bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, histological and molecular profiling of different stages of alcohol-related liver disease
Authors: Ventura-Cots Meritxell , Argemi Josepmaria , Jones Patricia D , Lackner Carolin , El Hag Mohamed , Abraldes Juan G , Alvarado Edilmar , Clemente Ana , Ravi Samhita , Alves Antonio , Alboraie Mohamed , Altamirano Jose , Barace Sergio , Bosques Francisco , Brown Robert , Caballeria Juan , Cabezas Joaquin , Carvalhana Sofia , Cortez-Pinto Helena , Costa Adilia , Degré Delphine , Fernandez-Carrillo Carlos , Ganne-Carrie Nathalie , Garcia-Tsao Guadalupe , Genesca Joan , Koskinas John , Lanthier Nicolas , Louvet Alexandre , Lozano Juan José , Lucey Michael R , Masson Steven , Mathurin Philippe , Mendez-Sanchez Nahum , Miquel Rosa , Moreno Christophe , Mounajjed Taofic , Odena Gemma , Kim Won , Sancho-Bru Pau , Warren Sands R , Szafranska Justyna , Verset Laurine , Schnabl Bern , Sempoux Christine , Shah Vijay , Shawcross Debbie Lindsay , Stauber Rudolf E , Straub Beate K , Verna Elizabeth , Tiniakos Dina , Trépo Eric , Vargas Victor , Villanueva Càndid , Woosley John T , Ziol Marianne , Mueller Sebastian , Stärkel Peter , Bataller Ramon 
Published: January 2022

ObjectiveAlcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.DesignTwo large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.ResultsAge and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.ConclusionsDespite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.
Reprogramming the spleen into a functioning ‘liver’ in vivo
Authors: Liu Chunyan , Wang Lintao , Xu Mengzhen , Sun Yajie , Xing Zhen , Zhang Junfeng , Wang Chunming , Dong Lei 
Published: January 2022

ObjectiveLiver regeneration remains one of the biggest clinical challenges. Here, we aim to transform the spleen into a liver-like organ via directly reprogramming the splenic fibroblasts into hepatocytes in vivo.DesignIn the mouse spleen, the number of fibroblasts was through silica particles (SiO2) stimulation, the expanded fibroblasts were converted to hepatocytes (iHeps) by lentiviral transfection of three key transcriptional factors (Foxa3, Gata4 and Hnf1a), and the iHeps were further expanded with tumour necrosis factor-α (TNF-α) and lentivirus-mediated expression of epidermal growth factor (EGF) and hepatocyte growth factor (HGF).ResultsSiO2stimulation tripled the number of activated fibroblasts. Foxa3, Gata4 and Hnf1a converted SiO2-remodelled spleen fibroblasts into 2×106functional iHeps in one spleen. TNF-α protein and lentivirus-mediated expression of EGF and HGF further enabled the total hepatocytes to expand to 8×106per spleen. iHeps possessed hepatic functions—such as glycogen storage, lipid accumulation and drug metabolism—and performed fundamental liver functions to improve the survival rate of mice with 90% hepatectomy.ConclusionDirect conversion of the spleen into a liver-like organ, without cell or tissue transplantation, establishes fundamental hepatic functions in mice, suggesting its potential value for the treatment of end-stage liver diseases.
Training to proficiency in surgery using simulation: is there a moral obligation?
Authors: Toale Conor , Morris Marie , Kavanagh Dara O 
Published: January 2022

A deontological approach to surgical ethics advocates that patients have the right to receive the best care that can be provided. The ‘learning curve’ in surgical skill is an observable and measurable phenomenon. Surgical training may therefore carry risk to patients. This can occur directly, through inadvertent harm, or indirectly through theatre inefficiency and associated costs. Trainee surgeon operating, however, is necessary from a utilitarian perspective, with potential risk balanced by the greater societal need to train future independent surgeons.New technology means that the surgical learning curve could take place, at least in part, outside of the operating theatre. Simulation-based deliberate practice could be used to obtain a predetermined level of proficiency in a safe environment, followed by simulation-based assessment of operative competence. Such an approach would require an overhaul of the current training paradigm and significant investment in simulator technology. This may increasingly be viewed as necessary in light of well-discussed pressures on surgical trainees and trainers.This article discusses the obligations to trainees, trainers and training bodies raised by simulation technology, and outlines the current arguments both against and in favour of a simulation-based training-to-proficiency model in surgery. The significant changes to the current training paradigm that would be required to implement such a model are also discussed.
Feasibility of one-shot dilation access in the pediatric age group
Authors: Srivastava Alok , Yadav Krishna Kumar , Singh Anjana , Srivastava Anoop Kumar , Singh Sanjeet Kumar 
Published: January 2022

