bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective evaluation of routine in-hospital observation in 433 patients after CT-guided biopsies
Authors: Fischer Tim , Baz Yassir El , Wildermuth Simon , Leschka Sebastian , Güsewell Sabine , Putora Paul Martin , Dietrich Tobias Johannes 
Published: May 2021

Background After computed tomography (CT)-guided interventions, routine in-hospital observation is recommended by the Cardiovascular and Interventional Radiological Society of Europe. Purpose To evaluate the frequency of delayed major complications or hospitalizations after CT-guided biopsies in patients with initially no or minor complications and to assess whether routine in-hospital observation is justified. Material and Methods This retrospective study included 433 outpatients after CT-guided biopsy of the thoracic (n = 176), abdominal (n = 129), or musculoskeletal (n = 128) region with subsequent in-hospital observation. Complications were graded according to the current Society of Interventional Radiology recommendations and grouped into minor or major. A complication that occurred during in-hospital observation was defined as delayed complication. A delayed major complication was a newly developed major complication or a progression from an initially minor to a major complication. Hospitalization frequencies were evaluated similarly. Occurrence, 95% confidence intervals (CI), and P values for significant differences between the three organ groups were calculated. If delayed major complications were more frequent than 1%, routine in-hospital observation was considered justified. Results Delayed, major complication frequencies were: thoracic, 8.2% (95% CI 4.6–13.4); abdominal, 0.0% (95% CI 0.0–2.9); and musculoskeletal, 0.0% (95% CI 0.0–2.9) ( P < 0.001). Delayed hospitalization frequencies were: thoracic, 8.8% (95% CI 5.0–14.2); abdominal, 1.6% (95% CI 0.2–5.6); and musculoskeletal, 0.0% (95% CI 0.0–2.9) ( P < 0.001). Conclusion After thoracic interventions, routine observation is considered justified for patient safety whereas routine observation may be omitted after musculoskeletal interventions. In the abdominal group, no delayed complications were observed, but delayed hospitalization occurred. Thus, in-hospital observation could be justified in a safe patient environment, but remains an individual decision.
Access to Palliative Care for Critically Ill Cancer Patients in Mexico
Authors: Ñamendys-Silva Silvio A. , López-Zamora Adán R. , Córdova-Sánchez Bertha M. , Sánchez-Hurtado Luis A. , García-Guillén Francisco J. , Vidal-Arrellano Luis J. , Herrera-Gómez Angel 
Published: May 2021

Objective: To determine the outcomes of hospitalized cancer patients requiring intensive care unit (ICU) intervention and receiving palliative care. Materials and Methods: An observational retrospective study was completed at a single academic critical care unit in Mexico City. All hospitalized cancer patients who were evaluated by the intensive care team to assess need for ICU were included between January and December 2018. Results: During the study period, the ICU group made 408 assessments of critically ill cancer patients in noncritical hospitalized areas. In total, 24.2% (99/408) of the patients in this population were consulted by the palliative care team. Of the patients evaluated, 46.5% (190/408) had advanced stage, but only 28.4% were receiving care by the palliative care team. The only risk factor for hospital mortality in the multivariate analysis was the quick Sequential Organ Failure Assessment (qSOFA) score at the time of the consultation by the ICU group (HR = 2.10, 95% CI = 1.34-3.29, p = 0.001). The median time between palliative care consultation and death was 3 days (IQR = 2-22). A total of 63% (37/58) of patients who were discharged from the hospital died during follow-up. The median follow-up time was 55 days (95% CI = 26.9-83.0). The overall mortality rate for the entire group during hospitalization and after hospital discharge was 80.8% (80/99). Conclusion: Fewer than 3 out of 10 hospitalized cancer patients requiring admission to the ICU were evaluated by the palliative care team despite having incurable cancer. The qSOFA score of patients at the time of the ICU consultation was the only risk factor for mortality during hospitalization. Future research efforts in Mexico should focus on earlier integration of palliation care with usual oncology care in incurable cancer patients.
FT-4202, an oral PKR activator, has potent antisickling effects and improves RBC survival and Hb levels in SCA mice
Authors: Shrestha Archana , Chi Mengna , Wagner Kimberly , Malik Astha , Korpik Jennifer , Drake Adam , Fulzele Keertik , Guichard Sylvie , Malik Punam 
Published: May 2021

