bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly contiguous genome assembly of Brassica nigra (BB) and revised nomenclature for the pseudochromosomes
Authors: Paritosh Kumar , Pradhan Akshay Kumar , Pental Deepak
Published: December 2020

Background

Brassica nigra(BB), also called black mustard, is grown as a condiment crop in India.B. nigrarepresents the B genome of U’s triangle and is one of the progenitor species ofB. juncea(AABB), an important oilseed crop of the Indian subcontinent. We report the genome assembly ofB. nigravariety Sangam.

Results

The genome assembly was carried out using Oxford Nanopore long-read sequencing and optical mapping. A total of 1549 contigs were assembled, which covered ~ 515.4 Mb of the estimated ~ 522 Mb of the genome. The final assembly consisted of 15 scaffolds that were assigned to eight pseudochromosomes using a high-density genetic map ofB. nigra. Around 246 Mb of the genome consisted of the repeat elements; LTR/Gypsy types of retrotransposons being the most predominant. The B genome-specific repeats were identified in the centromeric regions of theB. nigrapseudochromosomes. A total of 57,249 protein-coding genes were identified of which 42,444 genes were found to be expressed in the transcriptome analysis. A comparison of the B genomes ofB. nigraandB. juncearevealed high gene colinearity and similar gene block arrangements. A comparison of the structure of the A, B, and C genomes of U’s triangle showed the B genome to be divergent from the A and C genomes for gene block arrangements and centromeric regions.

Conclusions

A highly contiguous genome assembly of theB. nigragenome reported here is an improvement over the previous short-read assemblies and has allowed a comparative structural analysis of the A, B, and C genomes of the species belonging to the U’s triangle. Based on the comparison, we propose a new nomenclature forB. nigrapseudochromosomes, taking theB. rapapseudochromosome nomenclature as the reference.
Pseudomonas putida as a potential biocontrol agent against Salmonella Java biofilm formation in the drinking water system of broiler houses
Authors: Maes Sharon , De Reu Koen , Van Weyenberg Stephanie , Lories Bram , Heyndrickx Marc , Steenackers Hans
Published: December 2020

Background

Environmental biofilms can induce attachment and protection of other microorganisms including pathogens, but can also prevent them from invasion and colonization. This opens the possibility for so-called biocontrol strategies, wherein microorganisms are applied to control the presence of other microbes. The potential for both positive and negative interactions between microbes, however, raises the need for in depth characterization of the sociobiology of candidate biocontrol agents (BCAs). The inside of the drinking water system (DWS) of broiler houses is an interesting niche to apply BCAs, because contamination of these systems with pathogens plays an important role in the infection of broiler chickens and consequently humans. In this study, Pseudomonas putida, which is part of the natural microbiota in the DWS of broiler houses, was evaluated as BCA against the broiler pathogen Salmonella Java.

Results

To study the interaction between these species, an in vitro model was developed simulating biofilm formation in the drinking water system of broilers. Dual-species biofilms of P. putida strains P1, P2, and P3 with S. Java were characterized by competitive interactions, independent of P. putida strain, S. Java inoculum density and application order. When equal inocula of S. Java and P. putida strains P1 or P3 were simultaneously applied, the interaction was characterized by mutual inhibition, whereas P. putida strain P2 showed an exploitation of S. Java. Lowering the inoculum density of S. Java changed the interaction with P. putida strain P3 also into an exploitation of S. Java. A further increase in S. Java inhibition was established by P. putida strain P3 forming a mature biofilm before applying S. Java.

Conclusions

This study provides the first results showing the potential of P. putida as BCA against S. Java in the broiler environment. Future work should include more complex microbial communities residing in the DWS, additional Salmonella strains as well as chemicals typically used to clean and disinfect the system.
Cloning of long sterile lemma (lsl2), a single recessive gene that regulates spike germination in rice (Oryza sativa L.)
Authors: Yang Dewei , He Niqing , Zheng Xianghua , Zhen Yanmei , Xie Zhenxin , Cheng Chaoping , Huang Fenghuang
Published: December 2020

Background

Rice is a typical monocotyledonous plant and an important cereal crop. The structural units of rice flowers are spikelets and florets, and floral organ development and spike germination affect rice reproduction and yield.

