bluuebunny/crossref_metadata_2025 huggingface dataset:
Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation
Authors: Solomon Emilia , Davis-Anderson Katie , Hovde Blake , Micheva-Viteva Sofiya , Harris Jennifer Foster , Twary Scott , Iyer Rashi
Published: February 2021

Background

Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities.

Results

Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation.

Conclusions

Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.
Genome-wide characterization of 2-oxoglutarate and Fe(II)-dependent dioxygenase family genes in tomato during growth cycle and their roles in metabolism
Authors: Wei Shuo , Zhang Wen , Fu Rao , Zhang Yang
Published: February 2021

Background

2-Oxoglutarate and Fe(II)-dependent dioxygenases (2ODDs) belong to the 2-oxoglutarate-dependent dioxygenase (2OGD) superfamily and are involved in various vital metabolic pathways of plants at different developmental stages. These proteins have been extensively investigated in multiple model organisms. However, these enzymes have not been systematically analyzed in tomato. In addition, type I flavone synthase (FNSI) belongs to the 2ODD family and contributes to the biosynthesis of flavones, but this protein has not been characterized in tomato.

Results

A total of 131 2ODDs from tomato were identified and divided into seven clades by phylogenetic classification. The Sl2ODDs in the same clade showed similar intron/exon distributions and conserved motifs. The Sl2ODDs were unevenly distributed across the 12 chromosomes, with different expression patterns among major tissues and at different developmental stages of the tomato growth cycle. We characterized several Sl2ODDs and their expression patterns involved in various metabolic pathways, such as gibberellin biosynthesis and catabolism, ethylene biosynthesis, steroidal glycoalkaloid biosynthesis, and flavonoid metabolism. We found that the Sl2ODD expression patterns were consistent with their functions during the tomato growth cycle. These results indicated the significance of Sl2ODDs in tomato growth and metabolism. Based on this genome-wide analysis of Sl2ODDs, we screened six potential FNSI genes using a phylogenetic tree and coexpression analysis. However, none of them exhibited FNSI activity.

Conclusions

Our study provided a comprehensive understanding of the tomato 2ODD family and demonstrated the significant roles of these family members in plant metabolism. We also suggest that no FNSI genes in tomato contribute to the biosynthesis of flavones.
Trastuzumab immunogenicity development in patients’ sera and in laboratory animals
Authors: Kilany Lobna Abdel Aziz , Gaber Ayman Abdel Samie , Aboulwafa Mohammad Mabrouk , Zedan Hamdallah Hafez
Published: February 2021

Background

Immunogenicity is a major challenge in drug development and patient care. Clinicians and regulators are familiar with immunogenicity concerns of monoclonal antibody (mAb) therapeutics, growth factors and enzyme replacements. Although most small therapeutic molecules are unlikely to trigger undesirable immunogenic responses against themselves upon their administration, the biological therapeutic agents are likely to induce such kind of immunogenicity. This imparts a problem that has to be considered upon judging their risk–benefit ratio. In this article, we tested the immunogenicity developed in patients’ sera due to the use of trastuzumab and that developed in laboratory animals injected with this recombinant humanized IgG1 monoclonal antibody.

Methods

We studied trastuzumab immunogenicity by: I in vitro detection of anti-trastuzumab antibody (Ab) levels in patient’s serum samples withdrawn at different points during trastuzumab treatment course; I.1 using an Affinity Capture Elution (ACE) assay, the assay is both sensitive and highly tolerant to free drug; I.2 using MTT cytotoxicity method against MCF-7 cell line as confirmatory method used in sample showed high level of anti-trastuzumab Ab and to determine neutralizing activity of the anti-trastuzumab Ab. II in vivo immunogenicity testing of trastuzumab in lab animals.

Results

In vitro analysis of patients’ sera for antibodies developed against trastuzumab revealed that this monoclonal antibody has low immunogenicity since most samples showed low levels of anti-trastuzumab antibodies that decreased progressively along the treatment course. Only 1% of samples showed high levels of anti-trastuzumab antibodies which might affect treatment course. In vivo immunogenicity testing in mice showed also low immunogenicity of trastuzumab that could support the in vitro clinical assessment applied in our study.

