bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot isopropanol quenching procedure for automated microtiter plate scale 13C-labeling experiments
Authors: Nießer Jochen , Müller Moritz Fabian , Kappelmann Jannick , Wiechert Wolfgang , Noack Stephan
Published: May 2022

Background

Currently, the generation of genetic diversity for microbial cell factories outpaces the screening of strain variants with omics-based phenotyping methods. Especially isotopic labeling experiments, which constitute techniques aimed at elucidating cellular phenotypes and supporting rational strain design by growing microorganisms on substrates enriched with heavy isotopes, suffer from comparably low throughput and the high cost of labeled substrates.

Results

We present a miniaturized, parallelized, and automated approach to13C-isotopic labeling experiments by establishing and validating a hot isopropanol quenching method on a robotic platform coupled with a microbioreactor cultivation system. This allows for the first time to conduct automated labeling experiments at a microtiter plate scale in up to 48 parallel batches. A further innovation enabled by the automated quenching method is the analysis of free amino acids instead of proteinogenic ones on said microliter scale. Capitalizing on the latter point and as a proof of concept, we present an isotopically instationary labeling experiment inCorynebacterium glutamicumATCC 13032, generating dynamic labeling data of free amino acids in the process.

Conclusions

Our results show that a robotic liquid handler is sufficiently fast to generate informative isotopically transient labeling data. Furthermore, the amount of biomass obtained from a sub-milliliter cultivation in a microbioreactor is adequate for the detection of labeling patterns of free amino acids. Combining the innovations presented in this study, isotopically stationary and instationary automated labeling experiments can be conducted, thus fulfilling the prerequisites for13C-metabolic flux analyses in high-throughput.
Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder
Authors: Dell’Osso Liliana , Massoni Leonardo , Battaglini Simone , Cremone Ivan Mirko , Carmassi Claudia , Carpita Barbara
Published: May 2022

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex and multifaceted neurobehavioral syndrome. In the last decades, several studies highlighted an increased prevalence of sleep problems in ASD, which would be associated with autonomic system and circadian rhythm disruption. The present review aimed to summarize the available literature about sleep problems in ASD subjects and about the possible biological factors implicated in circadian rhythm and autonomic system deregulation in this population, as well as possible therapeutic approaches. Shared biological underpinnings between ASD symptoms and altered circadian rhythms/autonomic functions are also discussed. Studies on sleep showed how ASD subjects typically report more problems regarding insufficient sleep time, bedtime resistance and reduced sleep pressure. A link between sleep difficulties and irritability, deficits in social skills and behavioral problems was also highlighted. Among the mechanisms implicated, alteration in genes related to circadian rhythms, such asCLOCKgenes, and in melatonin levels were reported. ASD subjects also showed altered hypothalamic pituitary adrenal (HPA) axis and autonomic functions, generally with a tendency towards hyperarousal and hyper sympathetic state. Intriguingly, some of these biological alterations in ASD individuals were not associated only with sleep problems but also with more autism-specific clusters of symptoms, such as communication impairment or repetitive behaviors Although among the available treatments melatonin showed promising results, pharmacological studies for sleep problems in ASD need to follow more standardized protocols to reach more repeatable and reliable results. Further research should investigate the issue of sleep problems in ASD in a broader perspective, taking into account shared pathophysiological mechanisms for core and associated symptoms of ASD.
Students’ knowledge of and conservation attitude toward the black-necked crane (Grus nigricollis) in Guizhou, China: insights for conservation
Authors: Ruan Yun , Li Yalong , Xia Yuanping , Yu Tailin , Dai Chuanyin
Published: May 2022

Background

The persistence of threatened and protected wildlife depends not only on habitat suitability but also remarkably on local communities’ acceptance. The black-necked crane (Grus nigricollis) is a flagship species for conservation on the plateau in western China. However, the human dimension has been completely ignored in the decision-making process for conservation.

Methods

In this study, a questionnaire survey aiming to assess knowledge of and conservation attitude toward this bird was carried out among 1042 students of 7th and 9th grade from 12 schools in Weining county, Guizhou province, which has a large wintering population in an urban wetland. Logistic regression was used in the generalized linear model to identify the determinants that significantly affect students’ knowledge of and conservation attitude toward this species.

