Ala Musu , Liu Junzhong , Kou Jieli , Wang Xinhua , Sun Minfeng , Hao Changcheng , Wu Jianlin
Published: May 2022

Objectives

To retrospectively analyse the potential influencing factors of CT-guided hook wire localization failure prior to thoracoscopic resection surgery of ground glass nodules (GGNs), and determine the main risk elements for localization failure.

Methods

In all, 372 patients were included in this study, with 21 patients showing localization failure. The related parameters of patients, GGNs, and localization were analysed through univariate and multiple logistic regression analysis to determine the risk factors of localization failure.

Results

Univariate logistic regression analysis indicated that trans-fissure (odds ratio [OR] 4.896, 95% confidence interval [CI] 1.489–13.939); trans-emphysema (OR 3.538, 95% CI 1.343–8.827); localization time (OR 0.956, 95% CI 0.898–1.019); multi-nodule localization (OR 2.597, 95% CI 1.050–6.361); and pneumothorax (OR 10.326, 95% CI 3.414–44.684) were risk factors for localization failure, and the p-values of these factors were < 0.05. However, according to the results of multivariate analysis, pneumothorax (OR 5.998, 95% CI 1.680–28.342) was an exclusive risk factor for the failure of preoperative localization of GGNs.

Conclusion

CT-guided hook wire localization of GGNs prior to thoracoscopic surgery is often known to fail; however, the incidence is low. Pneumothorax is an independent risk factor for failure in the localization process.
Wideband spectrum sensing based on advanced sub-Nyquist sampling structure
Authors: Wang Xue , Chen Qian , Jia Min , Gu Xuemai
Published: May 2022

As the bandwidth increases, the high-speed sampling rate becomes the bottleneck for the development of wideband spectrum sensing. Wideband spectrum sensing with sub-Nyquist sampling attracts more attention and modulated wideband converter (MWC) is an attractive sub-Nyquist sampling system. For the purpose of breaking the system structure limit, an advanced sub-Nyquist sampling framework is proposed to simplify the MWC system structure, adopting the single sampling channel structure with a frequency shifting module to acquire the sub-Nyquist sampling values. In order to recover the signal support information, the sensing matrix must be built according to the only one mixing function. Most existing support recovery methods rely on some prior knowledge about the spectrum sparsity, which is difficult to acquire in practical electromagnetic environment. To address this problem, we propose an adaptive residual energy detection algorithm (ARED), which bypasses the need for the above-mentioned prior knowledge. Simulation results show that, without requiring the aforementioned prior knowledge, the ARED algorithm based on the advanced sub-Nyquist sampling framework has the similar performance as MWC and even higher than MWC in some cases using only one sampling channel.
Opportunities and challenges of using metagenomic data to bring uncultured microbes into cultivation
Authors: Liu Sijia , Moon Christina D. , Zheng Nan , Huws Sharon , Zhao Shengguo , Wang Jiaqi
Published: May 2022

Although there is now an extensive understanding of the diversity of microbial life on earth through culture-independent metagenomic DNA sequence analyses, the isolation and cultivation of microbes remains critical to directly study them and confirm their metabolic and physiological functions, and their ecological roles. The majority of environmental microbes are as yet uncultured however; therefore, bringing these rare or poorly characterized groups into culture is a priority to further understand microbiome functions. Moreover, cultivated isolates may find utility in a range of applications, such as new probiotics, biocontrol agents, and agents for industrial processes. The growing abundance of metagenomic and meta-transcriptomic sequence information from a wide range of environments provides more opportunities to guide the isolation and cultivation of microbes of interest. In this paper, we discuss a range of successful methodologies and applications that have underpinned recent metagenome-guided isolation and cultivation of microbe efforts. These approaches include determining specific culture conditions to enrich for taxa of interest, to more complex strategies that specifically target the capture of microbial species through antibody engineering and genome editing strategies. With the greater degree of genomic information now available from uncultivated members, such as via metagenome-assembled genomes, the theoretical understanding of their cultivation requirements will enable greater possibilities to capture these and ultimately gain a more comprehensive understanding of the microbiomes.
Frequency spectra of horizontal winds in the mesosphere and lower thermosphere region from multistatic specular meteor radar observations during the SIMONe 2018 campaign
Authors: Charuvil Asokan Harikrishnan , Chau Jorge L. , Marino Raffaele , Vierinen Juha , Vargas Fabio , Urco Juan Miguel , Clahsen Matthias , Jacobi Christoph
Published: May 2022

