bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptom presentation of SARS-CoV-2-positive and negative patients: a nested case–control study among patients calling the emergency medical service and medical helpline
Authors: Moeller Amalie Lykkemark , Mills Elisabeth Helen Anna , Collatz Christensen Helle , Gnesin Filip , Blomberg Stig Nikolaj Fasmer Nikolaj , Zylyftari Nertila , Jensen Britta , Ringgren Kristian Bundgaard , Broccia Marcella Ditte , Bøggild Henrik , Torp-Pedersen Christian 
Published: May 2021

ObjectiveCurrently effective symptom-based screening of patients suspected of COVID-19 is limited. We aimed to investigate age-related differences in symptom presentations of patients tested positive and negative for SARS-CoV-2.DesignSettingCalls to the medical helpline (1-8-1-3) and emergency number (1-1-2) in Copenhagen, Denmark. At both medical services all calls are recorded.ParticipantsWe included calls for patients who called for help/guidance at the medical helpline or emergency number prior to receiving a test for SARS-CoV-2 between April 1stand 20th2020 (8423 patients). Among these calls, we randomly sampled recorded calls from 350 patients who later tested positive and 250 patients tested negative and registered symptoms described in the call.OutcomeResultsAfter exclusions, 544 calls (312 SARS-CoV-2 positive and 232 negative) were included in the analysis. Fever and cough remained the two most common of COVID-19 symptoms across all age groups and approximately 42% of SARS-CoV-2 positive and 20% of negative presented with both fever and cough. Symptoms including nasal congestion, irritation/pain in throat, muscle/joint pain, loss of taste and smell, and headache were common symptoms of COVID-19 for patients younger than 60 years; whereas loss of appetite and feeling unwell were more commonly seen among patients over 60 years. Headache and loss of taste and smell were rare symptoms of COVID-19 among patients over 60 years.ConclusionOur study identified age-related differences in symptom presentations of SARS-CoV-2-positive patients calling for help or medical advice. The specific symptoms of loss of smell or taste almost exclusively reported by patients younger than 60 years. Differences in symptom presentation across age groups must be considered when screening for COVID-19.
Caesarean sections and health financing: a global analysis
Authors: Hoxha Ilir , Fink Günther 
Published: May 2021

ObjectivesThe objective of this study is to explore the association of health financing indicators with the proportion of births by caesarean section (CS) across countries.DesignEcological cross-country study.SettingThis study examines CS proportions across 172 countries.Main outcome measuresThe primary outcome was the percentage excess of CS proportion, defined as CS proportions above the global target of 19%. We also analysed continuous CS proportions, as well as excess proportion with a more restrictive 9% global target. Multivariable linear regressions were performed to test the association of health financing factors with the percentage excess proportions of CS. The health financing factors considered were total available health system resources (as percentage of gross domestic product), total contributions from private households (out-of-pocket, compulsory and voluntary health insurance contributions) and total national income.ResultsWe estimate that in 2018 there were a total of 8.8 million unnecessary CS globally, roughly two-thirds of which occurred in upper middle-income countries. Private health financing was positively associated with percentage excess CS proportion. In models adjusted for income and total health resources as well as human resources, each 10 per cent increase in out-of-pocket expenditure was associated with a 0.7 per cent increase in excess CS proportions. A 10 per cent increase in voluntary health insurance was associated with a 4 per cent increase in excess CS proportions.ConclusionsWe have found that health system finance features are associated with CS use across countries. Further monitoring of these indicators, within countries and between countries will be needed to understand the effect of financial arrangements in the provision of CS.
Slowly rotating neutron stars in scalar torsion theory
Authors: Boumaza Hamza 
Published: May 2021

AbstractIn this present paper, a slowly rotating stat is investigated in shift symmetric scalar torsion theory framework using a nondiagonal tetrad that gives an axially symmetric spacetime. We present the general equations for a general Lagrangian in a spherical symmetric space time and then in an axially symmetric spacetime. The obtained equations will allow us to study the behaviour of a specific model at the center of the star and at large distance. We find that this particular model affects the behaviour at the center but it is not case for large value of the radial coordinate r. The integration of the equations of motion, for different realistic equations of state (EoS), confirms that the mass, the radius as well as the moment of inertia are effected by varying the parameters of the model. Finally, we examine the universal relation of normalized moment of inertia and the stellar compactness of neutron star in slow rotation approximation. We showed that for all values of parameters present in the model leads to a deviation from GR for all EoS with a relative deviation below $$10\%$$

10
%

.
Efficacy and Safety of Scalp Acupuncture for Insomnia: A Systematic Review and Meta-Analysis
Authors: Liu Fu-gui , Tan Ai-hua , Peng Chao-qun , Tan Yun-xia , Yao Ming-chao 
Published: May 2021

