bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential serum exosomal microRNAs involved in acinar-ductal metaplasia that is a precursor of pancreatic cancer associated with chronic pancreatitis
Authors: Sheng Li-Ping , Han Chao-Qun , Nie Chi , Xu Tao , Zhang Kun , Li Xuan-Ji , Xie Xin-Ru , Lin Rong , Ding Zhen 
Published: May 2021

Abstract

Backgrounds:
Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP.

Objective:
To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis.

Methods:
The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0.

Results:
We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein–protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs.

Conclusions:
Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.
A case report of aggressive course of CD30+ primary cutaneous anaplastic large cell lymphoma
Authors: Lyu Wen-Tian , Song Qi-Bin , Qiong Wang , Liu Jing , Yong Ren , Yi Feng-Tao , Han Dong-liang 
Published: May 2021

Abstract

Introduction:
CD30+ primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare T-cell neoplasm, and has been reported to present with an indolent behavior. The PC-ALCL with aggressive behavior has not been reported in the literature.

Patient concerns:
We treated a patient with PC-ALCL that exhibited indolent behavior in the past 2 years and aggressive behavior within the last 3 months before presentation.

Diagnosis:
Aggressive CD30+ primary cutaneous anaplastic large cell lymphoma.

Interventions:
The radiotherapy regimen was individualized in terms of the target volume delineation and dose prescription, and the dose–response relationship was evaluated.

Outcomes:
The mean distance of microscopic infiltration was 14.1 mm in depth and 14.3 mm circumferentially. The lesion completely regressed after the delivery of 40 Gy in 20 fractions over 4 weeks. The tumor did not recur over the next year.

Conclusion:
An aggressive disease course is rare for indolent CD30+ PC-ALCL, which has similar histopathological characteristics as indolent PC-ALCL. The radiotherapy strategy should be individualized with curative intent.
Perfusion image guided mechanical thrombectomy combined with tirofiban successfully revascularize systemic lupus erythematosus related acute large vessel occlusion
Authors: Wang Han , Hu Haitao , Xu Jing , Qian Cong 
Published: May 2021

Abstract

Rationale:
Systemic lupus erythematosus (SLE) is an important cause of stroke, more than a half the cases present as acute ischemic stroke. Thrombolysis is an effective choice in most cases, but for large vessel occlusion, mechanical thrombectomy is more effective. Here we reported a case of SLE-related stroke with left middle cerebral artery (MCA) occlusion, who was successfully treated by MT and tirofiban.

Patient concern:
A 38-year-old female suffered from right hemiplegia and aphasia for 8 hours. She was diagnosed with SLE 20 years ago, and neuropsychiatric SLE was considered 8 months before this onset. One month ago, glucocorticoids were discontinued by herself because of deterioration of bilateral femoral head osteonecrosis.

Diagnosis:
Left MCA occlusion was confirmed by computed tomography perfusion.

Intervention:
Immediate mechanical thrombectomy was performed and tirofiban was given to prevent re-occlusion of left MCA. Twenty fourhours later oral antiplatelet was given after intracranial hemorrhage was ruled out.

Outcomes:
Her neurological symptom improved several days later, and she was transferred to further rehabilitation. At 4 months follow-up she can live independently with mild hypophrasia. There was no further events of ischemic stroke in 1-year follow-up.

Lessons:
Mechanical thrombectomy is a highly effective and indispensable treatment for SLE related large vessel occlusion. In addition, tirofiban may reduce vessel reocclusion in special cases such as SLE and artery stenosis.
Efficacy and safety of high and low dose recombinant human erythropoietin on neurodevelopment of premature infants
Authors: Qin Na , Qin Huibin 
Published: May 2021

Abstract

Background:
To evaluate the effect of recombinant human erythropoietin (rhEPO) in nervous system of premature infants including different dosage.

Methods:
The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge Database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of rhEPO for neurodevelopment among premature infants. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted.

Results:
Finally, 10 eligible studies were eventually satisfied the included criteria. The results showed that rhEPO was much higher than placebo group in composite cognitive score (MD = 5.89, 95% confidential interval {CI} [1.95, 9.82], P = .003; I

2
= 89%), there was no significant difference between rhEPO and placebo groups (RR = 0.93, 95% CI [0.60, 1.43], P = .74; I

2
= 51%) and no difference in neurodevelopmental impairment between rhEPO and placebo was insignificant (RR = 0.55 95% CI [0.30, 1.02], P = .06). Composite cognitive score in high dose rhEPO was much higher than placebo group (MD = 10.39, 95% CI [8.84, 11.93], P < .0001, I

2
= 0%) and low dose rhEPO also had higher composite cognitive score than placebo group (MD = 2.58, 95% CI [0.80, 4.37], P = .004, I

2
= 11%). Limited publication bias was observed in this study.