In recent years, multistatic specular meteor radars (SMRs) have been introduced to study the Mesosphere and Lower Thermosphere (MLT) dynamics with increasing spatial and temporal resolution. SMRs, compared to other ground-based observations, have the advantage of continuously measuring the region between 80 and 100 km independent of weather, season, or time of day. In this paper, frequency spectra of MLT horizontal winds are explored through observations from a campaign using the SIMONe (Spread-spectrum Interferometric Multistatic meteor radar Observing Network) approach conducted in northern Germany in 2018 (hereafter SIMONe 2018). The 7-day SIMONe 2018 comprised of fourteen multistatic SMR links and allows us to build a substantial database of specular meteor trail events, collecting more than one hundred thousand detections per day within a geographic area of $$\sim$$
∼
500 km $$\times$$
×
500 km. We have implemented two methods to obtain the frequency spectra of the horizontal wind components: (1) Mean Wind Estimation (MWE) and (2) Wind field Correlation Function Inversion (WCFI), which utilizes the mean and the covariances of the line of sight velocities, respectively. Monte Carlo simulations of a gravity wave spectral model were implemented to validate and compare both methods. The simulation analyses suggest that the WCFI helps us to capture the energy of smaller scale wind fluctuations than those capture with MWE. Characterization of the spectral slope of the horizontal wind at different MLT altitudes has been conducted on the SIMONe 2018, and it provides evidence that gravity waves with periods smaller than 7 h and greater than 2 h dominate with horizontal structures significantly larger than 500 km. In the future, these analyses can be extended to understand the significance of small-scale fluctuations in the MLT, which were not possible with conventional MWE methods.

Graphical Abstract
Rheological properties of halloysite soil slurry: a case study of weathered tephra involved in a shallow landslide triggered by the 2018 Eastern Iburi earthquake in Hokkaido, Japan
Authors: Kameda Jun
Published: May 2022

The 6.7 Mw Eastern Iburi earthquake of 6 September 2018 triggered destructive landslides in southern Hokkaido, Japan, many of which were characterized by the flow-like downslope movement of volcanic soils formed from weathered tephra containing halloysite. This study aims to elucidate the mechanism of landslide generation through rheological characterization of halloysite soil slurries. The examined slurries were prepared from either oven-dried or moist soil. Both slurries showed a power-law correlation between measured yield stress and moisture content. However, at a given water content, slurry made from dried soil showed stresses that are one-to-two orders of magnitude lower than those of slurry made from moist soil. Compared with the measurements for the slurry of dried soil, those for the slurry of moist soil are closer to prior numerical modeling of a specific landslide, indicating that the soils involved were moist. The yield stress also varied with slurry pH, generally increasing with decreasing pH, which is in part explained by the DLVO force model based on the electrical double layer and van der Waals forces between the colloidal particles. The pH dependence is more prominent in the slurry of moist soil, and thus the mechanical state of the slope appears to vary significantly with rainfall-induced changes in subsurface chemistry. Dynamic viscoelasticity measurement indicated that both initially solid-like slurries can become fluid under an applied oscillatory strain of 0.5 to 10 Hz: the susceptibility to fluidization depends greatly on water content and frequency. The ground motion during the earthquake easily fluidized the slurry, indicating this was a factor contributing to the observed flow-like landslides.