ObjectiveTo compare sequential fascial dilation (SFD) versus one-shot dilation (OSD) in the pediatric patients undergoing percutaneous nephrolithotomy.MethodsThe present study is an observational study. The study subjects were divided into two groups. In group 1, renal dilation was done using the SFD and in group 2, renal dilation was done using the OSD. The amount of time exposed to radiation during access to pelvicalyceal system was estimated. Complications, stone free rates, ancillary procedures for residual stones and hospital stay were compared. Modified Clavien-Dindo classification was used for grading the complications.ResultsRadiation exposure and operative time were less in OSD group (95% confidence interval (CI) 3.068 to 14.072, and 2.565 to 12.435, p<0.005). The mean drop of hematocrit was statistically less significant in OSD group (p=0.032). In both groups, complications, stone free rate and hospital stay were statistically insignificant.ConclusionsOSD is feasible in the children with reduced radiation exposure and shorter operative time. The outcome was similar to SFD.
Addressing barriers to evidence-based medicine in pediatric surgery: an introduction to the Canadian Association of Paediatric Surgeons Evidence-Based Resource
Authors: Grandpierre Viviane , Oltean Irina , Kaur Manvinder , Nasr Ahmed 
Published: January 2022

BackgroundPediatric surgical practice lags behind medicine in presence and use of evidence, primarily due to time constraints of using existing tools that are not specific to pediatric surgery, lack of sufficient patient data and unstructured pediatric surgery training methods.MethodWe developed, disseminated and tested the effectiveness of an evidence-based resource for pediatric surgeons and researchers that provides brief, informative summaries of quality-assessed systematic reviews and meta-analyses on conflicting pediatric surgery topics.ResultsResponses of 91 actively practicing surgeons who used the resource were analysed. The majority of participants found the resource useful (75%), improved their patient care (66.6%), and more than half (54.2%) found it useful in identifying research gaps. Almost all participants reported that the resource could be used as a teaching tool (93%).ConclusionLack of awareness of the resource is the primary barrier to its routine use, leading to potential calls for more active dissemination worldwide. Users of the Canadian Association of Paediatric Surgeons Evidence-Based Resource find that the summaries are useful, identify research gaps, help mitigate multiple barriers to evidence-based medicine, and may improve patient care.
Study of the Water Splitting Performance of Hematite Thin Films Prepared By DC and Reactive RF Sputtering
Authors: Sinha Rochan , Lavrijsen Reinoud , van de Sanden M. C. M. , Bieberle-Hütter Anja 
Published: January 2022

Metal oxides such as Fe2O3, WO3 or BiVO4 have been extensively studied as suitable materials for photoelectrochemical (PEC) water splitting [1]. However, the water splitting performance of these materials is limited by short charge carrier lifetime, high charge carrier recombination effects and slow water oxidation kinetics [2]. These material drawbacks lead to a high sensitivity of the water splitting efficiency on the synthesis technique utilised to fabricate the metal oxide films.
In this work, hematite thin films are utilised as a model system to understand the effect of variation in the synthesis process on the water splitting performance [3]. Thin films of 40-50 nm thickness are prepared by DC and reactive RF sputtering, followed by annealing at 800°C. It is observed that the DC sputtered films exhibit higher PEC performance with 40 times higher photocurrent at 1.23 V (versus RHE) and 300 mV lower onset potential, as shown in figure 1(a).
From electrochemical impedance spectroscopy (EIS) measurements we find that the DC sputtered thin films exhibit faster charge transfer kinetics as shown by the higher charge transfer rate constant for the oxygen evolution reaction (figure 1(b)). Intensity modulated photocurrent spectroscopy (IMPS) and hole scavenger measurements show that DC sputtered films also have lower surface and bulk recombination effects, respectively, as compared to the reactive RF sputtered films. The variation in the PEC properties is related to the large differences observed in the morphology, surface chemistry and optical properties of the DC and RF sputtered thin films as studied by techniques such as cross-sectional TEM, SEM, XPS and UV-Vis spectroscopy.

