bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative in-silico analysis discloses a novel molecular subset of colorectal cancer possibly eligible for immune checkpoint immunotherapy
Authors: Sibilio Pasquale , Belardinilli Francesca , Licursi Valerio , Paci Paola , Giannini Giuseppe 
Published: May 2022

Abstract
Background
Historically, the molecular classification of colorectal cancer (CRC) was based on the global genomic status, which identified microsatellite instability in mismatch repair (MMR) deficient CRC, and chromosomal instability in MMR proficient CRC. With the introduction of immune checkpoint inhibitors, the microsatellite and chromosomal instability classification regained momentum as the microsatellite instability condition predicted sensitivity to immune checkpoint inhibitors, possibly due to both high tumor mutation burden (TMB) and high levels of infiltrating lymphocytes. Conversely, proficient MMR CRC are mostly resistant to immunotherapy. To better understand the relationship between the microsatellite and chromosomal instability classification, and eventually discover additional CRC subgroups relevant for therapeutic decisions, we developed a computational pipeline that include molecular integrative analysis of genomic, epigenomic and transcriptomic data.

Results
The first step of the pipeline was based on unsupervised hierarchical clustering analysis of copy number variations (CNVs) versus hypermutation status that identified a first CRC cluster with few CNVs enriched in Hypermutated and microsatellite instability samples, a second CRC cluster with a high number of CNVs mostly including non-HM and microsatellite stable samples, and a third cluster (7.8% of the entire dataset) with low CNVs and low TMB, which shared clinical-pathological features with Hypermutated CRCs and thus defined Hypermutated-like CRCs. The mutational features, DNA methylation profile and base substitution fingerprints of these tumors revealed that Hypermutated-like patients are molecularly distinct from Hypermutated and non-Hypermutated tumors and are likely to develop and progress through different genetic events. Transcriptomic analysis highlighted further differences amongst the three groups and revealed an inflamed tumor microenvironment and modulation Immune Checkpoint Genes in Hypermutated-like CRCs.

Conclusion
Therefore, our work highlights Hypermutated-like tumors as a distinct and previously unidentified CRC subgroup possibly responsive to immune checkpoint inhibitors. If further validated, these findings can lead to expanding the fraction of patients eligible to immunotherapy.
Facilitating relaxation and stress reduction in healthy participants through a virtual reality intervention: study protocol for a non-inferiority randomized controlled trial
Authors: Kampa Miriam , Finke Johannes , Stalder Tobias , Bucher Leandra , Klapperich Holger , Mertl Fabian , Zimmer Christian , Geiger Christian , Hassenzahl Marc , Klucken Tim 
Published: May 2022

Abstract
Background
Repeated or chronic stress is considered a major source of disease, in terms of both somatic and mental illnesses. The prevention of stress-related disease by interventions for relaxation has thus increased societal relevance. In this randomized controlled non-inferiority trial, we will compare a newly developed virtual reality (VR) environment for relaxation to an active control group applying a freely chosen relaxation method. To test if our VR environment supports relaxation in a situation of acute stress, a standardized stress induction protocol will precede the relaxation phase.

Methods
One hundred healthy participants will be recruited from the University of Siegen and randomly assigned to the VR or the active control group that will be free to choose their own relaxation strategy. The multi-sensory VR includes visual, acoustic, and haptic features to induce a strong feeling of presence. The laboratory testing will comprise a baseline measurement, a stress induction, a relaxation intervention, and a recovery measurement. The primary outcomes are self-reported stress and relaxation measured with a visual analog scale (VAS) at pre- and post-baseline, at the start, middle, and end of the stress induction, at pre- and post-relaxation, at pre- and post-recovery, and in the evening of testing. Secondary outcomes are the physiological parameters, namely heart rate and heart rate variability, tonic skin conductance level as well as the number of non-specific skin conductance responses, systolic and diastolic blood pressure and respiratory rate recorded during the four experimental phases as well as state mood, and state rumination assessed at four time points (pre- and post-stress, post-relaxation, and in the evening of testing). Finally, post-event processing will be assessed after relaxation and in the evening of testing. Repeated measures ANOVAs will be performed to test for statistical effects of group, time, and group × time interaction.

