bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting chemotherapy response using a variational autoencoder approach
Authors: Wei Qi , Ramsey Stephen A.
Published: September 2021

Background

Multiple studies have shown the utility of transcriptome-wide RNA-seq profiles as features for machine learning-based prediction of response to chemotherapy in cancer. While tumor transcriptome profiles are publicly available for thousands of tumors for many cancer types, a relatively modest number of tumor profiles are clinically annotated for response to chemotherapy. The paucity of labeled examples and the high dimension of the feature data limit performance for predicting therapeutic response using fully-supervised classification methods. Recently, multiple studies have established the utility of a deep neural network approach, the variational autoencoder (VAE), for generating meaningful latent features from original data. Here, we report the first study of a semi-supervised approach using VAE-encoded tumor transcriptome features and regularized gradient boosted decision trees (XGBoost) to predict chemotherapy drug response for five cancer types: colon, pancreatic, bladder, breast, and sarcoma.

Results

We found: (1) VAE-encoding of the tumor transcriptome preserves the cancer type identity of the tumor, suggesting preservation of biologically relevant information; and (2) as a feature-set for supervised classification to predict response-to-chemotherapy, the unsupervised VAE encoding of the tumor’s gene expression profile leads to better area under the receiver operating characteristic curve and area under the precision-recall curve classification performance than the original gene expression profile or the PCA principal components or the ICA components of the gene expression profile, in four out of five cancer types that we tested.

Conclusions

Given high-dimensional “omics” data, the VAE is a powerful tool for obtaining a nonlinear low-dimensional embedding; it yields features that retain biological patterns that distinguish between different types of cancer and that enable more accurate tumor transcriptome-based prediction of response to chemotherapy than would be possible using the original data or their principal components.
Non-small-cell lung cancer classification via RNA-Seq and histology imaging probability fusion
Authors: Carrillo-Perez Francisco , Morales Juan Carlos , Castillo-Secilla Daniel , Molina-Castro Yésica , Guillén Alberto , Rojas Ignacio , Herrera Luis Javier
Published: September 2021

Background

Adenocarcinoma and squamous cell carcinoma are the two most prevalent lung cancer types, and their distinction requires different screenings, such as the visual inspection of histology slides by an expert pathologist, the analysis of gene expression or computer tomography scans, among others. In recent years, there has been an increasing gathering of biological data for decision support systems in the diagnosis (e.g. histology imaging, next-generation sequencing technologies data, clinical information, etc.). Using all these sources to design integrative classification approaches may improve the final diagnosis of a patient, in the same way that doctors can use multiple types of screenings to reach a final decision on the diagnosis. In this work, we present a late fusion classification model using histology and RNA-Seq data for adenocarcinoma, squamous-cell carcinoma and healthy lung tissue.

Results

The classification model improves results over using each source of information separately, being able to reduce the diagnosis error rate up to a 64% over the isolate histology classifier and a 24% over the isolate gene expression classifier, reaching a mean F1-Score of 95.19% and a mean AUC of 0.991.

Conclusions

These findings suggest that a classification model using a late fusion methodology can considerably help clinicians in the diagnosis between the aforementioned lung cancer cancer subtypes over using each source of information separately. This approach can also be applied to any cancer type or disease with heterogeneous sources of information.
Admixture with indigenous people helps local adaptation: admixture-enabled selection in Polynesians
Authors: Isshiki Mariko , Naka Izumi , Kimura Ryosuke , Nishida Nao , Furusawa Takuro , Natsuhara Kazumi , Yamauchi Taro , Nakazawa Minato , Ishida Takafumi , Inaoka Tsukasa , Matsumura Yasuhiro , Ohtsuka Ryutaro , Ohashi Jun
Published: September 2021

Background

Homo sapiens have experienced admixture many times in the last few thousand years. To examine how admixture affects local adaptation, we investigated genomes of modern Polynesians, who are shaped through admixture between Austronesian-speaking people from Southeast Asia (Asian-related ancestors) and indigenous people in Near Oceania (Papuan-related ancestors).

Methods

In this study local ancestry was estimated across the genome in Polynesians (23 Tongan subjects) to find the candidate regions of admixture-enabled selection contributed by Papuan-related ancestors.

Results

The mean proportion of Papuan-related ancestry across the Polynesian genome was estimated as 24.6% (SD = 8.63%), and two genomic regions, the extended major histocompatibility complex (xMHC) region on chromosome 6 and the ATP-binding cassette transporter sub-family C member 11 (ABCC11) gene on chromosome 16, showed proportions of Papuan-related ancestry more than 5 SD greater than the mean (> 67.8%). The coalescent simulation under the assumption of selective neutrality suggested that such signals of Papuan-related ancestry enrichment were caused by positive selection after admixture (false discovery rate = 0.045). The ABCC11 harbors a nonsynonymous SNP, rs17822931, which affects apocrine secretory cell function. The approximate Bayesian computation indicated that, in Polynesian ancestors, a strong positive selection (s = 0.0217) acted on the ancestral allele of rs17822931 derived from Papuan-related ancestors.