Objective. To systematically evaluate the efficacy and safety of scalp acupuncture in the treatment of insomnia. Methods. CNKI, Wanfang database, CQVIP database, CBM, Web of Science, Cochrane Library, and PubMed were searched for the literature on the treatment of insomnia by scalp acupuncture from the establishment of the database to July 23, 2020. Two researchers independently screened the literatures and extracted the data, then evaluated the quality of the literatures, and used RevMan 5.3 software for statistical analysis. Results. A total of 21 studies including 1606 cases were included. 21 studies were included in the analysis of effective rate. The heterogeneity test showed that there was no significant heterogeneity. The fixed effect model was used,

P

< 0.00001. The effective rate of scalp acupuncture in the treatment of insomnia was significantly higher than that of the control group. The analysis of PSQI score was finally included in 19 studies. The heterogeneity test showed that there was obvious heterogeneity. The random effect model was used, and the subgroup analysis was conducted according to the different intervention measures of the control group. The

P

values of the drug group and the blank group were both less than 0.05, indicating that the improvement of PSQI score in the scalp acupuncture treatment of insomnia was significantly better than that in the drug group and the blank group;

P

= 0.05 in other acupuncture groups, suggesting in scalp acupuncture treatment, there was no difference between insomnia and other acupuncture in improving the PSQI score. Six studies were included in the analysis of adverse events. The heterogeneity test showed no significant heterogeneity. The fixed effect model was used,

P

= 0.04 < 0.05, indicating that the adverse events of scalp acupuncture in the treatment of insomnia were better than those of the control group. No publication bias analysis was conducted due to the small number of adverse events included. Publication bias was analyzed for effective rate and PSQI score. Egger’s TSTs test (effective rate

P

= 0.001, PSQI score

P

= 0.001) and funnel plot showed publication bias. Conclusion. Scalp acupuncture is effective and safe in the treatment of insomnia, which is worthy of clinical application. However, due to the limited number of included literature, the methodology of some studies is slightly low and the quality of literature is slightly poor. In the future, we need to design rigorous, large sample, multiple center randomized controlled study to further verify the conclusion of this study.
Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
Authors: Abunasser Abdulhakim A. A. , Xue Jinmin , Balawi Ehab J. A. , Zhu Yuxi 
Published: May 2021

The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the same traditional regimen with etoposide and platinum (EP) as the mainstay of treatment with poor prognosis. This meta-analysis aims to assess the effect of adding Immune Checkpoint Inhibitors (CPIs) such as (ipilimumab, atezolizumab, pembrolizumab, and durvalumab) to the traditional EP regimen for small-cell lung cancer extensive stage (ES-SCLC). We searched through PubMed looking for studies that compare between EP and CPIs, with EP alone, and only Phase III randomized controlled trials were considered eligible for this study. A total of 3645 papers were the results of the initial search, and only 4 studies met our criteria. Each investigator extracted the data independently using the PRISMA MODEL (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Each author used a prespecified sheet. The primary endpoint was to calculate OS (overall survival) and PFS (progression-free survival) hazard ratios for both arms. We found that adding EP plus CPIs increased both OS (HR, 95% CI 0.80 [0.70, 0.93],

P

= 0.0001, I2 = 49%) and PFS (HR95% CI 0.81 [0.74, 0.88],

P

< 0.00001, I2 = 0%). On the other hand, ORR (overall response rate) was not affected by the addition of CPIs to EP compared to EP alone, and the same was true for adverse events. To conclude, CTLA-4 alone is not encouraging, but PD-1/PD-L1 adds survival benefits. A combined treatment regimen shows to be more effective, improving overall survival rate Durvalumab and atezolizumab showed improvement for OS, but pembrolizumab and ipilimumab did not show a significant increase of OS over EP; however, pembrolizumab showed significant prolongation of the disease-free period.
Opening of the Blood–Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models
Authors: Sabbagh Aria , Beccaria Kevin , Ling Xiaoyang , Marisetty Anantha , Ott Martina , Caruso Hillary , Barton Emily , Kong Ling-Yuan , Fang Dexing , Latha Khatri , Zhang Daniel Yang , Wei Jun , DeGroot John , Curran Michael A. , Rao Ganesh , Hu Jian , Desseaux Carole , Bouchoux Guillaume , Canney Michael , Carpentier Alexandre , Heimberger Amy B. 
Published: May 2021

Abstract

Purpose:
The blood–brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe therapeutic method of temporary BBB disruption (BBBD) to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma for treatment of glioblastoma.

Experimental Design:
We investigated if LIPU could enhance therapeutic efficacy of anti–PD-1 in C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen receptor (CAR) T cells in NSG mice with EGFRvIII-U87 gliomas, and a genetically engineered antigen-presenting cell (APC)-based therapy producing the T-cell attracting chemokine CXCL10 in the GL261-bearing mice.