Discussion
The newly developed, multi-sensory VR offers an intervention for relaxation without prior training. Its immersive character might increase efficacy compared to other relaxation methods, especially in situations of acute stress. Future directions could be the development of a mobile version of the VR to enhance accessibility for users. To achieve a transfer of training effects to real life, VR components should successively be eliminated until relaxation is practiced without guidance by the VR.

Trial registration
ISRCTN Registry ISRCTN11162338. Retrospectively registered on January 22, 2021
High-flow nasal cannula versus standard low-flow nasal cannula during deep sedation in patients undergoing radiofrequency atrial fibrillation catheter ablation: a single-centre randomised controlled trial
Authors: Homberg Marloes C. , Bouman Esther A. , Linz Dominik , van Kuijk Sander M. J. , Joosten Bert A. , Buhre Wolfgang F. 
Published: May 2022

Abstract
Background
To our knowledge, there are few trials studying the effect of high-flow nasal cannula (HFNC) during deep sedation. Our hypothesis is that high-flow nasal cannula (HFNC) will prevent hypoxemia and desaturation as compared to low-flow nasal cannula (LFNC) during prolonged deep sedation in patients with atrial fibrillation undergoing radiofrequency catheter ablation (RFCA).

Methods
A single-centre, randomised controlled trial with HFNC as the intervention and LFNC as the control group. A total of 94 adult patients per group undergoing elective radiofrequency atrial fibrillation catheter ablation under deep sedation. will be included. The primary outcome is the lowest oxygen saturation (SpO2). Secondary outcomes are as follows: the duration of lowest SpO2, cross over from oxygen therapy in both directions, incidence of SpO2 below 90% > 60 seconds, adverse sedation events, adverse effects of HFNC, mean CO2, peak CO2 and patients experience with oxygen therapy. The study will take place during the 2-day admission period for RFCA. Patients can fill out their questionnaires in the first week after treatment.

Discussion
HFNC is increasingly used as a technique for oxygen delivery in procedural sedation and analgesia. We hypothesise that HFNC is superior to the standard treatment LFNC in patients under deep sedation with respect to the incidence of desaturation. To our knowledge, there are no adequately powered clinical trial studies on the effects of HFNC in prolonged deep sedation.

Trial registration
ClinicalTrials.gov NCT04842253. Registered on 04 April 2021
Association between feline immunodeficiency virus and Leishmania infantum infections in cats: a retrospective matched case-control study
Authors: Priolo Vito , Masucci Marisa , Donato Giulia , Solano-Gallego Laia , Martínez-Orellana Pamela , Persichetti Maria Flaminia , Raya-Bermúdez Ana , Vitale Fabrizio , Pennisi Maria Grazia 
Published: May 2022

Abstract
Background
Feline leishmaniosis caused by Leishmania infantum is often associated with feline immunodeficiency virus (FIV) infection; however, the role and clinical significance of this coinfection remain unknown. This study aimed to assess whether FIV is associated with L. infantum infection in cats from canine leishmaniosis endemic areas and to report the clinical signs and hematological alterations associated with coinfection.

Methods
A retrospective matched case-control study (ratio 1:2) was conducted. Data of clinical examination and complete blood count (CBC) were selected from a cohort of 705 cats examined for epidemiological studies on feline leishmaniosis conducted between 2012 and 2019. Ninety-one FIV seropositive cases and 182 FIV seronegative control cats were selected. Matching was done according to age, sex, lifestyle and geographic provenience of case cats. Rapid ELISA devices were mainly used to detect anti-FIV antibodies. Anti-Leishmania IgG antibodies were detected by indirect-immunofluorescence test (IFAT). Leishmania DNA was searched in blood, oral and conjunctival swabs by quantitative real-time PCR.

Results
Feline immunodeficiency virus seropositive cats had no hematological abnormalities suggestive of an advanced stage of FIV infection and were statistically more frequently IFAT positive, and their risk of being L. infantum antibody positive was 2.8 greater than in the FIV seronegatives. The association of FIV seropositivity with L. infantum antibody positivity was confirmed in the univariable model of logistic regression. A multivariate model found FIV infection and L. infantum PCR positivity as predictors of a positive L. infantum IFAT result. Male outdoor cats from rural or suburban areas were at risk for FIV and L. infantum antibody positivity. Clinical signs more frequently associated with the coinfection were oral lesions, pale mucous membranes and low body condition score (BCS).