Conclusions

Our results suggest that admixture with Papuan-related ancestors contributed to the rapid local adaptation of Polynesian ancestors. Considering frequent admixture events in human evolution history, the acceleration of local adaptation through admixture should be a common event in humans.
Intraspecific differences in plant functional traits are related to urban atmospheric particulate matter
Authors: Zhu Jiyou , Xu Chengyang
Published: September 2021

Background

Functional trait-based ecological research has been instrumental in advancing our understanding of environmental changes. It is still, however, unclear how the functional traits of urban plants respond to atmospheric particulate matter, and which trade-off strategies are shown. In order to explore the variation of plant functional traits with the gradient of urban atmospheric particulate matter, we divided atmospheric particulate matter into three levels according to road distance, and measured the variation of six essential leaf functional traits and their trade-off strategies.

Results

Here, we show that the functional traits of plants can be used as predictors of plant response to urban atmospheric particulate matter. Within the study, leaf thickness, leaf dry matter content, leaf tissue density, stomatal density were positively correlated with atmospheric particulate matter. On the contrary, chlorophyll content index and specific leaf area were negatively correlated with atmospheric particulate matter. Plants can improve the efficiency of gas exchange by optimizing the spatial distribution of leaf stomata. Under the atmospheric particulate matter environment, urban plants show a trade-off relationship of economics spectrum traits at the intraspecific level.

Conclusion

Under the influence of urban atmospheric particulate matter, urban plant shows a “slow investment-return” type in the leaf economics spectrum at the intraspecific level, with lower specific leaf area, lower chlorophyll content index, ticker leaves, higher leaf dry matter content, higher leaf tissue density and higher stomatal density. This finding provides a new perspective for understanding the resource trades-off strategy of plants adapting to atmospheric particulate matter.
Different outcomes after proximal femoral replacement in oncologic and failed revision arthroplasty patients - a retrospective cohort study
Authors: Toepfer Andreas , Straßer Veit , Ladurner Andreas , Calek Anna-Katharina , Potocnik Primoz , von Eisenhart-Rothe Ruediger
Published: September 2021

Background

Proximal femoral replacement (PFR) is a technically demanding procedure commonly performed to restore extensive, oncological or non-oncological bone defects in a severely debilitated patient collective. Depending on different indications, a varying outcome has been reported. The aim of the study was to assess the functional outcomes and complication rates of PFR with the modular Munich-Luebeck (MML) femoral megaprosthesis (ESKA/Orthodynamics, Luebeck, Germany), and to highlight outcome differences in patients treated for failed revision total hip arthroplasty (THA) or malignant bone disease.

Methods

A retrospective review of patients treated with PFR for failed THA or malignant tumor disease between 2000 and 2012 was performed. Patient satisfaction, functional outcome (VAS, SF-12, MSTS, WOMAC, TESS), complications and failure types (Henderson’s failure classification) were assessed. A Kaplan-Meier analysis determined implant survival.

Results

Fifty-eight patients (age: 69.9 years, BMI: 26.7 kg/m2, mean follow-up: 66 months) were included. The mean SF-12 (physical / mental) was 37.9 / 48.4. MSTS averaged 68% at final follow-up, while mean WOMAC and TESS scored 37.8 and 59.5. TESS and WOMAC scores demonstrated significantly worse outcomes in the revision group (RG) compared to the tumor group (TG). Overall complication rate was 43.1%, and dislocation was the most common complication (27.6%). Implant survival rates were 83% (RG) and 85% (TG; p = n.s.) at 5 years, while 10-year survival was 57% (RG) and 85% (TG, p < 0.05).

Conclusions

PFR is a salvage procedure for restoration of mechanical integrity and limb preservation after extensive bone loss. Complications rates are considerably high.

Functional outcomes and 10-year implant survival rate were worse in the RG compared to the TG. Strict indications and disease-specific patient education are essential in preoperative planning and prognosis.
Headache and migraine clinical practice guidelines: a systematic review and assessment of complementary and alternative medicine recommendations
Authors: Ng Jeremy Y. , Hanna Christina
Published: September 2021

Background

Globally, 3 billion people suffer from either migraine or tension-type headache disorder over their lifetime. Approximately 50% of American adults suffering from headache or migraine have used complementary and alternative medicine (CAM), however, the quality and quantity of recommendations associated with such therapies across clinical practice guidelines (CPGs) for the treatment and/or management of these conditions are unknown. The purpose of this study was to identify the quantity and assess the quality of such CAM recommendations.

Methods

MEDLINE, EMBASE and CINAHL were systematically searched from 2009 to April 2020; the Guidelines International Network and the National Center for Complementary and Integrative Health websites were also searched for eligible CPGs. CPGs were included if they provided any therapy recommendations. Eligible CPGs included those written for adult patients with headache and migraine; CPGs containing CAM recommendations were assessed twice for quality using the AGREE II instrument, once for the overall CPG and once for the CAM sections.

Results

Of 486 unique search results, 21 CPGs were eligible and quality assessed; fifteen CPGs mentioned CAM, of which 13 CPGs made CAM recommendations. The overall CPG assessment yielded higher scaled domain percentages than the CAM section across all domains. The results from highest to lowest were as follows (overall, CAM): clarity of presentation (66.7% vs. 50.0%), scope and purpose (63.9% vs. 61.1%), stakeholder involvement (22.2% vs. 13.9%), rigour of development (13.5% vs. 9.4%), applicability (6.3% vs. 0.0%), and editorial independence (0.0% vs. 0.0%).

