bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of calsyntenin paralogs disrupts interneuron stability and mouse behavior
Authors: Mori Keita , Koebis Michinori , Nakao Kazuki , Kobayashi Shizuka , Kiyama Yuji , Watanabe Masahiko , Manabe Toshiya , Iino Yuichi , Aiba Atsu
Published: March 2022

Calsyntenins (CLSTNs) are important synaptic molecules whose molecular functions are not fully understood. Although mutations in calsyntenin (CLSTN) genes have been associated with psychiatric disorders in humans, their function is still unclear. One of the reasons why the function of CLSTNs in the nervous system has not been clarified is the functional redundancy among the three paralogs. Therefore, to investigate the functions of mammalian CLSTNs, we generated triple knockout (TKO) mice lacking all CLSTN paralogs and examined their behavior. The mutant mice tended to freeze in novel environments and exhibited hypersensitivity to stress. Consistent with this, glucose levels under stress were significantly higher in the mutant mice than in the wild-type controls. In particular, phenotypes such as decreased motivation, which had not been reported in single Clstn KO mice, were newly discovered. The TKO mice generated in this study represent an important mouse model for clarifying the function of CLSTN in the future.
Adverse stem cell clones within a single patient’s tumor predict clinical outcome in AML patients
Authors: Zeller Christina , Richter Daniel , Jurinovic Vindi , Valtierra-Gutiérrez Ilse A. , Jayavelu Ashok Kumar , Mann Matthias , Bagnoli Johannes W. , Hellmann Ines , Herold Tobias , Enard Wolfgang , Vick Binje , Jeremias Irmela
Published: March 2022

Acute myeloid leukemia (AML) patients suffer dismal prognosis upon treatment resistance. To study functional heterogeneity of resistance, we generated serially transplantable patient-derived xenograft (PDX) models from one patient with AML and twelve clones thereof, each derived from a single stem cell, as proven by genetic barcoding. Transcriptome and exome sequencing segregated clones according to their origin from relapse one or two. Undetectable for sequencing, multiplex fluorochrome-guided competitive in vivo treatment trials identified a subset of relapse two clones as uniquely resistant to cytarabine treatment. Transcriptional and proteomic profiles obtained from resistant PDX clones and refractory AML patients defined a 16-gene score that was predictive of clinical outcome in a large independent patient cohort. Thus, we identified novel genes related to cytarabine resistance and provide proof of concept that intra-tumor heterogeneity reflects inter-tumor heterogeneity in AML.
Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth
Authors: Zamberlan Margherita , Boeckx Amandine , Muller Florian , Vinelli Federica , Ek Olivier , Vianello Caterina , Coart Emeline , Shibata Keitaro , Christian Aurélie , Grespi Francesca , Giacomello Marta , Struman Ingrid , Scorrano Luca , Herkenne Stéphanie
Published: March 2022

Background

Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown.

Methods

We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo.

Results

We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness.

Conclusions

Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.
Re-creating reality: validation of fresh frozen full cadaver airway training with videolaryngoscopy and bougie FIRST strategy
Authors: Imach Sebastian , Kölbel Benny , Böhmer Andreas , Keipke Dorothee , Ahnert Tobias
Published: March 2022

Background

Tracheal intubation is the gold standard in emergency airway management. One way of measuring intubation quality is first pass success rate (FPSR). Mastery of tracheal intubation and maintenance of the skill is challenging for non-anesthesiologists. A combination of individual measures can increase FPSR. Videolaryngoscopy is an important tool augmenting laryngeal visualization. Bougie-first strategy can further improve FPSR in difficult airways. Standardized positioning maneuvers and manipulation of the soft tissues can enhance laryngeal visualization. Fresh frozen cadavers (FFC) are superior models compared to commercially manufactured manikins. By purposefully manipulating FFCs, it is possible to mimic the pre-hospital intubation conditions of helicopter emergency medical service (HEMS).

Methods

Twenty-four trauma surgeons (12 per Group, NOVICES: no pre-hospital experience, HEMS: HEMS physicians) completed an airway training course using FFCs. The FFCs were modified to match airway characteristics of 60 prospectively documented intubations by HEMS physicians prior to the study (BASELINE). In four scenarios the local HEMS airway standard (1: unaided direct laryngoscopy (DL), OLD) was compared to two scenarios with modifications of the intubation technique (2: augmented DL (bougie and patient positioning), 3: augmented videolaryngoscopy (aVL)) and a control scenario (4: VL and bougie, positioning by participant, CONTROL). FPSR, POGO score, Cormack and Lehane grade and duration of intubation were recorded. No participant had anesthesiological qualifications or experience in VL.