Results:
Mice treated with anti–PD-1 and LIPU-induced BBBD had a median survival duration of 58 days compared with 39 days for mice treated with anti–PD-1, and long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR T-cell administration with LIPU-induced BBBD resulted in significant increases in CAR T-cell delivery to the CNS after 24 (P &lt; 0.005) and 72 (P &lt; 0.001) hours and increased median survival by greater than 129%, in comparison with CAR T cells alone. Local deposition of CXCL10-secreting APCs in the glioma microenvironment with LIPU enhanced T-cell glioma infiltration during the therapeutic window (P = 0.004) and markedly enhanced survival (P &lt; 0.05).

Conclusions:
LIPU increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain.
HYAL4-V1/Chondroitinase (Chase) Drives Gemcitabine Resistance and Predicts Chemotherapy Failure in Patients with Bladder Cancer
Authors: Hasanali Sarrah L. , Morera Daley S. , Racine Ronny R. , Hennig Martin , Ghosh Santu , Lopez Luis E. , Hupe Marie C. , Escudero Diogo O. , Wang Jiaojiao , Zhu Huabin , Sarcan Semih , Azih Ijeoma , Zhou Michael , Jordan Andre R. , Terris Martha K. , Kuczyk Markus A. , Merseburger Axel S. , Lokeshwar Vinata B. 
Published: May 2021

Abstract

Purpose:
Gemcitabine-based chemotherapy regimens are first-line for several advanced cancers. Because of better tolerability, gemcitabine + cisplatin is a preferred neoadjuvant, adjuvant, and/or palliative chemotherapy regimen for advanced bladder cancer. Nevertheless, predicting treatment failure and overcoming resistance remain unmet clinical needs. We discovered that splice variant (V1) of HYAL-4 is a first-in-class eukaryotic chondroitinase (Chase), and CD44 is its major substrate. V1 is upregulated in bladder cancer and drives a malignant phenotype. In this study, we investigated whether V1 drives chemotherapy resistance.

Experimental Design:
V1 expression was measured in muscle-invasive bladder cancer (MIBC) specimens by qRT-PCR and IHC. HYAL-4 wild-type (Wt) and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for chemoresistance and associated mechanism in preclinical models.

Results:
V1 levels in MIBC specimens of patients who developed metastasis, predicted response to gemcitabine + cisplatin adjuvant/salvage treatment and disease-specific mortality. V1-expressing bladder cells were resistant to gemcitabine but not to cisplatin. V1 expression neither affected gemcitabine influx nor the drug-efflux transporters. Instead, V1 increased gemcitabine metabolism and subsequent efflux of difluorodeoxyuridine, by upregulating cytidine deaminase (CDA) expression through increased CD44–JAK2/STAT3 signaling. CDA inhibitor tetrahydrouridine resensitized V1-expressing cells to gemcitabine. While gemcitabine (25–50 mg/kg) inhibited bladder cancer xenograft growth, V1-expressing tumors were resistant. Low-dose combination of gemcitabine and tetrahydrouridine abrogated the growth of V1 tumors with minimal toxicity.

Conclusions:
V1/Chase drives gemcitabine resistance and potentially predicts gemcitabine + cisplatin failure. CDA inhibition resensitizes V1-expressing tumors to gemcitabine. Because several chemotherapy regimens include gemcitabine, our study could have broad significance.
Combining Clinical and Polygenic Risk Improves Stroke Prediction Among Individuals With Atrial Fibrillation
Authors: O’Sullivan Jack W. , Shcherbina Anna , Justesen Johanne M. , Turakhia Mintu , Perez Marco , Wand Hannah , Tcheandjieu Catherine , Clarke Shoa L. , Rivas Manuel A. , Ashley Euan A. 
Published: May 2021

Background:

Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable; however, current risk stratification tools (CHA
2
DS
2
-VASc) do not include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS).

Methods:
Using data from the largest available genome-wide association study in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank, both independently and integrated with clinical risk factors. The integrated PRS and clinical risk factors risk tool had the greatest predictive ability.

Results:

Compared with the currently recommended risk tool (CHA
2
DS
2
-VASc), the integrated tool significantly improved Net Reclassification Index (2.3% [95% CI, 1.3%–3.0%]) and fit (χ
2
P
=0.002). Using this improved tool, >115 000 people with AF would have improved risk classification in the United States. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (hazard ratio, 1.13 per 1 SD [95% CI, 1.06–1.23]). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson correlation coefficient, −0.018).