Conclusions

Of the eligible CPGs, the CAM sections were of lower quality compared to the overall recommendations across all domains of the AGREE II instrument. CPGs that scored well could serve as a framework for discussion between patients and healthcare professionals regarding use of CAM therapies in the context of headache and migraine.
Harvard Medical School Department of Global Health and Social Medicine COVID-19 seminar series: COVID and surgical, anesthetic and obstetric care
Authors: Miranda Elizabeth , Meara John G. , Pendleton Alaska , Peters Alexander W. , Santhirapala Vatshalan , Ashraf Nabeel , Alonso Nivaldo , Hakizimana Sadoscar , Bekele Abebe , Park Kee B. , Farmer Paul
Published: September 2021

On May 21, 2020, the Harvard Program in Global Surgery and Social Change (PGSSC) hosted a webinar as part of the Harvard Medical School Department of Global Health and Social Medicine’s COVID-19 webinar series. The goal of PGSSC’s virtual webinar was to share the experiences of surgical, anesthesia, and obstetric (SAO) providers on the frontlines of the COVID pandemic, from both high-income countries (HICs), such as the United States and the United Kingdom, as well as low- and middle-income countries (LMICs). Providers shared not only their experiences delivering SAO care during this global pandemic, but also solutions and innovations they and their colleagues developed to address these new challenges. Additionally, the seminar explored the relationship between surgery and health system strengthening and pandemic preparedness, and outlined the way forward, including a roadmap for prioritization and investment in surgical system strengthening. Throughout the discussion, other themes emerged as well, such as the definition of elective surgery and its implications during a persistent global pandemic, the safe and ethical reintroduction of surgical services, and the social inequities exposed by the stress placed on health systems by COVID-19. These proceedings document the perspectives shared by participants through their invited lectures as well as through the panel discussion at the end of the seminar.
NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis
Authors: Shersher Elena , Lahiry Mohini , Alvarez-Trotta Annamil , Diluvio Giulia , Robbins David J. , Shiekhattar Ramin , Capobianco Anthony J.
Published: September 2021

Background

Notch signaling drives many aspects of neoplastic phenotype. Here, we report that the Integrator complex (INT) is a new component of the Notch transcriptional supercomplex. Together with Notch Activation Complex Kinase (NACK), INT activates Notch1 target genes by driving RNA polymerase II (RNAPII)-dependent transcription, leading to tumorigenesis.

Methods

Size exclusion chromatography and CBF-1/RBPJ/Suppressor of Hairless/Lag-1 (CSL)-DNA affinity fast protein liquid chromatography (FPLC) was used to purify Notch/CSL-dependent complexes for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatin immunoprecipitation (ChIP) and quantitative polymerase chain reaction (qPCR) were performed to investigate transcriptional regulation of Notch target genes. Transfection of Notch Ternary Complex components into HEK293T cells was used as a recapitulation assay to study Notch-mediated transcriptional mechanisms. Gene knockdown was achieved via RNA interference and the effects of protein depletion on esophageal adenocarcinoma (EAC) proliferation were determined via a colony formation assay and murine xenografts. Western blotting was used to examine expression of INT subunits in EAC cells and evaluate apoptotic proteins upon INT subunit 11 knockdown (INTS11 KD). Gene KD effects were further explored via flow cytometry.

Results

We identified the INT complex as part of the Notch transcriptional supercomplex. INT, together with NACK, activates Notch-mediated transcription. While NACK is required for the recruitment of RNAPII to a Notch-dependent promoter, the INT complex is essential for RNAPII phosphorylated at serine 5 (RNAPII-S5P), leading to transcriptional activation. Furthermore, INT subunits are overexpressed in EAC cells and INTS11 KD results in G2/M cell cycle arrest, apoptosis, and cell growth arrest in EAC.

Conclusions

This study identifies the INT complex as a novel co-factor in Notch-mediated transcription that together with NACK activates Notch target genes and leads to cancer cell proliferation.
Inhibition of microglial β-glucocerebrosidase hampers the microglia-mediated antioxidant and protective response in neurons
Authors: Brunialti Electra , Villa Alessandro , Mekhaeil Marianna , Mornata Federica , Vegeto Elisabetta , Maggi Adriana , Di Monte Donato A. , Ciana Paolo
Published: September 2021

Background

Homozygotic mutations in the GBA gene cause Gaucher’s disease; moreover, both patients and heterozygotic carriers have been associated with 20- to 30-fold increased risk of developing Parkinson’s disease. In homozygosis, these mutations impair the activity of β-glucocerebrosidase, the enzyme encoded by GBA, and generate a lysosomal disorder in macrophages, which changes morphology towards an engorged phenotype, considered the hallmark of Gaucher’s disease. Notwithstanding the key role of macrophages in this disease, most of the effects in the brain have been attributed to the β-glucocerebrosidase deficit in neurons, while a microglial phenotype for these mutations has never been reported.