Results

Most students have positive attitudes toward conservation, which is significantly affected by awareness, knowledge of this bird and grade. However, they have somewhat limited knowledge of this bird’s biology and ecosystem services (nature’s contributions to people). Knowledge was found to link with observation of the bird and grade, while observation related to the experience of visiting the wetland. Social media is the most cited resource to obtain knowledge on this bird.

Conclusion

It is suggested that local conservation experts could help introduce more information on the black-necked crane in the schools and help conduct outdoor education activities in and around the wetland. Traditional knowledge and culture could also be incorporated into the conservation awareness enhancing program. This study focuses on the human dimension for conserving the black-necked crane in China, showing significant implications in the design and application of effective measurements to improve students’ perception and attitude toward its conservation. Future assessments should include other local populations, such as farmers, fishers, and urban citizens.
Accelerating leaf area measurement using a volumetric approach
Authors: Haghshenas Abbas , Emam Yahya
Published: May 2022

Background

Despite the advances in the techniques of indirect estimation of leaf area, the destructive measurement approaches have still remained as the reference and the most accurate methods. However, even utilizing the modern sensors and applications usually requires the laborious and time-consuming practice of unfolding and analyzing the single leaves, separately. In the present study, a volumetric approach was tested to determine the pile leaf area based on the ratio of leaf volume divided by thickness. For this purpose, the suspension technique was used for volumetry, which is based on the simple practice and calculations of the Archimedes’ principle.

Results

Wheat volumetric leaf area (VLA), had a high agreement and approximately 1:1 correlation with the conventionally measured optical leaf area (OLA). Exclusion of the midrib volume from calculations, did not affect the estimation error (NRMSE < 2.61%); however, improved the slope of the linear model by about 6%, and also reduced the bias between the methods. The error of sampling for determining mean leaf thickness of the pile, was also less than 2% throughout the season. Besides, a more practical and facilitated version of pile volumetry was tested using Specific Gravity Bench (SGB), which is currently available as a laboratory equipment. As an important observation, which was also expectable according to the leaf 3D expansion (i.e., in a given 2D plane), it was evidenced that the variations in the OLA exactly follows the pattern of the changes in the leaf volume. Accordingly, it was suggested that the relative leaf areas of various experimental treatments might be compared directly based on volume, and independently of leaf thickness. Furthermore, no considerable difference was observed among the OLAs measured using various image resolutions (NRMSE < 0.212%); which indicates that even the superfast scanners with low resolutions as 200 dpi may be used for a precision optical measurement of leaf area.

Conclusions

It is expected that utilizing the reliable and simple concept of volumetric leaf area, based on which the measurement time might be independent of sample size, facilitate the laborious practice of leaf area measurement; and consequently, improve the precision of field experiments.
Weight spectrum and executive function in adolescents: the moderating role of negative emotions
Authors: Lin Qingmin , Jiang Yanrui , Sun Xiaoning , Zhang Yunting , Shan Wenjie , Zhao Jin , Wang Xuelai , Zhu Qi , Sun Wanqi , Lu Hui , Jiang Fan
Published: May 2022

Background

While recent works suggested that overweight/obesity may impair executive function (EF), the overweight/obesity-EF relationship has not been well studied in adolescents. Furthermore, no research has investigated adolescent EF impairments across the weight spectrum (e.g., underweight or thinness, normal, overweight/obesity), especially those with underweight condition, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents.

Methods

We applied a subsample of the SCHEDULE-A project. Adolescents (11–18 years) were recruited using a multi-stage cluster random sampling approach. We measured the overall and abdominal weight spectrum by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional status (i.e., depression, anxiety, and stress).

Results

Of the 1935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI 1.07–2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI 1.04–1.72), particularly for plan and monitor areas.