Graphical Abstract
Miaodigounization and Erlitounization: the formation and evolution of the Hua-Xia ethnic group and Hua-Xia tradition from the perspective of archaeology
Authors: Bingwu Cao
Published: May 2022

What is Hua-Xia? How and when did the Hua-Xia ethnic group and Hua-Xia tradition come into being? As the spatial and temporal framework, the connotative features and the genealogy of the archaeological culture become increasingly clear, we can identify two important periods of prehistoric archaeological cultures that may have played key roles in the formation of the Hua-Xia ethnic group and its cultural identity. First is the Yangshao Culture (especially its Miaodigou Era), which was formed at the middle Neolithic age. During this period, agriculture was established as the main economic base, resulting in massive population growth, as well as rapid expansion of painted pottery, unique artifact collections and other highly consistent material culture, from the Central Plains of China to the upper and middle reaches of the Yellow River and beyond. Based on recent genetic, linguistic and other multidisciplinary research, it can be roughly confirmed that this culture is the archaeological manifestation of the emergence and formation of the Sino-Tibetan language family with a large population and a vast territory, so it is of fundamental significance for the formation of the Hua-Xia tradition in terms of ethnicity, language and culture. Second is the Erlitou Culture, which rose in the heart of the Central Plains of China after the Longshan Era, and stood out again in the Yangshao homeland in the competition among the regional cultural traditions of the early Chinese interaction circle after the collapse of the Yangshao Culture. Absorbing all the advanced cultural factors known at that time, it became the mainstream cultural tradition and great civilization tradition, including the political tradition, the ideological tradition, the lineage system and the unity and coherence in writing. The Erlitou Culture provided world views, values, even the instrumental systems and political institutions for the continuation of the Xia, Shang and Zhou dynasties to identify and follow, which roughly corresponded to the rise of the Xia dynasty as depicted in the literature. Thus, if Miaodigounization, with its great integration and expansion feature, was acclaimed as the foundation of the Hua-Xia tradition, Erlitounization enabled the establishment of Hua-Xia mainstream tradition.
Chronic neck pain and respiratory dysfunction: a review paper
Authors: Nair Shruti P. , Panchabhai Chaitrali S. , Panhale Vrushali
Published: May 2022

Background

Neck pain is one of the most frequently reported musculoskeletal complaints among adults; its prevalence in the world is ranging from 16.7 to 75.1%. It can have an impact on a person’s physical, psychological, and social well-being. Along with pain, disability, muscle weakness, and alterations in the posture, neck pain patients are likely to develop affection of the respiratory function as reported in numerous studies. However, these patients are primarily managed with a musculoskeletal perspective with little or no emphasis to the changes observed in the respiratory system. There is a paucity of literature evaluating the need for respiratory rehabilitation in these patients.

Main body

All relevant published literature related to respiratory dysfunction in patients with chronic neck pain were critically reviewed in this study. Patients having chronic neck pain were found to have alterations in respiratory function in terms of reduced lung volumes, reduced chest mobility, and decreased respiratory muscle strength. Various factors such as decreased cervical range of motion, decreased strength of deep neck flexors and extensors, forward head posture, and pain are known to cause these dysfunctions. Respiratory system intervention in the form of breathing re-education and respiratory exercises are significantly proven to improve treatment outcomes.

Conclusion

There is limited literature relating to respiratory dysfunction and its management in neck pain patients. Incorporation of both respiratory and musculoskeletal assessments can enhance their treatment outcomes. Additionally, it can be suggested to consider intervention in the form of respiratory rehabilitation while strategizing treatment goals for these patients.
Promoting Achievement for Community College STEM Students through Equity-Minded Practices
Authors: Varty Alison K.
Published: May 2022

HIGHLIGHT:This study aims to describe U.S. community college STEM students by highlighting the unique characteristics that distinguish them from other U.S. undergraduates while also illuminating their academic stumbling blocks and achievement disparities. These analyses are used to propose equity-based strategies to promote this group’s achievement in STEM.
Disparities in Cancer Genetic Testing and Variants of Uncertain Significance in the Hispanic Population of South Texas
Authors: Soewito Stephanie , Wyatt Rachel , Berenson Emily , Poullard Natalie , Gessay Shawn , Mette Lindsey , Marin Elena , Shelby Kristin , Alvarez Elise , Choi Byeong Yeob , Aviles Clarissa , Pulido-Saldivar Anna Maria , Otto Pamela M. , Jatoi Ismail , Ramamurthy Chethan , Ignatius Myron , Kaklamani Virginia G. , Tomlinson Gail E.
Published: May 2022

