bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual location of a second branchial cleft cyst presenting in the suprasternal notch
Authors: Xing Monica H. , Mundi Neil , Govindan Aparna , Khorsandi Azita , Urken Mark L. 
Published: February 2021

AbstractBackgroundSecond branchial cleft cysts (SBCCs) are congenital benign tumors that comprise up to 90% of all branchial cleft anomalies. SBCCs typically present in the lateral neck along the anterior border of the upper third of the sternocleidomastoid muscle. We describe a case of a SBCC presenting in an unusual location in the lower neck close to midline.MethodsAn 18‐year‐old male presented with a 2‐year history of a neck mass in the suprasternal notch. Imaging findings were reviewed with a head and neck radiologist who felt that the findings were highly suggestive of a fourth branchial cleft cyst.ResultsThe patient underwent surgical excision of the mass. Final pathologic evaluation confirmed the diagnosis of a second branchial cleft cyst.ConclusionsThough extremely uncommon, second branchial cleft cysts can extend to the suprasternal notch and should not be excluded from the differential diagnoses of lower neck masses.
Mitogen‐activated protein kinase inhibition‐induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma
Authors: Xie Guiqin , Zhu Ailin , Gu Xinbin 
Published: February 2021

AbstractBackgroundEpidermal growth factor receptor (EGFR) overexpression is one of the most notable characteristics in head and neck squamous cell carcinoma (HNSCC). The MAPK kinase (MEK) inhibitor trametinib has shown efficacy to treat HNSCC; however, the molecular mechanism remains unclear.MethodsHNSCC lines, mouse models, Western blot, and flow cytometry were employed to analyze the anticancer effects of trametinib.ResultsThe JHU‐011, JHU‐022, and JHU‐029 HNSCC cells with different genetic alterations were highly susceptible to trametinib. Trametinib effectively reduced EGFR expression, which was accompanied by the reduction of pro‐survival protein MYC, and the increased expression of a MYC‐targeted cyclin‐dependent kinase inhibitor p27kip1 and pro‐apoptotic protein BIM. Trametinib resulted in G1 arrest of the cells, markedly reduced cell numbers in S phase, and significantly increased apoptosis. In mouse models, trametinib strongly inhibited tumors growth.ConclusionsThe MAPK–ERK signaling inhibition by trametinib may target EGFR and the downstream proteins against HNSCC.
Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications
Authors: Tao Junyan , Krutsenko Yekaterina , Moghe Akshata , Singh Sucha , Poddar Minakshi , Bell Aaron , Oertel Michael , Singhi Aatur D. , Geller David , Chen Xin , Lujambio Amaia , Liu Silvia , Monga Satdarshan P. 
Published: February 2021

Background and Aims
HCC remains a major unmet clinical need. Although activating catenin beta‐1 (CTNNB1) mutations are observed in prominent subsets of HCC cases, these by themselves are insufficient for hepatocarcinogenesis. Coexpression of mutant CTNNB1 with clinically relevant co‐occurrence has yielded HCCs. Here, we identify cooperation between β‐catenin and nuclear factor erythroid 2–related factor 2 (Nrf2) signaling in HCC.

Approach and Results
Public HCC data sets were assessed for concomitant presence of CTNNB1 mutations and either mutations in nuclear factor erythroid‐2–related factor‐2 (NFE2L2) or Kelch like‐ECH‐associated protein 1 (KEAP1), or Nrf2 activation by gene signature. HCC development in mice and similarity to human HCC subsets was assessed following coexpression of T41A‐CTNNB1 with either wild‐type (WT)‐, G31A‐, or T80K‐NFE2L2. Based on mammalian target of rapamycin complex 1 activation in CTNNB1‐mutated HCCs, response of preclinical HCC to mammalian target of rapamycin (mTOR) inhibitor was investigated. Overall, 9% of HCC cases showed concomitant CTNNB1 mutations and Nrf2 activation, subsets of which were attributable to mutations in NFE2L2/KEAP1. Coexpression of mutated CTNNB1 with mutant NFE2L2, but not WT‐NFE2L2, led to HCC development and mortality by 12‐14 weeks. These HCCs were positive for β‐catenin targets, like glutamine synthetase and cyclin‐D1, and Nrf2 targets, like NAD(P)H quinone dehydrogenase 1 and peroxiredoxin 1. RNA‐sequencing and pathway analysis showed high concordance of preclinical HCC to human HCC subset showing activation of unique (iron homeostasis and glioblastoma multiforme signaling) and expected (glutamine metabolism) pathways. NFE2L2‐CTNNB1 HCC mice were treated with mTOR inhibitor everolimus (5‐mg/kg diet ad libitum), which led to >50% decrease in tumor burden.

