bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond PPE: a mixed qualitative–quantitative study capturing the wider issues affecting doctors’ well-being during the COVID-19 pandemic
Authors: Cubitt Lyndsey Jayne , Im Yu Ri , Scott Ciaran James , Jeynes Louise Claire , Molyneux Paul David 
Published: March 2021

The COVID-19 pandemic has brought unprecedented challenges to the medical workforce. This has put them at increased risk of burnout at a time when levels are already worryingly high in the profession, with recent studies consistently showing that around half of doctors meet the validated criteria for burnout.ObjectivesTo understand the wider factors influencing and impacting upon hospital doctors’ well-being during the COVID-19 pandemic in England.DesignCross-sectional survey and mixed quantitative–qualitative analysis.SettingAcute National Health Service (NHS) Foundation Trust in England.ParticipantsAn online survey was circulated in early June 2020 to all 449 doctors employed by the Trust. 242 doctors completed the survey (54% response rate).Primary outcome measuresQuestions assessed occupational details, self-reported changes in physical and mental health, satisfaction with working hours and patterns, availability of personal protective equipment (PPE), medication and facilities, communication and sought to identify areas seen as having a significant effect on doctors’ well-being.Results96% of respondents requiring PPE were able to access it. Nearly half of the respondents felt that their mental health had deteriorated since the start of the pandemic. Over a third stated that their physical health had also declined. Issues identified as having a negative impact on doctors included increased workload, redeployment, loss of autonomy, personal issues affecting family members, anxiety around recovery plans, inadequate access to changing and storage facilities and to rest areas that allow for social distancing. Doctors appreciated access to ‘calm rooms’ that were made available for staff, access to clinical psychology support, free drinks and free car parking on site.ConclusionThe emerging themes are suggestive of increased burnout risk among doctors during the COVID-19 pandemic and encompass factors well beyond shortage of PPE. Small organisational initiatives and the implementation of changes suggested by survey respondents can have a positive impact on doctors’ well-being.
Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages
Authors: Ou Da-Liang , Chen Chia-Wei , Hsu Chia-Lang , Chung Chih-Hung , Feng Zi-Rui , Lee Bin-Shyun , Cheng Ann-Lii , Yang Muh-Hwa , Hsu Chiun 
Published: March 2021

BackgroundRegorafenib and other multikinase inhibitors may enhance antitumor efficacy of anti-program cell death-1 (anti-PD1) therapy in hepatocellular carcinoma (HCC). Its immunomodulatory effects, besides anti-angiogenesis, were not clearly defined.MethodsIn vivo antitumor efficacy was tested in multiple syngeneic liver cancer models. Murine bone marrow–derived macrophages (BMDMs) were tested in vitro for modulation of polarization by regorafenib and activation of cocultured T cells. Markers of M1/M2 polarization were measured by quantitative reverse transcription PCR (RT-PCR), arginase activity, flow cytometry, and ELISA. Knockdown of p38 kinase and downstream Creb1/Klf4 signaling on macrophage polarization were confirmed by using knockdown of the upstream MAPK14 kinase, chemical p38 kinase inhibitor, and chromatin immunoprecipitation.ResultsRegorafenib (5 mg/kg/day, corresponding to about half of human clinical dosage) inhibited tumor growth and angiogenesis in vivo similarly to DC-101 (anti-VEGFR2 antibody) but produced higher T cell activation and M1 macrophage polarization, increased the ratio of M1/M2 polarized BMDMs and proliferation/activation of cocultured T cells in vitro, indicating angiogenesis-independent immunomodulatory effects. Suppression of p38 kinase phosphorylation and downstream Creb1/Klf4 activity in BMDMs by regorafenib reversed M2 polarization. Regorafenib enhanced antitumor efficacy of adoptively transferred antigen-specific T cells. Synergistic antitumor efficacy between regorafenib and anti-PD1 was associated with multiple immune-related pathways in the tumor microenvironment.ConclusionRegorafenib may enhance antitumor immunity through modulation of macrophage polarization, independent of its anti-angiogenic effects. Optimization of regorafenib dosage for rational design of combination therapy regimen may improve the therapeutic index in the clinic.
Higher postoperative plasma EV PD-L1 predicts poor survival in patients with gastric cancer
Authors: Li Gaopeng , Wang Guoliang , Chi Fenqing , Jia Yuqi , Wang Xi , Mu Quankai , Qin Keru , Zhu Xiaoxia , Pang Jing , Xu Baixue , Feng Guangen , Niu Yuhu , Gong Tao , Zhang Hongwei , Dong Xiushan , Liu Ting , Ma Jinfeng , Gao Zefeng , Tao Kai , Li Feng , Xu Jun , Yu Baofeng 
Published: March 2021