Conclusions

The study gives an evidence for the low trastuzumab immunogenicity when assessed in Egyptian patients under treatment with this biological therapeutic agent. This supports its prescription and continuous use across the approved indications as biological therapeutic agent.
Straw retention efficiently improves fungal communities and functions in the fallow ecosystem
Authors: Zhang Caifang , Lin Zhaoli , Que Youxiong , Fallah Nyumah , Tayyab Muhammad , Li Shiyan , Luo Jun , Zhang Zichu , Abubakar Ahmad Yusuf , Zhang Hua
Published: February 2021

Background

Straw retention is a substitute for chemical fertilizers, which effectively maintain organic matter and improve microbial communities on agricultural land. The purpose of this study was to provide sufficient information on soil fungal community networks and their functions in response to straw retention. Hence, we used quantitative real-time PCR (qRT-PCR), Illumina MiSeq (ITS rRNA) and FUNGuild to examine ITS rRNA gene populations, soil fungal succession and their functions under control (CK) and sugarcane straw retention (SR) treatments at different soil layers (0–10, 10–20, 20–30, and 30–40 cm) in fallow fields.

Result

The result showed that SR significantly enhanced ITS rRNA gene copy number and Shannon index at 0–10 cm soil depth. Fungi abundance, OTUs number and ACE index decreased with the increasing soil depth. The ANOSIM analysis revealed that the fungal community of SR significantly differed from that of CK. Similarly, significant difference was also observed between topsoil (0–20 cm) and subsoil (20–40 cm). Compared with CK, SR decreased the relative abundance of the pathogen, while increased the proportion of saprotroph. Regarding soil depth, pathogen relative abundance in topsoil was lower than that in subsoil. Besides, both sugarcane straw retention and soil depths (topsoil and subsoil) significantly altered the co-occurrence patterns and fungal keystone taxa closely related to straw decomposition. Furthermore, both SR and topsoil had higher average clustering coefficients (aveCC), negative edges and varied modularity.

Conclusions

Overall, straw retention improved α-diversity, network structure and fungal community, while reduced soil pathogenic microbes across the entire soil profile. Thus, retaining straw to improve fungal composition, community stability and their functions, in addition to reducing soil-borne pathogens, can be an essential agronomic practice in developing a sustainable agricultural system.
Detection of SARS-CoV-2 in fecal samples with different pretreatment methods and PCR kits
Authors: Cao Ranran , Bao Lirong , Pan Ming , Zhang Cheng , Liao Hongyu , Liu Li , Li Yan , Li Mingyuan
Published: February 2021

Background

Gastrointestinal symptoms are common in COVID-19 patients and SARS-CoV-2 RNA has been detected in the patients’ feces, which could lead to fecal–oral transmission. Therefore, fecal sample testing with real-time RT-PCR is highly recommended as a routine test for SARS-CoV-2 infection. However, varying rates of detection in fecal sample have been reported. The aim of this study was to provide insights into the detection rates of SARS-CoV-2 in COVID-19 patients’ fecal sample by using four real-time RT-PCR kits and two pretreatment methods (inactive and non-inactive).

Results

The detection rate of Trizol pretreatment group was slightly higher than that of Phosphate Buffered Saline (PBS) groups, showing that pretreatment and inactivation by Trizol had no influence to SARS-CoV-2 nucleic acid test (NAT) results. 39.29% detection rate in fecal sample by DAAN was obtained, while Bio-germ was 40.48%, Sansure 34.52%, and GeneoDx 33.33%. The former three kits had no significant difference. The DAAN kit detection rates of ORF1ab and N gene were nearly equal and Ct value distribution was more scattered, while the Bio-germ kit distribution was more clustered. The positive rate of SARS-COV-2 in fecal samples correlated with the severity of the disease, specifically, severe cases were less likely to be identified than asymptomatic infection in the DAAN group (adjusted OR 0.05, 95%CI = 0.00 ~ 0.91).

Conclusions

Trizol should be of choice as a valid and safe method for pretreatment of fecal samples of SARS-CoV-2. All real-time RT-PCR kits assessed in this study can be used for routine detection of SARS-CoV-2 in fecal samples. While DAAN, with high NAT positive rate, could be the best out of the 4 kits used in this study. SARS-CoV-2 positive rate in fecal sample was related to the severity of illness.
Overexpression of a methyl-CpG-binding protein gene OsMBD707 leads to larger tiller angles and reduced photoperiod sensitivity in rice
Authors: Qu Mengyu , Zhang Zhujian , Liang Tingmin , Niu Peipei , Wu Mingji , Chi Wenchao , Chen Zi-Qiang , Chen Zai-Jie , Zhang Shubiao , Chen Songbiao
Published: February 2021

Background

Methyl-CpG-binding domain (MBD) proteins play important roles in epigenetic gene regulation, and have diverse molecular, cellular, and biological functions in plants. MBD proteins have been functionally characterized in various plant species, including Arabidopsis, wheat, maize, and tomato. In rice, 17 sequences were bioinformatically predicted as putative MBD proteins. However, very little is known regarding the function of MBD proteins in rice.