Results

In this study, we identified a novellong sterile lemma(lsl2) mutant from an EMS population. First, we mapped thelsl2gene between the markers Indel7–22 and Indel7–27, which encompasses a 25-kb region. The rice genome annotation indicated the presence of four candidate genes in this region. Through gene prediction and cDNA sequencing, we confirmed that the target gene in thelsl2mutant is allelic toLONG STERILE LEMMA1(G1)/ELONGATED EMPTY GLUME(ELE), hereafter referred to aslsl2. Further analysis of the lsl2 and LSL2 proteins showed a one-amino-acid change, namely, the mutation of serine (Ser) 79 to proline (Pro) in lsl2 compared with LSL2, and this mutation might change the function of the protein. Knockout experimentsshowed that thelsl2gene is responsible for the long sterile lemma phenotype. Thelsl2gene might reduce the damage induced by spike germination by decreasing the seed germination rate, but other agronomic traits of rice were not changed in thelsl2mutant. Taken together, our results demonstrate that thelsl2gene will have specific application prospects in future rice breeding.

Conclusions

Thelsl2gene is responsible for the long sterile lemma phenotype and might reduce the damage induced by spike germination by decreasing the seed germination rate.
Correction to: Characterization of the virulence of Pseudomonas aeruginosa strains causing ventilator-associated pneumonia
Authors: Alonso Beatriz , Fernández-Barat Laia , Di Domenico Enea Gino , Marín Mercedes , Cercenado Emilia , Merino Irene , de Pablos Manuela , Muñoz Patricia , Guembe María
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Mutation screening of the UBE3A gene in Chinese Han population with autism
Authors: Zhao Xue , Zhang Ran , Yu Shunying
Published: December 2020

Background

15q11–13 region is one of the most complex chromosomal regions in the human genome. UBE3A is an important candidate gene of autism spectrum disorder (ASD), which located at the 15q11–13 region and encodes ubiquitin-protein ligase E3A. Previous studies about UBE3A gene and ASD have shown inconsistent results and few studies were performed in Chinese population. This study aimed to detect the genetic mutations of UBE3A gene in Chinese Han population with ASD and analyze genetic association between these variants and ASD.

Methods

The samples consisted of 192 patients with autism according to the DSM-IV diagnostic criteria and 192 healthy controls. We searched for mutations at coding sequence (CDS) regions and their adjacent non-coding regions of UBE3A gene using the high resolution melting (HRM) and Sanger sequencing methods. We further increased sample size to validate the detected variants using HRM and conducted association analysis between case and control groups.

Results

A known single nucleotide polymorphism (T > C, rs150331504) located at the CDS4 and a known 5 bp insertion/deletion variation (AACTC+/−, rs71127053) located at the intron region of the upstream 288 bp of the CDS2 of UBE3A gene were detected using Sanger sequencing method. The ASD samples of case group were 391 for rs71127053, 384 for rs150331504 and 384 healthy controls, which were used to make an association analysis. The results of association analysis suggested that there were no significant difference about the allele and genotype frequencies of rs71127053 and rs150331504 between case and control groups after extending the sample size. Besides, rs150331504 is a synonymous mutation and we compared the secondary structure and minimum free energy (MFE) of mRNA harboring the allele T or C of rs150331504 using RNAfold software. We found that the centroid secondary structure apparently differs along with the polymorphisms of rs150331504 T > C, the results suggested that this variant might change the secondary structure of mRNA of UBE3A gene. We did not detect mutations in other coding regions of UBE3A gene.

Conclusions

These findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.
Implementation of an electronic care pathway for hip fracture patients: a pilot before and after study
Authors: Talevski Jason , Guerrero-Cedeño Viviana , Demontiero Oddom , Suriyaarachchi Pushpa , Boersma Derek , Vogrin Sara , Brennan-Olsen Sharon , Duque Gustavo
Published: December 2020

Background

Care pathways are generally paper-based and can cause communication failures between multidisciplinary teams, potentially compromising the safety of the patient. Computerized care pathways may facilitate better communication between clinical teams. This study aimed to investigate whether an electronic care pathway (e-pathway) reduces delays in surgery and hospital length of stay compared to a traditional paper-based care pathway (control) in hip fracture patients.

Methods

A single-centre evaluation with a retrospective control group was conducted in the Orthogeriatric Ward, Nepean Hospital, New South Wales, Australia. We enrolled patients aged > 65 years that were hospitalized for a hip fracture in 2008 (control group) and 2012 (e-pathway group). The e-pathway provided the essential steps in the care of patients with hip fracture, including examinations and treatment to be carried out. Main outcome measures were delay in surgery and hospital length of stay; secondary outcomes were in-hospital mortality and discharge location.