Results

The comparison between CONTROL and BASELINE revealed a significant increase of FPSR and achieved C&L grade for HEMS group (FPSR 100%, absolute difference 23%, p ≤ .001). The use of videolaryngoscopy, bougie, and the application of positioning techniques required significantly more time in the CONTROL scenario (HEMS group: mean 34.0 s (IQR 28.3–47.5), absolute difference to BASELINE: 13.0 s, p = .045). The groups differed significantly in the median number of real-life intubations performed in any setting (NOVICES n = 5 (IQR 0–18.75), HEMS n = 68 (IQR 37.25–99.75)). In the control scenario no significant differences were found between both groups. The airway characteristics of the FFC showed no significant differences compared to BASELINE.

Conclusion

Airway characteristics of a pre-hospital patient reference group cared for by HEMS were successfully reproduced in a fresh frozen cadaver model. In this setting, a combination of evidence based airway management techniques results in high FPSR and POGO rates of non-anesthesiological trained users. Comparable results (FPSR, POGO, duration of intubation) were achieved regardless of previous provider experience. The BOAH concept can therefore be used in the early stages of airway training and for skill maintenance.
Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis
Authors: Aneman Anders , Frost Steven , Parr Michael , Skrifvars Markus B.
Published: March 2022

Background

Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM.

Methods

Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI).

Results

In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%.

Conclusions

The posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.
Caries inhibition with CO2-laser during orthodontic treatment: a study protocol for a randomized split-mouth controlled clinical trial
Authors: Belcheva Ani Bozhidarova , Shindova Maria Petrova
Published: March 2022

Introduction

White spot lesions associated with orthodontic treatment are a common problem. Recent studies reported increased resistance to acid demineralization of enamel after sub-ablative CO2-laser irradiation in a combination with fluoride application. The aim of the study is to assess the efficacy of CO2-laser in combination with a fluoride varnish in the prevention, severity, and extent of white spot lesions during orthodontic treatment with fixed appliances.

Methods and analysis

This is a protocol for a randomized, split-mouth controlled, clinical trial. The participants will be children aged 12–18 years at high caries risk, requiring fixed orthodontic treatment. The vestibular surfaces of maxillary anterior teeth of eligible patients will be exposed to CO2-laser irradiation in combination with fluoride therapy and fluoride therapy alone followed by bonding of orthodontic brackets. The patients will be recalled 6 and 12 months post-irradiation. Outcome measures will be visual examination with International Caries Detection and Assessment System criteria and SoproLife fluorescence. Data will be analyzed by Student’s t test for paired samples and proportional odds logistic regression model, p<0.05.

Ethics and dissemination

The study protocol has been approved by the Committee for Scientific Research Ethics, Medical University-Plovdiv, Bulgaria (Reference number P-605/27.03.2020, Protocol of approval No. 2/01.04.2021) and registered on a publicly accessible database. This research received institutional funding from the Medical University–Plovdiv, Bulgaria. The results will be presented through peer-reviewed publications and conference presentations.

Trial registration

ClinicalTrials.gov NCT04903275. Registered on June 2021.
Tolerance induction through early feeding to prevent food allergy in infants with eczema (TEFFA): rationale, study design, and methods of a randomized controlled trial
Authors: Kalb Birgit , Meixner Lara , Trendelenburg Valérie , Unterleider Nathalie , Dobbertin-Welsch Josefine , Heller Stephanie , Dölle-Bierke Sabine , Roll Stephanie , Lau Susanne , Lee Young-Ae , Fauchère Florent , Braun Julian , Babina Magda , Altrichter Sabine , Birkner Till , Worm Margitta , Beyer Kirsten
Published: March 2022

Background

Up to 8% of all children in industrialized countries suffer from food allergies, whereas children with atopic eczema are affected considerably more frequently. In addition, the type and starting time of weaning foods seem to influence the development of food allergies. However, data from interventional studies on weaning are controversial.

The aim of this randomized-controlled clinical trial is to investigate, whether an early introduction of hen's egg (HE), cow’s milk (CM), peanut (PN), and hazelnut (HN) in children with atopic eczema can reduce the risk for developing food allergies in the first year of life.

Methods

This is a protocol for a randomized, placebo controlled, double blind, single-center clinical trial.