Results

We explored the expression patterns of the rice OsMBD family genes and identified 13 OsMBDs with active expression in various rice tissues. We further characterized the function of a rice class I MBD protein OsMBD707, and demonstrated that OsMBD707 is constitutively expressed and localized in the nucleus. Transgenic rice overexpressing OsMBD707 displayed larger tiller angles and reduced photoperiod sensitivity—delayed flowering under short day (SD) and early flowering under long day (LD). RNA-seq analysis revealed that overexpression of OsMBD707 led to reduced photoperiod sensitivity in rice and to expression changes in flowering regulator genes in the Ehd1-Hd3a/RFT1 pathway.

Conclusion

The results of this study suggested that OsMBD707 plays important roles in rice growth and development, and should lead to further studies on the functions of OsMBD proteins in growth, development, or other molecular, cellular, and biological processes in rice.
Deciphering the dynamic gene expression patterns of pollen abortion in a male sterile line of Avena sativa through transcriptome analysis at different developmental stages
Authors: Zhang Lijun , Ma Mingchuan , Cui Lin , Liu Longlong
Published: February 2021

Background

Male sterility (MS) has important applications in hybrid seed production, and the abortion of anthers has been observed in many plant species. While most studies have focused on the genetic factors affecting male sterility, the dynamic gene expression patterns of pollen abortion in male sterile lines have not been fully elucidated. In addition, there is still no hybrid oat that is commercially planted due to the lack of a suitable system of male sterility for hybrid breeding.

Results

In this study, we cultivated a male sterile oat line and a near-isogenic line by crossbreeding to elucidate the expression patterns of genes that may be involved in sterility. The first reported CA male sterile (CAMS) oat line was used for cross-testing and hybridization experiments and was confirmed to exhibit a type of nuclear sterility controlled by recessive genes. Oat stamens of two lines were sampled at four different developmental stages separately. Paired-end RNA sequencing was performed for each sample and generated 252.84 Gb sequences. There were 295,462 unigenes annotated in public databases in all samples, and we compared the histological characteristics and transcriptomes of oat stamens from the two oat lines at different developmental stages. Our results demonstrate that the sterility of the male sterile oat line occurs in the early stage of stamen development and is primarily attributable to abnormal meiosis and the excessive accumulation of superoxide.

Conclusions

To the best of our knowledge, this study is the first to decipher the dynamic expression profiles of pollen abortion CAMS and CA male fertile (CAMF) oat lines, which may represent a valuable resource for further studies attempting to understand pollen abortion and anther development in oats.
Two Cyc2CL transcripts (Cyc2CL-1 and Cyc2CL-2) may play key roles in the petal and stamen development of ray florets in chrysanthemum
Authors: Liu Hua , Sun Ming , Pan Huitang , Cheng Tangren , Wang Jia , Zhang Qixiang
Published: February 2021

Background

Chrysanthemum morifolium is one of the most popular ornamental crops. The capitulum, which is the main ornamental part of chrysanthemum plants, consists of ligulate marginal ray florets, an attractive corolla (petals), and radially hermaphroditic disc florets, but no stamens. In Asteraceae species, the zygomorphic ray florets evolved from the actinomorphic disc florets. During this process, the zygomorphic ligulate corolla arose and the stamens were aborted. Although molecular genetic research has clarified ray floret development to some extent, the precise molecular mechanism underlying ray floret development in chrysanthemum remained unclear.

Results

A CYC2-like gene, Cyc2CL, was cloned from C. morifolium ‘Fenditan’. Subsequent analyses revealed that the alternative splicing of Cyc2CL, which occurred in the flower differentiation stage, resulted in the production of Cyc2CL-1 and Cyc2CL-2 in the apical buds. Prior to this stage, only Cyc2CL-1 was produced in the apical buds. A fluorescence in situ hybridization analysis of labeled Cyc2CL-1 and Cyc2CL-2 RNA indicated that Cyc2CL-2 was first expressed in the involucre tissue during the final involucre differentiation stage, but was subsequently expressed in the receptacle and floret primordia as the floral bud differentiation stage progressed. Moreover, Cyc2CL-2 was highly expressed in the inflorescence tissue during the corolla formation stage, and the expression remained high until the end of the floral bud differentiation stage. Furthermore, the overexpression of Cyc2CL-1 and Cyc2CL-2 in transgenic Arabidopsis inhibited stamen and petal development. Therefore, both Cyc2CL-1 and Cyc2CL-2 encode candidate regulators of petal development and stamen abortion and are important for the ray floret development in chrysanthemum.