Conclusions
This study documents that FIV seropositive cats with no hematological abnormalities suggestive of an advanced stage of FIV infection are more prone to be L. infantum seroreactive by IFAT in endemic areas. Therefore, FIV seropositive cats should be tested for L. infantum antibodies and treated for preventing sand fly bites. Pale mucous membranes, low BCS and oral lesions but no CBC abnormalities were significantly associated with the coinfection.

Graphical abstract
Detection of specific antibodies against Leishmania infantum in canine serum and oral transudate using an in-house ELISA
Authors: Baxarias Marta , Viñals Júlia , Álvarez-Fernández Alejandra , Alcover Mª Magdalena , Solano-Gallego Laia 
Published: May 2022

Abstract
Background
Canine leishmaniosis caused by the protozoan Leishmania infantum is a complex infection due to its variable clinical signs and laboratory findings. Therefore, a broad range of techniques is available for diagnosis. Testing for specific antibodies in serum is the most commonly used technique, although the testing of other body fluids, such as oral transudate (OT), can be an alternative as its collection is non-invasive and testing can be performed by untrained personnel. The aim of this study was to assess and compare the detection of L. infantum-specific antibodies in paired samples of serum and OT collected from apparently healthy dogs and dogs with clinical leishmaniosis using an in-house enyzme-linked immunosorbent assay (ELISA).

Methods
Serum and OT were collected from 407 dogs, which varied in breed, sex, age, lifestyle and clinical status, by many practicing veterinarians in Spain. The main geographical areas of sampling included Barcelona (n = 110), Mallorca (n = 94), Cadiz (n = 54) and Asturias (n = 47). The majority of infected dogs were apparently healthy (89.9%) while 41 presented clinical signs and/or clinicopathological abnormalities compatible with L. infantum infection and subsequently diagnosed with leishmaniosis (10.1%). An in-house ELISA was performed to quantify the anti-Leishmania antibodies in serum and OT.

Results
The L. infantum infection rate determined by the in-house ELISA was 37.1% in serum samples and 32.7% in OT samples. Serum and OT ELISA results showed a positive correlation (Spearman's correlation coefficient rs = 0.6687, P < 0.0001). The percent agreement between the serum and OT ELISA results was 84%, while agreement according to Cohen's kappa statistic (κ) was substantial (0.66) when all samples were analyzed. The highest percent agreement (92.1%) between both tests was found in dogs from low endemicity regions and from sick dogs, with both groups presenting almost perfect agreement according to Cohen’s κ agreement test (0.84). Few seronegative dogs (n = 23) tested positive by the OT ELISA. The agreement between serum and OT went from almost perfect to moderate when the geographical distribution and clinical status were analyzed.

Conclusions
The results of this study demonstrated an almost perfect to moderate agreement between OT and serum samples tested using the in-house ELISA. These results are particularly promising in sick dogs with high antibody levels while the results seem less optimal in apparently healthy dogs with low antibody levels.

Graphical Abstract
Use of preventive measures and serological screening tools for Leishmania infantum infection in dogs from Europe
Authors: Baxarias Marta , Homedes Josep , Mateu Cristina , Attipa Charalampos , Solano-Gallego Laia 
Published: May 2022

Abstract
Background
There are several screening tools for detecting Leishmania infantum infection in dogs and various preventive measures to protect against it. Some studies have investigated them, but not many have described their current use. The aim of this study was to investigate which preventive measures and serological screening tools for L. infantum infection were employed from 2012 to 2018 in dogs from different endemic European countries.

Methods
A set of electronic datasheets was completed for each dog from several veterinary centres. Classification of preventive measures included: (1) repellents, (2) vaccines and (3) immunomodulators. Classification of serological tests included the: (1) direct agglutination test (DAT), (2) enzyme-linked immunosorbent assay (ELISA), (3) indirect immunofluorescence (IFI), (4) rapid tests and (5) other assays. Dogs were also classified depending on their risk of exposure and living area.