One hundred fifty infants with atopic eczema at 4–8 months of age will be randomized in a 2:1 manner into an active group that will receive rusk-like biscuit powder with HE, CM, PN, and HN (initially approximately 2 mg of each food protein) for 6–8 months or a placebo group, whose participants will receive the same rusk-like biscuit powder without HE, CM, PN, and HN on a daily basis. During the interventional period, the amount of allergens in the study product will be increased three times, each after 6 weeks. All study participants who are sensitized to HE, CM, PN, or HN at the end of the interventional period will undergo an oral food challenge to the respective food in a further visit.

Primary endpoint is IgE-mediated food allergy to at least one of the four foods (HE, CM, PN or HN) after 6–8 months of intervention (i.e., at around 1 year of age). Secondary endpoints include multiple food allergies, severity of eczema, wheezing, and sensitization levels against food allergens.

Discussion

This clinical trial will assess whether an early introduction of allergenic foods into the diet of children with atopic eczema can prevent the development of food allergies. This trial will contribute to update food allergy prevention guidelines.

Trial registration

German Clinical Trials Register DRKS00016770. Registered on 09 January 2020.
Fluralaner 5.46% (w/w) flavored chewable tablet (Bravecto® 1-Month) is effective for treatment of canine generalized demodicosis
Authors: Rohdich Nadja , Meyer Leon , Guerino Frank
Published: March 2022

Background

Orally administered fluralaner (13.64% w/w) is effective for treating canine generalized demodicosis. A study was initiated to assess the efficacy of a novel 5.46% w/w fluralaner chewable tablet formulation for monthly administration in the treatment of this disease.

Methods

Client-owned dogs diagnosed with generalized demodicosis were acclimatized to laboratory conditions and randomized to receive either orally administered fluralaner (Bravecto®1-Month) (10.0 to 14.4 mg/kg body weight) (n = 8) or topical imidacloprid-moxidectin (Advocate®for dogs, Elanco) applied per label on days 0, 28, and 56 (n = 8), or more frequently for ongoing severe demodicosis. On days −2, 28, 56, and 84, deep skin scrapings were taken from five sites on each dog for mite identification and counting, and semiquantitative clinical assessments of generalized demodicosis were recorded. Primary efficacy was based upon arithmetic mean mite count reductions relative to pre-treatment.

Results

By day 28, mean pre-treatment mite counts, > 600 in both groups, were significantly reduced by 99.7% and 89.5% (bothP < 0.001) in the fluralaner and imidacloprid-moxidectin groups, respectively. Parasitological cure (100% reduction in mite counts on days 56 and 84) was achieved in all fluralaner-treated dogs (100%) and in two imidacloprid-moxidectin-treated dogs (25%). In the imidacloprid-moxidectin group, the reduction in mean mite counts was 89.5% (day 28), 94.4% (day 56), and 97.5% (day 84). All study dogs were free of crusts on days 56 and 84. Scales resolved by day 84 in all fluralaner-treated dogs and in three imidacloprid-moxidectin-treated dogs. All fluralaner-treated dogs and five imidacloprid-moxidectin-treated dogs had > 90% hair regrowth on day 84.

Conclusion

Three consecutive monthly orally administered treatments with fluralaner (5.46% w/w) flavored chewable tablets (minimum dose rate 10 mg/kg body weight) eliminatedDemodex canismites from dogs diagnosed with generalized demodicosis.

Graphical Abstract
Design and comparison of a hybrid to a traditional in-person point-of-care ultrasound course
Authors: Janjigian Michael , Dembitzer Anne , Srisarajivakul-Klein Caroline , Mednick Aron , Hardower Khemraj , Cooke Deborah , Zabar Sondra , Sauthoff Harald
Published: March 2022

Background

Traditional introductory point-of-care ultrasound (POCUS) courses are resource intensive, typically requiring 2–3 days at a remote site, consisting of lectures and hands-on components. Social distancing requirements resulting from the COVID-19 pandemic led us to create a novel hybrid course curriculum consisting of virtual and in-person components.

Methods

Faculty, chief residents, fellows and advanced practice providers (APPs) in the Department of Medicine were invited to participate in the hybrid curriculum. The course structure included 4 modules of recorded lectures, quizzes, online image interpretation sessions, online case discussions, and hands-on sessions at the bedside of course participant’s patients. The components of the course were delivered over approximately 8 months. Those participants who completed a minimum of 3 modules over the year were invited for final assessments. Results from the hybrid curriculum cohort were compared to the year-end data from a prior traditional in-person cohort.