Conclusion

In this study, we characterized the alternatively spliced transcripts of the CYC2-like gene that differ subtly regarding expression and function. The data presented herein will be useful for clarifying the regulatory mechanisms associated with the CYC2-like gene and may also be important for identifying the key genes and molecular mechanisms controlling the development of ray florets in chrysanthemum.
Anaesthesia challenges of a parturient with paramyotonia congenita and terminal filum lipoma presenting for labour and caesarean section under epidural anaesthesia – a case report
Authors: Siow Wei Shyan , Chiew Wan-Ling Alyssa
Published: February 2021

Background

Paramyotonia congenita is a rare autosomal dominant myopathy which presents with periodic weakness due to cold and exercise. It is caused by mutations of the SCN4 gene which encodes the sodium channel in skeletal muscles.

Case presentation

We report a full term obstetric patient with both paramyotonia congenita and terminal filum lipoma who presents for induction of labour followed by an emergency caesarean section performed under epidural anesthesia. Her recovery is subsequently complicated by a 3-day history of postpartum paraparesis attributed to hypokalemic periodic paralysis.

Conclusion

We describe the perioperative anesthesia considerations and challenges in this case with a review of the current literature. This case report highlights the importance of early proactive and collaborative multidisciplinary approach, maintaining normal temperature and electrolytes with a heightened vigilance for muscle-related perioperative complications.
Maintaining physical activity following myocardial infarction: a qualitative study
Authors: Coull Alex , Pugh Gemma
Published: February 2021

Background

Outcomes following myocardial infarction (MI) are improved by uptake and maintenance of physical activity (PA), but little is understood regarding patients experience of maintaining an active lifestyle once immediate support, such as cardiac-rehabilitation (CR), has ended.

Aim

The purpose of this study was to investigate MI survivors’ attitude and appraisal towards PA and the perceived barriers, motivators and facilitators for maintaining PA long-term.

Methods

Semi-structured interviews were carried out with 18 adults (mean age 60.5, range 37–73 years) from England and Scotland, who were a minimum of 5 months post-MI (mean 29 months, range 5–122 months). There were comparatively more male participants (n = 13, 72 %) than female (n = 5, 28 %). Overall 12 (67 %) participants had attended CR. The interviews were transcribed verbatim and thematic analysis was performed using qualitative data analysis software NVivo.

Results

Data analysis indicated that the following four core themes influenced MI survivors’ behaviour and attitude towards PA: (1) MI as a teachable moment for behaviour change, (2) affective response to MI: enjoyment versus fear, (3) cognitive response to MI: self-perception, attitude and self-efficacy, and (4) access to support and resources, including PA facilities and social support. Participants highlighted a lack of available guidance on maintaining PA behaviour change following CR and that advice on the frequency and intensity of exercise to follow was often unclear and confusing. Feelings of vulnerability and fear of overexertion were apparent, affecting participants self-efficacy to exercise.

Conclusions

Current CR programmes fail to address PA belief systems and perceptions of self-efficacy to exercise. Interventions that address feelings of vulnerability and fear of overexertion may be beneficial. Providing ongoing PA advice and access to social support may facilitate patients to maintain changes in PA.
Left intraventricular pressure gradient in hypertrophic cardiomyopathy patients receiving implantable cardioverter-defibrillators for primary prevention
Authors: Yazaki Kyoichiro , Suzuki Atsushi , Shiga Tsuyoshi , Minami Yuichiro , Arai Kotaro , Ashihara Kyomi , Shoda Morio , Hagiwara Nobuhisa
Published: February 2021

Background

Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention.

Methods

We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions.

Results

Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan–Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36–29.25, P = 0.02). Five patients experienced ICD implant-related complications.

