bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catheter-guided multilevel epidural blood patches in an adolescent boy
Authors: Walfish Laurel , Alobaikan Sultan , Lahijanian Zubin , Saint-Martin Christine , Cortes Nino Maria delPilar , Ingelmo Pablo Mauricio 
Published: March 2022

BackgroundThere is increasing evidence for the use of multilevel epidural catheter-guided blood patches to treat spontaneous cerebrospinal fluid leaks in adults. Yet, there are scarce data for their use in children. Furthermore, higher level epidural blood patches are uncommon in both adult and pediatric populations.Case presentationAn adolescent boy with multilevel cerebrospinal fluid leaks associated with status migrainosus failed conservative pain management treatment. As he remained severely symptomatic, epidural blood patches were required to mitigate his symptoms. Given his multilevel leaks, a catheter-guided blood patch approach was used to treat multiple cervicothoracic and thoracolumbar leaks. After three separate uneventful blood patch procedures, the patient was free of symptoms. Other than some rebound intracranial hypertension, the patient maintained full neurological capacity without further complications. Following the resolution of treatment, he has not sought help for pain since his last blood patch over a year ago.ConclusionsMultilevel catheter-guided blood patches have the potential to be administered to higher level spinal regions to the pediatric population suffering from multiple spontaneous cerebrospinal fluid leaks.
The Two-Hit Hypothesis Meets Epigenetics
Authors: Issa Jean-Pierre 
Published: April 2022

Abstract
The landmark paper by Kane and colleagues was the first report of DNA methylation in the promoter of the human MLH1 gene in sporadic colon cancers with mismatch repair (MMR) deficiency. In both cell lines and primary tumors, promoter methylation was associated with loss of MLH1 protein expression and with a lack of mutations in the MLH1 coding region. Together with subsequent papers that showed that this methylation was directly responsible for loss of MLH1 expression and MMR deficiency, the observation expanded the two-hit hypothesis of tumor suppressor gene loss in cancer to include both genetic and epigenetic mechanisms of gene inactivation. More broadly, the paper contributed to normalization of the hypothesis of an epigenetic basis for cancer development.
See related article by Kane and colleagues, Cancer Res 1997;57:808–11
Cancer Modeling as Learning Experience
Authors: Etzioni Ruth , Lange Jane 
Published: April 2022

Abstract
Cancer modeling has become an accepted method for generating evidence about comparative effectiveness and cost-effectiveness of candidate cancer control policies across the continuum of care. Models of early detection policies require inputs concerning disease natural history and screening test performance, which are often subject to considerable uncertainty. Model validation against an external data source can increase confidence in the reliability of assumed or calibrated inputs. When a model fails to validate, this presents an opportunity to revise these inputs, thereby learning new information about disease natural history or diagnostic performance that could both enhance the model results and inform real-world practices. We discuss the conditions necessary for validly drawing conclusions about specific inputs such as diagnostic performance from model validation studies. Doing so requires being able to faithfully replicate the validation study in terms of its design and implementation and being alert to the problem of non-identifiability, which could lead to explanations for failure to validate other than those identified.
See related article by Rutter et al., p. 775
The Role of the TP53 Pathway in Predicting Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma
Authors: Sihag Smita , Nussenzweig Samuel C. , Walch Henry S. , Hsu Meier , Tan Kay See , De La Torre Sergio , Janjigian Yelena Y. , Maron Steven B. , Ku Geoffrey Y. , Tang Laura H. , Shah Pari M. , Wu Abraham , Jones David R. , Solit David B. , Schultz Nikolaus , Ganesh Karuna , Berger Michael F. , Molena Daniela 
Published: April 2022

Abstract

Purpose:
In patients with locally advanced esophageal adenocarcinoma, response to neoadjuvant therapy strongly predicts survival, but robust molecular predictors of response have been lacking. We therefore sought to discover meaningful predictors of response in these patients.