PURPOSE:

Racial and ethnic disparities have included a lack of access to both genetic testing and research, resulting in poor understanding of the genomic architecture in under-represented populations. The South Texas population is primarily of Hispanic background and has been largely devoid of genetic services. We extended access to this underserved population and uncovered genetic variants previously not observed, emphasizing the need to continually improve both genomic databases and clarification of variant significance to provide meaningful patient counseling.

METHODS:

This study consisted of a retrospective cohort review of patients seen through a cancer genetics education and service program across 24 counties in South Texas. In total, 1,595 individuals were identified as appropriate for cancer genetic counseling and 1,377 completed genetic testing.

RESULTS:

Eighty percent of those receiving genetic counseling self-identified as Hispanic, 16% as non-Hispanic White (NHW), 3% as African American, and 1% as other race/ethnicity. Of reported variants, 18.8% were pathogenic and 13.7% were reported as a variant of uncertain significance (VUS). VUS was reported in 17.2% of the Hispanic individuals compared with 9% NHW ( P = .005).

CONCLUSION:

Individuals of Hispanic ethnicity were significantly more likely to harbor a VUS compared with NHW. The extended reach into our regional communities revealed a gap in the ability to accurately interpret genomic variation with implications for advising patients on screening, prevention, and management strategies. A higher percentage of VUS also emphasizes the challenge of continued follow-up amid existing barriers that led to disparities in access. As understanding of the variants develops, hopefully gaps in knowledge of the genomic landscape will be lessened with increased clarity to provide accurate cancer risk assessment and recommendations for implementing prevention initiatives.
Patterns of Colorectal Cancer in Texas Counties From 2000 to 2017
Authors: LaPelusa Michael , Diaz Fernando , Machiorlatti Michael
Published: May 2022

PURPOSE:

Residents living in Texas counties along the United States–Mexico border make up a unique demographic. These counties consist of a large proportion of Hispanic-Latinx people who experience a high rate of health uninsurance and underinsurance, low household income averages, and, as a whole, exhibiting relatively poor health outcomes compared to the US general population. Limited information exists regarding the effects of these characteristics on the incidence of colorectal cancer (CRC).

METHODS:

Using data from the Texas Department of State Health Service, we calculated that the overall age-adjusted incidence rate (AAIR) of CRC was lower and decreased at a slower rate over time in Texas border counties compared with nonborder counties in Texas.

RESULTS:

The AAIR of CRC was lower and decreased at a slower rate over time in Texas border counties compared with nonborder counties in Texas. Conversely to other groups analyzed, the AAIR of CRC in individuals age 50-64 years in border counties increased.

CONCLUSION:

These findings are likely a reflection of less utilization of cancer screening in border counties than in nonborder counties. The increase in AAIR of CRC among individuals age 50-64 years in border counties warrants further investigation.
Dónde Están? Latinx/Hispanic Representation in the Oncology Workforce: Present and Future
Authors: Duma Narjust , Velazquez Ana I. , Franco Idalid , Kiel Lauren , Levit Laura A. , Schenkel Caroline , Kirkwood Kelsey , Green Sybil , Rodriguez Gladys
Published: May 2022