Conclusions

Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.
Conducting household surveys on reproductive health in urban settings: lessons from Karachi, Pakistan
Authors: Khan Mir Baz , Nausheen Sidrah , Hussain Imtiaz , Hackett Kristy , Zehra Kaneez , Feroze Khalid , Canning David , Shah Iqbal , Soofi Sajid Bashir
Published: February 2021

Background

Data collection is the most critical stage in any population health study and correctly implementing fieldwork enhances the quality of collected information. However, even the most carefully planned large-scale household surveys can encounter many context-specific issues. This paper reflected on our research team’s recent experience conducting surveys for a quasi-experimental evaluation of a reproductive health program in urban areas of Karachi, Pakistan. We aim to describe the issues encountered and lessons learned from this process, and present some potential solutions for conducting future household surveys in similar urban environments.

Methods

The study followed a three-stage random sampling design. Initially, a Geographical Information System (GIS) was used to construct the sampling frame with union council (UC) area mapping and cluster demarcation followed by random selection of clusters in the selected UCs within the intervention and control sites. The second stage involved a complete household listing in selected clusters and the final stage was a random sampling of households with eligible women.

Result

This paper describes the issues that were encountered including technical problems related to GIS demarcation of cluster boundaries and hand-held devices for computer assisted personal interviews (CAPI), household listing, interviewing respondents on sensitive topics and their expectations, and ensuring privacy during the survey.

Conclusion

This study identifies a number of unique barriers to conducting household surveys in Karachi and highlights some key lessons for survey research in urban settlements. GIS mapping technology is a cost-effective method for developing sampling frames in resource-constrained settings. Secondly, the strategy of interviewing women immediately after the cluster is listed may be applied to make it easier to re-locate selected respondents and to reduce loss-to-follow up. Understanding local norms and developing culturally appropriate strategies to build trust with communities may significantly improve survey participation. Researchers should hire experienced female enumerators and provide continuous training on best practices for interviewing women on sensitive reproductive health topics in urban communities.
Living on the edge of the community: factors associated with discontinuation of community living among people with cognitive impairment
Authors: Ura Chiaki , Okamura Tsuyoshi , Sugiyama Mika , Miyamae Fumiko , Yamashita Mari , Nakayama Riko , Edahiro Ayako , Taga Tsutomu , Inagaki Hiroki , Ogawa Madoka , Awata Shuichi
Published: February 2021

Background

As Japanese society continues to age, the isolation of older people is increasing, and community living for people with cognitive impairment is becoming more difficult. However, the challenges faced by people with cognitive impairment living in the community have not been fully explored because of methodological difficulties. This study re-accessed people with cognitive impairment identified in a previous epidemiological survey to explore their current situation and the risk factors associated with all-cause discontinuation of community living.

Methods

Under a community-based participatory framework, we examined a high-risk approach for people with cognitive impairment and a community action approach in parallel, to build a dementia-friendly community. For the high-risk approach, we achieved stepwise access to 7614 older residents, which enabled us to select and visit the homes of 198 participants with a Mini-Mental State Examination score < 24 in 2016. In 2019, we re-accessed these individuals. For the community action approach, we built a community space in the study area to build partnerships with community residents and community workers and were able to re-access participants using multiple methods.

Results

We found that 126 (63.6%) participants had continued living in the same community, but 58 (29.3%) had discontinued community living. Of these, 18 (9.1%) had died, 18 (9.1%) were institutionalized, 9 (4.5%) were hospitalized, and 13 (6.6%) had moved out of the community. A multiple logistic regression analysis identified the following risk factors associated with discontinuation of community living: being certified under long-term care insurance, needing housing support, and needing rights protection.

Conclusions

Three years after the baseline survey, 29.3% of people with cognitive impairment had discontinued community living. Despite having cognitive impairment or living alone, older people were able to continue living in the community if their needs for housing support and rights protection were met. Both social interventions and medical interventions are important to build age-friendly communities.

Trial registration

UMIN, UMIN000038189, Registered 3 October 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043521
Assessing the efficacy of two dual-active ingredients long-lasting insecticidal nets for the control of malaria transmitted by pyrethroid-resistant vectors in Benin: study protocol for a three-arm, single-blinded, parallel, cluster-randomized controlled trial
Authors: Accrombessi Manfred , Cook Jackie , Ngufor Corine , Sovi Arthur , Dangbenon Edouard , Yovogan Boulais , Akpovi Hilaire , Hounto Aurore , Thickstun Charles , Padonou Gil G. , Tokponnon Filemon , Messenger Louisa A. , Kleinschmidt Immo , Rowland Mark , Akogbeto Martin C. , Protopopoff Natacha
Published: February 2021

Background

Long-lasting insecticidal nets (LLINs) are currently the primary method of malaria control in sub-Saharan Africa and have contributed to a significant reduction in malaria burden over the past 15 years. However, this progress is threatened by the wide-scale selection of insecticide-resistant malaria vectors. It is, therefore, important to accelerate the generation of evidence for new classes of LLINs.