Abstract
Sickle cell anemia (SCA) results from an abnormal sickle hemoglobin (HbS). HbS polymerizes upon deoxygenation, resulting in red blood cell (RBC) sickling and membrane damage that cause vaso-occlusions and hemolysis. Sickle RBCs contain less adenosine triphosphate and more 2,3-diphosphoglycerate than normal RBCs, which allosterically reduces hemoglobin (Hb) oxygen (O2) affinity (ie, increases the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen [P50]), potentiating HbS polymerization. Herein, we tested the effect of investigational agent FT-4202, an RBC pyruvate kinase (PKR) activator, on RBC sickling and membrane damage by administering it to Berkeley SCA mice. Two-week oral FT-4202 administration was well tolerated, decreasing HbS P50 to levels similar to HbA and demonstrating beneficial biological effects. In FT-4202–treated animals, there was reduced sickling in vivo, demonstrated by fewer irreversibly sickled cells, and improved RBC deformability, assessed at varying shear stress. Controlled deoxygenation followed by reoxygenation of RBCs obtained from the blood of FT-4202–treated mice showed a shift in the point of sickling to a lower partial pressure of oxygen (pO2). This led to a nearly 30% increase in RBC survival and a 1.7g/dL increase in Hb level in the FT-4202–treated SCA mice. Overall, our results in SCA mice suggest that FT-4202 might be a potentially useful oral antisickling agent that warrants investigation in patients with SCA.
Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients
Authors: Eertink J. J. , Burggraaff C. N. , Heymans M. W. , Dührsen U. , Hüttmann A. , Schmitz C. , Müller S. , Lugtenburg P. J. , Barrington S. F. , Mikhaeel N. G. , Carr R. , Czibor S. , Györke T. , Ceriani L. , Zucca E. , Hutchings M. , Kostakoglu L. , Loft A. , Fanti S. , Wiegers S. E. , Pieplenbosch S. , Boellaard R. , Hoekstra O. S. , Zijlstra J. M. , de Vet H. C. W. 
Published: May 2021

Abstract
Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was &gt;80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.
Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes
Authors: Mármol-Sánchez Emilio , Luigi-Sierra María Gracia , Castelló Anna , Guan Dailu , Quintanilla Raquel , Tonda Raul , Amills Marcel 
Published: May 2021

AbstractBackgroundMature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The presence of polymorphic sites in miRNA genes and their corresponding 3′UTR binding sites can disrupt canonical conserved miRNA–mRNA pairings, and thus modify gene expression patterns. However, to date such polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits are poorly characterized in pigs.ResultsBy analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we identified 285 single nucleotide polymorphisms (SNPs) that map to miRNA loci, and 109,724 SNPs that are located in predicted 7mer-m8 miRNA binding sites within porcine 3′UTR. In porcine miRNA genes, SNP density is reduced compared with their flanking non-miRNA regions. By sequencing the genomes of five Duroc boars, we identified 12 miRNA SNPs that were subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses of miRNA SNPs with 38 lipid-related traits and hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were performed. The most relevant detected association was between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor andPPP1CCmRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits.ConclusionsOur findings show a reduced variability of porcine miRNA genes, which is consistent with strong purifying selection, particularly in the seed region that plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are those with the most pronounced consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with hepatic mRNA levels of thePPP1CCgene, one of its predicted targets. Although experimental confirmation of such an interaction is reported in humans but not in pigs, this result highlights the need to further investigate the functional effects of miRNA polymorphisms that are located outside the seed region on gene expression in pigs.
Transcriptome of different fruiting stages in the cultivated mushroom Cyclocybe aegerita suggests a complex regulation of fruiting and reveals enzymes putatively involved in fungal oxylipin biosynthesis
Authors: Orban Axel , Weber Annsophie , Herzog Robert , Hennicke Florian , Rühl Martin 
Published: May 2021

Abstract
Background
Cyclocybe aegerita (syn. Agrocybe aegerita) is a commercially cultivated mushroom. Its archetypal agaric morphology and its ability to undergo its whole life cycle under laboratory conditions makes this fungus a well-suited model for studying fruiting body (basidiome, basidiocarp) development. To elucidate the so far barely understood biosynthesis of fungal volatiles, alterations in the transcriptome during different developmental stages of C. aegerita were analyzed and combined with changes in the volatile profile during its different fruiting stages.

Results
A transcriptomic study at seven points in time during fruiting body development of C. aegerita with seven mycelial and five fruiting body stages was conducted. Differential gene expression was observed for genes involved in fungal fruiting body formation showing interesting transcriptional patterns and correlations of these fruiting-related genes with the developmental stages. Combining transcriptome and volatilome data, enzymes putatively involved in the biosynthesis of C8 oxylipins in C. aegerita including lipoxygenases (LOXs), dioxygenases (DOXs), hydroperoxide lyases (HPLs), alcohol dehydrogenases (ADHs) and ene-reductases could be identified. Furthermore, we were able to localize the mycelium as the main source for sesquiterpenes predominant during sporulation in the headspace of C. aegerita cultures. In contrast, changes in the C8 profile detected in late stages of development are probably due to the activity of enzymes located in the fruiting bodies.

Conclusions
In this study, the combination of volatilome and transcriptome data of C. aegerita revealed interesting candidates both for functional genetics-based analysis of fruiting-related genes and for prospective enzyme characterization studies to further elucidate the so far barely understood biosynthesis of fungal C8 oxylipins.
Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice
Authors: Yuan Siqi , Fang Yao , Tang Mengling , Hu Zhiqiang , Rao Chenglong , Chen Jiangao , Xia Yupei , Zhang Meijuan , Yan Jingmin , Tang Bin , He Xiaoyi , Xie Jianping , Mao Xuhu , Li Qian 
Published: May 2021

Abstract
Background
Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent.