BackgroundThe satisfactory prognostic indicator of gastric cancer (GC) patients after surgery is still lacking. Perioperative plasma extracellular vesicular programmed cell death ligand-1 (ePD-L1) has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of postoperative plasma ePD-L1 has not been characterized.MethodsWe evaluated the prognostic value of preoperative, postoperative and change in plasma ePD-L1, as well as plasma soluble PD-L1, in short-term survival of GC patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyzes were used. And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and CA72-4) in prognostic of GC patients was made.ResultsThe prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). The levels of postoperative ePD-L1 and ePD-L1 change are independent prognostic factors for overall survival and recurrence free survival of GC patients. High plasma level of postoperative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit.ConclusionsThe level of plasma postoperative ePD-L1 could be considered as a candidate prognostic biomarker of GC patients after resection.
Analyzing and Estimating Thermal Conductivity of Sedimentary Rocks from Mineral Composition and Pore Property
Authors: Tang Boning , Zhu Chuanqing , Qiu Nansheng , Cui Yue , Guo Sasa , Luo Xin , Zhang Baoshou , Li Kunyu , Li Wenzheng , Fu Xiaodong 
Published: March 2021

In this study, thermal conductivities of 128 rock samples located in the Xiong’an New Area and Tarim Basin were measured using the optical scanning and transient plane source methods. The thermal conductivities of the Xiong’an New Area samples range from 1.14 to 6.69 W/(m·K), in which the mean thermal conductivities of dolomite and sandstone are

4.95
±
1.19

and

1.80
±
0.44

W
/

m
·
K

, respectively. In the Tarim Basin, sandstone samples have thermal conductivities ranging from 1.21 to 3.56 W/(m·K) with a mean value of

2.51
±
0.66

W
/

m
·
K

. The results can provide helpful reference data for studies of geothermics and petroleum geology. Calculation correction and water-saturated measurements were conducted to acquire in situ rock thermal conductivity, and good consistency was found between both. Compaction diagenesis enhances bulk thermal conductivity of sedimentary rocks, particularly sandstones, by decreasing the rock porosity and mineral particle size. Finally, correction factors with respect to mineral grains were proposed to correct the thermal resistance of intergrain contacts and degree of intactness of crystals, and an optimized formula was adopted to calculate the thermal conductivity of sedimentary rock based on rock structure and mineral constituents.
Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7–APEH–Proteasome Axis in High-grade Serous Ovarian Carcinoma
Authors: Tangri Apoorva , Lighty Kinzie , Loganathan Jagadish , Mesmar Fahmi , Podicheti Ram , Zhang Chi , Iwanicki Marcin , Drapkin Ronny , Nakshatri Harikrishna , Mitra Sumegha 
Published: March 2021

AbstractHigh-grade serous ovarian cancer (HGSOC) is characterized by chromosomal instability, DNA damage, oxidative stress, and high metabolic demand that exacerbate misfolded, unfolded, and damaged protein burden resulting in increased proteotoxicity. However, the underlying mechanisms that maintain protein homeostasis to promote HGSOC growth remain poorly understood. This study reports that the neuronal deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), is overexpressed in HGSOC and maintains protein homeostasis. UCHL1 expression was markedly increased in HGSOC patient tumors and serous tubal intraepithelial carcinoma (HGSOC precursor lesions). High UCHL1 levels correlated with higher tumor grade and poor patient survival. UCHL1 inhibition reduced HGSOC cell proliferation and invasion, as well as significantly decreased the in vivo metastatic growth of ovarian cancer xenografts. Transcriptional profiling of UCHL1-silenced HGSOC cells revealed downregulation of genes implicated with proteasome activity along with upregulation of endoplasmic reticulum stress–induced genes. Reduced expression of proteasome subunit alpha 7 (PSMA7) and acylaminoacyl peptide hydrolase (APEH), upon silencing of UCHL1, resulted in a significant decrease in proteasome activity, impaired protein degradation, and abrogated HGSOC growth. Furthermore, the accumulation of polyubiquitinated proteins in the UCHL1-silenced cells led to attenuation of mTORC1 activity and protein synthesis, and induction of terminal unfolded protein response. Collectively, these results indicate that UCHL1 promotes HGSOC growth by mediating protein homeostasis through the PSMA7–APEH–proteasome axis.Implications:This study identifies the novel links in the proteostasis network to target protein homeostasis in HGSOC and recognizes the potential of inhibiting UCHL1 and APEH to sensitize cancer cells to proteotoxic stress in solid tumors.
Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation‐Induced Myocardial Dysfunction
Authors: Lin Yu‐Wen , Chen Chin‐Yu , Shih Jhih‐Yuan , Cheng Bor‐Chih , Chang Ching‐Ping , Lin Mao‐Tsun , Ho Chung‐Han , Chen Zhih‐Cherng , Fisch Sudeshna , Chang Wei‐Ting 
Published: March 2021

Background
Mitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR‐induced HF.