Conclusions
Coactivation of β‐catenin and Nrf2 is evident in 9% of all human HCCs. Coexpression of mutant NFE2L2 and mutant CTNNB1 led to clinically relevant HCC development in mice, which responded to mTOR inhibitors. Thus, this model has both biological and therapeutic implications.
The Impact of Direct‐Acting Antiviral Therapy on End‐Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders
Authors: Park Haesuk , Jiang Xinyi , Song Hyun Jin , Lo Re Vincent , Childs‐Kean Lindsey M. , Lo‐Ciganic Wei‐Hsuan , Cook Robert L. , Nelson David R. 
Published: February 2021

Background and Aims
Our aim was to evaluate the impact of direct‐acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD.

Approach and Results
This retrospective cohort study used the MarketScan database (2013‐2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06‐0.30) and non‐SUD (aHR 0.11; 95% CI, 0.07‐0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33‐2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13‐0.88) and non‐SUD (aHR, 0.40; 95% CI, 0.25‐0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37‐1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03‐2.24) and HCC (aHR, 1.69; 95% CI, 1.05‐2.72) compared with non‐SUD group.

Conclusions
Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.
Sleep Disturbance Is Associated With the Presence of Portosystemic Collaterals in Patients With Compensated Cirrhosis
Authors: Balakrishnan Maya , Falker Caroline , Conley Samantha , Ciarleglio Maria , Deng Yanhong , Redeker Nancy S. , Garcia‐Tsao Guadalupe 
Published: February 2021

Disturbed sleep is common among patients with cirrhosis. The extent to which this is associated with the different stages of compensated cirrhosis is unknown. This study examines whether the presence of portosystemic collaterals, an indicator of clinically significant portal hypertension, is associated with sleep disturbance in compensated cirrhosis. We conducted a cross‐sectional study among patients with compensated cirrhosis, comparing sleep characteristics, sleep quality, and excessive daytime sleepiness between 21 patients without and 21 patients with portosystemic collaterals. Patients were assessed with wrist actigraphy, Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale. Collateral presence was determined by imaging and esophagogastroduodenoscopy. Differences in sleep characteristics were analyzed using t tests and computed effect sizes. Multivariable linear regression analysis was used to evaluate the association between collaterals and sleep disturbance while controlling for possible confounders. The group of patients with collaterals had greater beta‐blocker and tobacco use, lower albumin, and higher international normalized ratio compared to the group without collaterals. Patients with collaterals had more sleep fragmentation (Cohen’s d = −0.86), lower sleep efficiency (Cohen’s d = 0.59), and lower total sleep time (Cohen’s d = 0.75) than patients without collaterals. The presence of collaterals was independently associated with greater sleep fragmentation (P = 0.046) and greater daytime sleepiness (P = 0.030). Conclusion: Patients with compensated cirrhosis complicated by portosystemic collaterals experienced more sleep disturbance than those without collaterals.
Relationship between social cohesion and the care burden of primary family caregivers in central Tokyo, Japan
Authors: Naganuma Yuki , Yamaoka Kazue , Takahashi Kenzo 
Published: February 2021