Conclusions

Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight. Future longitudinal studies are needed to investigate the causal relationship between abdominal weight spectrum and EF, as well as the underlying mechanisms among adolescents suffering from depression.
Bi-order multimodal integration of single-cell data
Authors: Dou Jinzhuang , Liang Shaoheng , Mohanty Vakul , Miao Qi , Huang Yuefan , Liang Qingnan , Cheng Xuesen , Kim Sangbae , Choi Jongsu , Li Yumei , Li Li , Daher May , Basar Rafet , Rezvani Katayoun , Chen Rui , Chen Ken
Published: May 2022

Integration of single-cell multiomics profiles generated by different single-cell technologies from the same biological sample is still challenging. Previous approaches based on shared features have only provided approximate solutions. Here, we present a novel mathematical solution named bi-order canonical correlation analysis (bi-CCA), which extends the widely used CCA approach to iteratively align the rows and the columns between data matrices. Bi-CCA is generally applicable to combinations of any two single-cell modalities. Validations using co-assayed ground truth data and application to a CAR-NK study and a fetal muscle atlas demonstrate its capability in generating accurate multimodal co-embeddings and discovering cellular identity.
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

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

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

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

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

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

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

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

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

Key message

The 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.

Context

Efficient 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.

Aims

Various tree phenotyping techniques were reviewed and analyzed along with their different applications.

Methods

This article presents the definition and characteristics of forest tree phenotyping and reviews newly developed imaging-based practices in forest tree phenotyping.

Results

This 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.

Conclusion

With 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

With 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.
The associations between caregivers’ psychosocial characteristics and caregivers’ depressive symptoms in stroke settings: a cohort study
Authors: Koh Yen Sin , Subramaniam Mythily , Matchar David Bruce , Hong Song-Iee , Koh Gerald Choon-Huat
Published: May 2022

Background

Studies have found that caregivers can influence stroke survivors’ outcomes, such as mortality. It is thus pertinent to identify significant factors associated with caregivers’ outcomes. The study objective was to examine the associations between caregivers’ psychosocial characteristics and caregivers’ depressive symptoms.

Methods

The analysis obtained three-month and one-year post-stroke data from the Singapore Stroke Study, which was collected from hospital settings. Caregivers’ depressive symptoms were assessed via the Center for Epidemiologic Studies Depression instrument. Psychosocial characteristics of caregivers included subjective burden (Zarit Burden Interview), quality of care-relationship (a modified 3-item scale from the University of Southern California Longitudinal Study of Three-Generation Families) and expressive social support (an 8-item scale from Pearlin et al.). Mixed effect Tobit regressions were used to examine the associations between these study variables.

Results

A total of 214 caregivers of stroke patients hospitalized were included in the final analysis. Most caregivers were Chinese women with secondary school education, unemployed and married to the patients. Caregivers' subjective burden was positively associated with their depressive symptoms (Partial regression coefficient: 0.18, 95% CI 0.11–0.24). Quality of care-relationship (Partial regression coefficient: − 0.35, 95% CI − 0.63 to − 0.06) and expressive social support (partial regression coefficient: − 0.28, 95% CI − 0.37 to − 0.19) were negatively associated with caregivers’ depressive symptoms. Caregivers’ depressive symptoms were higher at three-month post-stroke than one-year post-stroke (Partial regression coefficient: − 1.00, 95% CI − 1.80 to − 0.20).

Conclusion

The study identified subjective burden, quality of care-relationship and expressive social support as significantly associated with caregivers’ depressive symptoms. Caregivers’ communication skills may also play a role in reducing caregivers’ depressive symptoms.
Analysis of crowdfunding platforms for microgrid project investors via a q-rung orthopair fuzzy hybrid decision-making approach
Authors: Wu Xiaohang , Dinçer Hasan , Yüksel Serhat
Published: May 2022