References

[1] M.G. Walter, E.L. Warren, J.R. McKone, S.W. Boettcher, Q. Mi, E.A. Santori, N.S. Lewis, Chemical Reviews, 110 (2010) 6446-6473.
[2] K. Rajeshwar, A. Thomas, C. Janáky, Photocatalytic Activity of Inorganic Semiconductor Surfaces: Myths, Hype, and Reality, The Journal of Physical Chemistry Letters, 6 (2015) 139-147
[3] R. Sinha, R. Lavrijsen, M. C. M. van de Sanden, A. Bieberle-Hütter, In Preparation

Figure 1
Safety and Efficacy of Combination Maintenance Therapy with Ixazomib and Lenalidomide in Patients with Posttransplant Myeloma
Authors: Patel Krina K. , Shah Jatin J. , Feng Lei , Lee Hans C. , Manasanch Elisabet M. , Olsem Jasper , Morphey Ashley , Huo Xiao Jiao , Thomas Sheeba K. , Bashir Qaiser , Qazilbash Muzaffar H. , Weber Donna M. , Orlowski Robert Z. 
Published: January 2022

AbstractPurpose:In this study, the addition of ixazomib to lenalidomide maintenance post-autologous stem cell transplant (ASCT) in 64 patients with newly diagnosed multiple myeloma was evaluated on the basis of the observed benefit of lenalidomide-only maintenance in prior studies.Patients and Methods:Patients were started on maintenance therapy with lenalidomide and ixazomib within 60–180 days of stem cell infusion.Results:Response rates deepened over time from baseline post-ASCT for 39 patients. The complete response (CR)/stringent CR rate was 43% and median overall survival was not reached with a median follow-up of 62 months (range, 25–82 months). Median PFS (mPFS) for all patients was 73 months and has not been reached for those with International Staging System (ISS) stage 1 disease. mPFS in 9 patients who had ISS stage 3 disease and 14 patients who had high-risk cytogenetics was 34 and 25 months, respectively. Twenty-two patients had progressive disease, while 19 patients continue to receive dual maintenance. The most common grade 3/4 adverse events included neutropenia, leukopenia, thrombocytopenia, lung infections, diarrhea, and maculopapular rash. Second primary malignancies occurred in 9 patients. Toxicity led to dose reductions in ixazomib and lenalidomide in 20 and 31 patients, respectively. Discontinuation of ixazomib due to toxicity occurred in 4 patients. Grade 1/2 neuropathy occurred in 22 patients and led to reduction or discontinuation of ixazomib in 2 patients.Conclusions:The addition of ixazomib to lenalidomide maintenance demonstrated a better than expected PFS compared with historical data using lenalidomide alone and was safe and tolerable.
An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations
Authors: Chakroborty Deepankar , Ojala Veera K. , Knittle Anna M. , Drexler Jasmin , Tamirat Mahlet Z. , Ruzicka Regina , Bosch Karin , Woertl Johanna , Schmittner Susanne , Elo Laura L. , Johnson Mark S. , Kurppa Kari J. , Solca Flavio , Elenius Klaus 
Published: January 2022

Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional screen to identify potential activating ERBB4 mutations from a randomly mutated ERBB4 expression library. Ten potentially activating ERBB4 mutations were identified and subjected to validation by functional and structural analyses. Two of the 10 ERBB4 mutants, E715K and R687K, demonstrated hyperactivity in all tested cell models and promoted cellular growth under two-dimensional and three-dimensional culture conditions. ERBB4 E715K also promoted tumor growth in in vivo Ba/F3 cell mouse allografts. Importantly, all tested ERBB4 mutants were sensitive to the pan-ERBB tyrosine kinase inhibitors afatinib, neratinib, and dacomitinib. Our data indicate that rare ERBB4 mutations are potential candidates for ERBB4-targeted therapy with pan-ERBB inhibitors.