Conclusions:
In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors; however, the prediction of stroke remains challenging.
Disconnectomics of the Rich Club Impacts Motor Recovery After Stroke
Authors: Egger Philip , Evangelista Giorgia G. , Koch Philipp J. , Park Chang-Hyun , Levin-Gleba Laura , Girard Gabriel , Beanato Elena , Lee Jungsoo , Choirat Christine , Guggisberg Adrian G. , Kim Yun-Hee , Hummel Friedhelm C. 
Published: May 2021

Background and Purpose:
Structural brain networks possess a few hubs, which are not only highly connected to the rest of the brain but are also highly connected to each other. These hubs, which form a rich-club, play a central role in global brain organization. To investigate whether the concept of rich-club sheds new light on poststroke recovery, we applied a novel network-theoretical quantification of lesions to patients with stroke and compared the outcomes with what lesion size alone would indicate.

Methods:
Whole-brain structural networks of 73 patients with ischemic stroke were reconstructed using diffusion-weighted imaging data. Disconnectomes, a new type of network analyses, were constructed using only those fibers that pass through the lesion. Fugl-Meyer upper extremity scores and their changes were used to determine whether the patients show natural recovery or not.

Results:

Cluster analysis revealed 3 patient clusters: small-lesion-good-recovery, midsized-lesion-poor-recovery (MLPR), and large-lesion-poor-recovery (LLPR). The small-lesion-good-recovery consisted of subjects whose lesions were small, and whose prospects for recovery were relatively good. To explain the nondifference in recovery between the MLPR and LLPR clusters despite the difference (LLPR>MLPR) in lesion volume, we defined the

metric to be the sum of the entries in the disconnectome and, more importantly, the

to be the sum of all entries in the disconnectome corresponding to edges with at least one node in the rich-club. Unlike lesion volume and corticospinal tract damage (MLPR<LLPR), for

, this relationship was reversed (MLPR>LLPR) or showed no difference for

.

Conclusions:
Smaller lesions that focus on the rich-club can be just as devastating as much larger lesions that do not focus on the rich-club, pointing to the role of the rich-club as a backbone for functional communication within brain networks and for recovery from stroke.
Public Emotional Diffusion over COVID-19 Related Tweets Posted by
Major Public Health Agencies in the United States
Authors: Xi Haixu , Zhang Chengzhi , Zhao Yi , He Sheng 
Published: May 2021

Abstract
Since the end of 2019, the COVID-19 outbreak worldwide has not only presented challenges for government agencies in addressing public health emergency, but also tested their capacity in dealing with public opinion on social media and responding to social emergencies. To understand the impact of COVID-19 related tweets posted by the major public health agencies in the United States on public emotion, this paper studied public emotional diffusion in the tweets network, including its process and characteristics, by taking Twitter users of four official public health systems in the United States as an example. We extracted the interactions between tweets in the COVID-19-TweetIds data set and drew the tweets diffusion network. We proposed a method to measure the characteristics of the emotional diffusion network, with which we analyzed the changes of the public emotional intensity and the proportion of emotional polarity, investigated the emotional influence of key nodes and users, and the emotional diffusion of tweets at different tweeting time, tweet topics and the tweet posting agencies. The results show that the emotional polarity of tweets has changed from negative to positive with the improvement of pandemic management measures. The public's emotional polarity on pandemic related topics tends to be negative, and the emotional intensity of management measures such as pandemic medical services turn from positive to negative to the greatest extent, while the emotional intensity of pandemic related knowledge changes the most. The tweets posted by the Centers for Disease Control and Prevention and the Food and Drug Administration of the United States have a broad impact on public emotions, and the emotional spread of tweets' polarity eventually forms a very close proportion of opposite emotions.
<p><strong>Taxonomic position and circumscription of Cardamine barbaraeoides (Brassicaceae), a systematically challenging taxon from the Balkan Peninsula</strong></p>
Authors: ŠLENKER MAREK , PERNÝ MARIÁN , ZOZOMOVÁ-LIHOVÁ JUDITA , MARHOLD KAROL 
Published: May 2021

The Balkan Peninsula, and the territory of Greece in particular, is a significant biodiversity hotspot in the Mediterranean that is rich in endemic plants. The focal species of this study, Cardamine barbaraeoides, is a narrow Greek endemic that has been confused taxonomically since its original description. Based on a detailed multivariate morphometric study, we provide here a set of morphological characters that enables the reliable identification of this species. In addition, we present an identification key to C. barbaraeoides and related taxa. We have revised herbarium specimens and literature data on the occurrence of this species in Greece and ascertained that it occurs only in the Pindos mountains (the Southern Pindos and partly the Northern Pindos floristic regions). All reports of this species from the Greek floristic regions of North Central, Sterea Ellas and partly also Northern Pindos were based on misidentifications of specimens of C. acris.