Results
We demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo.

Conclusion
Taken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.
Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort
Authors: Quaranta Maria Giovanna , Ferrigno Luigina , Tata Xhimi , D’Angelo Franca , Coppola Carmine , Ciancio Alessia , Bruno Serena Rita , Loi Martina , Giorgini Alessia , Margotti Marzia , Cossiga Valentina , Brancaccio Giuseppina , Dallio Marcello , De Siena Martina , Cannizzaro Marco , Cavalletto Luisa , Massari Marco , Mazzitelli Maria , De Leo Pasqualina , Laccabue Diletta , Baiocchi Leonardo , Kondili Loreta A. 
Published: May 2021

Abstract
Background
The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA.

Methods
Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication.

Results
We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6).
After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C).
Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08–2.85) and increased INR (HR = 2.41; 95% CI 1.51–3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83).

Conclusions
Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.
SARS-CoV-2 transmission in educational settings during an early summer epidemic wave in Luxembourg, 2020
Authors: Mossong Joël , Mombaerts Laurent , Veiber Lisa , Pastore Jessica , Coroller Gwenaëlle Le , Schnell Michael , Masi Silvana , Huiart Laetitia , Wilmes Paul 
Published: May 2021

Abstract
Background
Following a first wave in spring and gradual easing of lockdown, Luxembourg experienced an early second epidemic wave of SARS-CoV-2 before the start of summer school holidays on 15th July. This provided the opportunity to investigate the role of school-age children and school settings for transmission.

Methods
We compared the incidence of SARS-CoV-2 in school-age children, teachers and the general working population in Luxembourg during two epidemic waves: a spring wave from March–April 2020 corresponding to general lockdown with schools being closed and May–July 2020 corresponding to schools being open. We assessed the number of secondary transmissions occurring in schools between May and July 2020 using routine contact tracing data.

Results
During the first wave in March–April 2020 when schools were closed, the incidence in pupils peaked at 28 per 100,000, while during the second wave in May–July 2020 when schools were open, incidence peaked 100 per 100,000. While incidence of SARS-CoV-2 was higher in adults than in children during the first spring wave, no significant difference was observed during the second wave in early summer. Between May and July 2020, we identified a total of 390 and 34 confirmed COVID-19 cases among 90,150 school-age children and 11,667 teachers, respectively. We further estimate that 179 primary cases caused 49 secondary cases in schools. While some small clusters of mainly student-to-student transmission within the same class were identified, we did not observe any large outbreaks with multiple generations of infection.

Conclusions
Transmission of SARS-CoV-2 within Luxembourg schools was limited during an early summer epidemic wave in 2020. Precautionary measures including physical distancing as well as easy access to testing, systematic contact tracing appears to have been successful in mitigating transmission within educational settings.
COVID-19: first long-term care facility outbreak in the Netherlands following cross-border introduction from Germany, March 2020
Authors: van Hensbergen Mitch , den Heijer Casper D. J. , Wolffs Petra , Hackert Volker , ter Waarbeek Henriëtte L. G. , Oude Munnink Bas B. , Sikkema Reina S. , Heddema Edou R. , Hoebe Christian J. P. A. 
Published: May 2021

Abstract
Background
The Dutch province of Limburg borders the German district of Heinsberg, which had a large cluster of COVID-19 cases linked to local carnival activities before any cases were reported in the Netherlands. However, Heinsberg was not included as an area reporting local or community transmission per the national case definition at the time. In early March, two residents from a long-term care facility (LTCF) in Sittard, a Dutch town located in close vicinity to the district of Heinsberg, tested positive for COVID-19. In this study we aimed to determine whether cross-border introduction of the virus took place by analysing the LTCF outbreak in Sittard, both epidemiologically and microbiologically.

Methods
Surveys and semi-structured oral interviews were conducted with all present LTCF residents by health care workers during regular points of care for information on new or unusual signs and symptoms of disease. Both throat and nasopharyngeal swabs were taken from residents suspect of COVID-19, based on regional criteria, for the detection of SARS-CoV-2 by Real-time Polymerase Chain Reaction. Additionally, whole genome sequencing was performed using a SARS-CoV-2 specific amplicon-based Nanopore sequencing approach. Moreover, twelve random residents were sampled for possible asymptomatic infections.

Results
Out of 99 residents, 46 got tested for COVID-19. Out of the 46 tested residents, nineteen (41%) tested positive for COVID-19, including 3 asymptomatic residents. CT-values for asymptomatic residents seemed higher compared to symptomatic residents. Eleven samples were sequenced, along with three random samples from COVID-19 patients hospitalized in the regional hospital at the time of the LTCF outbreak. All samples were linked to COVID-19 cases from the cross-border region of Heinsberg, Germany.

Conclusions
Sequencing combined with epidemiological data was able to virtually prove cross-border transmission at the start of the Dutch COVID-19 epidemic. Our results highlight the need for cross-border collaboration and adjustment of national policy to emerging region-specific needs along borders in order to establish coordinated implementation of infection control measures to limit the spread of COVID-19.