Results

A total of 181 patients were enrolled in the study (129 control; 54 e-pathway group). There was a significant reduction in delay to surgery in the e-pathway group compared to control group in unadjusted (OR = 0.19; CI 0.09–0.39; p < 0.001) and adjusted (OR = 0.22; CI 0.10–0.49; p < 0.001) models. There were no significant differences between groups for length of stay (median 11 vs 12 days; p = 0.567), in-hospital mortality (1 vs 7 participants; p = 0.206) or discharge location (p = 0.206).

Conclusions

This pilot study suggests that, compared to a paper-based care pathway, implementation of an e-pathway for hip fracture patients results in a reduction in total number of delays to surgery, but not hospital length of stay. Further evaluation is warranted using a larger cohort investigating both clinical and patient-reported outcome measures.
The epidemiology of infant shaft fractures of femur or humerus by incidence, birth, accidents, and other causes
Authors: von Heideken Johan , Thiblin Ingemar , Högberg Ulf
Published: December 2020

Background

The purpose of this population-based registry study was to analyze both birth-related femur and humerus shaft fractures and diagnosed later in infancy, as regards incidence, perinatal characteristics, other diagnoses, and reported accidents.

Methods

Children born in 1997–2014, diagnosed with a femur or humerus shaft fracture before age 1 year, were identified in the Swedish Health Registries. Rate of birth fractures were estimated by combining femur and humerus shaft fractures coded as birth-related with femur and humerus shaft fractures diagnosed during day 1–7 without registered trauma or abuse. Incidence was computed by comparing infants with femur or humerus shaft fractures to the total at-risk population.

Results

The incidence for birth-related femur shaft fractures was 0.024 per 1000 children (n = 45) and that for birth-related humerus shaft fractures was 0.101 per 1000 children (n = 188). The incidence was 0.154 per 1000 children for later femur shaft fractures (n = 287) and 0.073 per 1000 children for later humerus shaft fractures (n = 142). Birth-related femur shaft fracture was associated with shoulder dystocia, cesarean, multiple birth, breech, preterm, and small-for-gestational age, while humerus shaft fracture was associated with maternal obesity, dystocic labor, shoulder dystocia, vacuum-assisted delivery, male sex, multiple birth, breech, preterm, large-for-gestational age, birth weight > 4000 g, and injury of brachial plexus. A bone fragility diagnosis was recorded in 5% of those with birth-related or later femur shaft fractures. Among infants with birth-related humerus shaft fractures, 1% had a bone fragility diagnosis; the figure for later fractures was 6%. Maltreatment diagnosis was associated with later fractures of both types, especially among those aged < 6 months, where approximately 20% (femur) and 14% (humerus) of cases, respectively, were associated with abuse. Fall accidents were reported in 73 and 56% among those with later femur and humerus shaft fractures, respectively.

Conclusion

This study provides data on epidemiology, birth, parental characteristics, and reported accidents in relation to femur and humerus shaft fractures during infancy. Few children had a bone fragility diagnosis. Fall accidents were the main contributor to femur or humerus shaft fracture during infancy; however, the proportion of fractures attributed to maltreatment was high in children under 6 months.
Mucinous cystic neoplasm of the liver with biliary communication: case report and surgical therapeutic option
Authors: Ferreira Raphaella , Abreu Phillipe , Jeismann Vagner Birk , Segatelli Vanderlei , Coelho Fabricio Ferreira , David Andre Ibrahim
Published: December 2020

Background

Mucinous cyst neoplasm of the liver (MCN-L) comprise less than 5% of all cystic liver lesions and is characterized by the presence of ovarian stroma and absence of bile duct communication.

Case presentation

Here, we discuss a 45-year-old woman who presented with symptomatic liver mass. Diagnostic workup detected a 4.2 × 3.6 cm septate cyst located in segments I, V, and VIII of the liver in communication with the right hepatic duct. An open right liver resection with total bile duct excision and hilar lymphadenectomy was performed. Pathology revealed a multiloculated cyst with lined mucinous epithelium and ovarian-like stroma, consistent with low-grade MCN-L.

Conclusions

This case shows that unusual location and bile duct communication can be present in MCN-L.
Determinants of periodontitis according to the immunological and virological profiles of HIV-infected patients in Yaoundé, Cameroon
Authors: Fokam Joseph , Geh Buolikeze Kuoh Nji , Sosso Samuel Martin , Takou Desire , Ngufack Ezechiel Semengue , Nka Alex Durand , Bissek Anne-Cecile Z.-K. , Eko David Mindja , Ndjolo Alexis
Published: December 2020

Background

HIV infection is associated to different oral manifestations (including periodontal diseases), which have decreased with the advent of antiretroviral therapy (ART). Yet, the occurrence of periodontitis is still consistent among patients with HIV living in sub Saharan-Africa, with limited evidence on the driven factors and mitigating measures in these settings. We aimed at evaluating the occurrence of periodontitis and its associated immunological and virological factors in patients with HIV living in Yaoundé, Cameroon.