Results

Participant knowledge scores were not different between traditional (n = 19) and hybrid (n = 24) groups (81% and 84%, respectively, P = 0.9). There was no change in POCUS skills as measured by the hands-on test from both groups at end-of-course (76% and 76%, respectively, P = 0.93). Confidence ratings were similar across groups from 2.73 traditional to 3.0 hybrid (out of possible 4, P = 0.46). Participants rated the course highly, with an average overall rating of 4.6 out 5.

Conclusions

A hybrid virtual and in-person POCUS course was highly rated and as successful as a traditional course in improving learner knowledge, hands-on skill and confidence at 8 months after course initiation. These results support expanding virtual elements of POCUS educational curricula.
Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models
Authors: Klibaite Ugne , Kislin Mikhail , Verpeut Jessica L. , Bergeler Silke , Sun Xiaoting , Shaevitz Joshua W. , Wang Samuel S.-H.
Published: March 2022

Background

Repetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD.

Methods

We used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait.

Results

Both Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy.

Limitations

Genetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability.

Conclusions

Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria.
Therapeutic role of uterine-derived stem cells in acute kidney injury
Authors: Mamillapalli Ramanaiah , Cho SiHyun , Mutlu Levent , Taylor Hugh S.
Published: March 2022

Background

Acute kidney injury (AKI) causes abrupt deterioration in kidney function that disrupts metabolic, electrolyte and fluid homeostasis. Although the prevalence of AKI is steadily increasing, no definitive treatment options are available, leading to severe morbidity and mortality. We evaluated the role of uterine-derived multipotent stem cells in kidney regeneration after ischemic AKI.

Methods

Female C57BL/6J mice were hysterectomized and subsequently subject to AKI by either unilateral or bilateral renal ischemia–reperfusion injury. Uterine-derived cells (UDCs), containing a population of uterine stem cells, were isolated from the uteri of female transgenic DsRed mice and injected intravenously to AKI mice. Engraftment of DsRed cells was analyzed by flow cytometry while serum creatinine levels were determined colorimetrically. Expression of UDC markers and cytokine markers were analyzed by immunohistochemical and qRT-PCR methods, respectively. The Kaplan–Meier method was used to analyze survival time while unpaired t test with Welch’s correction used for data analysis between two groups.

Results

Mice with an intact uterus, and hence an endogenous source of UDCs, had a higher survival rate after bilateral ischemic AKI compared to hysterectomized mice. Mice treated with infusion of exogenous UDCs after hysterectomy/AKI had lower serum creatinine levels and higher survival rates compared to controls that did not receive UDCs. Engraftment of labeled UDCs was significantly higher in kidneys of bilateral ischemic AKI mice compared to those that underwent a sham surgery. When unilateral ischemic AKI was induced, higher numbers of UDCs were found in the injured than non-injured kidney. Immunofluorescence staining demonstrated double-positive DsRed/Lotus tetragonolobus agglutinin (LTA) positive cells and DsRed/CD31 positive cells indicating contribution of UDCs in renal tubular and vascular regeneration. Expression of Cxcl12, Bmp2, Bmp4, and Ctnf in renal tissue was significantly higher in the UDCs injection group than the control group.

Conclusions

UDCs engrafted injured kidneys, contributed to proximal tubule and vascular regeneration, improved kidney function and increased survival in AKI mice. UDC administration is a promising new therapy for AKI. Endogenous uterine stem cells likely also preserve kidney function, suggesting a novel interaction between the uterus and kidney. We suggest that hysterectomy may have a detrimental effect on response to renal injury.
Integrative analysis reveals a lineage-specific circular RNA landscape for adipo-osteogenesis of human mesenchymal stem cells
Authors: Huang Hai-Bo , Luo Hai-Tao , Wei Na-Na , Liu Miao-Ling , He Fei , Yang Wei , Dong Jun , Yang Xiao-Fei , Li Fu-Rong
Published: March 2022

Background

The balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) is critical to skeletal development and diseases. As a research hotspot, circular RNAs (circRNAs) have expanded our understanding of a hidden layer of the transcriptome. Yet, their roles during adipo-osteogenesis remain poorly described.

Methods

The identity of human MSCs derived from bone marrow and adipose were first determined by flow cytometry, cellular staining, and quantitative polymerase chain reaction (qPCR). Multi-strategic RNA-sequencing was performed using Poly A, RiboMinus and RiboMinus/RNase R methods. Integrative analysis was performed to identify lineage-specific expressed circRNAs. The structural and expressional characteristics were identified by Sanger sequencing and qPCR, respectively. The regulatory effects of adipogenesis-specific circ-CRLF1 were confirmed using siRNA transcfection and qPCR.