Methods and Results
Using a novel, mini‐invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR‐induced impairment including partial restoration of left ventricular ejection fraction and end‐systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing‐induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress‐associated proteins.

Conclusions
DAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR‐induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio‐protective function, provides a plausible point of DAPA as a potential strategy for MR‐induced HF.
Friend or foe? A qualitative study exploring the relationship of people with obesity and food consumption
Authors: Broers Valérie JV , De Mol Jan , Van den Broucke Stephan , Luminet Olivier 
Published: March 2021

Background: Obesity is a major health problem worldwide, and one of its causes is unhealthy eating. A healthy diet should ensure that energy intake (calories) is in balance with energy expenditure, but in this paper a subjective experience of healthy eating will be discussed. Research has revealed many determinants of food consumption, but a more holistic view of food consumption is often overlooked. Aim: The aim was to go beyond identifying determinants of eating by exploring the experience of (healthy) food for people with obesity. Methods: Semi-structured interviews were conducted with eight patients with obesity. Results: Interpretative phenomenological analysis identified four superordinate themes: ambivalence in the emotional relationship with food, an obesogenic environment where it is less acceptable to society to be obese, an experience of unfairness in the relationship to eating in comparison with other people, and the parental role as an existential motivation to eat healthier. Conclusion: The relationship of people with obesity and food is highly complex and personal, and is influenced by the uncontrollability of the social and physical environment. These personal experiences of people with obesity should be taken into account in the psychological treatment of obesity. The current research adds to the mostly motivational determinants discovered with social cognition models, by showing the subjective experience of (healthy) food consumption for people with obesity.
Exploring the Link Between Wages and Psychological Capital
Authors: Beck Jason 
Published: March 2021

Traditional Mincer-type hedonic wage equations typically fail to account for the effect of psychological capital, in part because such factors are often regarded as unobservable. This article incorporates a measure of psychological capital (specifically, self-esteem) that has been validated in the psychology literature into an otherwise typical hedonic wage model. Then, the sample is divided into race and gender subgroups and estimates are compared. The results suggest that self-esteem does play a role in determining wages for Whites (White men, in particular), but it has no detectable effect on the wages of African-Americans. Data are drawn from the 1979 National Longitudinal Study of Youth. JEL: D (‘Microeconomics’), J (‘Labor and demographic economics’), J31 (‘Wage levels and structure, wage differentials’)
Projection-specific dopamine neurons in the ventral tegmental area participated in morphine-induced hyperalgesia and anti-nociceptive tolerance in male mice
Authors: Sun Guo-Lin , Song Zhi-Jing , Peng Xiao-Han , Chen Pan-Pan , Song Ying , Qin Xia , Hua Rong , Zhang Yong-Mei 
Published: March 2021

Background: Long-term morphine use is associated with serious side effects, such as morphine-induced hyperalgesia and analgesic tolerance. Previous investigations have documented the association between dopamine (DA) neurons in the ventral tegmental area (VTA) and pain. However, whether VTA DA neurons are implicated in morphine-induced hyperalgesia and analgesic tolerance remains elusive. Methods: Initially, we observed behavioural effects of lidocaine administration into VTA or ablation of VTA DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance. Subsequently, c-Fos expression in nucleus accumbens (NAc) shell-projecting and medial prefrontal cortex (mPFC)-projecting VTA DA neurons after chronic morphine treatment was respectively investigated. Afterwards, the effects of chemogenetic manipulation of NAc shell-projecting or mPFC-projecting DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance were observed. Additionally, effects of chemogenetic manipulation of VTA GABA neurons on c-Fos expression in VTA DA neurons were investigated. Results: Lidocaine injection into VTA relieved established hyperalgesia and anti-nociceptive tolerance whereas ablation of VTA DA neurons prevented the development of morphine-induced hyperalgesia and anti-nociceptive tolerance. Chronic morphine treatment increased c-Fos expression in NAc shell-projecting DA neurons, rather than in mPFC-projecting DA neurons. Chemogenetic manipulation of NAc shell-projecting DA neurons had influence on morphine-induced hyperalgesia and tolerance. However, chemogenetic manipulation of mPFC-projecting DA neurons had no significant effects on morphine-induced hyperalgesia and anti-nociceptive tolerance. Chemogenetic manipulation of VTA GABA neurons affected the c-Fos expression in VTA DA neurons. Conclusions: These findings revealed the involvement of NAc shell-projecting VTA DA neurons in morphine-induced hyperalgesia and anti-nociceptive tolerance, and may shed new light on the clinical management of morphine-induced hyperalgesia and analgesic tolerance. Perspective: This study demonstrated that NAc shell-projecting DA neurons rather than mPFC-projecting DA neurons in the VTA were implicated in morphine-induced hyperalgesia and anti-nociceptive tolerance. Our findings may pave the way for the discovery of novel therapies for morphine-induced hyperalgesia and analgesic tolerance.
Giant mantle cell lymphoma in the soft tissue of the leg: rare presentation
Authors: Erdem Büşra Erşan , Kiraz Umay , Vural Çiğdem , Atmaca Halil , Eruyar Ahmet Tuğrul 
Published: March 2021

