bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical castration versus chemical castration in donkeys: response of stress, lipid profile and redox potential biomarkers
Authors: Abou-Khalil Nasser S. , Ali Marwa F. , Ali Magda M. , Ibrahim Ahmed
Published: August 2020

Background

Castration is a husbandry practice raising important questions on the welfare and physiological status of farm animals. Searching for effective castration methods that minimally compromise the body physiology is worthy of attention. Therefore, this study aimed to evaluate the differential response of biological systems in donkeys to surgical castration versus the chemical one by CaCl2 with special emphasis on stress, lipid profile, and oxidative stress biomarkers. Donkeys were divided randomly and equally into two groups; the chemical (Ch) and surgical (S) groups (n = 6). The Ch group was chemically castrated by intratesticular injection of 20% CaCl2 dissolved in absolute ethanol. Blood samples were collected prior to castration and at 15, 30, 45, and 60 days after the beginning of experiment.

Results

Surprisingly, the Ch group at the end of the experiment was characterized by significantly higher cortisol level compared to the S group. TC and LDL-C levels in the S group significantly decreased at day 45, while TG levels significantly increased at days 45 and 60 in comparison with day 0. HDL-C levels at days 30 and 60 in the Ch group significantly increased in comparison with day 0. At day 30 post-castration, HDL-C was significantly higher and LDL-C was significantly lower in the Ch group than the S group. A significant elevation in TC and LDL-C was observed at day 45 and in HDL-C at the end of experimental duration in the Ch group when compared with the S group. TPX level was significantly lower and TAC was significantly higher in the Ch group at day 45 than the S group.

Conclusion

Surgical castration evoked less stress and minor changes in lipid profile and oxidant/antioxidant balance relative to chemical castration by intratesticular 20% CaCl2 dissolved in absolute ethanol.
A novel neoantigen discovery approach based on chromatin high order conformation
Authors: Shi Yi , Zhang Mingxuan , Meng Luming , Su Xianbin , Shang Xueying , Guo Zehua , Li Qingjiao , Lin Mengna , Zou Xin , Luo Qing , Yu Yaoliang , Wu Yanting , Da Lintai , Cai Tom Weidong , He Guang , Han Ze-Guang
Published: August 2020

Background

High-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate the immune response of the T cell. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response.

Methods

Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Based on our previous discoveries, we propose to investigate the distribution of neoantigens with different immunogenicity abilities in 3D genome and propose to adopt this important information into neoantigen prediction.

Results

We retrospect the DNA origins of the immuno-positive and immuno-negative neoantigens in the context of 3D genome and discovered that DNA loci of the immuno-positive neoantigens and immuno-negative neoantigens have very different distribution pattern. Specifically, comparing to the background 3D genome, DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We thus used this information into neoantigen prediction and demonstrated the effectiveness of this approach.

Conclusion

We believe that the 3D genome information will help to increase the precision of neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.
Active case detection of malaria in pregnancy using loop-mediated amplification (LAMP): a pilot outcomes study in South West Ethiopia
Authors: Tadesse Guluma , Kamaliddin Claire , Doolan Cody , Amarasekara Ranmalee , Legese Ruth , Mohon Abu Naser , Cheaveau James , Yewhalaw Delenasaw , Pillai Dylan R.
Published: August 2020

Background

125 million women are pregnant each year in malaria endemic areas and are, therefore, at risk of Malaria in Pregnancy (MiP). MiP is the direct consequence of Plasmodium infection during pregnancy. The sequestration of Plasmodium falciparum parasites in the placenta adversely affects fetal development and impacts newborn birth weight. Importantly, women presenting with MiP commonly develop anaemia. In Ethiopia, the Ministry of Health recommends screening symptomatic women only at antenatal care visits with no formal intermittent preventive therapy. Since MiP can display low-level parasitaemia, current tests which include microscopy and RDT are challenged to detect these cases. Loop mediated isothermal Amplification (LAMP) technology is a highly sensitive technique for DNA detection and is field compatible. This study aims to evaluate the impact of active malaria case detection during pregnancy using LAMP technology in terms of birth outcomes.

Methods

A longitudinal study was conducted in two health centres of the Kafa zone, South West Ethiopia. Both symptomatic and asymptomatic pregnant women were enrolled in the first or second trimester and allocated to either Standard of Care (SOC—microscopy and RDT) or LAMP (LAMP, microscopy and RDT). Women completed at least three visits prior to delivery, and the patient was referred for treatment if Plasmodium infection was detected by any of the testing methods. The primary outcome was to measure absolute birth weight, proportion of low birth weight, and maternal/neonatal haemoglobin in each arm. Secondary outcomes were to assess the performance of microscopy and RDT versus LAMP conducted in the field.