Results

We generated a whole transcriptome map during adipo-osteogenesis based on 10 Poly A, 20 RiboMinus and 20 RiboMinus/ RNase R datasets. A total of 31,326 circRNAs were identified and quantified from ~ 3.4 billion paired-end reads. Furthermore, the integrative analysis revealed that 1166 circRNA genes exhibited strong lineage-specific expression patterns. Their host genes were enriched in distinct biological functions, such as cell adhesion, cytokine signaling, and cell division. We randomly selected and validated the back-spliced junction sites and expression patterns of 12 lineage-specific circRNAs. Functional analysis indicated that circ-CRLF1 negatively regulated adipogenesis.

Conclusions

Our integrative analysis reveals an accurate and generally applicable lineage-specific circRNA landscape for adipo-osteogenesis of MSCs and provides a potential therapeutic target, circ-CRLF1, for the treatment of skeleton-related disease.
Application of deep metric learning to molecular graph similarity
Authors: Coupry Damien E. , Pogány Peter
Published: March 2022

Graph based methods are increasingly important in chemistry and drug discovery, with applications ranging from QSAR to molecular generation. Combining graph neural networks and deep metric learning concepts, we expose a framework for quantifying molecular graph similarity based on distance between learned embeddings separate from any endpoint. Using a minimal definition of similarity, and data from the ZINC database of public compounds, this work demonstrate the properties of the embedding and its suitability for a range of applications, among them a novel reconstruction loss method for training deep molecular auto-encoders. Finally, we compare the applications of the embedding to standard practices, with a focus on known failure points and edge cases; concluding that our approach can be used in conjunction to existing methods.
Deep learning-driven prediction of drug mechanism of action from large-scale chemical-genetic interaction profiles
Authors: Liu Chengyou , Hogan Andrew M. , Sturm Hunter , Khan Mohd Wasif , Islam Md. Mohaiminul , Rahman A. S. M. Zisanur , Davis Rebecca , Cardona Silvia T. , Hu Pingzhao
Published: March 2022

Motivation

Chemical–genetic interaction profiling is a genetic approach that quantifies the susceptibility of a set of mutants depleted in specific gene product(s) to a set of chemical compounds. With the recent advances in artificial intelligence, chemical–genetic interaction profiles (CGIPs) can be leveraged to predict mechanism of action of compounds. This can be achieved by using machine learning, where the data from a CGIP is fed into the machine learning platform along with the chemical descriptors to develop a chemogenetically trained model. As small molecules can be considered non-structural data, graph convolutional neural networks, which can learn from the chemical structures directly, can be used to successfully predict molecular properties. Clustering analysis, on the other hand, is a critical approach to get insights into the underlying biological relationships between the gene products in the high-dimensional chemical-genetic data.

Methods and results

In this study, we proposed a comprehensive framework based on the large-scale chemical-genetics dataset built in Mycobacterium tuberculosis for predicting CGIPs using graph-based deep learning models. Our approach is structured into three parts. First, by matching M. tuberculosis genes with homologous genes in Escherichia coli (E. coli) according to their gene products, we grouped the genes into clusters with distinct biological functions. Second, we employed a directed message passing neural network to predict growth inhibition against M. tuberculosis gene clusters using a collection of 50,000 chemicals with the profile. We compared the performance of different baseline models and implemented multi-label tasks in binary classification frameworks. Lastly, we applied the trained model to an externally curated drug set that had experimental results against M. tuberculosis genes to examine the effectiveness of our method. Overall, we demonstrate that our approach effectively created M. tuberculosis gene clusters, and the trained classifier is able to predict activity against essential M. tuberculosis targets with high accuracy.

Conclusion

This work provides an analytical framework for modeling large-scale chemical-genetic datasets for predicting CGIPs and generating hypothesis about mechanism of action of novel drugs. In addition, this work highlights the importance of graph-based deep neural networks in drug discovery.
Second malignant neoplasms in lymphomas, secondary lymphomas and lymphomas in metabolic disorders/diseases
Authors: Yu Youxi , Shi Xiaoju , Wang Xingtong , Zhang Ping , Bai Ou , Li Yan
Published: March 2022

With inconsistent findings, evidence has been obtained in recent years that metabolic disorders are closely associated with the development of lymphomas. Studies and multiple analyses have been published also indicating that some solid tumor survivors develop a secondary lymphoma, whereas some lymphoma survivors subsequently develop a second malignant neoplasm (SMN), particularly solid tumors. An interaction between the multiple etiologic factors such as genetic factors and late effects of cancer therapy may play an important role contributing to the carcinogenesis in patients with metabolic diseases or with a primary cancer. In this review, we summarize the current knowledge of the multiple etiologic factors for lymphomagenesis, focusing on the SMN in lymphoma, secondary lymphomas in primary cancers, and the lymphomas associated to metabolic disorders/diseases, which have been received less attention previously. Further, we also review the data of coexistence of lymphomas and hepatocellular carcinoma (HCC) in patients with infection of hepatitis C virus and hepatitis B virus.