Methods

We included 165 (44 ART-naïve and 121 ART-experienced) patients > 18 years old attending the Yaoundé Central Hospital and the Chantal BIYA International Reference Centre, from January-April 2018. The periodontal status was assessed by measuring the clinical attachment loss, periodontal pocket depth, plaques index and gingival bleeding index. CD4+/CD8+ cells and viremia were measured using the fluorescence-activated cell sorting method (FACS Calibur) and the Abbott m2000 RT HIV-1 RNA kit respectively. A standard-questionnaire concerning participants’ medical records and oral hygiene methods was filled. Data was analyzed and p < 0.05 considered statistically significant.

Results

There was a significantly high prevalence of periodontitis in the ART-naïve (53.2%) compared to the ART-experienced group (37.3%), with a twofold increased risk of the ART-naïve population presenting with periodontitis than the ART-experienced population (OR 2.06, p = 0.03). More importantly, ART-naïve, patients with CD4 < 200 cells presented with higher risk of having periodontitis compared to those with higher CD4-values, with a threefold difference (OR 3.21). Worth noting, males presented with a higher risk of having clinical attachment loss (OR 6.07). There was no significant association between the occurrence of periodontitis and the CD8 (p = 0.45) or viremia (p = 0.10).

Conclusion

In the Cameroonian context, a considerable number of adults infected with HIV suffer from periodontitis regardless of their treatment profile. Nonetheless, ART-naïve patients have a higher risk, indicating the protective role of ART. Interestingly, severely immune-compromised patients and men are vulnerable to periodontitis, thereby highlighting the need for clinicians to refer patients for regular periodontal screening especially male patients and those with low CD4. Such measures could greatly improve the quality of life of the population living with HIV in Cameroon.
Utilisation of dental services for people with special health care needs in Australia
Authors: Lim Mathew Albert Wei Ting , Liberali Sharon Andrea Corinne , Borromeo Gelsomina Lucia
Published: December 2020

Background

To explore the profile of patients and treatment delivered at specialist referral centres for individuals with special needs.

Methods

A cross-sectional audit was conducted of the health records of all patients with appointments at two of Australia’s largest referral centres for patients with special needs, the Integrated Special Needs Department at the Royal Dental Hospital of Melbourne and the Special Needs Unit at the Adelaide Dental Hospital, for the month of August 2015.

Results

The profile of patients treated at these specialist units demonstrates the diversity of individuals with additional health care needs that general dentists feel require specialised oral health care. The Adelaide-based clinic had a greater proportion of complex medical patients in comparison to those treated in Melbourne who were more likely to have a disability or psychiatric condition and were less likely to be able to self-consent for treatment. Interestingly, despite similar workforce personnel numbers, there were approximately twice as many appointments at the Special Needs Unit in Adelaide than the Integrated Special Needs Department in Melbourne during the study period which may have reflected differences in workforce composition with a greater use of dental auxiliaries at the Adelaide clinic.

Conclusions

The results of this study provide an initial profile of patients with special needs referred for specialist care in Australia. However, the differences in patient profiles between the two units require further investigation into the possible influence of service provision models and barriers to access of care for individuals with special needs and to ensure equitable access to health care.
Nurses’ educational needs in the oral health of inpatients at Yazd Province in Iran: a Delphi study
Authors: Tabatabaei Seyed Hosein , Owlia Fatemeh , Ayatollahi Fatemeh , Maybodi Fahimeh Rashidi , Ahadian Hakimeh , Azizian Fatemeh , Nasiriani Khadijeh
Published: December 2020

Background

Oral hygiene is an integral part of general health of a person. Nurses qualified about oral care can play an important role in improving the quality of oral health in hospitalized patients. This study investigated the educational needs of nurses in the field of oral health of hospitalized patients.

Methods

The study used the modified Delphi method in three rounds. Fifty faculty members of the School of Dentistry and Nursing were selected via purposive sampling. The data collection tool was a demographic form and an open-ended questionnaire in the first round and a structured questionnaire in the next rounds. The analysis was performed using both content and descriptive analysis techniques.

Results

The top ten oral health education priorities for nurses were greater than 75% with a consensus level: oral anatomy and physiology, learning the signs and symptoms of common oral diseases, learning of oral medications and administration, learning the drugs that cause damage to the mouth and teeth, training in managing dental emergencies, patient education for tooth brushing and taking care of the mouth, especially in the elderly patient, providing oral and dental care, training for unconscious and fasting patients, undergoing chemotherapy and radiotherapy, and hospitalization in intensive care unit.