Results

One hundred and ninety-nine women were included and assigned to either LAMP or SOC. Six were lost to follow up. In this cohort, 66.8% of women did not display any clinical symptoms and 70.9% were multi-parous. A reduced proportion of low birth weight newborns was observed in the LAMP group (0%) compared to standard of care (14%) (p <0.001). Improved neonatal haemoglobin was observed in the LAMP (13.1 g/dL) versus the SOC (12.8 g/dL) (p = 0.024) arm. RDT and microscopy had an analytical sensitivity of 66.7% and 55.6% compared to LAMP as a reference standard.

Conclusions

These results support the use of highly sensitive tools for rapid on-site active case detection of MiP which may improve birth outcomes in the absence of IPT. However, further large-scale studies are required to confirm this finding.
Evaluating the predictive performance of malaria antibodies and FCGR3B gene polymorphisms on Plasmodium falciparum infection outcome: a prospective cohort study
Authors: Dwomoh Duah , Adu Bright , Dodoo Daniel , Theisen Michael , Iddi Samuel , Gerds Thomas A.
Published: August 2020

Background

Malaria antigen-specific antibodies and polymorphisms in host receptors involved in antibody functionality have been associated with different outcomes ofPlasmodium falciparuminfections. Thus, to identify key prospective malaria antigens for vaccine development, there is the need to evaluate the associations between malaria antibodies and antibody dependent host factors with more rigorous statistical methods. In this study, different statistical models were used to evaluate the predictive performance of malaria-specific antibodies and host gene polymorphisms onP. falciparuminfection in a longitudinal cohort study involving Ghanaian children.

Methods

Models with different functional forms were built using known predictors (age, sickle cell status, blood group status, parasite density, and mosquito bed net use) and malaria antigen-specific immunoglobulin (Ig) G and IgG subclasses andFCGR3Bpolymorphisms shown to mediate antibody-dependent cellular functions. Malaria antigens studied were Merozoite surface proteins (MSP-1 and MSP-3), Glutamate Rich Protein (GLURP)-R0, R2, and the Apical Membrane Antigen (AMA-1). The models were evaluated through visualization and assessment of differences between the Area Under the Receiver Operating Characteristic Curve and Brier Score estimated by suitable internal cross-validation designs.

Results

This study found that theFCGR3B-c.233C>A genotype and IgG against AMA1 were relatively better compared to the other antibodies andFCGR3Bgenotypes studied in classifying or predicting malaria risk among children.

Conclusions

The data supports theP. falciparum, AMA1 as an important malaria vaccine antigen, whileFCGR3B-c.233C>A under the additive and dominant models of inheritance could be an important modifier of the effect of malaria protective antibodies.
A comprehensive assessment of predictors of fertility outcomes in men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction
Authors: Kavoussi Parviz K. , West Brady T. , Chen Shu-Hung , Hunn Caitlin , Gilkey Melissa S. , Machen G. Luke , Kavoussi Keikhosrow M. , Esqueda Amy , Wininger J. David , Kavoussi Shahryar K.
Published: August 2020

Background

Microdissection testicular sperm extraction (microTESE) in men with non-obstructive azoospermia (NOA) is the procedure that results in the highest number of sperm cells retrieved for in vitro fertilization (IVF). This study presents a novel assessment of predictors of sperm retrieval as well as downstream embryology and pregnancy outcomes in cases of men with NOA undergoing microTESE.

Methods

A retrospective chart review of 72 men who underwent microTESE for predictors of fertility outcomes including sperm retrieved at microTESE, embryology progression to embryo transfer (ET), clinical pregnancy, live birth, and surplus sperm retrieved for additional IVF/intracytoplasmic injection cycles beyond one initial cycle. Statistical models for each of these outcomes were fitted, with ap-value of < 0.05 considered significant for the parameters estimated in each model.

Results

Seventy-two men underwent microTESE, and 51/72 (70.8%) had sperm retrieved. Of those, 29/43 (67.4%) reached ET. Of the couples who underwent ET, 21/29 (72.4%) achieved pregnancy and 18/29 (62.1%) resulted in live birth. Of the men with sperm retrieved, 38/51 (74.5%) had surplus sperm cryopreserved beyond the initial IVF cycle.