Conclusion:
Recombinant human erythropoietin might be a promotor for neurodevelopment among premature infants with limited adverse events.
Off-label tocilizumab and adjuvant iron chelator effectiveness in a group of severe COVID-19 pneumonia patients
Authors: Birlutiu Victoria , Birlutiu Rares Mircea , Chicea Liana 
Published: May 2021

Abstract
Tocilizumab (TCZ), a monoclonal recombinant antibody against IL-6 receptor, is currently used in managing the cytokine release syndrome (CRS) that occurred in coronavirus disease 2019 (COVID-19) selected cases. The primary objective of our study was to establish the effectiveness of TCZ in patients with severe or critical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia.
We retrospectively analyzed 25 consecutive patients, admitted in the Academic Emergency Hospital Sibiu, Romania from April 1, 2020 until May 25, 2020, all with confirmed SARS-CoV-2 infection and severe pneumonia. All patients were treated off-label with TCZ, beside their standard care. Adjuvant iron chelator was associated in 11 patients.
Six female and 19 male patients admitted in our hospital all with confirmed SARS-CoV-2 infection and severe pneumonia as defined by Chinese Centers for Disease Control and Prevention were enrolled in this study. Seventeen of the 25 enrolled patients (68%) were seriously ill requiring noninvasive ventilation or oxygen mask, and 8 cases (32%) were critically ill requiring invasive mechanical ventilation. All patients received TCZ, and also received hydroxychloroquine, and lopinavir/ritonavir 200/50 mg for 10 days. Adjuvant iron chelator (deferasirox – marketed as Exjade) was associated in 11 patients who had ferritin serum levels above 1000 ng/mL. No side effects were encountered during infusions or after TCZ. We observed a rapid increase in arterial oxygen saturation for 20 of the 25 cases (80%) with a favorable evolution toward healing. Survivors were younger than 60 years old (80%), had less comorbidities (10% no comorbidities, 70% with 1 or 2 comorbidities), lower serum ferritin levels (30% under 1000 ng/mL), and 50% had no serum glucose elevation. Our patients with CRS had no response to corticosteroid therapy. Five out of the 25 patients had an unfavorable evolution to death. The off-label use of TCZ in patients with severe or critically ill form of SARS-CoV-2 infection had good results in our study.
Off-label use of TCZ in severe and critical cases of COVID-19 pneumonia is effective in managing the “cytokine storm.” Better outcomes were noted in younger patients. Associated adjuvant iron chelators may contribute to a good outcome and needs to be confirmed in larger studies.
Determination of Force Required to Produce Stab Wounds in Cadaveric Chest Tissues
Authors: Gitto Lorenzo , Serinelli Serenella , Werner Frederick W. , Ordway Nathaniel R. , Stoppacher Robert 
Published: May 2021

Abstract
When investigating deaths due to stab wounds, a common question asked to the forensic pathologist concerns the force required to inflict a given wound.
In this study, tests were performed on 6 human cadavers. A material testing machine was used to produce the stab wounds and to record the force required to penetrate skin, muscle, cartilage, and rib bone of the chest. Three different blades were used: a steak knife, a butcher knife, and a lock-blade knife. On each cadaver, chest injuries were produced at the following locations: (a) skin, intercostal soft tissues; (b) skin, muscle, and cartilage; and (c) skin, muscle, and bone. After the experiment, a chest dissection was performed to confirm the correct locations of the produced stab wounds.
The force required to insert a knife into cartilage or bone was significantly greater than the force to insert it into a region only covered by skin. There was wide variation in the force required to insert a knife into different bodies, but no force for any knife at any location for all bodies was greater than 261 N.
This study allowed us to obtain quantitative measures of the force required to penetrate human chest tissues, removing subjective factors.
Frequency of Extracorporeal Membrane Oxygenation Support and Outcomes After Implementation of a Structured PICU Network in Neonates and Children: A Prospective Population-Based Study in the West of France
Authors: Bourgoin Pierre , Aubert Lucie , Joram Nicolas , Launay Elise , Beuchee Alain , Roue Jean Michel , Baruteau Alban , Fernandez Modesto , Pavy Carine , Baron Olivier , Flamant Cyril , Liet Jean Michel , Ozanne Bruno , Chenouard Alexis 
Published: May 2021

OBJECTIVES:
To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers.

