bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in unit sales of cooling flavoured e-cigarettes, USA, 2017–2021
Authors: Ali Fatma Romeh M , Seaman Elizabeth L , Diaz Megan C , Ajose Julianah , King Brian A 
Published: July 2022

ObjectiveFlavours that produce a cooling sensation, such as menthol, enhance the appeal of e-cigarettes among youth; but not all e-cigarettes that produce cooling sensations are labelled as menthol. This study assessed trends in unit sales of cooling flavoured e-cigarettes in the USA.DesignE-cigarette retail sales during 26 January 2017 to 28 November 2021 were licensed from Information Resources, Inc, which records brick-and-mortar retail scanner sales but not online or vape shop sales. Cooling flavours were identified using six descriptors: menthol, ice, cool, chill, freeze or frost; ambiguous flavours were verified using online searches. Cooling flavours were categorised by characterising flavour (menthol, mint, other) and product type (prefilled cartridges, disposables, e-liquids). Joinpoint regression was used to assess sales and price trends.ResultsDuring January 2017 to November 2021, unit sales of cooling flavoured e-cigarettes increased by 693.0% (1.5 to 12.0 million units); the percentage of these sales from total sales increased from 26.4% to 54.9%. Among cooling flavours, percentage of menthol sales decreased from 94.5% to 73.0% (p<0.001). Among menthol cooling flavours, percentage of prefilled cartridges increased from 67.2% to 96.6% (p<0.001); among non-menthol cooling flavours, percentage of disposable e-cigarettes increased from 5.2% to 99.2% (p<0.001). There were no significant price differences between cooling and non-cooling flavoured disposable e-cigarettes.ConclusionThe percentage of cooling flavoured e-cigarette sales from total sales doubled during 2017–2021, and sales of non-menthol cooling disposable e-cigarettes experienced the highest percentage increase. Cooling flavoured e-cigarettes are important to consider when developing strategies to address flavoured e-cigarette use among youth.
Cushioned on the way up, controlled on the way down during resuscitative endovascular balloon occlusion of the aorta (REBOA): investigating a novel compliant balloon design for optimizing safe overinflation combined with partial REBOA ability
Authors: Power Adam , Parekh Asha , Parry Neil , Moore Laura J 
Published: July 2022

BackgroundThere are a variety of devices capable of performing resuscitative endovascular balloon occlusion of the aorta (REBOA), with most containing compliant balloon material. While compliant material is ideal for balloon inflation due to its “cushioning” effect, it can be problematic to “control” during deflation. The COBRA-OS (Control Of Bleeding, Resuscitation, Arterial Occlusion System) was designed to optimize inflation and deflation of its compliant balloon and was tested in vitro and in vivo with respect to its overinflation and partial REBOA abilities.MethodsFor overinflation, the COBRA-OS was inflated in three differently sized inner diameter (ID) vinyl tubes until balloon rupture. It was then overinflated in six harvested swine aortas and in all three REBOA zones of three anesthetized swine. For partial REBOA, the COBRA-OS underwent incremental deflation in a pulsatile benchtop aortic model and in zone 1 of three anesthetized swine.ResultsFor overinflation, compared with the known aortic rupture threshold of 4 atm, the COBRA-OS exceeded this value in only the smallest of the vinyl tubes: 8 mm ID tube, 6.5 atm; 9.5 mm ID tube, 3.5 atm; 13 mm ID tube, 1.5 atm. It also demonstrated greater than 500% overinflation ability without aortic damage in vitro and caused no aortic damage when inflated to maximum inflation volume in vivo. For partial REBOA, the COBRA-OS was able to provide a titration window of between 3 mL and 4 mL in both the pulsatile vascular model (3.4±0.12 mL) and anesthetized swine (3.8±0.35 mL).DiscussionThe COBRA-OS demonstrated the ability to have a cushioning effect during inflation combined with titration control on deflation in vitro and in vivo. This study suggests that despite its balloon compliance, both safe overinflation and partial REBOA can be successfully achieved with the COBRA-OS.Level of evidenceBasic science.
Trichomycetes from the Columbia Mountains, British Columbia, Canada
Authors: Strongman D.B. , White Merlin M. 
Published: July 2022