Results
Information from 3762 dogs was gathered. Preventive measures were applied in 91.5% of dogs and the most frequently used were repellents (86.2%) followed by vaccines (39.8%) and Leisguard® (15.3%). The different types of repellents (collar and spot-on) were used similarly. A combination of a vaccine and repellents was preferred in the high-risk group while the low-risk preferred a combination of Leisguard® and a repellent (Chi-square test: X2 = 88.41, df = 10, P < 0.001). Furthermore, all preventive measures were similarly used through the years except for repellents, which were predicted to have a small increase of use each year. Regarding serological screening tools, the most used were rapid and ELISA tests. Rapid tests, ELISA tests and DAT were used similarly through the years, but a significant change was found in the use of IFI and other assays whose use decreased a little each year.

Conclusions
Repellents were the preferred measure, while vaccines and Leisguard® were second-line options. Some dogs were not treated by any measures, which highlights the need for dog owner education. Moreover, there seems to be a preference for rapid tests in the clinical setting to detect specific L. infantum antibodies while ELISA or IFI are less often employed. This underlines an increasing problem, as qualitative rapid tests have a variable diagnostic performance limiting the adequate diagnosis of seropositive dogs in endemic areas.

Graphical abstract
Leishmania tropica and Leishmania infantum infection in dogs and cats in central Israel
Authors: Baneth Gad , Nachum-Biala Yaarit , Adamsky Offir , Gunther Idit 
Published: May 2022

Abstract
Background
Three species of Leishmania cause disease in humans in Israel and are endemic in the Middle East: Leishmania infantum, Leishmania tropica and Leishmania major. These species infect dogs and cats, but little is known about their prevalence in pet populations and their clinical manifestations. A study on dog and cat Leishmania infection was conducted in a focus of human L. tropica infection in central Israel with the aim of getting insight on leishmaniosis in pets in an area where human infection is highly prevalent.

Methods
Blood, demographic and clinical data were collected from dogs and cats brought for veterinary care in a focus of human L. tropica infection during 2018–2020. kDNA PCR and internal transcribed spacer1 high-resolution melt analysis PCR (ITS1 HRM PCR) with DNA sequencing were performed for the detection of Leishmania and species determination.

Results
Forty-three of 189 dogs (22.8%) and 44 of 152 cats (28.9%) were positive for Leishmania spp. infection by kDNA PCR. The ITS1 HRM PCR detected six dogs (3.3%) infected with L. infantum and one (0.5%) with L. tropica, whereas six cats (3.9%) were found infected by L. infantum and five (3.3%) by L. tropica. Four of the five L. tropica-positive cats suffered from weight loss, four had azotemia, two with mild and two with severe azotemia and progressive renal disease. Three cats had gingivostomatitis; three had skin lesions with abscess and ulcers in two and scales and hair loss in another cat, which was also FIV +. This is the first report of feline L. tropica infection in Israel. Clinical information on cats with this infection from previous studies elsewhere is scarce.

Conclusions
A high rate of Leishmania spp. infection, mostly estimated as sub-clinical, was found in dogs and cats admitted for veterinary care in an L. tropica focus. Among the animals in which infection could be characterized to the species level, more dogs were infected with L. infantum than with L. tropica while 5 of 11 cats were infected with L. tropica and had signs of systemic and skin disease not described before in feline L. tropica infection.

Graphical Abstract
Bronchial thermoplasty in severe asthma: a real-world study on efficacy and gene profiling
Authors: Facciolongo Nicola , Bonacini Martina , Galeone Carla , Ruggiero Patrizia , Menzella Francesco , Ghidoni Giulia , Piro Roberto , Scelfo Chiara , Catellani Chiara , Zerbini Alessandro , Croci Stefania 
Published: May 2022

Abstract
Background
Bronchial thermoplasty (BT) is an effective treatment in severe asthma. How to select patients who more likely benefit from BT is an unmet clinical need. Moreover, mechanisms of BT efficacy are still largely unknown. We sought to determine BT efficacy and to identify potential mechanisms of response.

Methods
This retrospective cohort study evaluated clinical outcomes in 27 patients with severe asthma: 13 with T2-high and 14 with T2-low endotype. Expression levels of 20 genes were compared by real-time PCR in bronchial biopsies performed at the third BT session versus baseline. Clinical response was measured based on Asthma Control Questionnaire (ACQ) score < 1.5, asthma exacerbations < 2, oral corticosteroids reduction of at least 50% at 12 months post-BT. Patients were classified as responders when they had at least 2 of 3 outcome measures.