Methods

We applied the bioluminescence imaging technology, immunohistochemistry and gene expression analysis to investigate the consequences of microglial β-glucocerebrosidase inhibition in the brain of reporter mice, in primary neuron/microglia cocultures and in cell lines. The use of primary cells from reporter mice allowed for the first time, to discriminate in cocultures neuronal from microglial responses consequent to the β-glucocerebrosidase inhibition; results were finally confirmed by pharmacological depletion of microglia from the brain of mice.

Results

Our data demonstrate the existence of a novel neuroprotective mechanism mediated by a direct microglia-to-neuron contact supported by functional actin structures. This cellular contact stimulates the nuclear factor erythroid 2-related factor 2 activity in neurons, a key signal involved in drug detoxification, redox balance, metabolism, autophagy, lysosomal biogenesis, mitochondrial dysfunctions, and neuroinflammation. The central role played by microglia in this neuronal response in vivo was proven by depletion of the lineage in the brain of reporter mice. Pharmacological inhibition of microglial β-glucocerebrosidase was proven to induce morphological changes, to turn on an anti-inflammatory/repairing pathway, and to hinder the microglia ability to activate the nuclear factor erythroid 2-related factor 2 response, thus increasing the neuronal susceptibility to neurotoxins.

Conclusion

This mechanism provides a possible explanation for the increased risk of neurodegeneration observed in carriers of GBA mutations and suggest novel therapeutic strategies designed to revert the microglial phenotype associated with β-glucocerebrosidase inhibition, aimed at resetting the protective microglia-to-neuron communication.
Chiropractic website claims related to non-musculoskeletal conditions: a cross-sectional study
Authors: Goncalves Guillaume , Fleuriau Philippe , Cheron Charlène , Picchiottino Mathieu , Pigeon Sylvain , Jensen Rikke Krüger
Published: September 2021

Background

Chiropractors frequently use spinal manipulation therapy as a treatment modality in the management of musculoskeletal (MSK) conditions such as spinal pain and sometimes in the treatment of non-MSK disorders. The latter is not supported by evidence. This study aimed to investigate the extent of non-MSK website claims from French chiropractors to assess if websites were aligned with current recommendations on evidence-based practice.

Methods

This was a cross-sectional study of a representative sample of French chiropractors. Information on non-MSK conditions was collected from chiropractic professional websites by two independent observers in June 2020. For each non-MSK condition, it was noted whether a clarifying explanation justifying the mentioning of the condition was available. In addition, data on professional association affiliation status, country of education, years since graduation, and special clinical focus (e.g., seniors, children) were collected.

Results

A total of 287 randomly selected websites were included in the study corresponding to 22% of all chiropractors registered in France. One or more of 42 different non-MSK conditions were identified on 231 websites, of which 5 (2.2%) provided a clarifying explanation. 226 (79%) websites mentioned a non-MSK condition without a clarifying explanation. The non-MSK conditions most often mentioned were sleep problems, constipation/digestive problems, unease/discontent in children and menstrual cramps/pains. A larger proportion of the websites advertising treatment for non-MSK disorders was found among those claiming a special clinical focus on infants/children, seniors, pregnant women or athletes compared to those that did not. Also, a larger proportion of chiropractors who were affiliated with a professional association were advertising treatment for non-MSK disorders compared to those who were not affiliated.

Conclusions

Eight out of ten chiropractic websites mentioned one or more non-MSK diagnoses or symptoms. It is unclear if this reflects inaccurate communication or if treatments for non-MSK conditions are provided by the chiropractors.
Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing
Authors: Zhang Qingyang , Zhang Juan , Ye Jin , Li Xiaohui , Liu Hongda , Ma Xiaolin , Wang Chao , He Keqiang , Zhang Wei , Yuan Ji , Zhao Yingjun , Xu Huaxi , Liu Qiang
Published: September 2021

Background

Aberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer’s disease (AD), remain elusive.

Methods

Immunoblotting and immunostaining were performed to determine expression patterns and cellular/subcellular localization of the long isoform of hnRNP D-like (L-DL), which is a hnRNP family member, in mouse hippocampus. Downregulation of L-DL in WT mice was achieved by AAV-mediated shRNA delivery, followed by memory-related behavioural tests. L-DL interactome was analysed by affinity-precipitation and mass spectrometry. Alternative RNA splicing was measured by RNA-seq and analyzed by bioinformatics-based approaches. Downregulation and upregulation of L-DL in APP/PS1 mice were performed using AAV-mediated transduction.

Results

We show that L-DL is specifically localized to nuclear speckles. L-DL levels are decreased in the hippocampus of aged mouse brains and downregulation of L-DL impairs cognition in mice. L-DL serves as a structural component to recruit other speckle proteins, and regulates cytoskeleton- and synapse-related gene expression by altering RNA splicing. Mechanistically, these splicing changes are modulated via L-DL-mediated interaction of SF3B3, a core component of U2 snRNP, and U2AF65, a U2 spliceosome protein that guides U2 snRNP’s binding to RNA. In addition, L-DL levels are decreased in APP/PS1 mouse brains. While downregulation of L-DL deteriorates memory deficits and overexpression of L-DL improves cognitive function in AD mice, by regulating the alternative splicing and expression of synaptic geneCAMKV.