AbstractObjectivesTo clarify how the care burden of primary family caregivers is associated with social cohesion in an urban area of Tokyo, Japan.Study designCross‐sectional study.MethodsA questionnaire survey of primary family caregivers was conducted in Tokyo in 2015. Social cohesion was examined using the social capital indicators of Kondo et al, and the care burden of primary family caregivers was assessed by the Zarit Care Burden Interview Scale in Japanese short version (J‐ZBI_8). Data were analyzed by multiple regression models. Ethics approval was obtained to carry out this research.ResultsSeventy‐nine caregivers responded to the questionnaires. After excluding 6 caregivers who did not respond appropriately to the questionnaire, 73 caregivers were included in the analyses. The average age of the primary family caregivers was 68.9 ± 12.7 years old, and that of the patients receiving care was 83.1 ± 10.0 years old. “Receipt of instrumental support” was significantly associated with reduced burden of care for family caregivers as assessed by the J‐ZBI_8 score (P = .027).ConclusionThis study suggested that social cohesion was significantly associated with reduced burden of care for primary family caregivers. Especially, the results suggested that “social support: receipt of instrumental support” was associated with a lower burden of care after adjustment for confounding factors. It is important to understand family structure and social community differences such as informal social support for future policy making.
Estimating water balance components in irrigated agriculture using a combined approach of soil moisture and energy balance monitoring, and numerical modelling
Authors: Schulz Stephan , Becker Rike , Richard‐Cerda Juan Carlos , Usman Muhammad , aus der Beek Tim , Merz Ralf , Schüth Christoph 
Published: February 2021

AbstractInformation on water balance components such as evapotranspiration and groundwater recharge are crucial for water management. Due to differences in physical conditions, but also due to limited budgets, there is not one universal best practice, but a wide range of different methods with specific advantages and disadvantages. In this study, we propose an approach to quantify actual evapotranspiration, groundwater recharge and water inflow, i.e. precipitation and irrigation, that considers the specific conditions of irrigated agriculture in warm, arid environments. This approach does not require direct measurements of precipitation or irrigation quantities and is therefore suitable for sites with an uncertain data basis. For this purpose, we combine soil moisture and energy balance monitoring, remote sensing data analysis and numerical modelling using Hydrus. Energy balance data and routine weather data serve to estimate ET0. Surface reflectance data from satellite images (Sentinel‐2) are used to derive leaf area indices, which help to partition ET0 into energy limited evaporation and transpiration. Subsequently, first approximations of water inflow are derived based on observed soil moisture changes. These inflow estimates are used in a series of forward simulations that produce initial estimates of drainage and ETact, which in turn help improve the estimate of water inflow. Finally, the improved inflow estimates are incorporated into the model and then a parameter optimization is performed using the observed soil moisture as the reference figure. Forward simulations with calibrated soil parameters result in final estimates for ETact and groundwater recharge. The presented method is applied to an agricultural test site with a crop rotation of cotton and wheat in Punjab, Pakistan. The final model results, with an RMSE of 2.2% in volumetric water content, suggest a cumulative ETact and groundwater recharge of 769 and 297 mm over a period of 281 days, respectively. The total estimated water inflow accounts for 946 mm, of which 77% originates from irrigation.
Variation and attribution of water use efficiency in sunflower and maize fields in an irrigated semi‐arid area
Authors: Wang Weishu , Wang Xingwang , Huo Zailin , Rong Yao , Huang Quanzhong , Huang Guanhua 
Published: February 2021

AbstractWater use efficiency (WUE) links carbon and water exchanges between farmlands and the atmosphere. Understanding the variation and attribution of WUE is essential to reveal the physiological and ecological adaptation mechanisms of crops to the changing environment, and to better allocate, regulate and conserve water resources. However, few studies on the variation and attribution of WUE have been conducted in irrigated arid or semi‐arid farmlands. Therefore, in this study, water and carbon fluxes were measured using eddy covariance systems in two farmlands (one sunflower field and one maize field) in a semi‐arid irrigation district in China. It was found that the average WUE of sunflower during its full growth period was 1.72 g C kg−1 H2O, much lower than that of maize (4.07 g C kg−1 H2O). At each growth stage, the WUE of both crops were negatively correlated with vapour pressure deficit (VPD), net radiation (Rn) and soil water content (SWC). The negative correlations could be attributed to the arid meteorological condition and the relatively abundant soil moisture due to irrigation and shallow groundwater levels. VPD was the main factor affecting WUE, followed by Rn and SWC. It was also found that the response of WUE to crop leaf area index (LAI) and to canopy conductance (gc) depended on the VPD ranges: when VPD increased, the response of WUE to LAI and to gc decreased. Our findings could improve the understanding of the coupling effect of water and carbon fluxes over farmland ecosystems in arid and semi‐arid irrigation areas and help improve agricultural production and save water resources in such areas.
Ruxolitinib inhibits poly(I:C) and type 2 cytokines‐induced CCL5 production in bronchial epithelial cells: A potential therapeutic agent for severe eosinophilic asthma
Authors: Sada Mitsuru , Watanabe Masato , Inui Toshiya , Nakamoto Keitaro , Hirata Aya , Nakamura Masuo , Honda Kojiro , Saraya Takeshi , Kurai Daisuke , Kimura Hirokazu , Ishii Haruyuki , Takizawa Hajime 
Published: February 2021