DESIGN:
Observational prospective population-based study from January 2015 to December 2019.

PATIENTS:
Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2–10‰]) and 35 newborns (9.4% [95% CI, 6.4–12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival.

CONCLUSIONS:
Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions.
A randomized clinical trial of single dose liposomal bupivacaine versus indwelling analgesic catheter in patients undergoing surgical stabilization of rib fractures
Authors: Leasia Kiara N. , Ciarallo Christopher , Prins Jonne T.H. , Preslaski Candice , Perkins-Pride Elizabeth , Hardin Kimberly , Cralley Alexis , Burlew Clay Cothren , Coleman Jamie J. , Cohen Mitchell J. , Lawless Ryan , Platnick K. Barry , Moore Ernest E. , Pieracci Fredric M. 
Published: May 2021

INTRODUCTION
Locoregional analgesia (LRA) remains underused in patients with chest wall injuries. Surgical stabilization of rib fractures (SSRF) offers an opportunity to deliver surgeon-directed LRA under direct visualization at the site of surgical intervention. We hypothesized that a single-dose liposomal bupivacaine (LB) intercostal nerve block provides comparable analgesia to an indwelling, peripheral nerve plane analgesic catheter with continuous bupivacaine infusion (IC), each placed during SSRF.

METHODS
Noninferiority, single-center, randomized clinical trial (2017–2020) was performed. Patients were randomized to receive either IC or LB during SSRF. The IC was tunneled into the surgical field (subscapular space), and LB involved thoracoscopic intercostal blocks of ribs 3 to 8. The primary outcome was the Sequential Clinical Assessment of Respiratory Function score, measured daily for 5 days postoperatively. Secondary outcomes included daily narcotic equivalents and failure of primary LRA, defined as requiring a second LRA modality.

RESULTS
Thirty-four patients were enrolled: 16 IC and 18 LB. Age, Injury Severity Score, RibScore, Blunt Pulmonary Contusion Score, and use of nonnarcotic analgesics was similar between groups. Duration of IC was 4.5 days. There were three failures in the IC group versus one in the LB group (p = 0.23). There was no significant difference in Sequential Clinical Assessment of Respiratory Function score between the IC and LB groups. On postoperative days 2 to 4, narcotic requirements were less than half in the LB, as compared with the IC group; however, this difference was not statistically significant. Average wholesale price was US $605 for IC and US $434 for LB.

CONCLUSION
In this noninferiority trial, LB provided at least comparable and potentially superior LRA as compared with IC among patients undergoing SSRF.

LEVEL OF EVIDENCE
Therapeutic, level II.
dPQL: a lossless distributed algorithm for generalized linear mixed model with application to privacy-preserving hospital profiling
Authors: Luo Chongliang , Islam Md. Nazmul , Sheils Natalie E. , Buresh John , Chen Yong 
Published: May 2021

AbstractHospital profiling provides a quantitative comparison of health care providers for their quality of care regarding certain clinical outcomes. To implement hospital profiling, the generalized linear mixed model (GLMM) is usually used to fit clinical or administrative claims data, adjusting for the effects of covariates. For better generalizability, data across multiple hospitals, databases or networks are desired. However, due to the privacy regulation and the computation complexity of GLMM, a convenient distributed algorithm for hospital profiling is needed. In this paper, we develop a novel distributed Penalized Quasi Likelihood algorithm (dPQL) to fit GLMM, when only aggregated data, rather than the individual patient data are available across hospitals. The dPQL algorithm is based on a newly-developed distributed linear mixed model (DLMM) algorithm. This proposed dPQL algorithm is lossless, i.e. it obtains identical results as if the individual patient data are pooled from all hospitals. We demonstrate the usage of the dPQL algorithms by ranking 929 hospitals for COVID-19 mortality or referral to hospice in Asch, et al. 2020.
Genomic risk prediction for breast cancer in older women
Authors: Lacaze Paul , Bakshi Andrew , Riaz Moeen , Orchard Suzanne G , Tiller Jane , Neumann Johannes T , Carr Prudence R , Joshi Amit D , Cao Yin , Warner Erica T , Manning Alisa , Nguyen-Dumont Tú , Southey Melissa C. , Milne Roger L , Ford Leslie , Sebra Robert , Schadt Eric , Gately Lucy , Gibbs Peter , Thompson Bryony A , Macrae Finlay A , James Paul , Winship Ingrid , McLean Catriona , Zalcberg John R , Woods Robyn L , Chan Andrew T , Murray Anne M , McNeil John J 
Published: May 2021

AbstractBackgroundGenomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged less than 70 years. Prospective studies of women aged 70 years or older have been limited.MethodsWe assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6,339 women of European ancestry aged ≥70 years. We evaluated incident BC diagnoses over a median follow-up of 4.7 years. A multivariable Cox regression model including conventional risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) with BC in susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM).ResultsThe PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio [HR] per standard deviation (SD)=1.4, 95% confidence interval [CI] 1.3-1.6, N=110 cases) and hormone receptor (ER/PR)-positive disease (HR=1.5 [CI 1.2-1.9], N=79 cases). Women in the top quintile of the PRS distribution had higher risk of BC than women in the lowest quintile (HR=2.2 [CI 1.2-3.9]). The concordance index of the model without the PRS was 0.62 (95% CI 0.56-0.68) which improved after addition of the PRS to 0.65 (95% CI 0.59-0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses.ConclusionThe 313-variant PRS predicts BC risk in women aged 70 years and older.
Splice-specificlynknockout mice reveal a dominant function of LynB in preventing autoimmunity
Authors: Brian Ben F. , Sauer Monica L. , Ruis Brian , Auger Jennifer L. , Senevirathne S. Erandika , Swanson Whitney L. , Nunez Myra G. , Moriarity Branden S. , Lowell Clifford A. , Binstadt Bryce A. , Freedman Tanya S. 
Published: May 2021

AbstractThe unique roles of the Src-family kinases LynA and LynB in immune activating and inhibitory signaling have eluded definition. Here we report that LynB, the shorter splice product oflyn, carries the dominant immunosuppressive function. We used CRISPR/Cas9 gene editing to constrainlynsplicing and expression to a single product: LynAKOor LynBKOmice. While activities of both isoforms regulate homeostatic Lyn expression, only LynB protects against autoimmune disease. LynBKOmonocytes and dendritic cells are TLR4-hyper-responsive, and TLR4 expression increases with age in LynBKOmyeloid and B cells. These changes are accompanied by the development of an inflammatory disease that resembles human systemic lupus erythematosus (SLE). The interplay between LynB and TLR4 likely underlies the autoimmunity risk associated withLYNhypomorph andTLR4hypermorph alleles.
Longitudinal SARS-CoV-2 infection study in a German medical school
Authors: Schön Michael , Lindenau Clemens , Böckers Anja , Altrock Claire-Marie , Messerer David A. C. , Krys Lydia , Nosanova Anastasia , Lang Nicole , Renz Andrea , Kroschel Joris , Beil Alexandra , Pensel Elke , Grab Claudia , Mayer Benjamin , Fassnacht Ulrich , Delling Jan Philipp , Engelmann Magdalena , Horneffer Astrid , Zernickel Maria , Debatin Klaus-Michael , Münch Jan , Kirchhoff Frank , Wirth Thomas , Boeckers Tobias M. 
Published: May 2021

AbstractIn light of the COVID-19 pandemic, universities around the world were challenged by the difficult decision whether classes could be held face-to-face in the winter semester 20/21. The gross anatomy course is considered an essential practical element of medical school. In order to protect the participants and teaching staff and to gain more knowledge about SARS-CoV-2 infections among students during a semester with face-to-face teaching a longitudinal test study was conducted. Medical students from the first three years of medical school were also invited. Out of a total of almost 1,000 swabs, only two active asymptomatic infections were detected at the start of the semester, none during the semester. At semester start, approximately 6% of the students had antibodies. At the end of the semester, only nine seroconversions after infection in 671 individuals occurred. This was surprisingly low because a massive second wave of infections hit Germany during the same period. The conclusion therefore is that face-to-face teaching under these measures was not infection-promoting even with high incidence rates in the overall population with the SARS-CoV-2 variants present at that time period. Moreover, the results are indicative of a preventive effect of hygiene concepts together with repetitive testings before and during a semester.