Graphical Abstract
Flight maneuver intelligent recognition based on deep variational autoencoder network
Authors: Tian Wei , Zhang Hong , Li Hui , Xiong Yuan
Published: March 2022

The selection and training of aircraft pilots has high standards, long training cycles, high resource consumption, high risk, and high elimination rate. It is the particularly urgent and important requirement for the current talent training strategy of national and military to increase efficiency and speed up all aspects of pilot training, reduce the training cycle and reduce the elimination rate. To this end, this paper uses deep variational auto-encoder network and adaptive dynamic time warping algorithms as support to explore the establishment of an integrated evaluation system for flight maneuver recognition and quality evaluation, solve the industry difficulty faced by current flight training data mining applications, and achieve accurate recognition and reliable quality evaluation of flight regimes under the background of high mobility. It will fully explore the benefits of existing airborne flight data for military trainee pilots, support the personalized and accurate training of flight talents, and reduce the rate of talent elimination.
Prevalence of periodontal disease among Indigenous and non-Indigenous populations: protocol for systematic review and meta-analysis
Authors: Nath Sonia , Poirier Brianna , Ju Xiangqun , Kapellas Kostas , Haag Dandara , Jamieson Lisa
Published: March 2022

Background

Indigenous populations globally experience worse oral health than their non-Indigenous counterpart. Globally, the occurrence of periodontal diseases such as gingivitis and chronic periodontitis is high among Indigenous people. This systematic review aims to quantify, at a global level, the prevalence of periodontal disease among Indigenous populations compared to non-Indigenous populations.

Methods

This review will only consider studies that have reported the prevalence (%) of periodontal disease among Indigenous and compared against non-Indigenous populations. Studies that have no comparative population or data only on one particular population or lack of data on periodontal clinical assessment will be excluded. An electronic search will be conducted using keywords and appropriate MeSH terms across several databases capturing both published and unpublished articles. The search will be conducted from the time of database inception to February 2021. After the initial search, duplicates will be removed, and the remaining titles and abstracts will be assessed for eligibility. The full text of eligible studies will be assessed by two independent reviewers who will also complete the critical appraisals and data extraction. Outcomes measures would be the mean prevalence (%) and standard deviation of periodontal disease among Indigenous and non-Indigenous populations. From the selected studies, we will conduct a random-effects meta-analysis using standardized mean difference as the effect measure. Forest plots will be used for the visualization of differences in the prevalence of periodontitis. A subgroup analysis will be conducted based on the definition of periodontitis, age, publication type, and geographical location. Heterogeneity among studies will be assessed by I2 and chi-square test. Egger’s test and funnel plots will be used to assess publication bias.

Discussion

Our systematic review and meta-analysis will facilitate an increased understanding of the magnitude of periodontal disease inequalities that exist globally for Indigenous populations through pooled prevalence estimates. The findings will be helpful to design selective targeted preventive and interventional strategies for periodontal disease for reducing oral health inequalities at a global level.

Systematic review registration

PROSPERO CRD42020188531
A second-order low-regularity integrator for the nonlinear Schrödinger equation
Authors: Ostermann Alexander , Wu Yifei , Yao Fangyan
Published: March 2022

In this paper, we analyze a new exponential-type integrator for the nonlinear cubic Schrödinger equation on the d dimensional torus $\mathbb{T}^{d}$

T
d

. The scheme has also been derived recently in a wider context of decorated trees (Bruned et al. in Forum Math. Pi 10:1–76, 2022). It is explicit and efficient to implement. Here, we present an alternative derivation and give a rigorous error analysis. In particular, we prove the second-order convergence in $H^{\gamma }(\mathbb{T}^{d})$

H
γ

(

T
d

)
for initial data in $H^{\gamma +2}(\mathbb{T}^{d})$

H

γ
+
2

(

T
d

)
for any $\gamma > d/2$
γ
>
d
/
2
. This improves the previous work (Knöller et al. in SIAM J. Numer. Anal. 57:1967–1986, 2019).