Effective crowdfunding platforms positively contribute toward improving microgrid energy management systems. Therefore, a comprehensive analysis is required to understand the key factors responsible for success in crowdfunding systems by considering various criteria. This study evaluates crowdfunding platforms for microgrid project investments. In this context, a novel fuzzy decision-making model that includes two different stages is proposed. First, the selected criteria for the crowdfunding platforms for microgrid project investments are evaluated. Second, alternatives, regarding the microgrid project investments, are ranked. In this process, a multi-stepwise weight assessment ratio analysis (M-SWARA) approach based on q-rung orthopair fuzzy sets (q-ROFSs) is considered. Intuitionistic and Pythagorean fuzzy sets are also used in the calculation process to make a comparative evaluation. Similarly, a sensitivity analysis of the ranking alternatives is also conducted with 12 different q values. All the results are rather similar; thus, the findings are reliable. Another model is also created for this purpose with the help of the decision-making trial and evaluation laboratory (DEMATEL) and the technique for order preference by similarity to ideal solution methodologies to check the performance of the proposed model. It is defined that by considering the q-ROF DEMATEL weights, the ranking results vary for different cases. The proposed model with a M-SWARA is more reliable than the model created via the DEMATEL method. This situation provides information regarding the superiority of the model proposed in this study. It is concluded that security is the most important factor in crowdfunding platforms for smart-grid project investors. Additionally, solar panels and energy storage systems/batteries are the most significant alternatives for microgrid project investors. Necessary measures should be taken to forestall the risk of fraud that may occur on this platform. Therefore, the website to be established must be secure against possible hacking attacks. Another important conclusion of this study is that solar panels should be preliminarily developed to increase the effectiveness of microgrid systems.
Time-course changes in DNA damage of corneal epithelial cells in rabbits following ocular instillation with genotoxic compounds
Authors: Tahara Haruna , Yamagiwa Yoshinori , Haranosono Yu , Kurata Masaaki
Published: May 2022

Background

In eye-drop drug development, the additional genotoxicity tests in some cases might be necessary to assess genotoxicity in the ocular surface since the ocular surface is exposed directly to high drug concentrations. Recently, an in vivo comet assay using corneal epithelial cells in rabbits following single ocular instillation was developed as an assay to evaluate genotoxicity in ocular tissues. In this study, we investigated the time-course changes in DNA damage after ocular instillation of genotoxic compounds to evaluate the optimal sampling timing for in vivo comet assay of the ocular surface tissue. Ethidium bromide (EtBr), methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4-NQO) were administered to the eyes of the rabbits. Corneas were collected at 0.5, 2, 4, 6, and 24 h after administration, and the comet assay was performed. In addition, the in vitro comet assay was performed to assess the time-course changes in DNA damage induced by short-time exposure to the genotoxic compounds.

Results

The mean % tail DNA, which is an indicator for DNA damage, in the corneal epithelial cells treated with all compounds exhibited statistically significant increases compared with those in the negative controls of saline at 0.5, 2, 4, and 6 h. There was a difference in the DNA damage response between EtBr and the other two compounds. In the 3% MMS- and 1% 4-NQO-treated eyes, the values of the % tail DNA were the highest at 0.5 h and then decreased gradually. In contrast, in the 1% EtBr-treated eyes, the highest value was noted at 4 h. The results of the in vitro comet assay showed that the % tail DNA increased in all groups. A further increase in the % tail DNA occurred in the EtBr-treated cells even after removing the compound but not in the MMS- and 4-NQO-treated cells.

Conclusion

Relatively high values of the % tail DNA were maintained from 0.5 to 6 h after administration, suggesting that the optimal sampling time is any one point from 0.5 to 6 h in the comet assay of the corneal surface.
Biomarker Assay Validation by Mass Spectrometry
Authors: Fernández-Metzler Carmen , Ackermann Brad , Garofolo Fabio , Arnold Mark E. , DeSilva Binodh , Gu Huidong , Laterza Omar , Mao Yan , Rose Mark , Vazvaei-Smith Faye , Steenwyk Rick
Published: May 2022