Methods

This protocol presents a three-arm superiority, single-blinded, cluster randomized controlled trial to evaluate the impact of 2 novel dual-active ingredient LLINs on epidemiological and entomological outcomes in Benin, a malaria-endemic area with highly pyrethroid-resistant vector populations. The study arms consist of (i) Royal Guard® LLIN, a net combining a pyrethroid (alpha-cypermethrin) plus an insect growth regulator (pyriproxyfen), which in the adult female is known to disrupt reproduction and egg fertility; (ii) Interceptor G2® LLIN, a net incorporating two adulticides (alpha-cypermethrin and chlorfenapyr) with different modes of action; and (iii) the control arm, Interceptor® LLIN, a pyrethroid (alpha-cypermethrin) only LLIN. In all arms, one net for every 2 people will be distributed to each household. Sixty clusters were identified and randomised 1:1:1 to each study arm. The primary outcome is malaria case incidence measured over 24 months through active case detection in a cohort of 25 children aged 6 months to 10 years, randomly selected from each cluster. Secondary outcomes include 1) malaria infection prevalence (all ages) and prevalence of moderate to severe anaemia in children under 5 years old, measured at 6 and 18 months post-intervention; 2) entomological indices measured every 3 months using human landing catches over 24 months. Insecticide resistance intensity will also be monitored over the study period.

Discussion

This study is the second cluster randomised controlled trial to evaluate the efficacy of these next-generation LLINs to control malaria transmitted by insecticide-resistant mosquitoes. The results of this study will form part of the WHO evidence-based review to support potential public health recommendations of these nets and shape malaria control strategies of sub-Saharan Africa for the next decade.

Trial registration

ClinicalTrials.gov, NCT03931473, registered on 30 April 2019.
CT-based radiomics combined with signs: a valuable tool to help radiologist discriminate COVID-19 and influenza pneumonia
Authors: Huang Yilong , Zhang Zhenguang , Liu Siyun , Li Xiang , Yang Yunhui , Ma Jiyao , Li Zhipeng , Zhou Jialong , Jiang Yuanming , He Bo
Published: February 2021

Background

In this COVID-19 pandemic, the differential diagnosis of viral pneumonia is still challenging. We aimed to assess the classification performance of computed tomography (CT)-based CT signs and radiomics features for discriminating COVID-19 and influenza pneumonia.

Methods

A total of 154 patients with confirmed viral pneumonia (COVID-19: 89 cases, influenza pneumonia: 65 cases) were collected retrospectively in this study. Pneumonia signs and radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models. The predictive performance of the radiomics model, CT sign model, the combined model was constructed based on the whole dataset and internally invalidated by using 1000-times bootstrap. Diagnostic performance of the models was assessed via receiver operating characteristic (ROC) analysis.

Results

The combined models consisted of 4 significant CT signs and 7 selected features and demonstrated better discrimination performance between COVID-19 and influenza pneumonia than the single radiomics model. For the radiomics model, the area under the ROC curve (AUC) was 0.888 (sensitivity, 86.5%; specificity, 78.4%; accuracy, 83.1%), and the AUC was 0.906 (sensitivity, 86.5%; specificity, 81.5%; accuracy, 84.4%) in the CT signs model. After combining CT signs and radiomics features, AUC of the combined model was 0.959 (sensitivity, 89.9%; specificity, 90.7%; accuracy, 90.3%).

Conclusions

CT-based radiomics combined with signs might be a potential method for distinguishing COVID-19 and influenza pneumonia with satisfactory performance.
Breast cancer and background parenchymal enhancement at breast magnetic resonance imaging: a meta-analysis
Authors: Hu Na , Zhao Jinghao , Li Yong , Fu Quanshui , Zhao Linwei , Chen Hong , Qin Wei , Yang Guoqing
Published: February 2021

Background

The background parenchymal enhancement at breast magnetic resonance imaging use to predict breast cancer attracts many searchers to draw a possible relationship. However, the results of their relationships were conflicting. This meta-analysis was performed to assess breast cancer frequency associations with background parenchymal enhancement.

Methods

A systematic literature search up to January 2020 was performed to detect studies recording associations between breast cancer frequency and background parenchymal enhancement. We found thirteen studies including 13,788 women at the start with 4046 breast cancer. We calculated the odds ratio (OR) and the 95% confidence intervals (CIs) between breast cancer frequency and background parenchymal enhancement by the dichotomous technique with a random or fixed-effect model.