Age, testicular volume, FSH, and testicular histopathology were assessed as predictors for sperm retrieved at microTESE, progression to ET, pregnancy, live birth, and surplus sperm. There were no preoperative predictors of sperm retrieval, clinical pregnancy, or live birth. Age predicted reaching ET, with older men having increased odds. FSH level had a negative relationship with surplus sperm retrieved. Men with hypospermatogenesis histology had higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm.

Conclusions

Men who underwent microTESE with a hypospermatogenesis histopathology had better outcomes, including higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm retrieved. Increasing male partner age increased the odds of reaching ET. No other clinical factors were predictive for the outcomes considered.
Health technology assessment of biosimilars worldwide: a scoping review
Authors: Ascef Bruna de Oliveira , Lopes Ana Carolina de Freitas , de Soárez Patrícia Coelho
Published: August 2020

Background

Health technology assessment (HTA) should provide an assessment of a technology’s effects on health and of the related social, economic, organisational and ethical issues. HTA reports on biosimilars can specifically assess their immunogenicity, their extrapolation to one or more conditions, and the risks of interchangeability and substitution. We aimed to complete a scoping review within the context of HTA organisations to synthesise HTA reports on biosimilars and to map the extension, scope and methodological practices.

Main body

A scoping review methodology was applied. The sources for biosimilars HTA reports were database searches and grey literature from HTA organisation websites up to June 2019. HTA reports of biosimilars were classified as full HTA, mini-HTA or rapid reviews. Data were extracted and recorded on a calibrated predefined data form. We identified 70 HTA reports of biosimilars of 16 biologic products (65.71% in 2015–2018) produced by 13 HTA organisations from 10 countries; 2 full HTAs, 4 mini-HTAs and 64 rapid reviews met the inclusion criteria. Almost all the rapid reviews gave no information regarding any evidence synthesis method and approximately half of the rapid reviews did not appraise the risk of bias of primary studies or the overall quality of evidence. All full-HTAs and mini-HTAs addressed organisational, ethical, social and legal considerations, while these factors were assessed in less than half of the rapid reviews. The immunogenicity and extrapolation of one or more conditions were often considered. The majority of full-HTAs and mini-HTAs contained an assessment of switching and a discussion of an educational approach about biosimilars. No HTA report rejected the adoption/reimbursement of the biosimilar assessed.

Conclusion

HTA of biosimilars are emerging in the context of HTA organisations and those that exist often duplicate reports of the same biosimilar. Most HTA reports of biosimilars do not conduct a systematic literature review or consider economic issues. No report has rejected the adoption/reimbursement of biosimilars. There is a need to standardise the minimum criteria for the development of HTA on biosimilars to ensure a better understanding and better decision-making.
Correction to: Help-seeking intention and associated factors towards mental illness among residents of Mertule Mariam town, East Gojam Zone, Amhara Region, Ethiopia: a mixed-method study
Authors: Yeshanew Berhanu , Belete Asmare , Necho Mogesie , Shumet Shegaye , Maja Zegeye Yohannis , Agnaw Dessie Abebaw
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Psychosocial barriers and enablers of exclusive breastfeeding: lived experiences of mothers in low-income townships, North West Province, South Africa
Authors: Witten Chantell , Claasen Nicole , Kruger Herculina S. , Coutsoudis Anna , Grobler Herman
Published: August 2020

Background

Despite national efforts to promote exclusive breastfeeding (EBF), South Africa’s EBF rate is only 32 %. The aim of this study was to examine the rate of EBF discontinuation and the lived experiences of breastfeeding mothers at postnatal time points 3–14 days, 4–8 weeks, 10–14 weeks and 20–24 weeks.

Methods

This community-based mixed-methods study collected data within a prospective cohort study on sociodemographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) at 6–8 weeks with infant feeding data collected at 4–8, 10–14 and 20–24 weeks from 159 mothers living in low income areas. Six focus groups with 32 mothers with infants aged 6–24 weeks were conducted. Descriptive statistics was used for the quantitative data and thematic analysis for qualitative data.

Results

The majority of mothers were unmarried (84.9%), living with family (69.2%) and unemployed (74.2%). Exclusive breastfeeding decreased from 34% at 4–8 weeks to 9.7% at 20–24 weeks. Mixed feeding with infant formula increased from 17.0 to 30.6% and food feeding from 3.1 to 54.2%. While there were no statistically significant associations between EBF and any of the quantitative sociodemographic variables, in the qualitative data, codes associated with barriers were more than enablers. The themes wereMothers’ attributes (wellbeing, experiences and relationships)with the codemother’s stressthe strongest barrier,Mother’s knowledge, attitudes and practices of breastfeedingwith the codeconventional medicinesthe strongest barrier,Family environmentwith the codehome settingthe strongest barrier,Social environmentwithpublic spaces and placesa barrier and inBaby cuesthe codebaby stomach ailmentsthe barrier. Within these same themesmother’s positive emotions,benefits of breastfeeding,support in the home, access to information and services fromhealth professionalsandbaby’s healthwere strong enabling factors.