This manuscript reviews the status of Hispanic/Latinx physicians in oncology, the benefits and challenges to achieving equitable representation, and potential solutions and actions to increase diversity in the oncology workforce. Persons of Hispanic/Latinx origin comprise 18.7% of the population and 16.8% of the adult population in the United States but are only 4.7% of practicing oncologists. The reasons for the lack of representation of Hispanic/Latinx individuals in medicine are multifaceted and include discrimination and biases, exclusionary practices, financial barriers, and lack of role modeling. As a result, patients are deprived the benefits of a representative workforce, such as improved access, enhanced culturally and linguistically competent care, and minimization of health disparities. Solutions included in the manuscript include a description of efforts by ASCO to improve the representativeness of the oncology workforce through its awards programs and educational efforts, especially for Hispanic/Latinx clinicians. The manuscript also outlines individual actions that attending physicians, senior oncologists, oncology leaders, and hospital/cancer center leadership can take to improve the diversity of the oncology workforce and support our Latinx/Hispanic trainees and colleagues. Improving the representativeness of the oncology workforce will require collective action by institutions, medical societies, and individuals. Nevertheless, widespread commitment to creating an inclusive and supported workforce is necessary to ensure the quality of care for minority patients, reduce existing cancer care disparities, and advance innovation in oncology.
Negative Ultraselection of Patients With RAS/BRAF Wild-Type, Microsatellite-Stable Metastatic Colorectal Cancer Receiving Anti–EGFR-Based Therapy
Authors: Randon Giovanni , Maddalena Giulia , Germani Marco Maria , Pircher Chiara Carlotta , Manca Paolo , Bergamo Francesca , Giordano Mirella , Sposetti Caterina , Montagna Aldo , Vetere Guglielmo , Zambelli Luca , Rasola Cosimo , Boccaccino Alessandra , Pagani Filippo , Ambrosini Margherita , Massafra Marco , Fontanini Gabriella , Milione Massimo , Fassan Matteo , Cremolini Chiara , Lonardi Sara , Pietrantonio Filippo
Published: May 2022

PURPOSE

Several uncommon genomic alterations beyond RAS and BRAFV600E mutations drive primary resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer (mCRC). Our PRESSING panel (including PIK3CA exon 20/ AKT1/ PTEN mutations, ERBB2/ MET amplifications, gene fusions, and microsatellite instability-high status) represented a paradigm of negative hyperselection with more precise tailoring of EGFR blockade. However, a modest proportion of hyperselected mCRC has intrinsic resistance potentially driven by even rarer genomic alterations.

MATERIALS AND METHODS

A prospective data set at three Italian Academic Hospitals included 650 patients with mCRC with comprehensive genomic profiling by FoundationOne CDx and treated with anti-EGFRs. PRESSING2 panel alterations were selected on the basis of previous clinico-biologic studies and included NTRKs, ERBB3, NF1, MAP2K1/ 2/ 4, AKT2 pathogenic mutations; PTEN/ NF1 loss; ERBB3, FGFR2, IGF1R, KRAS, ARAF, and AKT1-2 amplification; and EGFR rearrangements. These were collectively associated with outcomes in patients with hyperselected disease, ie, RAS/ BRAF wild-type, PRESSING-negative, and microsatellite stable.

RESULTS

Among 162 hyperselected patients, 24 (15%) had PRESSING2 alterations, which were mutually exclusive except in two samples and were numerically higher in right-sided versus left-sided cancers (28% v 13%; P = .149). Independently of sidedness and other factors, patients with PRESSING2-positive status had significantly worse progression-free survival and overall survival compared with PRESSING2-negative ones (median progression-free survival: 6.4 v 12.8 months, adjusted hazard ratio 4.19 [95% CI, 2.58 to 6.79]; median overall survival: 22.6 v 49.9 months, adjusted hazard ratio 2.98 [95% CI, 1.49 to 5.96]). The combined analysis of primary tumor sidedness and PRESSING2 status allowed us to better stratify outcomes.

CONCLUSION

Negative ultraselection warrants further investigation with the aim of maximizing the benefit of EGFR blockade strategies in patients with RAS and BRAF wild-type, microsatellite stable mCRC.
Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery
Authors: Togioka Brandon M. , Zarnegarnia Yalda , Bleyle Lisa A. , Koop Dennis , Brookfield Kathleen , Yanez N. David , Treggiari Miriam M.
Published: May 2022

BACKGROUND:

Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11–21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability.