Trichomycetes are a group of fungi and protists living in the guts of immature aquatic insects and other arthropods. The nature of this relationship is poorly understood but it is mostly described as obligately commensalistic, with the microbes exploiting a unique microhabitat. Collections of trichomycetes were made from freshwater insects in aquatic habitats near Castlegar in the Columbia Mountains, part of the Rocky Mountain Range in southeastern British Columbia. The collection sites were at altitudes ranging from 435 to 935 m and were made in July 2006. A total of 32 species were recorded including four new species, Harpella filispora sp. nov., Orphella columbiensis sp. nov., Smittium nodiradicatum sp. nov., and Smitium basiangustatum sp. nov. described here. These are the first records from Western Canada and two, Austrosmittium patagonicum and Glotzia distorta are new continental records. These findings are compared to reports from the western edge of the Rocky Mountain range near the Boise Mountains in Idaho and the Southern Rockies in Colorado.
General considerations for effective thermal neutron shielding in detector applications
Authors: Backis Alexander , Al Jebali Ramsey , Fissum Kevin , Bentley Phillip , Hall-Wilton Richard , Kanaki Kalliopi , Kittelmann Thomas , Livingston Kenneth 
Published: July 2022

AbstractFor thermal neutron detectors, effective shielding is a crucial aspect of signal-to-background optimization. This is especially important for cold to thermal neutrons, as the detectors are most sensitive in this energy range. In this work, a few common shielding materials, such as cadmium, B4C and epoxy-Gd2O3 mixtures, are analytically evaluated based on interaction cross sections extracted from Geant4. For these materials, the neutron absorption and scattering dependence on material thickness and incident neutron energy are examined. It is also considered how the absorption and scattering change with different material compositions, such as 10B-content in B4C, and component ratio in epoxy-Gd2O3 mixtures. In addition, a framework is introduced to quantify the effectiveness of the neutron shielding, comparing the relationship between absorption and scattering of different shielding materials. The aim is to provide a general tool kit, which can be used to quickly identify an appropriate shielding material, with the required thickness, to reach a desired thermal neutron shielding performance. Finally, as an example, the developed tool kit is applied to the specific shielding application for the Multi-Grid CSPEC detector, currently in development for the European Spallation Source.
Anesthesia Effect of Remifentanil Combined with Propofol in Laparoscopic Cholecystectomy and Its Impact on Postoperative Cognitive Recovery
Authors: Jiang Wei , Wang Jun , Ni Xin-xin , Huang Zu-chao 
Published: July 2022

Objective. To investigate the anesthesia effect of remifentanil combined with propofol for laparoscopic cholecystectomy and its impact on postoperative cognitive recovery. Methods. A total of 120 patients who underwent laparoscopic cholecystectomy in our hospital from February 2019 to June 2021 were recruited and assigned into either control group or experimental group at a ratio of 1 : 1 via the random number table method. The patients in the control group were anesthetized with fentanyl combined with propofol, and the patients in the experimental group were anesthetized with remifentanil combined with propofol. The clinical basic indicators (extubation time, recovery time, breathing recovery time, and orientation recovery time), and observer’s assessment of awareness/sedation (OAA/S) scores and complications were compared between the two groups. Results. There was no significant difference in extubation time between the two groups (

P
>
0.05

). The postoperative wake-up time, respiratory recovery time, and orientation recovery time of the experimental group were significantly better than those of the control group (

P

<
0.05

). The OAA/S scores of the patients in the experimental group were significantly higher than those in the control group immediately after surgery, 1 h after surgery, and 3 h after surgery (

P

<
0.05

). There was no significant difference in the OAA/S scores between the two groups on the 1st day after operation (

P
>
0.05

). The incidence of complications in the experimental group was significantly lower than that in the control group (

P

<
0.05

). Conclusion. Remifentanil + propofol for laparoscopic cholecystectomy patients has a significant anesthesia effect. This strategy effectively shortens the extubation, awakening, respiratory recovery, orientation recovery time of patients, and OAA/S score, suggest a minor impact on the postoperative cognitive function and state of consciousness. It has a high safety profile and thus is worthy of clinical application.
The Mechanisms of Action of Tumor Treating Fields
Authors: Moser Justin C. , Salvador Ellaine , Deniz Karina , Swanson Kenneth , Tuszynski Jack , Carlson Kristen W. , Karanam Narasimha Kumar , Patel Chirag B. , Story Michael , Lou Emil , Hagemann Carsten 
Published: July 2022