Experimental Design:
We retrospectively identified all patients with adenocarcinoma of the lower esophagus or gastroesophageal junction who (i) were treated with multimodality therapy with curative intent at our institution from 2014 through 2020 and (ii) underwent prospective sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Clinicopathologic and genomic data were analyzed to identify potential genomic features, somatic alterations, and oncogenic pathways associated with treatment response.

Results:
In total, 237 patients were included. MDM2 amplification was independently associated with poor response to neoadjuvant therapy [OR, 0.10 (95% confidence interval, 0.01–0.55); P = 0.032], when accounting for significant clinicopathologic variables, including clinical stage, tumor grade, and chemotherapy regimen. Moreover, TP53 pathway alterations, grouped according to inferred severity of TP53 dysfunction, were significantly associated with response to neoadjuvant therapy (P = 0.004, q = 0.07). Patients with MDM2 amplifications or truncating biallelic TP53 mutations had similar outcomes in terms of poor responses to neoadjuvant therapy and, consequently, shorter progression-free survival, compared with patients with TP53 pathway wild-type tumors. Thus, worsening TP53 dysfunction was directly correlated with worse outcomes.

Conclusions:
MDM2 amplification and TP53 status are associated with response to therapy in patients with esophageal adenocarcinoma. Given the dearth of actionable targets in esophageal adenocarcinoma, MDM2 inhibition, in combination with cytotoxic chemotherapy, may represent an important therapeutic strategy to overcome treatment resistance and improve outcomes in these patients.
PARPs: All for One and One for All? Enhancing Diversity in Clinical Trials
Authors: Nicum Shibani , Blagden Sarah P. 
Published: March 2022

SummaryPARP inhibitors have revolutionized the management of ovarian cancer and are being licensed for other cancer indications. The clinical trials prompting licensing decisions in ovarian cancer were dominated by White participants, or participant ethnicity was not documented. To compensate for this, replicative studies like L-MOCA can be run in specific ethnic groups. In the future, strategies such as mandatory collection and publication of race and ethnicity data are essential alongside concerted efforts to widen the inclusivity of trial recruitment.See related article by Gao et al., p. 2278
Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment
Authors: Sidiropoulos Dimitrios N. , Rafie Christine I. , Jang Julie K. , Castanon Sofi , Baugh Aaron G. , Gonzalez Edgar , Christmas Brian J. , Narumi Valerie H. , Davis-Marcisak Emily F. , Sharma Gaurav , Bigelow Emma , Vaghasia Ajay , Gupta Anuj , Skaist Alyza , Considine Michael , Wheelan Sarah J. , Ganesan Sathish Kumar , Yu Min , Yegnasubramanian Srinivasan , Stearns Vered , Connolly Roisin M. , Gaykalova Daria A. , Kagohara Luciane T. , Jaffee Elizabeth M. , Fertig Elana J. , Roussos Torres Evanthia T. 
Published: March 2022

Abstract

Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential to improve responses to immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown. Here, we employed single-cell RNA sequencing on HER2-overexpressing breast tumors from mice treated with entinostat and ICIs to fully characterize changes across multiple cell types within the TME. This analysis demonstrates that treatment with entinostat induced a shift from a protumor to an antitumor TME signature, characterized predominantly by changes in myeloid cells. We confirmed myeloid-derived suppressor cells (MDSC) within entinostat-treated tumors associated with a less suppressive granulocytic (G)-MDSC phenotype and exhibited altered suppressive signaling that involved the NFκB and STAT3 pathways. In addition to MDSCs, tumor-associated macrophages were epigenetically reprogrammed from a protumor M2-like phenotype toward an antitumor M1-like phenotype, which may be contributing to a more sensitized TME. Overall, our in-depth analysis suggests that entinostat-induced changes on multiple myeloid cell types reduce immunosuppression and increase antitumor responses, which, in turn, improve sensitivity to ICIs. Sensitization of the TME by entinostat could ultimately broaden the population of patients with breast cancer who could benefit from ICIs.
Analysis of the Consumption Patterns of Health Supplements in Health Care Worker in the Era of the COVID-19 Pandemic
Authors: Sari Wening 
Published: March 2022