Background: Mantle cell lymphomas are aggressive, mature B-cell neoplasms characteristically showing overexpression of cyclin D1. Although lymphadenopathy is the most common presentation, involvement of extranodal sites including bone marrow, peripheral blood, liver, gastrointestinal system, and Waldeyer ring is also seen frequently. Soft tissue localization is extremely rare. It has blastoid and pleomorphic subtypes associated with aggressive course. Case description: We describe a 74-year-old man who had been diagnosed 3 years previously with “mantle cell lymphoma-blastoid type” and presented 3 months ago with a giant mass in the right lower extremity that enlarged rapidly up to 15 cm in a few months. Conclusion: We present this rare presentation, which was evaluated in favor of hemangioma before biopsy, together with the data in the literature to emphasize the need for differential diagnosis, especially in cases with a clinical history.
COVID-19 and slowdown of residents’ activity: Feedback from a novel e-learning event and overview of the literature
Authors: Calcagnile Tommaso , Sighinolfi Maria Chiara , Sarchi Luca , Assumma Simone , Filippi Beatrice , Bonfante Giulia , Cassani Alessandra , Spandri Valentina , Turri Filippo , Puliatti Stefano , Bozzini Giorgio , Moschovas Marcio , Bianchi Giampaolo , Micali Salvatore , Rocco Bernardo 
Published: March 2021

Objective: To evaluate the impact of an e-learning online event, created for supporting resident’s training during the slowdown of surgical and clinical activities caused by COVID-19 pandemic. An overview of PubMed literature depicting the state of the art of urology residency in the COVID-19 era was performed as well, to contextualize the issue. Methods: An online learning event for residents was set up at the beginning of the pandemic; the faculty consisted of experts in urology who provided on-line lectures and videos on surgical anatomy, procedures, updates in guidelines, technology, training. The audience was composed of 30–500 attendees from Italy, USA, India and Belgium. A questionnaire to analyze relevance, satisfaction and popularity of the lessons was mailed to 30 local residents. Results and limitations: Almost all residents defined the web environment suitable to achieve the learning outcomes; the method, the number and the competence of the faculty were appropriate/excellent. Most of the younger residents (81.8%) stated their surgical knowledge would improve after the course; 72.7% declared they would take advantage into routine inpatients clinical activity. Nineteen more expert residents agreed that the course would improve their surgical knowledge and enhance their practical skills; almost all stated that the initiative would change their outpatients and inpatients practice. Overall, 44 articles available in PubMed have addressed the concern of urological learning and training during the pandemic from different standpoints; four of them considered residents’ general perception towards web-based learning programs. Conclusions: The paper confirms residents’ satisfaction with e-learning methods and, to our knowledge, is the first one focusing on a specific event promptly settled up at the beginning of the outbreak. Web-based educational experience developed during the pandemic may represent the very basis for the implementation of prospective on-site training and overall scientific update of future urologists.
Critical Care Transport of Patients With COVID-19
Authors: Frakes Michael A. , Richards Jeremy B. , Cocchi Michael N. , Cohen Ari , Cohen Jason E. , Dargin James , Friedman Franklin D. , Kaye Adam S. , Rettig Jordan S. , Seethala Raghu , Wilcox Susan R. 
Published: March 2021

Purpose: Critical care transport is associated with a high rate of adverse events, and the risks and outcomes of transporting critically ill patients during the COVID-19 pandemic have not been previously described. Materials and Methods: We performed a retrospective review of transports of subjects with suspected or confirmed COVID-19 from sending hospitals to tertiary care hospitals in Boston. Follow-up data were obtained for patients transported between March 1st and April 20th, 2020. Results: Of 254 charts identified, 250 patients were transported. Nine patients (3.5%) had cardiac arrest prior to transport. Twenty-nine (11.6%) had hypotension, 22 (8.8%) had a critical desaturation, and 4 (1.6%) had both en route. Hospital follow-up data were available for 189 patients. Of those intubated during their hospitalization, 44 (25.0%) had died, 59 (33.5%) had been extubated, and 13 (17.6%) had been discharged alive. For the subgroup with prior cardiac arrest, follow-up data available for 6. Of these 6, 2 died and 4 (66.7%) have been discharged alive. Conclusions: Few patients with COVID-19 had an adverse event in transport. The in-hospital mortality rate was 25%, with a 33.5% extubation rate. Patients resuscitated from cardiac arrest prior to transport had a 66.7% discharge rate among those transported to consortium hospitals.