Decades of discussion and publication have gone into the guidance from the scientific community and the regulatory agencies on the use and validation of pharmacokinetic and toxicokinetic assays by chromatographic and ligand binding assays for the measurement of drugs and metabolites. These assay validations are well described in the FDA Guidance on Bioanalytical Methods Validation (BMV, 2018). While the BMV included biomarker assay validation, the focus was on understanding the challenges posed in validating biomarker assays and the importance of having reliable biomarker assays when used for regulatory submissions, rather than definition of the appropriate experiments to be performed. Different from PK bioanalysis, analysis of biomarkers can be challenging due to the presence of target analyte(s) in the control matrices used for calibrator and quality control sample preparation, and greater difficulty in procuring appropriate reference standards representative of the endogenous molecule. Several papers have been published offering recommendations for biomarker assay validation. The situational nature of biomarker applications necessitates fit-for-purpose (FFP) assay validation. A unifying theme for FFP analysis is that method validation requirements be consistent with the proposed context of use (COU) for any given biomarker. This communication provides specific recommendations for biomarker assay validation (BAV) by LC-MS, for both small and large molecule biomarkers. The consensus recommendations include creation of a validation plan that contains definition of the COU of the assay, use of the PK assay validation elements that support the COU, and definition of assay validation elements adapted to fit biomarker assays and the acceptance criteria for both.
Hydrogenation-induced high-temperature superconductivity in two-dimensional molybdenum carbide Mo2C3
Authors: Jiao Na , Liu Hao-Dong , Yang Liu , Li Ya-Ping , Zheng Mengmeng , Lu Hong-Yan , Zhang Ping
Published: May 2022

Two-dimensional (2D) superconductors have important potential applications in constructing nano superconducting devices, thus, 2D superconductors with high critical temperature (T

c
) are highly desired. Till now, the T

c
of 2D superconductors are still relatively low. Based on density functional first-principles calculations, we predicted a new stable 2D transition metal molybdenum carbide 2H-Mo2C3. Based on the Eliashberg theory, we predict that it is not a superconductor. However, after hydrogenation, the hydrogen atoms increase the electronic density of states at the Fermi level, and strengthen the electron-phonon coupling. Accordingly, the hydrogenated 2H-Mo2C3, i.e., 2H-Mo2C3H2, is a 2D superconductor with T

c
of 53 K, exceeding the McMillan limit. Thus, hydrogenation is an important strategy for obtaining 2D high-temperature superconductors at atmosphere pressure. In view of the high superconducting T

c
of 2H-Mo2C3H2, it is highly expected to be synthesized in future experiments.
Can the abyss swallow gravitational waves or why do we not observe echoes?
Authors: Konoplya Roman A. , Zhidenko Alexander
Published: May 2022

Here we propose a simple explanation why echoes from wormholes mimicking black holes may be so small that they cannot be observed. The essence of the effect is in the redistribution of the initial energy of gravitational wave among multiple universes, connected by a wormhole.
Absence and Disappearance
Authors: Harding Warren
Published: May 2022

This essay argues for a comparative approach to studying and reading Black Caribbean women’s poetry. In particular, it focuses on the works of Cuban Soleida Ríos and Tobagonian Canadian M. NourbeSe Philip in their publications at the close of the 1980s. The essay asks, How does a recuperation of a poetics between Ríos and Philip enhance a study of the body? Through a close reading of two poems, it points to instances of absence and disappearance as generative signals that enable these women to transgress the silences that structure imaginative and lived experiences. In doing so, language, interiority, and grammar become critical spaces for readers to witness the transformative subjectivities that abound when journeying with these women’s poetry.
Mémoire and Vindicationism in Revolutionary Saint-Domingue
Authors: Stieber Chelsea
Published: May 2022

This essay analyzes the genre of mémoire produced by gens de couleur (free people of color) within the colonial and military bureaucracy of revolutionary Saint-Domingue. Building on recent scholarship on Toussaint Louverture’s 1802 “Mémoire du général Toussaint Louverture,” it situates the genre in broader conversation with the mass of bureaucratic and administrative writing in the colony by offering close readings of mémoires from Julien Raimond and André Rigaud. Though written for different purposes, these mémoires evince a shared formal and rhetorical strategy: they present textual evidence and employ forensic rhetoric to refute competing claims and vindicate their cause. By elucidating the generic conventions of the mémoire, this essay contributes to the growing body of scholarship on Black writing that has moved beyond the paradigm of the slave narrative toward other forms and genres of Black protest. In so doing, it refocuses vindicationism on these rhetorical evidentiary practices, rather than on the mythos of romance and romantic overcoming that has categorized vindicationist narratives of the Haitian Revolution.