METHODS:

We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity.

RESULTS:

The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0–6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts.

CONCLUSIONS:

The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11–21 seconds). However, maximum plasma concentrations of chloroprocaine (Cmax range, 0.05–79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6–2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery.
Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients
Authors: Sundar Swetha J. , Lu Elaine , Schmidt Eric S. , Kondylis Efstathios D. , Vegh Deborah , Poturalski Matthew J. , Bulacio Juan C. , Jehi Lara , Gupta Ajay , Wyllie Elaine , Bingaman William E.
Published: May 2022

BACKGROUND:

Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures.

OBJECTIVE:

To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution.

METHODS:

Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist.

RESULTS:

We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case.

CONCLUSION:

Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.
Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components
Authors: Hantel Friederike , Liu Huaize , Fechtner Lisa , Neuhaus Herbert , Ding Jie , Arlt Danilo , Walentek Peter , Villavicencio-Lorini Pablo , Gerhardt Christoph , Hollemann Thomas , Pfirrmann Thorsten
Published: May 2022

Cilia are evolutionarily conserved organelles that orchestrate a variety of signal transduction pathways, such as sonic hedgehog (SHH) signaling, during embryonic development. Our recent studies have shown that loss of GID ubiquitin ligase function results in aberrant AMP-activated protein kinase (AMPK) activation and elongated primary cilia, which suggests a functional connection to cilia. Here, we reveal that the GID complex is an integral part of the cilium required for primary cilia-dependent signal transduction and the maintenance of ciliary protein homeostasis. We show that GID complex subunits localize to cilia in both Xenopus laevis and NIH3T3 cells. Furthermore, we report SHH signaling pathway defects that are independent of AMPK and mechanistic target of rapamycin (MTOR) activation. Despite correct localization of SHH signaling components at the primary cilium and functional GLI3 processing, we find a prominent reduction of some SHH signaling components in the cilium and a significant decrease in SHH target gene expression. Since our data reveal a critical function of the GID complex at the primary cilium, and because suppression of GID function in X. laevis results in ciliopathy-like phenotypes, we suggest that GID subunits are candidate genes for human ciliopathies that coincide with defects in SHH signal transduction.
Program Barriers and Facilitators in Virtual Cancer Exercise Implementation: A Qualitative Analysis
Authors: Gorzelitz Jessica S. , Bouji Nour , Stout Nicole L.
Published: May 2022

Introduction/Purpose

Because of the coronavirus disease 2019 (COVID-19) pandemic, many in-person cancer exercise and rehabilitation programs necessarily transitioned to virtual formats to meet the needs of individuals living with and beyond cancer. The purpose of this study was to qualitatively assess program-level facilitators and barriers to virtual exercise program implementation and to identify preferred strategies to overcome implementation barriers.

Methods

U.S.-based virtual cancer exercise and rehabilitation programs were recruited from professional networks via an e-mailed screening questionnaire. Eligible programs identified a point of contact for a one-on-one semistructured interview to discuss program-level barriers and facilitators to implementing virtual exercise programs. Interview transcript analysis was conducted via inductive coding techniques using NVivo software. Barriers were categorized according to the Consolidated Framework for Implementation Research, and a prioritized list of strategies to support implementation was created by mapping barriers to a list of Expert Recommendations for Implementing Change.

Results

Of the 41 unique responses received, 24 program representatives completed semistructured interviews. Interviewees represented individual programs, community-based programs, and hospital-based cancer exercise/rehabilitation programs. Analysis showed high correlation between facilitators and barriers by program type, with both program- and individual-level strategies used to implement exercise programs virtually. Strategies that ranked highest to support implementation include promoting program adaptability, building a coalition of stakeholders and identifying program champions, developing an implementation blueprint, altering organizational incentives and allowances, providing education across stakeholder groups, and accessing funding.