Statement of Significance:
ERBB4 is a member of the ERBB family of oncogenes that is frequently mutated in different cancer types but the functional impact of its somatic mutations remains unknown. Here, we have analyzed the function of over 8,000 randomly mutated ERBB4 variants in an unbiased functional genetics screen. The data indicate the presence of rare activating ERBB4 mutations in cancer, with potential to be targeted with clinically approved pan-ERBB inhibitors.
Mitigating Initial Orthostatic Hypotension: Mechanistic Roles of Muscle Contraction Versus Sympathetic Activation
Authors: Sheikh Nasia A. , Phillips Aaron A. , Ranada Shaun , Lloyd Matthew , Kogut Karolina , Bourne Kate M. , Jorge Juliana G. , Lei Lucy Y. , Sheldon Robert S. , Exner Derek V. , Runte Mary , Raj Satish R. 
Published: January 2022

Background:
Initial orthostatic hypotension (IOH) is defined by a large drop in blood pressure (BP) within 15 s of standing. IOH often presents during an active stand, but not with a passive tilt, suggesting that a muscle activation reflex involving lower body muscles plays an important role. To our knowledge, there is no literature exploring how sympathetic activation affects IOH. We hypothesized involuntary muscle contractions before standing would significantly reduce the drop in BP seen in IOH while increasing sympathetic activity would not.

Methods:
Study participants performed 4 sit-to-stand maneuvers including a mental stress test (serial 7 mental arithmetic stress test), cold pressor test, electrical stimulation, and no intervention. Continuous heart rate and beat-to-beat BP were measured. Cardiac output and systemic vascular resistance were estimated from these waveforms. Data are presented as mean±SD.

Results:

A total of 23 female IOH participants (31±8 years) completed the study. The drops in systolic BP following the serial 7 mental arithmetic stress test (−26±12 mm Hg;
P
=0.004), cold pressor test (−20±15 mm Hg;
P
<0.001), and electrical stimulation (−28±12 mm Hg;
P
=0.01) were significantly reduced compared with no intervention (−34±11 mm Hg). The drops in systemic vascular resistance following the serial 7 mental arithmetic stress test (−391±206 dyne×s/cm
5
;
P
=0.006) and cold pressor test (−386±179 dyne×s/cm
5
;
P
=0.011) were significantly reduced compared with no intervention (−488±173 dyne×s/cm
5
). Cardiac output was significantly increased upon standing (7±2 L/min) compared with during the sit (6±1 L/min;
P
<0.001) for electrical stimulation.

Conclusion:
Sympathetic activation mitigates the BP response in IOH, while involuntary muscle contraction mitigates the BP response and reduces symptoms. Active muscle contractions may induce both of these mechanisms of action in their pretreatment of IOH.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03970551.
The Dissolution of the Soviet Union
Authors: Kramer Mark 
Published: January 2022

Abstract
In late December 1991—some 74 years after the Bolsheviks had taken power in Russia under the leadership of Vladimir Lenin—the Soviet Communist regime and the Soviet state itself ceased to exist. The demise of the Soviet Union occurred less than seven years after Mikhail Gorbachev became the leader of the Soviet Communist Party. Soon after taking office in March 1985, Gorbachev had launched a series of drastic political and economic changes that he hoped would improve and strengthen the Communist system and bolster the country's superpower status. But in the end, far from strengthening Communism, Gorbachev's policies of perestroika (restructuring) and glasnost (official openness) led inadvertently to the collapse of the Soviet regime and the unraveling of the Soviet state. This article analyzes the breakup of the Soviet Union, explaining why that outcome, which had seemed so unlikely at the outset, occurred in such a short period of time.
Does Disabling Cloud Radiative Feedbacks Change Spatial Patterns of Surface Greenhouse Warming and Cooling?
Authors: Chalmers Jason , Kay Jennifer E. , Middlemas Eleanor A. , Maroon Elizabeth A. , DiNezio Pedro 
Published: January 2022