Health workers are at the forefront of handling COVID-19, so they have a high risk of contracting the virus. There have been 1.967 deaths in Indonesian health workers due to COVID-19, the highest number in Asia. While on the job, health workers must maintain a healthy immune system and use personal protective equipment. It is believed that taking vitamins, minerals, and herbs can help boost endurance. This study aims to examine the pattern of health supplement consumed in health workers during the COVID-19 pandemic. This research was conducted with a Cross-Sectional approach carried out on 100 health workers by providing questionnaires related to the types and effects of health supplements consumed by health workers in the era of the COVID-19 pandemic. From all respondents who took supplements, 75.2% consumed every day during the pandemic, whereas only 40.6% did before the pandemic. Prior to the pandemic, it was discovered that 33% of respondents took more than two types of health supplements. However, during the pandemic, it was revealed that 65% took more than two types of health supplements. There was an increase in respondents who took supplements believed to improve the immune system (80.2% vs 50.5%). Consumption of herbs and honey increased during the pandemic (19.8% vs 40.6%), with honey the most consumed. During the pandemic, health workers take more health supplements and a more comprehensive range of supplements.
Dove avrebbe messo Dante Ser Ciappelletto?
Authors: Aguiar Leonardo Ferreira , Casini Maria Cecilia 
Published: April 2022

Il presente testo propone un po' audacemente una lettura di una possibile assoluzione, in termini danteschi, di un famoso personaggio 'cattivo' del Decameron, opera di Giovanni Boccaccio, ovvero, Ser Ciappelletto da Prato, protagonista della prima Novella della Prima Giornata. A partire dai propri testi e dalla struttura morale conferita da Dante Alighieri al suo universo oltremondano descritto nella Divina Commedia, abbiamo usato l'immaginazione per attribuire un luogo possibile al malvagio Ciappelletto. Secondo la nostra interpretazione, esisterebbero per questo due possibilità: la Giudecca, il luogo più buio dell'Inferno; o l'antipurgatorio, luogo di espiazione dei peccati da parte di chi attende ancora una possibilità di salvezza, insieme a Belacqua nel Canto IV della cantica del Purgatorio. Nonostante si tratti di una speculazione, il testo è stato sviluppato alla luce delle ultime teorie critiche sui due grandi autori italiani, in modo da porsi come un contributo al dibattito letterario in corso per il settecentenario delle commemorazioni dantesche del 2021.
Randomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study)
Authors: Shishehbor Mehdi H. , Zeller Thomas , Werner Martin , Brodmann Marianne , Parise Helen , Holden Andrew , Lichtenberg Michael , Parikh Sahil A. , Kashyap Vikram S. , Pietras Cody , Tirziu Daniela , Ardakani Shiva , Beschorner Ulrich , Krishnan Prakash , Niazi Khusrow A. , Wali Andreas U. , Lansky Alexandra J. 
Published: April 2022

Background:
First-generation drug-coated balloons (DCBs) have significantly reduced the rate of restenosis compared with balloon angioplasty alone; however, high rates of bailout stenting and dissections persist. The Chocolate Touch DCB is a nitinol constrained balloon designed to reduce acute vessel trauma and inhibit neointima formation and restenosis.

Methods:
Patients with claudication or ischemic rest pain (Rutherford class 2–4) and superficial femoral or popliteal disease (≥70% stenosis) were randomized 1:1 to Chocolate Touch or Lutonix DCB at 34 sites in the United States, Europe, and New Zealand. The primary efficacy end point was DCB success, defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of clinically driven bailout stenting). The primary safety end point was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. Both primary end points were tested for noninferiority, and if met, sequential superiority testing for efficacy followed by safety was prespecified. An independent clinical events committee, and angiographic and duplex ultrasound core laboratories blinded to treatment allocation reviewed all end points.