Conclusions

Learning from the transition of cancer exercise and rehabilitation programs to virtual formats due to the COVID-19 pandemic, we identify program-level barriers and facilitators encountered in the implementation of virtual programs and highlight implementation strategies that are most relevant to overcome common barriers. We present a roadmap for programs to use these strategies for future work in virtual exercise and rehabilitation program implementation.
Health Fitness Professionals’ Perceptions to Offering a Cancer Exercise Program: A Qualitative Study
Authors: DeScenza Victoria R. , Chaplow Zachary L. , Bowman Jessica , Sutherland Sue , Focht Brian C.
Published: May 2022

Introduction/Purpose

The purpose of this study is to qualitatively investigate fitness professionals’ perceptions of barriers and enablers to offering community-based exercise programs targeting cancer survivors at their fitness and/or community centers.

Methods

A qualitative case study approach incorporating Web-based survey and semistructured interview components was used to evaluate community-based fitness professionals’ programming perceptions.

Results

A total of seven subjects completed a semistructured interview. Data analysis using content analysis and the constant comparative method process revealed three primary domains with 11 underlying themes: 1) program barriers (education and awareness, physician referral, cost, and care along the cancer continuum); 2) program enablers (champion advocacy, sponsor/funding, personnel, and propositional solutions); and 3) program perceptions (social support, gym atmosphere, and cancer-specific modifications).

Conclusions

Findings from this qualitative study identified multiple domains and themes articulating health and fitness professionals’ perceptions of key barriers, enablers, and programmatic aspects in offering community-based exercise cancer programming. These results have important implications for guiding the design and delivery of community-based exercise programs for cancer survivors and represent an advance in the current literature surrounding implementation strategies in a clinic-to-community translational model of exercise-based supportive cancer care.
Διερεύνηση του εννοιολογικού πεδίου εκπαιδευτικών προσχολικής εκπαίδευσης και νηπίων για την έννοια του οικοσυστήματος
Authors: Μαλκοπούλου Ευμορφία
Published: May 2022