Abstract
Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of action.
Neoantigen Identification and Response to Adoptive Cell Transfer in Anti–PD-1 Naïve and Experienced Patients with Metastatic Melanoma
Authors: Levi Shoshana T. , Copeland Amy R. , Nah Shirley , Crystal Jessica S. , Ivey Gabriel D. , Lalani Almin , Jafferji Mohammad , White Bradley S. , Parikh Neilesh B. , Leko Vid , Krishna Sri , Lowery Frank , Prickett Todd D. , Gartner Jared J. , Jia Li , Li Yong F. , Sachs Abraham , Sindiri Sivasish , Robinson Welles , Gasmi Billel , Yang James C. , Goff Stephanie L. , Rosenberg Steven A. , Robbins Paul F. 
Published: July 2022

Abstract

Purpose:
Immune checkpoint blockade (ICB) agents and adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) are prominent immunotherapies used for the treatment of advanced melanoma. Both therapies rely on activation of lymphocytes that target shared tumor antigens or neoantigens. Recent analysis of patients with metastatic melanoma who underwent treatment with TIL ACT at the NCI demonstrated decreased responses in patients previously treated with anti–PD-1 agents. We aimed to find a basis for the difference in response rates between anti–PD-1 naïve and experienced patients.

Patients and Methods:
We examined the tumor mutational burden (TMB) of resected tumors and the repertoire of neoantigens targeted by autologous TIL in a cohort of 112 anti–PD-1 naïve and 69 anti–PD-1 experienced patients.

Results:
Anti–PD-1 naïve patients were found to possess tumors with higher TMBs (352.0 vs. 213.5, P = 0.005) and received TIL reactive with more neoantigens (2 vs. 1, P = 0.003) compared with anti–PD-1 experienced patients. Among patients treated with TIL ACT, TMB and number of neoantigens identified were higher in ACT responders than ACT nonresponders in both anti–PD-1 naïve and experienced patients. Among patients with comparable TMBs and predicted neoantigen loads, treatment products administered to anti–PD-1 naïve patients were more likely to contain T cells reactive against neoantigens than treatment products for anti–PD-1 experienced patients (2.5 vs. 1, P = 0.02).

Conclusions:
These results indicate that decreases in TMB and targeted neoantigens partially account for the difference in response to ACT and that additional factors likely influence responses in these patients.
See related commentary by Blass and Ott, p. 2980
AmplifiedEPOR/JAK2Genes Define a Unique Subtype of Acute Erythroid Leukemia
Authors: Takeda June , Yoshida Kenichi , Nakagawa Masahiro M. , Nannya Yasuhito , Yoda Akinori , Saiki Ryunosuke , Ochi Yotaro , Zhao Lanying , Okuda Rurika , Qi Xingxing , Mori Takuto , Kon Ayana , Chiba Kenichi , Tanaka Hiroko , Shiraishi Yuichi , Kuo Ming-Chung , Kerr Cassandra M. , Nagata Yasunobu , Morishita Daisuke , Hiramoto Nobuhiro , Hangaishi Akira , Nakazawa Hideyuki , Ishiyama Ken , Miyano Satoru , Chiba Shigeru , Miyazaki Yasushi , Kitano Toshiyuki , Usuki Kensuke , Sezaki Nobuo , Tsurumi Hisashi , Miyawaki Shuichi , Maciejewski Jaroslaw P. , Ishikawa Takayuki , Ohyashiki Kazuma , Ganser Arnold , Heuser Michael , Thol Felicitas , Shih Lee-Yung , Takaori-Kondo Akifumi , Makishima Hideki , Ogawa Seishi 
Published: July 2022