Results

Women with minimal or mild background parenchymal enhancement at breast magnetic resonance imaging did not have any risk of breast cancer compared to control women (OR, 1.20; 95% CI 0.54–2.67). However, high background parenchymal enhancement at breast magnetic resonance imaging (OR, 2.66; 95% CI 1.36–5.19) and moderate (OR, 2.51; 95% CI 1.49–4.21) was associated with a significantly higher rate of breast cancer frequency compared to control women.

Conclusions

Our meta-analysis showed that the women with high and moderate background parenchymal enhancement at breast magnetic resonance imaging have higher risks, up to 2.66 fold, of breast cancer. We suggest that women with high or moderate background parenchymal enhancement at breast magnetic resonance imaging to be scheduled for more frequent follow-up and screening for breast cancer to avoid any complications.
Quality measurement of out-patient neuropsychological therapy after stroke in Germany: definition of indicators and retrospective pilot study
Authors: Padberg I. , Heel S. , Thiem P. , Diebel A. , Mordhorst E. , Strohmeyer U. , Meisel A.
Published: February 2021

Background

In contrast to the hospital setting, today little work has been directed to the definition, measurement, and improvement of the quality of out-patient medical and therapeutic care. We developed a set of indicators to measure the quality of out-patient neuropsychological therapy after stroke.

Methods

The indicators cover core and interdisciplinary aspects of out-patient neuropsychological work such as mediation of patients into social care in case of need. Selection of the quality-indicators was done together with a consensus group of out-patient therapists and supported by evidence, validity, reliability as well as estimated relevance and variability with the quality of care. The set of indicators was further tested in a retrospective cohort study. Anonymous data of 104 patients were collected from out-patient clinical records of five clinics between November 2017 and April 2018. Associations between process and outcome quality were estimated exploitatively.

Results

Results allowed for the identification of areas with greater variability in the quality of process care and indicated that attention training as recommended by current guidelines had the lowest overall rate for meeting the quality-aim (met in 44% of the cases). This was followed by time < 1 month until the start of therapy (63% met) and mediation into social care in case of need (65% met). We further observed that overall quality and involving relatives in the therapy was associated with higher rates of professional reintegration (p-value = 0.03). However, the need for mediation into social care was associated with a reduced chance for successful professional reintegration (p-value = 0.009).

Conclusion

In conclusion, we describe a first set of quality indicators which cover different aspects of out-patient neuropsychological therapy and sufficient variability with care. First data further suggests that meeting the specified quality aims may indeed have relevant effects on outcomes.
Single-shot bevacizumab for cerebral radiation injury
Authors: Voss Martin , Wenger Katharina J. , Fokas Emmanouil , Forster Marie-Thérèse , Steinbach Joachim P. , Ronellenfitsch Michael W.
Published: February 2021

Background

Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations.

Methods

We performed a retrospective analysis of patients treated in our clinic for cerebral radiation injury who received only a singular treatment with bevacizumab. Single-shot was defined as a singular administration of bevacizumab without a second administration during an interval of at least 6 weeks.

Results

We identified 11 patients who had received a singular administration of bevacizumab to treat cerebral radiation injury. Prior radiation had been administered to treat gliomas (ten patients) or breast cancer brain metastases (one patient). 9 of 10 patients with available MRIs showed a marked reduction of edema at first follow-up. Discontinuation of Dexamethasone was possible in 6 patients and a significant dose reduction could be achieved in all other patients. One patient developed pulmonary artery embolism 2 months after bevacizumab administration. The median time to treatment failure of any cause was 3 months.

Conclusions

Single-shot bevacizumab therefore has meaningful activity in cerebral radiation injury, but durable control is rarely achieved. In patients where a complete protocol of four infusions with bevacizumab is not feasible due to medical contraindications or lack of reimbursement, single-shot bevacizumab treatment may be considered.
Fetal growth restriction in a cohort of migrants in Germany
Authors: Ankert Juliane , Groten Tanja , Pletz Mathias W. , Mishra Sasmita , Seliger Gregor , Lobmaier Silvia M. , da Costa Clarissa Prazeres , Seidel Vera , von Weizsäcker Katharina , Jablonka Alexandra , Dopfer Christian , Schleenvoigt Benjamin T.
Published: February 2021

Background

Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants.

Method

Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany.

Results

The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort.