Results
81% of patients were defined as responders. BT induced a reduction in alpha smooth muscle actin (ACTA2) and an increase in CD68, fibroblast activation protein-alpha (FAP), alpha-1 and alpha-2 type I collagen (COL1A1, COL1A2) gene expression in the majority of patients. A higher reduction in ubiquitin carboxy-terminal-hydrolase L1 (PGP9.5) mRNA correlated with a better response based on Asthma Quality of Life Questionnaire (AQLQ). Lower changes in CD68 and FAP mRNAs correlated with a better response based on ACQ. Lower levels of occludin (OCLN), CD68, connective tissue growth factor (CTGF), higher levels of secretory leukocyte protease inhibitor (SLPI) and lower changes in CD68 and CTGF mRNAs were observed in patients who had less than 2 exacerbations post-BT. Lower levels of COL1A2 at baseline were observed in patients who had ACQ < 1.5 at 12 months post-BT.

Conclusions
BT is effective irrespective of the asthma endotypes and seems associated with airway remodelling. Quantification of OCLN, CD68, CTGF, SLPI, COL1A2 mRNAs could be useful to identify patients with better results.
Trial registration: The study protocol was approved by the Local Ethics Committee (Azienda USL-IRCCS of Reggio Emilia—Comitato Etico Area Vasta Nord of Emilia Romagna; protocol number: 2019/0014076) and all the patients provided written informed consent before participating in the study.
Closing the gap between phenotyping and genotyping: review of advanced, image-based phenotyping technologies in forestry
Authors: Bian Liming , Zhang Huichun , Ge Yufeng , Čepl Jaroslav , Stejskal Jan , EL-Kassaby Yousry A. 
Published: May 2022

AbstractKey messageThe lack of efficient phenotyping capacities has been recognized as a bottleneck in forestry phenotyping and breeding. Modern phenotyping technologies use systems equipped with various imaging sensors to automatically collect high volume phenotypic data that can be used to assess trees' various attributes.ContextEfficient phenotyping has the potential to spark a new Green Revolution, and it would provide an opportunity to acquire growth parameters and dissect the genetic bases of quantitative traits. Phenotyping platforms aim to link information from several sources to derive knowledge about trees' attributes.AimsVarious tree phenotyping techniques were reviewed and analyzed along with their different applications.MethodsThis article presents the definition and characteristics of forest tree phenotyping and reviews newly developed imaging-based practices in forest tree phenotyping.ResultsThis review addressed a wide range of forest trees phenotyping applications, including a survey of actual inter- and intra-specific variability, evaluating genotypes and species response to biotic and abiotic stresses, and phenological measurements.ConclusionWith the support of advanced phenotyping platforms, the efficiency of traits phenotyping in forest tree breeding programs is accelerated.
Study on Mechanical Properties of Polycaprolactone Modified Cement-Based Material
Authors: Lu Hai-feng , Zhang Kai , Yi Jin-long , Wei Ai-chao 
Published: May 2022

AbstractWith the continuous development of economy, engineering construction is developing towards deep high-stress area, and the problems of large-deformation engineering are becoming more and more serious. Anchoring grouting is a very effective support reinforcement method. The anchoring grouting materials used in the project are mainly cement paste and cement mortar. The characteristics of the grouting material have a decisive influence on the grouting effect. However, it is difficult for the existing grouting materials to satisfy the requirements of strength and deformation at the same time, and improvement is urgently needed. Polycaprolactone (PCL) is an organic polymer material of good engineering properties, including high ductility, good stability and strong impact resistance. In this paper, PCL was added as an auxiliary additive to cement-based materials innovatively, and the mechanical test and micro-test of PCL-cement-based materials were carried out. The results show that adding PCL can significantly increase the compressive strength of cement paste. By adjusting the content of PCL, the strength and ductility of cement mortar can be effectively improved. When the content of PCL is 15%, ideal high performance cement mortar material can be obtained. Anchor grouting is a very effective reinforcement and support method.