AbstractAcute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we analyzed 121 AEL using whole-genome, whole-exome, and/or targeted-capture sequencing, together with transcriptome analysis of 21 AEL samples. Combining publicly available sequencing data, we found a high frequency of gains and amplifications involving EPOR/JAK2 in TP53-mutated cases, particularly those having &gt;80% erythroblasts designated as pure erythroid leukemia (10/13). These cases were frequently accompanied by gains and amplifications of ERG/ETS2 and associated with a very poor prognosis, even compared with other TP53-mutated AEL. In addition to activation of the STAT5 pathway, a common feature across all AEL cases, these AEL cases exhibited enhanced cell proliferation and heme metabolism and often showed high sensitivity to ruxolitinib in vitro and in xenograft models, highlighting a potential role of JAK2 inhibition in therapeutics of AEL.Significance:This study reveals the major role of gains, amplifications, and mutations of EPOR and JAK2 in the pathogenesis of pure erythroleukemia. Their frequent response to ruxolitinib in patient-derived xenograft and cell culture models highlights a possible therapeutic role of JAK2 inhibition for erythroleukemia with EPOR/JAK2-involving lesions.This article is highlighted in the In This Issue feature, p. 369
A Phase I Study of Pelabresib (CPI-0610), a Small-Molecule Inhibitor of BET Proteins, in Patients with Relapsed or Refractory Lymphoma
Authors: Blum Kristie A. , Supko Jeffrey G. , Maris Michael B. , Flinn Ian W. , Goy Andre , Younes Anas , Bobba Suresh , Senderowicz Adrian M. , Efuni Sergey , Rippley Ronda , Colak Gozde , Trojer Patrick , Abramson Jeremy S. 
Published: July 2022

Purpose:NF-κB, a transcription factor essential for inflammatory responses, is constitutively activated in many lymphomas. In preclinical studies, pelabresib (CPI-0610), an investigational (BET) bromodomain inhibitor, downregulated NF-κB signaling and demonstrated antitumor activity in vitro. Here we report the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity from the first-in-human phase I study of pelabresib in patients with relapsed/refractory lymphomas (NCT01949883).Experimental Design:Sixty-four patients with relapsed/refractory lymphoma (median of 4 prior lines of therapy) were treated with either capsule (6, 12, 24, 48, 80, 120, 170, 230, 300 mg) or tablet (125, 225 mg) doses of pelabresib orally once daily on a 14 days on, 7 days off schedule.Results:The MTD was determined as the 225 mg tablet daily. The most frequent adverse events were fatigue, nausea, and decreased appetite. Thrombocytopenia, a class effect for all BET inhibitors, was dose-dependent, reversible, and noncumulative. Pelabresib exhibited dose-proportional increases in systemic exposure, rapid absorption, and a half-life of approximately 15 hours (supporting once daily dosing). The bioavailability of the tablet formulation was 60% greater than the capsules. Pelabresib suppressed IL8 and CCR1 mRNA at doses above 120 and 170 mg, respectively. Four patients (6.2%) had an objective response (2 complete response and 2 partial response) and 5 patients had prolonged stable disease.Conclusions/Discussion:Pelabresib is capable of BET target gene suppression in an exposure-dependent manner with an acceptable safety profile leading to the recommended phase II dose of the 125 mg tablet once daily.Significance:BET proteins inhibition can potentially modify the pathogenic pathways which contribute to many diseases including malignancies. Pelabresib (CPI-0610), a potent and selective small molecule BET proteins inhibitor, has a MTD of 225 mg once daily for 14 days with a 7-day break, clear pharmacokinetic/pharmacodynamic relationship, and manageable clinical safety profile. These findings are part of the foundation for the ongoing pivotal study of pelabresib in patients with myelofibrosis.
Incidence and Risk Factors of Pulmonary Hypertension After Venous Thromboembolism: An Analysis of a Large Health Care Database
Authors: Lutsey Pamela L. , Evensen Line H. , Thenappan Thenappan , Prins Kurt W. , Walker Rob F. , Farley Joel F. , MacLehose Richard F. , Alonso Alvaro , Zakai Neil A. 
Published: July 2022

Background
Pulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism, a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE are poorly characterized.

Methods and Results

International Classification of Diseases
(
ICD
) codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011 to 2018 were used to identify cases of VTE, comorbidities before the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% CI, were calculated. The 170 021 VTE cases included in the analysis were on average (±SD) 57.5±15.8 years old and 50.5% were female. A total of 5943 PH cases accrued over an average follow‐up of 1.94 years. Two years after incident VTE, the cumulative incidence (95% CI) of PH was 3.5% (3.4%–3.7%) overall. It was higher among older individuals, among women (3.9% [3.8%–4.1%]) than men (3.2% [3.0%–3.3%]), and among patients presenting with pulmonary embolism (6.2% [6.0%–6.5%]) than those presenting with deep vein thrombosis only (1.1% [1.0%–1.2%]). Adjusting for age and sex, risk of PH was higher among patients with VTE with underlying comorbidities. Using the Charlson comorbidity index, there was a dose–response relationship, whereby greater scores were associated with increased PH risk (score ≥5 versus 0: HR, (2.50 [2.30–2.71])). When evaluating individual comorbidities, the strongest associations were observed with concomitant heart failure (HR, 2.17 [2.04–2.31]), chronic pulmonary disease (2.01 [1.90–2.14]), and alcohol abuse (1.66 [1.29–2.13]).