The design of the scheme is based on a new method to approximate the nonlinear frequency interaction. This allows us to deal with the complex resonance structure in arbitrary dimensions. Numerical experiments that are in line with the theoretical result complement this work.
Some parameterized Simpson’s type inequalities for differentiable convex functions involving generalized fractional integrals
Authors: You Xuexiao , Ali Muhammad Aamir , Budak Hüseyin , Kara Hasan , Zhao Dafang
Published: March 2022

In this paper, we establish some new inequalities of Simpson’s type for differentiable convex functions involving some parameters and generalized fractional integrals. The results given in this study are a generalization of results proved in (Du, Li and Yang in Appl. Math. Comput. 293:358–369, 2017).
Improved firefly algorithm with courtship learning for unrelated parallel machine scheduling problem with sequence-dependent setup times
Authors: Huang Xingwang , Chen Lingqing , Zhang Yuxin , Su Shubin , Lin Yangbin , Cao Xuhui
Published: March 2022

The Unrelated Parallel Machines Scheduling Problem (UPMSP) with sequence-dependent setup times has been widely applied to cloud computing, edge computing and so on. When the setup times are ignored, UPMSP will be a NP problem. Moreover, when considering the sequence related setup times, UPMSP is difficult to solve, and this situation will be more serious in the case of high-dimensional. This work firstly select the maximum completion time as the optimization objective, which establishes a mathematical model of UPMSP with sequence-dependent setup times. In addition, an improved firefly algorithm with courtship learning is proposed. Finally, in order to provide an approximate solution in an acceptable time, the proposed algorithm is applied to solve the UPMSP with sequence-dependent setup times. The experimental results show that the proposed algorithm has competitive performance when dealing with UPMSP with sequence-dependent setup times.
What evidence exists for the impact of climate change on the physiology and behaviour of important aquaculture marine crustacean species in Asia? A systematic map protocol
Authors: Azra Mohamad Nor , Noor Mohd Iqbal Mohd , Eales Jacqualyn , Sung Yeong Yik , Ghaffar Mazlan Abd
Published: March 2022

Background

Climate is one of the most important driving factors of future changes in terrestrial, coastal, and marine ecosystems. Any changes in these environments can significantly influence physiological and behavioural responses in aquatic animals, such as crustacea. Crustacea play an integral role as subsistence predators, prey, or debris feeders in complex food chains, and are often referred to as good indicators of polluted or stressed conditions. They also frequently have high production, consumption, and commercial significance. However, crustacean’s responses to climate change are likely to vary by species, life-history stage, reproduction status and geographical distribution. This map is undertaken as part of the Long-Term Research Grant project which aims to identify any interactive effect on physiological compensation and behavioural strategy of how marine organisms, especially crustaceans, deal with stress from environmental change. Our proposed map will aim to outline the evidence currently existing for the impacts of climate change on the physiology and behaviour of important aquaculture crustacean species within Asia.

Methods

We will document peer-reviewed articles in English using published journal articles and grey literature. Two bibliographic databases (Scopus and Web of Science) and multiple organizational websites with Google scholars will be searched. The systematic map protocol will follow in accordance with the Collaboration for Environmental Evidence Guidelines and Standards. Literature will be screened at the title, abstract, and full-text level using pre-defined inclusion criteria. The map will highlight marine crustacea physiological compensation and behavioural strategies to cope with climate change. It will also improve our knowledge of the available evidence and current gaps for future research recommendations.
Reorganization of 3D genome architecture across wild boar and Bama pig adipose tissues
Authors: Zhang Jiaman , Liu Pengliang , He Mengnan , Wang Yujie , Kui Hua , Jin Long , Li Diyan , Li Mingzhou
Published: March 2022

Background

A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression. Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs. However, how chromatin organization differs among pig breeds is poorly understood.

Results

In this study, we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots (upper layer of backfat [ULB] and greater omentum [GOM]) in wild boars and Bama pigs; the latter is a typical indigenous pig in China. We found that over 95% of the A/B compartments and topologically associating domains (TADs) are stable between wild boars and Bama pigs. In contrast, more than 70% of promoter-enhancer interactions (PEIs) are dynamic and widespread, involving over a thousand genes. Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions, endocrine function, energy metabolism and the immune response. Approximately 95% and 97% of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB, respectively.