Conclusions

Our findings define a molecular mechanism by which hnRNP L-DL regulates alternative RNA splicing, and establish a direct role for L-DL in AD-related synaptic dysfunction and memory decline.
RETRACTED ARTICLE: LNCAROD enhances hepatocellular carcinoma malignancy by activating glycolysis through induction of pyruvate kinase isoform PKM2
Authors: Jia Guizhi , Wang Yan , Lin Chengjie , Lai Shihui , Dai Hongliang , Wang Zhiqian , Dai Luo , Su Huizhao , Song Yanjie , Zhang Naiwen , Feng Yukuan , Tang Bo
Published: September 2021

Background

Mounting evidence has suggested the essential role of long non-coding RNAs (lncRNAs) in a plethora of malignant tumors, including hepatocellular carcinoma. However, the underlyling mechanisms of lncRNAs remain unidentified in HCC. The present work was aimed to explore the regulatory functions and mechanisms of LncRNA LNCAROD in HCC progression and chemotherapeutic response.

Methods

The expression of LNCAROD in HCC tissues and cell lines were detected by quantitative reverse transcription PCR (qPCR). Cancer cell proliferation, migration, invasion, and chemoresistance were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and chemosensitivity assays. Methylated RNA immunoprecipitation qRCR (MeRIP-qPCR) was used to determine N6-methyladenosine (m6A) modification level. RNA immunoprecipitation (RIP) and RNA pull down were applied to identify the molecular sponge role of LNCAROD for modulation of miR-145-5p via the competing endogenous RNA (ceRNA) mechanism, as well as the interaction between LNCAROD and serine-and arginine-rich splicing factor 3 (SRSF3). The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and LNCAROD was also identified by RIP assay. Gain- or-loss-of-function assays were used to identify the function and underlying mechanisms of LNCAROD in HCC.

Results

We found that LNCAROD was significantly upregulated and predicted a poorer prognosis in HCC patients. LNCAROD upregulation was maintained by increased m6A methylation-mediated RNA stability. LNCAROD significantly promoted HCC cell proliferation, migration, invasion, and chemoresistance both in vitro and in vivo. Furthermore, mechanistic studies revealed that pyruvate kinase isoform M2 (PKM2)-mediated glycolysis enhancement is critical for the role of LNACROD in HCC. According to bioinformatics prediction and our experimental data, LNCAROD directly binds to SRSF3 to induce PKM switching towards PKM2 and maintains PKM2 levels in HCC by acting as a ceRNA against miR-145-5p. The oncogenic effects of LNCAROD in HCC were more prominent under hypoxia than normoxia due to the upregulation of hypoxia-triggered hypoxia-inducible factor 1α.

Conclusions

In summary, our present study suggests that LNCAROD induces PKM2 upregulation via simultaneously enhancing SRSF3-mediated PKM switching to PKM2 and sponging miR-145-5p to increase PKM2 level, eventually increasing cancer cell aerobic glycolysis to participate in tumor malignancy and chemoresistance, especially under hypoxic microenvironment. This study provides a promising diagnostic marker and therapeutic target for HCC patients.
Knowledge, attitudes and practices pertaining to urogenital schistosomiasis in Lambaréné and surrounding areas, Gabon
Authors: Dejon-Agobé Jean Claude , Zinsou Jeannot Fréjus , Honkpehedji Yabo Josiane , Edoa Jean Ronald , Adegbité Bayodé Roméo , Beh-Mba Romuald , Kremsner Peter Gottfried , Adegnika Ayola Akim , Grobusch Martin Peter
Published: September 2021

Background

Control of schistosomiasis remains a priority in endemic areas. Local epidemiological data are necessary for a tailored control programme, including data on population behaviour in relation to the disease. The objective of this study was to assess schistosomiasis-related knowledge, attitudes and practices in the general population of Lambaréné, a small city in Gabon, in order to optimise the design and implementation of a local control programme that is tailored to need.

Methods

The study was cross-sectional in nature. Eligible adults and children living in the study area who volunteered (with informed consent) to participate in the study were interviewed using standardised questionnaires, one of which was a simplified version of the primary questionnaire for participants aged 6–13 years. Data on the participants’ knowledge, attitudes and practices that enhance the risk for contracting schistosomiasis were collected.

Results

A total of 602 participants were included. The mean (± standard deviation) age was 21.2 (± 15.0) years, the female:male gender ratio was 1.6 and 289 (48%) participants completed the simplified version the questionnaire. Of the 602 participants, 554 (92%) reported past or current contact with freshwater, 218 (36%) reported a history of a diagnosis of schistosomiasis and 193 (32%) reported past intake of praziquantel medication. The overall levels of knowledge and adequate attitudes toward schistosomiasis among young adults and adults were 68 and 73%, respectively. The proportion of participants pursuing risk-enhancing practices (REP) was 60% among the whole study population. Location was significantly associated with differences in knowledge and REP levels. A history of confirmed schistosomiasis and larger family size were significantly associated with an increase in good knowledge and REP levels. However, the indication of freshwater-associated activities was only associated with a significant increase in the REP level.