Η παρούσα έρευνα έχει ως σκοπό την διερεύνηση του βαθμού, που τα νήπια και οι νηπιαγωγοί κατανοούν τη δομή, την οργάνωση και τη λειτουργία του οικοσυστήματος όπως και τους μηχανισμούς αλληλεπίδρασης και αλληλόδρασης, που διέπουν τη λειτουργία αυτή. Η συστημική μελέτη της έννοιας επικεντρώνεται στους παράγοντες του συστήματος και στη λειτουργία του. Τα ερευνητικά ερωτήματα που διατυπώθηκαν αφορούσαν τον τρόπο με τον οποίο κατανοείται η δομή, τα όρια, τα συνιστώμενα στοιχεία, το εσωτερικό και εξωτερικό δίκτυο σχέσεων των συνιστώμενων στοιχείων και η λειτουργία ενός οικοσυστήματος. Εφαρμόστηκε στα νήπια η μέθοδος της συνέντευξης σε ζεύγη (Pair Depth Interviews) και η μέθοδος της ομαδικής συνέντευξης (Focus Group) στις νηπιαγωγούς καθώς και οι δύο παρέχουν τη δυνατότητα ανάπτυξης συζητήσεων και την ανάδειξη ευρέος φάσματος απαντήσεων. Η έρευνα πραγματοποιήθηκε με τέσσερις εφταμελείς ομάδες νηπιαγωγών και με 25 ζεύγη νηπίων. Έλαβαν συνολικά μέρος 50 νήπια στις συνεντεύξεις ανά ζεύγη και 28 Νηπιαγωγοί στις ομαδικές συνεντεύξεις. Το πρωτόκολλο της ομαδικής και σε ζεύγη συνέντευξης βασίζεται σε ερωτήσεις, που σχεδιάστηκαν για να καταγραφεί η κατανόηση ιδιαίτερων εννοιών, που αποτελούν την έννοια του οικοσυστήματος και λειτουργούν ολιστικά. Επιλέχθηκαν ζητήματα, ώστε να καταγραφούν αντιλήψεις για οικοσυστήματα όπως και διαφοροποιημένα δεδομένα για την τοποθέτηση του ανθρώπου, ως μέλος του οικοσυστήματος και ως εξωτερικός παράγοντας προς αυτό. Η ποιοτική ανάλυση περιεχομένου εξασφάλισε αντικειμενικότητα και συστηματικότητα. Τα κυριότερα συμπεράσματα, που προέκυψαν από την ανάλυση των δεδομένων ήταν ότι η έννοια του οικοσυστήματος για τα νήπια είναι οργανισμοί, που ο ένας τρώει τον άλλο, φύση και άνθρωπος. Έχουν στη διάθεση τους πληροφορίες, που δεν τις επεξεργάζονται με συστημικό τρόπο αλλά με γραμμικό τρόπο. Για τις νηπιαγωγούς η έννοια είναι φυσικό περιβάλλον, ζωντανοί οργανισμοί που αλληλεπιδρούν, χλωρίδα και πανίδα. Αναφέρουν ως συνιστώμενα στοιχεία ενός οικοσυστήματος τους ζωντανούς οργανισμούς, τις αλυσίδες τροφής, τα απορρίμματα, το κλίμα και τον άνθρωπο. Ως βασικές λειτουργίες του οικοσυστήματος καταγράφηκαν τα εξής: αλληλεξάρτηση, εξέλιξη διαβίωση, επιβίωση, αναπαραγωγή και ο ανθρώπινος παράγοντας. Η βιοποικιλότητα περιγράφηκε κυρίως ως τροφικές αλυσίδες σε ζεύγη, ως αιτία επιβίωσης και καλυτέρευση της ζωής, αισθητική άποψη, τελολογική και θεϊκή παρέμβαση, ανάγκη προσαρμογής στο κλίμα και αποτέλεσμα κρυφών πειραμάτων και συνωμοσιών. Η ροή ενέργειας- βιοχημικοί κύκλοι περιγράφηκαν ελάχιστα. Τα είδη κριτηρίων που τέθηκαν για την επεξήγηση των ανθρώπινων παρεμβάσεων είναι ανθρωποκεντρικά και αιτιολογούνται από τις φυσικές συνθήκες.
Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial
Authors: Fritz Bradley A. , Tellor Pennington Bethany R. , Palanca Ben J.A. , Schweiger Julie A. , Willie Jon T. , Farber Nuri B.
Published: May 2022

Background: Postoperative depressive symptoms are associated with pain, readmissions, death, and other undesirable outcomes. Ketamine produces rapid but transient antidepressant effects in the perioperative setting. Longer infusions confer lasting antidepressant activity in patients with treatment-resistant depression, but it is unknown whether a similar approach may produce a lasting antidepressant effect after surgery. This protocol describes a pilot study that will assess the feasibility of conducting a larger scale randomized clinical trial addressing this knowledge gap.

Methods: This single-center, double-blind, placebo-controlled pilot trial involves the enrollment of 32 patients aged 18 years or older with a history of depression scheduled for surgery with planned intensive care unit admission. On the first day following surgery and extubation, participants will be randomized to an intravenous eight-hour infusion of either ketamine (0.5 mg kg-1 over 10 minutes followed by a continuous rate of 0.3 mg kg-1 h-1) or an equal volume of normal saline. Depressive symptoms will be quantified using the Montgomery-Asberg Depression Rating Scale preoperatively and serially up to 14 days after the infusion. To detect ketamine-induced changes on overnight sleep architecture, a wireless headband will be used to record electroencephalograms preoperatively, during the study infusion, and after infusion. The primary feasibility endpoints will include the fraction of patients approached who enroll, the fraction of randomized patients who complete the study infusion, and the fraction of randomized patients who complete outcome data collection.

Conclusions: This pilot study will evaluate the feasibility of a future large comparative effectiveness trial of ketamine to reduce depressive symptoms in postsurgical patients.

Registration: K-PASS is registered on ClinicalTrials.gov: NCT05233566; registered February 10, 2022.