Conclusions

We reported 3D genome organization in adipose depots from different pig breeds. In a comparison of Bama pigs and wild boar, large-scale compartments and TADs were mostly conserved, while fine-scale PEIs were extensively reorganized. The chromatin architecture in these two pig breeds was reorganized in an adipose depot-specific manner. These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.
The compassionate love for humanity scale (CLS-H-SF): psychometric properties of the Persian version
Authors: Hajiheydari Zahra , Abdollahi Abbas , Jasim Saade Abdalkareem , Alghazali Tawfeeq Abdulameer Hashim , Chupradit Supat , McGlinchey Caomhán , Allen Kelly A.
Published: March 2022

Compassionate love is beneficial in a variety of domains, including in education, health, and law, as well as in people’s personal lives. The topic of compassionate love has therefore attracted growing interest from researchers interested in its psychological and social dimensions. Given the importance of compassion to the education and health sectors, and the expansion of these sectors in Iran, this paper aims to provide Persian (Farsi) speaking practitioners and researchers with an effective instrument for measuring compassion. As such, the authors have translated the compassionate love for humanity scale-short form (CLS-H-SF) into the Persian language, and assessed the psychometric properties of this instrument among a sample of the Iranian population. A sample of 827 adults (49.9% women and 51.1% men) completed the Persian version of the CLS-H-SF through an online survey. Concurrent validity was assessed using the Persian versions of the positive and negative affect scale, self-esteem scale, and satisfaction with life scale. The CLS-H-SF positively correlated with positive affect, self-esteem and life satisfaction, and negatively correlated with negative affect. These findings indicate acceptable concurrent validity for the CLS-H-SF. Cronbach’s alpha for the scale was 0.88, indicating good internal consistency between items. A confirmatory factor analysis supported a one-factor model same as the English version of the CLS-H-SF. The findings of this study showed the Persian version of CLS-H-SF had acceptable validity and reliability in assessing compassionate love for humanity in Iranian adults.
Flexible material formulations for 3D printing of ordered porous beds with applications in bioprocess engineering
Authors: Dimartino Simone , Galindo-Rodriguez Giuseppe Rafael , Simon Ursula , Conti Mariachiara , Sarwar M. Sulaiman , Athi Narayanan Selva Manikandan , Jiang Qihao , Christofi Nick
Published: March 2022

Background

3D printing is revolutioning many industrial sectors and has the potential to enhance also the biotechnology and bioprocessing fields. Here, we propose a new flexible material formulation to 3D print support matrices with complex, perfectly ordered morphology and with tuneable properties to suit a range of applications in bioprocess engineering.

Findings

Supports were fabricated using functional monomers as the key ingredients, enabling matrices with bespoke chemistry, such as charged groups, chemical moieties for further functionalization, and hydrophobic/hydrophilic groups. Other ingredients, e.g. crosslinkers and porogens, can be employed to fabricate supports with diverse characteristics of their porous network, providing an opportunity to further regulate the mechanical and mass transfer properties of the supports. Through this approach, we fabricated and demonstrated the operation of Schoen gyroid columns with (I) positive and negative charges for ion exchange chromatography, (II) enzyme bioreactors with immobilized trypsin to catalyse hydrolysis, and (III) bacterial biofilm bioreactors for fuel desulphurization.

Conclusions

This study demonstrates a simple, cost-effective, and flexible fabrication of customized 3D printed supports for different biotechnology and bioengineering applications.
Work histories and provision of grandparental childcare among Italian older women
Authors: Zanasi Francesca , Arpino Bruno , Pirani Elena , Bordone Valeria
Published: March 2022

This work investigates the link between grandmothers’ participation in the labour market during adult life (between ages 18 and 49) and their provision of grandparental childcare later in life. Our contribution is twofold. First, we consider the Italian case, that despite its reliance on informal care has been under-researched. Second, we test two contrasting arguments on the association between grandchild care provision and grandmother’s work histories. On the one hand, lifelong homemakers could be more family-oriented and more likely to provide grandchild care in later life. On the other hand, ever-employed grandmothers could be more likely to have employed daughters and provide grandchild care to support their working careers. With data from the Multipurpose surveys on Families and Social Subjects (2003, 2009, 2016), we estimate logistic regression models, considering various specifications of grandparental childcare, and measuring labour market attachment in three different ways (having ever worked, length of working career, employment interruptions for family reasons). Results show a dualism between grandmothers who ever worked and those who never did, with the former more likely to provide grandparental childcare, especially when parents are at work. Grandmothers who worked only a few years are more similar, in terms of grandchild care provision, to those who worked throughout their life, than to lifelong homemakers. This association is stronger in the South and North-West of Italy. Overall, we showed that care responsibilities are inextricable from labour market participation, as grandmothers who already juggled family and work are those supporting the most their adult children’s work–family reconciliation.