Conclusions

The results of this survey reveal a high level of population exposure to schistosomiasis, which is in line with known prevalence of schistosomiasis in Lambaréné and its surroundings. The local population has a reasonable level of knowledge of and adequate attitudes toward schistosomiasis but the level of REP is high, particularly in areas where piped water is absent. In terms of interventions, improving hygiene should have the highest priority, but in a context where provision of safe water is difficult to achieve, the effectiveness of praziquantel treatment and the education of at-risk populations on the need for protective behaviours should be a prominent feature of any local control programme.

Graphical abstract
Upconverting phosphor technology-based lateral flow assay for the rapid and sensitive detection of anti-Trichinella spiralis IgG antibodies in pig serum
Authors: Li Jian , Ding Jing , Liu Xiao-Lei , Tang Bin , Bai Xue , Wang Yang , Qiao Wei-Dong , Liu Ming-Yuan , Wang Xue-Lin
Published: September 2021

Background

Trichinella spiralis is a zoonotic food-borne parasite. A disease caused by infection with T. spiralis is called trichinellosis in humans. It is important to investigate the epidemic situation and the surveillance of herds and then prevent infection in humans. Therefore, this study is to develop a rapid and sensitive diagnostic method for on-site test in domestic and wild animals.

Methods

Upconverting phosphor nanoparticles (UCNPs), an excellent optical label, were conjugated with the excretory-secretory (ES) antigens from T. spiralis muscle larvae (ML) or goat anti-rabbit IgG, and a lateral flow (LF) assay based on these probes (UCNPs-ES/goat anti-rabbit IgG) was developed for the rapid and sensitive detection of anti-T. spiralis IgG antibodies in pig serum. The assay is named the UPT-LF-ES assay. In addition, the probes were characterized, and the assay was optimized. A cut-off threshold of the assay was also identified by using 169 known negative pig samples. Performance of the assay to T. spiralis with different infective numbers, cross-reactivity with other parasitic infections, the single-blinded experiment, and coincidence were evaluated with the assay.

Results

The UPT-LF-ES assay was successfully constructed and optimized based on the probes of UCNPs-ES/goat anti-rabbit IgG. In the pigs infected with 100, 1000, and 10,000 ML, positive results were first presented at 35 days post-infection (dpi), 30 dpi, and 25 dpi, respectively. The assay had no cross-reaction with other parasitic infections. A single-blinded experiment indicated that the sensitivity and specificity of the UPT-LF-ES assay were 100% and 100%, respectively, the area under the receiver operating characteristic (ROC) curve was 1.000. In addition, the value detected by the UPT-LF-ES assay was significantly different between positive and negative samples. Moreover, compared with the “gold standard” magnetic stirrer method, the coincidence rate of the UPT-LF-ES assay was 87.27%, and the kappa (K) coefficient was 0.7454, showing a substantial agreement.

Conclusions

The UPT-LF-ES assay is a useful point-of-care test (POCT) with T. spiralis in the detection of pig, which contributes to preventing human trichinellosis.

Graphical Abstract
Changes in serum biomarkers of inflammation in bovine besnoitiosis
Authors: González-Barrio David , Huertas-López Ana , Diezma-Díaz Carlos , Ferre Ignacio , Cerón José Joaquín , Ortega-Mora Luis Miguel , Álvarez-García Gema
Published: September 2021

Background

Acute and chronic besnoitiosis in extensive natural-service herds can have relevant effects in the health of bulls and negative consequences in their productive performance. Recent progress has been made in order to elucidate the pathogenesis of this disease. In this context, the study of biomarkers of inflammation in serum would contribute to gaining knowledge about the physiopathology of bovine besnoitiosis. Serological biomarkers could help in early diagnosis and prognosis, as seropositive bulls may have mild or severe testicular lesions.

Methods

Herein, we have investigated the diagnostic and/or prognostic value of a panel of serum (serological) biomarkers related to inflammation, including total protein, globulin and albumin, haptoglobin (Hp), adenosine deaminase (ADA) paraoxonase-1 (PON-1) and acetylcholinesterase (AChE) in naturally and experimentally B. besnoiti-infected males classified according to different clinical phases of the disease (acute, chronic and subclinical besnoitiosis).

Results

Results showed a similar response pattern in these biomarkers for naturally and experimentally infected cattle, with a few relevant variations. Most significant changes occurred during the acute phase of infection, although significant changes in a few biomarkers were also observed during the chronic infection. Haptoglobin, albumin, PON-1 and ADA were identified as the biomarkers that showed changes of higher magnitude in the acute phase of the infection, whereas high total protein and globulin values were found in chronically infected cattle. We have described the changes of a panel of inflammatory biomarkers of acute and chronic bovine besnoitiosis.

Conclusions

In summary, several biomarkers with promising diagnostic value have been identified. The biomarkers associated with acute infection are related to previously reported molecular biomarkers in testicular parenchyma of infected bulls and could help in the diagnosis of early infections and complement results from specific immunoglobulin M (IgM) detection.

Graphical abstract
API2CAN: a dataset & service for canonical utterance generation for REST APIs
Authors: Yaghoub-Zadeh-Fard Mohammad-Ali , Benatallah Boualem
Published: September 2021

Objectives

Recently natural language interfaces (e.g., chatbots) have gained enormous attention. Such interfaces execute underlying application programming interfaces (APIs) based on the user's utterances to perform tasks (e.g., reporting weather). Supervised approaches for building such interfaces rely upon a large set of user utterances paired with APIs. Collecting such pairs is typically starts with obtaining initial utterances for a given API method. Generating initial utterances can be considered as a machine translation task in which an API method is translated into an utterance. However, the key challenge is the lack of training samples for training domain-independent translation models. In this paper, we propose a dataset for training supervised models to generate initial utterances for APIs.