Conclusion

The findings of the study emphasized the need for interdisciplinary cooperation between nursing and dental professionals for the development of an oral health curriculum for nurses to promote and improve oral health and prevent dental diseases in hospitalized patients and the community.
A mixed-methods evaluation of the impact of a person-centered family planning intervention for community health workers on family planning outcomes in India
Authors: Diamond-Smith Nadia , McDonell Claire , Sahu Ananta Basudev , Roy Kali Prasad , Giessler Katie
Published: December 2020

Background

Person-centered quality for family planning has been gaining increased attention, yet few interventions have focused on this, or measured associations between person-centered quality for family planning and family planning outcomes (uptake, continuation, etc.). In India, the first point of contact for family planning is often the community health care worker, in this case, Accredited Social Health Activists (ASHAs).

Methods

In this study, we evaluate a training on person-centered family planning as an add-on to a training on family planning provision for urban ASHAs in Varanasi, India in 2019 using mixed methods. We first validate a scale to measure person-centered family planning in a community health worker population and find it to be valid. Higher person-centered family planning scores are associated with family planning uptake.

Results

Comparing women who saw intervention compared to control ASHAs, we find that the intervention had no impact on overall person-centered family planning scores. Women in the intervention arm were more likely to report that their ASHA had a strong preference about what method they choose, suggesting that the training increased provider pressure. However, qualitative interviews with ASHAs suggest that they value person-centered care for their interactions and absorbed the messages from the intervention.

Conclusions

More research is needed on how to intervene to change behaviors related to person-centered family planning.

Trial registration

This study received IRB approval from the University of California, San Francisco (IRB # 15–25,950) and was retrospectively registered at clinicaltrials.gov (NCT04206527).
Differential genetic mutations of ectoderm, mesoderm, and endoderm-derived tumors in TCGA database
Authors: Gao Xingjie , Cui Xiaoteng , Zhang Xinxin , Zhao Chunyan , Zhang Nan , Zhao Yan , Ren Yuanyuan , Su Chao , Ge Lin , Wu Shaoyuan , Yang Jie
Published: December 2020

Background

In terms of biological behavior, gene regulation, or signaling pathways, there is a certain similarity between tumorigenesis and embryonic development of humans. Three germ layer structure exhibits the distinct ability to form specific tissues and organs.

Methods

The present study set out to investigate the genetic mutation characteristics of germ layer differentiation-related genes using the tumor cases of the cancer genome atlas (TCGA) database.

Results

These tumor samples were divided into three groups, including the ectoderm, mesoderm, and endoderm. Children cases less than 9 years old accounted for a larger proportion for the cases in the ectoderm and mesoderm groups; whereas the middle-aged and elderly individuals (from 50 to 89 years old) were more susceptible to tumors of endoderm. There was a better prognosis for the cases of mesoderm, especially the male with the race of White, compared with the other groups. A missense mutation was frequently detected for the cases of ectoderm and endoderm, while deletion mutation was common for that of mesoderm. We could not identify the ectoderm, mesoderm, or endoderm-specific mutated genes or variants with high mutation frequency. However, there was a relatively higher mutation incidence of endoderm markers (GATA6,FOXA2,GATA4,AFP) in the endoderm group, compared with the groups of ectoderm and mesoderm. Additionally, four members (SMO, GLI1,GLI2,GLI3) within the Hedgehog signaling pathway genes showed a relatively higher mutation rate in the endoderm group than the other two groups.

Conclusions

TCGA tumors of ectoderm, mesoderm, and endoderm groups exhibit the distinct subject distribution, survival status, and genomic alteration characteristics. The synergistic mutation effect of specific genes closely related to embryonic development may contribute to the tumorigenesis of tissues or organs derived from the specific germ layers. This study provides a novel reference for exploring the functional connection between embryogenesis and tumorigenesis.
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway
Authors: Li Xiaomin , He Jiefeng , Ren Xiaojing , Zhao Haichao , Zhao Haoliang
Published: December 2020

Background

The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC).

Methods

The expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models.

Results

Circ_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression.