Conclusions

Low EBF, high mixed feeding and a high EPDS score were explained by the barriers identified in the qualitative data. The data suggests that mothers from low-income households would be better supported through interventions that address food insecurity; family relationships and those that build confidence in mothers and resilience in confronting difficult and hostile breastfeeding environments.
Haematoma block: a safe method for pre-surgical reduction of distal radius fractures
Authors: Maleitzke Tazio , Plachel Fabian , Fleckenstein Florian Nima , Wichlas Florian , Tsitsilonis Serafeim
Published: August 2020

Background

The haematoma block (HB) has been successfully used to minimise pain prior to otherwise painful closed reduction manoeuvres for distal radius fractures. However, the invasive manner of the procedure, which technically produces an open fracture, still raises the question, whether HBs increase the risk of infection compared to conventional intravenous analgesia (IA). The purpose of this study was to assess complication rates and safety of the HB procedure for the closed reduction of surgically treated distal radius fractures.

Methods

We included 176 distal radius fractures in 170 patients in a retrospective mono-centric study, who underwent closed reduction and casting followed by definitive surgical care over a period of two years. Patients either received a HB or IA before closed reduction and were evaluated for minor and major complications over a follow-up period of four years.

Results

Overall, 42 distal radius fractures were treated with a HB (23.9%) and 134 with IA (76.1%) before closed reduction. There were a single major (2.3%) and eight minor (19%) complications observed in the HB group compared to two major (1.4%) and 24 minor (17.9%) complications in the IA group. No significant differences were identified between the two groups. Sex and type of fracture had no effect on complication rates, however, younger patients experienced higher complication rates in comparison to older ones (p = 0.035).

Conclusion

According to our data, the apprehensions that clinicians may have of creating open fractures through HB procedures, are unnecessary and may be abandoned confidently.
Development of simultaneous interaction prediction approach (SiPA) for the expansion of interaction network of traditional Chinese medicine
Authors: Rui Mengjie , Pang Hui , Ji Wei , Wang Siqi , Yu Xuefei , Wang Lilong , Feng Chunlai
Published: August 2020

Background

Due to the lack of enough interaction data among compositions, targets and diseases, it is difficult to construct a complete network of Traditional Chinese Medicine (TCM) that comprehensively reflects active compositions and their synergistic network in terms of specific diseases. Therefore, mapping of the full spectrum of interaction between compounds and their targets is of central importance when we use network pharmacology approach to explore the therapeutic potential of the TCM.

Methods

To address this challenge, we developed a large-scale simultaneous interaction prediction approach (SiPA) integrated one interaction network based simple inference model (SIM), focusing on ‘logical relevance’ between compounds, proteins or diseases, and another compound-target correlation space based interaction prediction model (CTCS-IPM) that was built on the basis of the canonical correlation analysis (CCA) to estimate the position of compounds (or targets) in compound-protein correlated space. Then SiPA was applied to discover reliable multiple interactions for interaction network expansion of a TCM, compound Salvia miltiorrhiza. By means of network analysis, potential active compounds and their related network synergy underlying cardiovascular diseases were evaluated between expanded and original interaction networks. Part of new interactions were validated with existing experimental evidence and molecular docking.

Results

As evaluated with known test dataset, the established combination approach was proved to make highly accurate prediction, showing a well prediction performance for the SIM and a high recall rate of 85.2% for the CTCS-IPM. Then 710 pairs of new compound-target interactions, 24 pairs of new compound-cardiovascular disease interactions and 294 pairs of new cardiovascular disease-protein interactions were predicted for compound Salvia miltiorrhiza. Results of network analysis suggested the network expansion could dramatically improve the completeness and effectiveness of the network. Validation results of literature and molecular docking manifested that inferred interactions had good reliability.

Conclusions

We provided a practical and efficient way for large-scale inference of multiple interactions of TCM ingredients, which was not limited by the lack of negative samples, sample size and target 3D structures. SiPA could help researchers more accurately prioritize the effective compounds and more completely explore network synergy of TCM for treating specific diseases, indicating a potential way for effectively identifying candidate compound (or target) in drug discovery.
Early management of sight threatening retinopathy in incontinentia pigmenti
Authors: Michel Sarah , Reynaud Clothilde , Daruich Alejandra , Hadj-Rabia Smail , Bremond-Gignac Dominique , Bodemer Christine , Robert Matthieu P.
Published: August 2020

Background

Early blindness secondary to incurable retinal detachment is one of the main complications of incontinentia pigmenti (IP). The efficiency of ophthalmological management for preventing such evolution has not been proven.