Conclusions
In this large, real‐world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among patients with VTE.
Use of Clinical Pathway Simulation and Machine Learning to Identify Key Levers for Maximizing the Benefit of Intravenous Thrombolysis in Acute Stroke
Authors: Allen Michael , James Charlotte , Frost Julia , Liabo Kristin , Pearn Kerry , Monks Thomas , Everson Richard , Stein Ken , James Martin 
Published: July 2022

Background:
Expert opinion is that about 20% of emergency stroke patients should receive thrombolysis. Currently, 11% to 12% of patients in England and Wales receive thrombolysis, ranging from 2% to 24% between hospitals. The aim of this study was to assess how much variation is due to differences in local patient populations, and how much is due to differences in clinical decision-making and stroke pathway performance, while estimating a realistic target thrombolysis use.

Methods:
Anonymised data for 246 676 emergency stroke admissions to 132 acute hospitals in England and Wales between 2016 and 2018 was obtained from the Sentinel Stroke National Audit Programme data. We used machine learning to learn decisions on who to give thrombolysis to at each hospital. We used clinical pathway simulation to model effects of changing pathway performance. Qualitative research was used to assess clinician attitudes to these methods. Three changes were modeled: (1) arrival-to-treatment in 30 minutes, (2) proportion of patients with determined stroke onset times set to at least the national upper quartile, (3) thrombolysis decisions made based on majority vote of a benchmark set of hospitals.

Results:
Of the modeled changes, any single change was predicted to increase national thrombolysis use from 11.6% to between 12.3% to 14.5% (clinical decision-making having the most effect). Combined, these changes would be expected to increase thrombolysis to 18.3%, but there would still be significant variation between hospitals depending on local patient population. Clinicians engaged well with the modeling, but those from hospitals with lower thrombolysis use were most cautious about the methods.

Conclusions:
Machine learning and clinical pathway simulation may be applied at scale to national stroke audit data, allowing extended use and analysis of audit data. Stroke thrombolysis rates of at least 18% look achievable in England and Wales, but each hospital should have its own target.
Impact of El Niño–Southern Oscillation on the Benguela Upwelling
Authors: Rouault M. , Tomety F. S. 
Published: July 2022

Abstract
The impact of El Niño–Southern Oscillation (ENSO) on the southern African climate is well documented and provides skill in the seasonal forecast of rainfall, but less is known about the impact of ENSO on the Benguela Current west of southern Africa. There is a significant weak correlation between ENSO and the Benguela Current upwelling sea surface temperature (SST) in austral summer. Correlation is positive for southern Benguela and negative for northern Benguela. A significant correlation exists with up to 8 months lag when ENSO leads. The impact of ENSO is due to weaker-than-normal upwelling favorable southeasterly winds during El Niño in southern Benguela, leading to warmer-than-normal coastal SST. In contrast, during La Niña, stronger-than-normal southeasterly winds lead to cooler-than-normal SST. The opposite effect applies to northern Benguela. The coastal wind change is part of an ENSO large-scale basinwide perturbation in the tropical and South Atlantic. However, non-ENSO-related SST variation in the Benguela upwelling can be as important as ENSO-related SST perturbation, and some ENSO events do not lead to the expected changes. Changes in the Benguela upwelling are linked to changes in the intensity of the trade winds associated with a change of the South Atlantic anticyclone intensity and position. In southern Benguela, changes are also associated with variations in midlatitude low pressure systems and associated upwelling unfavorable westerly winds. La Niñas favor the development of Benguela Niños in Angola and Namibia. This study shows the potential for SST seasonal predictability in the Benguela upwelling due to the leading lag correlation between ENSO and the Benguela upwelling SST.