Conclusion

Circ_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC.
Impact of a tuberculosis treatment adherence intervention versus usual care on treatment completion rates: results of a pragmatic cluster randomized controlled trial
Authors: Puchalski Ritchie Lisa M. , van Lettow Monique , Makwakwa Austine , Kip Ester C. , Straus Sharon E. , Kawonga Harry , Hamid Jemila S. , Lebovic Gerald , Thorpe Kevin E. , Zwarenstein Merrick , Schull Michael J. , Chan Adrienne K. , Martiniuk Alexandra , van Schoor Vanessa
Published: December 2020

Background

With the global shortage of skilled health workers estimated at 7.2 million, outpatient tuberculosis (TB) care is commonly task-shifted to lay health workers (LHWs) in many low- and middle-income countries where the shortages are greatest. While shown to improve access to care and some health outcomes including TB treatment outcomes, lack of training and supervision limit the effectiveness of LHW programs. Our objective was to refine and evaluate an intervention designed to address common causes of non-adherence to TB treatment and LHW knowledge and skills training needs.

Methods

We employed a pragmatic cluster randomized controlled trial. Participants included 103 health centres (HCs) providing TB care in four districts in Malawi, randomized 1:1 stratified by district and HC funding (Ministry of Health, non-Ministry funded). At intervention HCs, a TB treatment adherence intervention was implemented using educational outreach, a point-of-care reminder tool, and a peer support network. Clusters in the control arm provided usual care. The primary outcome was the proportion of patients with successful TB treatment (i.e., cure or treatment completion). We used a generalized linear mixed model, with district as a fixed effect and HC as a random effect, to compare proportions of patients with treatment success, among the trial arms, with adjustment for baseline differences.

Results

We randomized 51 HCs to the intervention group and 52 HCs to the control group. Four intervention and six control HCs accrued no eligible patients, and 371 of 1169 patients had missing outcome, HC, or demographic data, which left 74 HCs and 798 patients for analysis. Randomization group was not related to missing outcome, however, district, age, and TB type were significantly related and included in the primary analysis model. Among the 1153 patients with HC and demographic data, 297/605 (49%) and 348/548 (64%) in the intervention and control arms, respectively, had treatment success. The intervention had no significant effect on treatment success (adjusted odds ratio 1.35 [95% confidence interval 0.93–1.98]).

Conclusion

We found no significant effect of the intervention on TB treatment outcomes with high variability in implementation quality, highlighting important challenges to both scale-up and sustainability.

Trial registration

ClinicalTrials.gov NCT02533089. Registered August 20, 2015.
Gene expression profiling of orbital muscles in treatment-resistant ophthalmoplegic myasthenia gravis
Authors: Europa Tarin A. , Nel Melissa , Heckmann Jeannine M.
Published: December 2020

Background

Unbiased in silico approaches applied to genome-wide data prioritized putative functional gene variants associating with treatment-resistant ophthalmoplegic myasthenia gravis (OP-MG). Although altered expression of genes harbouring these variants, or associated pathways, were shown in patient-derived transdifferentiated-myocyte models, gene expression in orbital-derived muscle was required to test the validity of the predictions.

Methods

We sampled orbicularis oculi muscle (OOM) and one paralysed extraocular muscle (EOM) from six individuals with OP-MG during blepharoptosis and re-alignment surgeries, respectively. For controls, the OOMs were sampled from four individuals without myasthenia undergoing surgery for non-muscle causes of ptosis, and one non-paralysed EOM. Using a qPCR array, expression of 120 genes was compared between OP-MG and control OOMs, profiling putative “OP-MG” genes, genes in related biological pathways and genes reported to be dysregulated in MG cases or experimental MG models, and in EOMs of cases with strabismus. Normalization was performed with two stable reference genes. Differential gene expression was compared between OP-MG and control samples using the ΔΔCT method. Co-expression was analysed by pairwise correlation of gene transcripts to infer expression networks.

Results

Overall, transcript levels were similar in OOMs and EOMs (p = 0.72). In OOMs, significant downregulated expression of eight genes was observed in OP-MG cases compared with controls (> twofold; p ≤ 0.016), including TFAM, a mitochondrial transcription factor, and genes related to the following pathways: atrophy signalling; muscle regeneration and contraction; glycogen synthesis; and extracellular matrix remodelling. Several microRNAs, known to be highly expressed in EOMs, are predicted to regulate some of these genes. Co-expression analyses of gene-pairs suggested high interconnectedness of gene expression networks in OP-MG muscle, but not controls (r > 0.96, p < 0.01). Significant inverse directions of gene-pair correlations were noted in OP-MG versus controls OOM networks (r ≥ 0.92, p < 0.001) involving most OP-MG genes overlapping prominently with muscle atrophy/contractility and oxidative metabolism genes.