AbstractThe processes controlling idealized warming and cooling patterns are examined in 150-yr-long fully coupled Community Earth System Model, version 1 (CESM1), experiments under abrupt CO2forcing. By simulation end, 2 × CO2global warming was 20% larger than 0.5 × CO2global cooling. Not only was the absolute global effective radiative forcing ∼10% larger for 2 × CO2than for 0.5 × CO2, global feedbacks were also less negative for 2 × CO2than for 0.5 × CO2. Specifically, more positive shortwave cloud feedbacks led to more 2 × CO2global warming than 0.5 × CO2global cooling. Over high-latitude oceans, differences between 2 × CO2warming and 0.5 × CO2cooling were amplified by familiar linked positive surface albedo and lapse rate feedbacks associated with sea ice change. At low latitudes, 2 × CO2warming exceeded 0.5 × CO2cooling almost everywhere. Tropical Pacific cloud feedbacks amplified the following: 1) more fast warming than fast cooling in the west, and 2) slow pattern differences between 2 × CO2warming and 0.5 × CO2cooling in the east. Motivated to quantify cloud influence, a companion suite of experiments was run without cloud radiative feedbacks. Disabling cloud radiative feedbacks reduced the effective radiative forcing and surface temperature responses for both 2 × CO2and 0.5 × CO2. Notably, 20% more global warming than global cooling occurred regardless of whether cloud feedbacks were enabled or disabled. This surprising consistency resulted from the cloud influence on non-cloud feedbacks and circulation. With the exception of the tropical Pacific, disabling cloud feedbacks did little to change surface temperature response patterns including the large high-latitude responses driven by non-cloud feedbacks. The findings provide new insights into the regional processes controlling the response to greenhouse gas forcing, especially for clouds.Significance StatementWe analyze the processing controlling idealized warming and cooling under abrupt CO2forcing using a modern and highly vetted fully coupled climate model. We were especially interested to compare simulations with and without cloud radiative feedbacks. Notably, 20% more global warming than global cooling occurred regardless of whether cloud feedbacks were enabled or disabled. This surprising consistency resulted from the cloud influence on forcing, non-cloud feedbacks, and circulation. With the exception of the tropical Pacific, disabling cloud feedbacks did little to change surface temperature response patterns including the large high-latitude responses driven by non-cloud feedbacks. The findings provide new insights into the regional processes controlling the response to greenhouse gas forcing, especially for clouds. When combined with estimates of cooling at the Last Glacial Maximum, the findings also help rule out large (4+ K) values of equilibrium climate sensitivity.
A National Analysis of Inpatient Pediatric Adenoidectomy
Authors: Yan Flora , Huang Victoria , Nguyen Shaun A. , Carroll William W. , Clemmens Clarice S. , Pecha Phayvanh P. 
Published: January 2022

Objective: Hospital admission following pediatric adenoidectomy without tonsillectomy is not well characterized. The objective of our study is to better characterize risk factors for post-operative complications in younger children undergoing inpatient adenoidectomy. Methods: A cross-sectional analysis using data derived from the Kid’s Inpatient Database (KID) was performed. Study participants included children <3 years of age who underwent an adenoidectomy and were admitted to hospitals participating in the KID for years 1997, 2000, 2003, 2006, 2009, and 2012. Descriptive statistical analysis and a multivariate logistic regression analysis were performed to identify risk factors for post-operative complication. Results: A total of 3406 children (mean age 1.1 ± 0.7 years) were included. The overall post-operative bleeding and respiratory complication rates were 0.6% and 5.4%, respectively. Children less than 18 months of age demonstrated increased rates of post-operative respiratory complications ( P = .009), but not bleeding complications ( P = .857). Presence of cardiopulmonary congenital malformations (OR 1.54, 95% CI 1.07-2.20), chronic respiratory disease of the newborn (OR 5.03, 95% CI 2.86-8.85), and neuromuscular disorders (OR 1.97, 95% CI 1.09-3.57) were associated with post-operative respiratory distress. Conclusions: This analysis of a national dataset suggests that otherwise healthy children less than 18 months of age and children 18 months to 3 years of age with certain comorbidities may benefit from overnight observation following adenoidectomy.