Results:

A total of 313 patients were randomized to Chocolate Touch (n=152) versus Lutonix DCB (n=161). Follow-up at 1 year was available in 94% of patients. The mean age was 69.4±9.5 years, the average lesion length was 78.1±46.9 mm, and 46.2% had moderate-to-severe calcification. The primary efficacy rates of DCB success at 12 months was 78.8% (108/137) with Chocolate Touch and 67.7% (88/130) with Lutonix DCB (difference, 11.1% [95% CI, 0.6–21.7]), meeting noninferiority (
P
noninferiority
<0.0001) and sequential superiority (
P
superiority
=0.04). The primary safety event rate was 88.9% (128/144) with Chocolate Touch and 84.6% (126/149) with Lutonix DCB (
P
noninferiority
<0.001;
P
superiority
=0.27).

Conclusions:
In this prospective, multicenter, randomized trial, the second-generation Chocolate Touch DCB met both noninferiority end points for efficacy and safety and was more effective than Lutonix DCB at 12 months for the treatment of femoropopliteal disease.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02924857.
Comparison of Lagrangian Superdroplet and Eulerian Double-Moment Spectral Microphysics Schemes in Large-Eddy Simulations of an Isolated Cumulus Congestus Cloud
Authors: Chandrakar Kamal Kant , Morrison Hugh , Grabowski Wojciech W. , Bryan George H. 
Published: April 2022

Abstract
Advanced microphysics schemes (such as Eulerian bin and Lagrangian superdroplet) are becoming standard tools for cloud physics research and parameterization development. This study compares a double-moment bin scheme and a Lagrangian superdroplet scheme via large-eddy simulations of nonprecipitating and precipitating cumulus congestus clouds. Cloud water mixing ratio in the bin simulations is reduced compared to the Lagrangian simulations in the upper part of the cloud, likely from numerical diffusion, which is absent in the Lagrangian approach. Greater diffusion in the bin simulations is compensated by more secondary droplet activation (activation above cloud base), leading to similar or somewhat higher droplet number concentrations and smaller mean droplet radius than the Lagrangian simulations for the nonprecipitating case. The bin scheme also produces a significantly larger standard deviation of droplet radius than the superdroplet method, likely due to diffusion associated with the vertical advection of bin variables. However, the spectral width in the bin simulations is insensitive to the grid spacing between 50 and 100 m, suggesting other mechanisms may be compensating for diffusion as the grid spacing is modified. For the precipitating case, larger spectral width in the bin simulations initiates rain earlier and enhances rain development in a positive feedback loop. However, with time, rain formation in the superdroplet simulations catches up to the bin simulations. Offline calculations using the same drop size distributions in both schemes show that the different numerical methods for treating collision–coalescence also contribute to differences in rain formation. The stochastic collision–coalescence in the superdroplet method introduces more variability in drop growth for a given rain mixing ratio.
Global Middle-Atmosphere Response to Winter Stratospheric Variability in SABER and MLS Mean Temperature
Authors: Smith A. K. , Pedatella N. M. , Bardeen C. G. 
Published: April 2022

Abstract
Satellite observations of middle-atmosphere temperature are used to investigate the short-term global response to planetary wave activity in the winter stratosphere. The focus is on the relation between variations in the winter and summer hemispheres. The analysis uses observations from Thermosphere–Ionosphere–Mesosphere Energetics and Dynamics (TIMED) Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) for 2002–21 and Aura Microwave Limb Sounder (MLS) for 2004–21, and reanalysis temperatures and winds from MERRA-2 for 2002–21. We calculate temporal correlations of the Eliassen–Palm flux divergence in the winter stratosphere with global temperature. Results show a robust perturbation extending to midlatitudes of the Southern Hemisphere (SH) stratosphere during Northern Hemisphere (NH) winter. An increase in wave forcing is followed by a decrease in temperatures over the depth of the stratosphere in the SH, peaking at a lag of 3 days. Summer mesospheric temperature perturbations of the opposite sign are seen in many winters. Comparable signals in the NH summer middle-atmosphere are present during some SH winters but are weaker and less consistent than those in the SH during NH winter. A diagnostic evaluation of the patterns of correlation, the mesospheric zonal winds, and the stability criteria suggests that the temperature perturbations in the midlatitude summer mesosphere are more closely associated with the summer stratosphere directly below than with the wave activity in the winter stratosphere. This suggests that the interhemispheric coupling in the stratosphere is driving or contributing to the coupling between the winter stratosphere and the summer mesosphere that has been reported in several investigations.