Conclusions

Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.
Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China
Authors: Liu Jianqiong , Dai Qiong , Li Wei , Guo Yan , Dai Anna , Wang Yanqing , Deng Mengyao , Tang Zhao , She Lu , Chen Xiaohong , Yang Mei
Published: February 2021

Background

Gestational diabetes mellitus (GDM) increased risk of perinatal complications for both the women and the fetuses. The association between the vitamin D receptor (VDR) gene polymorphism and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. Moreover, we aimed to explore their combined effects on the risk of GDM.

Methods

Pregnant women who had prenatal examinations at 24 to 28 weeks’ gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and associations with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM.

Results

Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs.

Conclusions

The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.
Cross-sectional association between vitamin B12 status and probable postpartum depression in Indian women
Authors: Dhiman Pooja , Pillai Raji Ramachandran , Wilson Anand Babu , Premkumar Nancy , Bharadwaj Balaji , Ranjan Veena P. , Rajendiran Soundravally
Published: February 2021

Background

Vitamin B12 is an essential micronutrient for neurological function, as it leads to the regeneration of methionine from homocysteine, which is precursor of biologically active molecule S-Adenosyl Methionine (SAM). Pregnancy is a state of increased demand and delayed postpartum repletion of nutrients may predispose women to depression.

Methods

We included women who visited the hospital at 6-weeks postpartum for a regular checkup. Inclusion criteria were age (18–50 years), and willingness to donate venous sample for analysis. Exclusion criteria included previous history of mood disorders or antidepressant medication use, and any systemic illness like hypothyroidism, epilepsy, diabetes, and hypertension. Based on EPDS score of 10 as a cutoff, 217 women with probable postpartum depression (PPD) and equal number of age and BMI matched controls were included.

Plasma total vitamin B12, holotranscobalamin (holotc), homocysteine (hcy), methyl malonic acid (MMA), 5-methyl tetrahydrofolate (THF), SAM and serotonin levels were estimated using commercially available ELISA kits. Combined B12 (cB12) score was calculated from study parameters. Multivariate analysis was performed to assess the risk of probable postpartum depression.

Results

Total vitamin B12 and combined B12 score were found to be significantly lower (p = 0.001) and MMA (p = 0.002) and 5-methyl THF (p < 0.001) levels were higher in women with probable depression than women without probable PPD. Women in the lowest vitamin B12 quartile had 4.53 times higher likelihood of probable postpartum depression (p < 0.001). Multivariate analysis demonstrated that decreasing vitamin B12 (OR = 0.394; 95% CI: 0.189–0.822) and cB12 (OR = 0.293; 95% CI: 0182–0.470) and increasing MMA (OR = 2.14; 95% CI: 1.63–2.83) and 5-methyl THF levels (OR = 3.29; 95% CI: 1.59–6.83) were significantly associated with the risk of probable PPD.

Conclusion

Low vitamin B12 may contribute to depressive symptoms in vulnerable postpartum period.
Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells
Authors: Guo Jing , Satoh Kiyotoshi , Tabata Sho , Mori Masaru , Tomita Masaru , Soga Tomoyoshi
Published: February 2021

Background

Cisplatin (CDDP) significantly prolongs survival in various cancers, but many patients also develop resistance that results in treatment failure. Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance.

Methods

We evaluated the metabolic profiles in CDDP-sensitive ovarian cancer A2780 cells and CDDP-resistant A2780cis cells using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We further examined the expression of glutamine metabolism enzymes using real-time PCR and Western blot analyses. Cell viability was accessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Results

The results showed that levels of glutamine, glutamate, and glutathione (GSH), a key drug resistance mediator synthesized from glutamate, were significantly elevated in A2780cis cells than those in A2780 cells. Furthermore, glutamine starvation decreased the GSH levels and CDDP resistance in A2780cis cells. Interestingly, the expression of glutamine synthetase (GS/GLUL), which synthesizes glutamine from glutamate and thereby negatively regulates GSH production, was almost completely suppressed in resistant A2780cis cells. In addition, treatment of A2780cis cells with 5-aza-2′-deoxycytidine, a DNA-demethylating agent, restored GS expression and reduced CDDP resistance. In contrast, GS knockdown in CDDP-sensitive A2780 cells induced CDDP resistance.

Conclusions

The results indicate that upregulation of GSH synthesis from glutamine via DNA methylation-mediated silencing of GS causes CDDP resistance in A2780cis cells. Therefore, glutamine metabolism could be a novel therapeutic target against CDDP resistance.