AbstractRationaleSevere eosinophilic asthma is characterized by airway eosinophilia and corticosteroid‐resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C‐C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus‐associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib.MethodsWe stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS‐2B cells with poly(I:C) along with interleukin‐13 (IL‐13) or IL‐4, and assessed CCL5 production. We also evaluated the signals involved in virus‐ and Th2‐cytokine‐induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production.ResultsPoly(I:C) stimulated NHBE and BEAS‐2B cells to produce CCL5. Poly(I:C) and IL‐13 increased CCL5 production. Poly(I:C)‐induced CCL5 production occurred via the TLR3–IRF3 and IFNAR/JAK1–phosphoinositide 3‐kinase (PI3K) pathways, but not the IFNAR/JAK1–STATs pathway. In addition, IL‐13 did not augment poly(I:C)‐induced CCL5 production via the canonical IL‐13R/IL‐4R/JAK1–STAT6 pathway but likely via subsequent TLR3‐IRF3‐IFNAR/JAK1‐PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS‐2B cells than fluticasone propionate.ConclusionWe have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid‐resistant asthma with airway eosinophilia and persistent Th2‐type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy.
Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12‐week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials
Authors: Graeser Monika , Schrading Simone , Gluz Oleg , Strobel Kevin , Würstlein Rachel , Kümmel Sherko , Schumacher Claudia , Grischke Eva‐Maria , Forstbauer Helmut , Braun Michael , Christgen Matthias , Adams Jascha , Nitzsche Henrik , Just Marianne , Fischer Hans Holger , Aktas Bahriye , Potenberg Jochem , von Schumann Raquel , Kolberg‐Liedtke Cornelia , Harbeck Nadia , Kuhl Christiane K. , Nitz Ulrike 
Published: February 2021

AbstractWe evaluated the role of early response after 3 weeks of neoadjuvant treatment (NAT) assessed by ultrasound (US), magnetic resonance imaging (MRI) and Ki‐67 dynamics for prediction of pathologic complete response (pCR) in different early breast cancer subtypes. Patients with HR+/HER2+, HR−/HER2− and HR−/HER2+ tumors enrolled into three neoadjuvant WSG ADAPT subtrials underwent US, MRI and Ki‐67 assessment at diagnosis and after 3 weeks of NAT. Early response was defined as complete or partial response (US, MRI) and ≥30% proliferation decrease or <500 invasive tumor cells (Ki‐67). Predictive values and area under the receiver operating characteristic (AUC) curves for prediction of pCR (ypT0/is ypN0) after 12‐week NAT were calculated. Two hundred twenty‐six had MRI and 401 US; 107 underwent both MRI and US. All three methods yielded a similar AUC in HR+/HER2+ (0.66‐0.67) and HR−/HER2− tumors (0.53‐0.63), while MRI and Ki‐67 performed better than US in HR−/HER2+ tumors (0.83 and 0.79 vs 0.56). Adding MRI+/‐Ki‐67 increased AUC of US in HR−/HER2+ tumors to 0.64 to 0.75. MRI and Ki‐67 demonstrated highest sensitivity in HR−/HER2− (0.8‐1) and HR−/HER2+ tumors (1, both). Negative predictive value was similar for all methods in HR+/HER2+ (0.71‐0.74) and HR−/HER2− tumors (0.85‐1), while it was higher for MRI and Ki‐67 compared to US in HR−/HER2+ subtype (1 vs 0.5). Early response assessed by US, MRI and Ki‐67 is a strong predictor for pCR after 12‐week NAT. Strength of pCR prediction varies according to tumor subtype. Adding MRI+/‐Ki‐67 to US did not improve pCR prediction in majority of our patients.
Cross‐sectional survey of the impact of the COVID‐19 pandemic on cancer screening programs in selected low‐ and middle‐income countries: Study from the IARC COVID‐19 impact study group
Authors: Villain Patricia , Carvalho Andre L. , Lucas Eric , Mosquera Isabel , Zhang Li , Muwonge Richard , Selmouni Farida , Sauvaget Catherine , Basu Partha ,   for the IARC COVID‐19 Impact Study Group
Published: February 2021