Significance Statement
There are many instances in which one part of the atmosphere is found to regularly respond to perturbations occurring in a distant region. In this study, we use observations to investigate one such pattern: temperature changes at high altitude (60–100 km) in the summer that follow dynamical changes near the winter pole at 40–60 km. Such analysis is useful to understand which physical processes contribute to the global connectivity and variability of the atmosphere.
Effects of Sea Spray on Large-Scale Climatic Features over the Southern Ocean
Authors: Song Yajuan , Qiao Fangli , Liu Jiping , Shu Qi , Bao Ying , Wei Meng , Song Zhenya 
Published: April 2022

Abstract
The Southern Ocean, characterized by strong westerly winds and a rough sea state, exhibits the most pronounced sea spray effects. Sea spray ejected by ocean surface waves enhances heat and water exchange at the air–sea interface. However, this process has not been considered in current climate models, and the influence of sea spray on the coupled air–sea system remains largely unknown. This study incorporated a parameterization of the sea spray influence on latent and sensible heat fluxes into the First Institute of Oceanography Earth System Model version 2.0 (FIO-ESM v2.0), a climate model coupled with an ocean surface waves component. The results indicate that the spray-mediated enthalpy flux accounted for over 20%–50% of the total value. Sea spray promoted ocean evaporation and heat transport, resulting in air and ocean surface cooling and strengthened westerly winds. Furthermore, a moist and stable atmosphere favored an increase in cloud fraction over the Southern Ocean, particularly low-level clouds. Increased clouds reflected downward shortwave radiation and reduced solar radiation absorption at the surface. At present, the climate models participating in phase 6 of the Coupled Model Intercomparison Project (CMIP6) still suffer notable deficiencies in reasonably reproducing the climatological features of the Southern Ocean, including warm SST and underestimated clouds biases with more absorbed shortwave radiation. Our results suggest that consideration of sea spray effects is a feasible solution to mitigate these common biases and enhance the confidence in simulations and predictions with climate models.
Intraseasonal Oscillatory Modes in the Eastern Mediterranean Sea
Authors: Feliks Yizhak , Gildor Hezi , Mantel Nadav 
Published: March 2022

Abstract
The intraseasonal oscillations (ISOs) in sea currents in the eastern Mediterranean Sea near the central coast of Israel were analyzed by examining the velocity components of the sea currents at different depths as measured by acoustic Doppler current profilers located at various depths between 0 and 675 m. The total period covered by the observations was from December 2016 to May 2018. Prominent intraseasonal oscillations, much stronger than tidal velocity components, were observed in the upper part of the sea, at 30–70 m. The amplitudes of these oscillations are between 4 and 10 cm s−1 and their periods are 7, 11, 22, and 34–36 days. The strongest oscillations are found in the boreal winter. The ISOs in the sea currents were apparently induced by corresponding oscillations found in atmospheric wind velocity over the eastern Mediterranean at the surface and at 500 and 250 hPa, as suggested by the high correlations, 0.6–0.9, between the wind velocity components of the oscillatory modes in the atmosphere and the velocity component of the oscillatory modes in the sea currents with similar periods. We propose that the source of the ISOs in the atmosphere over the eastern Mediterranean is the South Asian jet wave train. The track of this wave train passes over the eastern Mediterranean, and the periods of the ISOs in the wave train are in the same band as the oscillations found here. The wave train is equivalently barotropic and strongest in the upper troposphere. This property of the wave train can explain the high correlation found between the oscillatory modes of wind velocity at 250 or 500 hPa and those in the sea currents. In all the cases besides the 7-day oscillatory mode, the significant oscillatory modes found at 250 or 500 hPa are also significant in the velocity components of the surface wind.