Conclusions

The gene expression in orbital muscles derived from OP-MG individuals compared with normal controls, support the pathogenic hypothesis previously generated from whole genome sequence analyses. Repression of gene transcripts in OP-MG orbital muscle implicate tissue-specific regulatory mechanisms, which may inform future biomarker discovery approaches.
Determinants of Staphylococcus aureus carriage in the developing infant nasal microbiome
Authors: Accorsi Emma K. , Franzosa Eric A. , Hsu Tiffany , Joice Cordy Regina , Maayan-Metzger Ayala , Jaber Hanaa , Reiss-Mandel Aylana , Kline Madeleine , DuLong Casey , Lipsitch Marc , Regev-Yochay Gili , Huttenhower Curtis
Published: December 2020

Background

Staphylococcus aureusis a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carryS. aureusasymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influenceS. aureusacquisition and retention in early life.

Results

We recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, particularly within the first 2 months. It is weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns ofS. aureuscarriage, positively associated withAcinetobacterspecies,Streptococcus parasanguinis,Streptococcus salivarius, andVeillonellaspecies and inversely associated with maternalDolosigranulum pigrum. Furthermore, we identify a gene family, likely acting as a taxonomic marker for an unclassified species, that is significantly anti-correlated withS. aureusin infants and mothers. In gene content-based strain profiling, infantS. aureusstrains are more similar to maternal strains.

Conclusions

This improved understanding ofS. aureuscolonization is an important first step toward the development of novel, ecological therapies for controllingS. aureuscarriage.
Developing a core outcome set for the treatment of pregnant women with pregestational diabetes—a study protocol
Authors:   On behalf of the INSPIRED group, Kgosidialwa Oratile , Bogdanet Delia , Egan Aoife , O’Shea Paula M. , Biesty Linda , Devane Declan , Dunne Fidelma
Published: December 2020

Background

Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes including increased rates of caesarean section birth, macrosomia, congenital malformation, prematurity, admission to the neonatal intensive care unit and stillbirth. As a result, there has been an increase in interventions to improve outcomes in both mother and infant. To date, meaningful comparisons between these studies are limited due to heterogeneity in outcome selection and reporting. The aim of this study is to develop a core outcome set (COS) for randomised controlled trials evaluating the effectiveness of interventions for the treatment of pregnant women with PGDM.

Methods

The study consists of three steps. The first step is a systematic review of the literature to assess outcomes reported in randomised controlled trials assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. The second step is a three round, online Delphi survey to prioritise these outcomes. In this step, stakeholders (including women with PGDM, healthcare workers, researchers and policymakers) will be asked to rank the importance of outcomes for inclusion in the COS using a 9-point Likert type scale. Outcomes that meet the inclusion criteria after completion of the Delphi surveys will be brought to the consensus meeting. The consensus meeting will be the third and final step, where the COS will be finalised. The consensus meeting will include members from each stakeholder group.

Discussion

This paper describes the process used to develop a COS for the reporting of studies evaluating the effectiveness of interventions in pregnant women with PGDM. The COS will enable greater comparison between and information synthesis across RCTs in the treatment of PGDM. In addition, this COS will also help improve trial reporting and minimise research waste by prioritising the collection and reporting of outcomes that matter to all relevant stakeholder groups.

Trial registration

This COS has been registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative (http://www.comet-initiative.org/studies/details/1425) on the 4th of November 2019. The systematic review component of this study has also been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173549).
Detection of SARS-CoV-2 pneumonia: two case reports
Authors: Seibert Felix S. , Toma Daniela , Bauer Frederic , Paniskaki Krystallenia , Anft Moritz , Rohn Benjamin J. , Wang Simon , Racovitan Diana , Babel Nina , Westhoff Timm H.
Published: December 2020

Background

Developing therapeutic strategies for a SARS-CoV-2 infection is challenging, but first the correct diagnosis has to be made. Unspecific upper and lower respiratory tract symptoms can be misleading; hence, a nasopharyngeal swab test with a real-time reverse-transcription-polymerase chain reaction is of great importance. However, early viral clearing jeopardizes a sound diagnosis of COVID-19.

Case presentation

We report on two Caucasian patients who had negative pharyngeal swab tests at the onset of SARS-CoV-2 pneumonia. In one patient, the virus was not even detectable in bronchoalveolar lavage despite typical radiomorphologic changes.