AbstractWe conducted a study to document the impact of COVID‐19 pandemic on cancer screening continuum in selected low‐ and middle‐income countries (LMICs). LMICs having an operational cancer control plan committed to screen eligible individuals were selected. Managers/supervisors of cancer screening programs were invited to participate in an online survey and subsequent in‐depth interview. Managers/supervisors from 18 programs in 17 countries participated. Lockdown was imposed in all countries except Brazil. Screening was suspended for at least 30 days in 13 countries, while diagnostic‐services for screen‐positives were suspended in 9 countries. All countries except Cameroon, Bangladesh, India, Honduras and China managed to continue with cancer treatment throughout the outbreak. The participants rated service availability compared to pre‐COVID days on a scale of 0 (no activities) to 100 (same as before). A rating of ≤50 was given for screening services by 61.1%, diagnostic services by 44.4% and treatment services by 22.2% participants. At least 70% participants strongly agreed that increased noncompliance of screen‐positive individuals and staff being overloaded or overwhelmed with backlogs would deeply impact screening programs in the next 6 months at least. Although many of the LMICs were deficient in following the “best practices” to minimize service disruptions, at least some of them made significant efforts to improve screening participation, treatment compliance and program organization. A well‐coordinated effort is needed to reinitiate screening services in the LMICs, starting with a situational analysis. Innovative strategies adopted by the programs to keep services on‐track should be mutually shared.
On the effect of oil price in the context of Covid‐19
Authors: Jawadi Fredj , Sellami Mohamed 
Published: February 2021

AbstractThis article studies the impact of oil price change on the stock market, the exchange rate and the real estate market in the US over the last decade. To this end, we model the dynamics of the returns for these markets and test the effect of oil market volatility on their dynamics. Through different econometric investigations, we show, in the context of Covid‐19, that oil price has experienced significant effects on the US stock market and the US dollar exchange rate, while it has no significant impact on the US real estate market. In particular, we highlight, first, a positive and significant reaction of the stock market toward an oil price shock, which might be explained by the effect of high oil financialization over the last decade. Second, we show an adverse effect of the oil price change on the US dollar, suggesting a negative relationship between the oil price and the US dollar. Accordingly, the information provided by the oil sector might help to improve the forecast of the Dow Jones and the US$\€ exchange rate.
Covid‐19 outbreak and stocks return on the West African Economic and Monetary Union's stock market: An empirical analysis of the relationship through the event study approach
Authors: Zoungrana Tibi Didier , Toé Daouda Lawa tan , Toé Mamadou 
Published: February 2021

AbstractThis study uses the Wilcoxon's signed ranks test to identify the effect of the Covid‐19 outbreak on the stocks returns of companies listed on the West African Economic and Monetary Union's (WAEMU) stock market by considering two event dates (January 23, 2020 and March 2, 2020). To account for the temporal volatility in the event approach, the study resort to a GARCH model. Empirical findings suggest that January 23, 2020 event (first case of death due to Covid‐19 in China) have had a minor impact on the WAEMU stock market while the event on March 2, 2020 (first case of Covid‐19 in the WAEMU) strongly affected the financial market. This negative impact is much more pronounced for the distribution sectors (−34.16%). Robustness analysis reveals that the main information leading to disruption on the market is the weekly death cases and not the confirmed cases. In addition, government anti‐Covid‐19 measures such as social distancing and governance positively affect the stock return whereas lockdown, public health measures and movement restrictions contribute to a decline in the stock's price.