Data description

The dataset contains 14,370 pairs of API methods and utterances. It is built automatically by converting method descriptions of a large number of APIs to user utterances; and it is cleaned manually to ensure quality. The dataset is also accompanied with a set of microservices (e.g., translating API methods to utterances) which can facilitate the process of collecting training samples for building natural language interfaces.
Problematic familial alcohol use and heavy episodic drinking among upper secondary students: a moderator analysis of teacher-rated school ethos
Authors: Olsson Gabriella , Brolin Låftman Sara , Wahlström Joakim , Modin Bitte
Published: September 2021

Objective

Building on findings reported in a previous publication, the objective of this study is to explore if teacher-rated indicators of school ethos modify the association between problematic familial alcohol use and heavy episodic drinking among upper secondary students. Data were based on combined information from two separate surveys conducted in 2016 among 4709 students and 1061 teachers in 46 Stockholm upper secondary schools, with linked school-level information from administrative registers. Multilevel binary logistic regression analyses were performed.

Results

Problematic familial alcohol use was associated with an increased likelihood of heavy episodic drinking among upper secondary students (OR 1.36, 95% CI 1.12–1.65). Cross-level interactions revealed that the association was weaker among students attending schools with higher levels of teacher-rated ethos. This was true for overall school ethos (OR 0.79, 95% CI 0.65–0.97) and for four of five studied sub-dimensions of ethos: staff stability (OR 0.78, 95% CI 0.65–0.95); teacher morale (OR 0.79, 95% CI 0.65–0.97); student focus (OR 0.80, 95% CI 0.65–0.97); and academic atmosphere (OR 0.79, 95% CI 0.65–0.96). The sub-dimension “structure and order for dealing with unwanted behaviour” did however not moderate the association between problematic familial alcohol use and heavy episodic drinking (OR 0.95, 95% CI 0.77–1.18).
Epidemiology of comorbidities and their association with asthma control
Authors: Tomisa Gábor , Horváth Alpár , Sánta Balázs , Keglevich András , Tamási Lilla
Published: September 2021

Background

The prevalence of comorbidities and their relation to asthma control and treatment is a topic of increasing interest, however comprehensive studies are scarce. We aimed to determine the prevalence of the most common comorbidities in asthma in relation to patient characteristics (age, gender and body mass index [BMI]) and their association with asthma control in a large, specialist-managed representative patient population.

Methods

A secondary, exploratory analysis of the Asthma Reality (ARL), across-sectional, non-interventional real-life study was conducted. Basic patient characteristics, the prevalence of comorbidities and data on asthma control and risk factors had been collected and their interactions examined. Descriptive statistics and binomial regression were used to assess the distribution of the prevalence of comorbidities and propensity matching was applied to assess their effect on asthma control.

Results

Overall, 12,743 patients were enrolled in our study in 187 treatment centres covering all regions of Hungary. Most comorbidities showed significantly different distribution for all basic patient characteristics. Gender, age group, smoking status, BMI and the duration of asthma had a significant impact on asthma control. The frequency of uncontrolled asthma was higher in females (37.1%), in the age group of 46–65 years (39.6%), in severely obese patients (43.2%), in patients who had been diagnosed with asthma for more than 20 years (40.4%), and in active heavy smokers (55%), compared with respective groups in the same category. Based on the binomial regression with propensity score matching, concomitant chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 2.06, 95% confidence interval [CI] 1.80–2.36), ischaemic heart disease (OR = 1.86, 95% CI 1.64–2.10) and cerebrovascular events (OR = 1.85, 95% CI 1.47–2.32) had the strongest negative effect on asthma control, with the presence of all of these conditions increasing the risk of uncontrolled asthma.

Conclusions

This evaluation of comorbidity data of more than 12,000, adult asthmatic patients has provided a clearer picture of diseases that can frequently co-exist with asthma, and their influence on asthma control, assessed by the prevalence of symptoms. Our study suggests that most asthmatic patients have at least one comorbidity, and the presence of comorbidities may have a high impact on asthma control measures.
In vitro genome editing rescues parkinsonism phenotypes in induced pluripotent stem cells-derived dopaminergic neurons carrying LRRK2 p.G2019S mutation
Authors: Chang Kuo-Hsuan , Huang Cheng-Yen , Ou-Yang Chih-Hsin , Ho Chang-Han , Lin Han-Yi , Hsu Chia-Lang , Chen You-Tzung , Chou Yu-Chi , Chen Yi-Jing , Chen Ying , Lin Jia-Li , Wang Ji-Kuan , Lin Pei-Wen , Lin Ying-Ru , Lin Miao-Hsia , Tseng Chi-Kang , Lin Chin-Hsien
Published: September 2021

Background

The c.G6055A (p.G2019S) mutation in leucine-rich repeat kinase 2 (LRRK2) is the most prevalent genetic cause of Parkinson’s disease (PD). CRISPR/Cas9-mediated genome editing by homology-directed repair (HDR) has been applied to correct the mutation but may create small insertions and deletions (indels) due to double-strand DNA breaks. Adenine base editors (ABEs) could convert targeted A·T to G·C in genomic DNA without double-strand breaks. However, the correction efficiency of ABE in LRRK2 c.G6055A (p.G2019S) mutation remains unknown yet. This study aimed to compare the mutation correction efficiencies and off-target effects between HDR and ABEs in induced pluripotent stem cells (iPSCs) carrying LRRK2 c.G6055A (p.G2019S) mutation.