Conclusions

Negative PCR findings in both the pharynx and bronchoalveolar lavage do not exclude COVID-19 pneumonia. Computed tomography is a crucial diagnostic prerequisite in this context.
Knockdown of Parkinson’s disease-related gene ATP13A2 reduces tumorigenesis via blocking autophagic flux in colon cancer
Authors: Chen Qian , Zhong Li , Zhou Chao , Feng Yan , Liu Quan-xing , Zhou Dong , Lu Xiao , Du Guang-Sheng , Jian Dan , Luo Hao , Wang Dong , Zheng Hong , Qiu Yuan
Published: December 2020

Background

Accumulating evidence shows that Parkinson’s disease is negatively associated with colon cancer risk, indicating that Parkinson’s disease family proteins may be involved in the initiation of colon cancer. Here, we aimed to identify a Parkinson’s disease-related gene involved in colon cancer, elucidate the underlying mechanisms, and test whether it can be used as a target for cancer therapy.

Methods

We first screened colon cancer and normal tissues for differential expression of Parkinson’s disease-associated genes and identified ATP13A2, which encodes cation-transporting ATPase 13A2, as a putative marker for colon cancer. We next correlated ATP13A2 expression with colon cancer prognosis. We performed a series of ATP13A2 knockdown and overexpression studies in vitro to identify the contribution of ATP13A2 in the stemness and invasive capacity of colon cancer cells. Additionally, autophagy flux assay were determined to explore the mechanism of ATP13A2 induced stemness. Finally, we knocked down ATP13A2 in mice using siRNA to determine whether it can be used as target for colon cancer treatment.

Results

Colon cancer patients with high ATP13A2 expression exhibit shorter overall survival than those with low ATP13A2. Functionally, ATP13A2 acts as a novel stimulator of stem-like traits. Furthermore, knockdown of ATP13A2 in HCT116 resulted in decreased levels of cellular autophagy. Additionally, bafilomycin A1, an autophagy inhibitor, reversed the ATP13A2-induced stemness of colon cancer cells. Lastly treatment with ATP13A2 siRNA reduced the volume of colon cancer xenografts in mice.

Conclusions

The PD-associated gene ATP13A2 is involved in colon cancer stemness through regulation of autophagy. Furthermore, ATP13A2 is a novel prognostic biomarker for colon cancer and is a potential target for colon cancer therapy.
Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium
Authors:   BIOS Consortium, Qi Cancan , Vonk Judith M. , van der Plaat Diana A. , Nieuwenhuis Maartje A. E. , Dijk F. Nicole , Aïssi Dylan , Siroux Valérie , Boezen H. Marike , Xu Cheng-jian , Koppelman Gerard H.
Published: December 2020

Background

Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission.

Methods

Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA).

Results

We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes.

Conclusion

We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway.
Client-side rogue access-point detection using a simple walking strategy and round-trip time analysis
Authors: Kitisriworapan Songrit , Jansang Aphirak , Phonphoem Anan
Published: December 2020

Traditional rogue access-point (AP) detection mechanisms are employed in network administration to protect network infrastructure and organization; however, these mechanisms do not protect end users from connecting to a rogue-AP. In this paper, a rogue-AP detection technique on the mobile-user side is proposed. By using a simple method involving walking, the round-trip time (RTT) and the modulation and coding scheme values are obtained, and a more accurate transmission rate for particular RTT values is thereby calculated. Further, the cleansed data are classified using the k-means method and the cumulative distribution function for the detection process. The results demonstrate that a rogue-AP can be detected with an F-measure value of up to 0.9. In the future, the proposed algorithm can be implemented as an application installed on mobile devices so that nontechnical users can detect rogue-APs.
A reverse Hardy–Hilbert-type integral inequality involving one derivative function
Authors: Chen Qian , Yang Bicheng
Published: December 2020

In this article, by using weight functions, the idea of introducing parameters, the reverse extended Hardy–Hilbert integral inequality and the techniques of real analysis, a reverse Hardy–Hilbert-type integral inequality involving one derivative function and the beta function is obtained. The equivalent statements of the best possible constant factor related to several parameters are considered. The equivalent form, the cases of non-homogeneous kernel and some particular inequalities are also presented.
Stabilization of nonlinear systems via aperiodic intermittent stochastic noise driven by G-Brownian motion with application to epidemic models
Authors: Zhong Xiaojing , Deng Feiqi , Zhang Bo , Ouyang Haibin
Published: December 2020

To stabilize a nonlinear system $dx(t)=f(t,x(t))\,dt$
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, we stochastically perturb the deterministic model by using two types of aperiodic intermittent stochastic noise driven by G-Brownian motion. We demonstrate quasi-sure exponential stability for the perturbed system and give the convergence rate, which is related to the control intensity. An application to SIS epidemic model is presented to confirm the theoretical results.
Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice
Authors: Bao Guili , Zhang Yinglong , Yang Xiaoguang
Published: December 2020

In this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.