Methods

A set of mutation-corrected isogenic lines by editing the LRRK2 c.G6055A (p.G2019S) mutation in a PD patient-derived iPSC line using HDR or ABE were established. The mutation correction efficacies, off-target effects, and indels between HDR and ABE were compared. Comparative transcriptomic and proteomic analyses between the LRRK2 p.G2019S iPSCs and isogenic control cells were performed to identify novel molecular targets involved in LRRK2-parkinsonism pathways.

Results

ABE had a higher correction rate (13/53 clones, 24.5%) than HDR (3/47 clones, 6.4%). Twenty-seven HDR clones (57.4%), but no ABE clones, had deletions, though 14 ABE clones (26.4%) had off-target mutations. The corrected isogenic iPSC-derived dopaminergic neurons exhibited reduced LRRK2 kinase activity, decreased phospho-α-synuclein expression, and mitigated neurite shrinkage and apoptosis. Comparative transcriptomic and proteomic analysis identified different gene expression patterns in energy metabolism, protein degradation, and peroxisome proliferator-activated receptor pathways between the mutant and isogenic control cells.

Conclusions

The results of this study envision that ABE could directly correct the pathogenic mutation in iPSCs for reversing disease-related phenotypes in neuropathology and exploring novel pathophysiological targets in PD.
DTi2Vec: Drug–target interaction prediction using network embedding and ensemble learning
Authors: Thafar Maha A. , Olayan Rawan S. , Albaradei Somayah , Bajic Vladimir B. , Gojobori Takashi , Essack Magbubah , Gao Xin
Published: September 2021

Drug–target interaction (DTI) prediction is a crucial step in drug discovery and repositioning as it reduces experimental validation costs if done right. Thus, developingin-silicomethods to predict potential DTI has become a competitive research niche, with one of its main focuses being improving the prediction accuracy. Using machine learning (ML) models for this task, specifically network-based approaches, is effective and has shown great advantages over the other computational methods. However, ML model development involves upstream hand-crafted feature extraction and other processes that impact prediction accuracy. Thus, network-based representation learning techniques that provide automated feature extraction combined with traditional ML classifiers dealing with downstream link prediction tasks may be better-suited paradigms. Here, we present such a method, DTi2Vec, which identifies DTIs using network representation learning and ensemble learning techniques. DTi2Vec constructs the heterogeneous network, and then it automatically generates features for each drug and target using the nodes embedding technique. DTi2Vec demonstrated its ability in drug–target link prediction compared to several state-of-the-art network-based methods, using four benchmark datasets and large-scale data compiled from DrugBank. DTi2Vec showed a statistically significant increase in the prediction performances in terms of AUPR. We verified the "novel" predicted DTIs using several databases and scientific literature. DTi2Vec is a simple yet effective method that provides high DTI prediction performance while being scalable and efficient in computation, translating into a powerful drug repositioning tool.
Improved CRISPR/Cas9 gene editing in primary human myoblasts using low confluency cultures on Matrigel
Authors: Goullée Hayley , Taylor Rhonda L. , Forrest Alistair R. R. , Laing Nigel G. , Ravenscroft Gianina , Clayton Joshua S.
Published: September 2021

Background

CRISPR/Cas9 is an invaluable tool for studying cell biology and the development of molecular therapies. However, delivery of CRISPR/Cas9 components into some cell types remains a major hurdle. Primary human myoblasts are a valuable cell model for muscle studies, but are notoriously difficult to transfect. There are currently no commercial lipofection protocols tailored for primary myoblasts, and most generic guidelines simply recommend transfecting healthy cells at high confluency. This study aimed to maximize CRISPR/Cas9 transfection and editing in primary human myoblasts.

Methods

Since increased cell proliferation is associated with increased transfection efficiency, we investigated two factors known to influence myoblast proliferation: cell confluency, and a basement membrane matrix, Matrigel. CRISPR/Cas9 editing was performed by delivering Cas9 ribonucleoprotein complexes via lipofection into primary human myoblasts, cultured in wells with or without a Matrigel coating, at low (~ 40%) or high (~ 80%) confluency.

Results

Cells transfected at low confluency on Matrigel-coated wells had the highest levels of transfection, and were most effectively edited across three different target loci, achieving a maximum editing efficiency of 93.8%. On average, editing under these conditions was >4-fold higher compared to commercial recommendations (high confluency, uncoated wells).

Conclusion

This study presents a simple, effective and economical method of maximizing CRISPR/Cas9-mediated gene editing in primary human myoblasts. This protocol could be a valuable tool for improving the genetic manipulation of cultured human skeletal muscle cells, and potentially be adapted for use in other cell types.