The objective of this retrospective study was to report a screening and treatment strategy of the vascular retinopathy in newborns and infants with IP.

Results

All files of patients diagnosed with IP within the two first months of life in a single tertiary referral center, between 2010 and 2015, were retrospectively included. The minimum follow-up duration was three years.

Patients had undergone systematic indirect ophthalmoscopy examination, looking for signs of peripheric retinal vasculopathy, according to a standardized schedule: at diagnosis, at age 1, 2, 3, 6, 9, 12, 18 and 24 months, and then once a year. Urgent laser therapy was performed under anesthesia in case of signs of retinal ischemia.

Nineteen children files (17 girls) were studied. Median age at IP diagnosis was 1 day [0–44]; median age at first retinal evaluation was 25 days. Retinal manifestations occurred in 7 patients (n = 10/38 eyes, 26.3%); they were diagnosed at median age 19 days [3–59]. These patients underwent one or two ablative session per eye (mean 1.7, median 2), under general anaesthesia. No retinal detachment or fold occurred during the follow-up (median 6 years [3–9.8]).

Conclusion

Ocular screening should be performed in all cases of IP as soon as possible after diagnosis. A strict ophthalmological monitoring and prophylactic treatment of retinal vasculopathy can efficiently prevent the early blinding complications of the disease.
Roles of METTL3 in cancer: mechanisms and therapeutic targeting
Authors: Zeng Chengwu , Huang Wanxu , Li Yangqiu , Weng Hengyou
Published: August 2020

N6-methyladenosine (m6A) is the most abundant mRNA modification and is catalyzed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. Accumulating evidence in recent years reveals that METTL3 plays key roles in a variety of cancer types, either dependent or independent on its m6A RNA methyltransferase activity. While the roles of m6A modifications in cancer have been extensively reviewed elsewhere, the critical functions of METTL3 in various types of cancer, as well as the potential targeting of METTL3 as cancer treatment, have not yet been highlighted. Here we summarize our current understanding both on the oncogenic and tumor-suppressive functions of METTL3, as well as the underlying molecular mechanisms. The well-documented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is also discussed in this review.
CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway
Authors: Wang Yu , Yin Lili , Sun Xiaofei
Published: August 2020

Background

Endometrial cancer (EC) is a common gynecologic malignancy worldwide. This study investigated the regulatory effects of circular RNA (circRNA) hsa_circ_0002577 on the tumorigenesis of EC.

Methods

Tumor samples and adjacent normal tissues were obtained from 84 EC patients. Recombinant lentiviral vectors expressing hsa_circ_0002577 (Lv-circRNA), short hairpin RNAs against hsa_circ_0002577 (sh-circRNA), miR-625-5p mimics, miR-625-5p inhibitor, lentiviral vectors expressing insulin-like growth factor 1 receptor (IGF1R) and their corresponding controls were transfected into EC cells as designated. A mouse xenograft model was established in BALB/c mice by inoculating Ishikawa cells transfected with sh-circRNA or control sequence.

Results

Hsa_circ_0002577 was upregulated in EC tissue samples and cells as compared to normal controls. EC patients with higher expression of hsa_circ_0002577 showed poorer overall survival and more advanced tumor stage. EC cells transfected with Lv-circRNA showed promoted proliferation, migration, and invasion, whereas the delivery of sh-circRNA exerted an opposite effect. Further analyses showed that hsa_circ_0002577 acted as a miR-625-5p sponge in EC cells. IGF1R was a potential downstream target of miR-625-5p. The expression of IGF1R in EC tissues was significantly higher than that in matched controls. Hsa_circ_0002577 accelerated EC development by inducing IGF1R expression and activating PI3K/Akt signaling pathway. Also, the knockdown of hsa_circ_0002577 delayed tumor growth and metastasis in the inoculated mice.

Conclusion

Our study showed that circRNA hsa_circ_002577 accelerated EC progression by acting as a miR-625-5p sponge, upregulating IGF1R and activating the PI3K/Akt pathway, suggesting the potential therapeutic use of hsa_circ_002577 in EC treatment.

Trial registration

Not Applicable.
KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma
Authors: Wang Boshi , Jing Tiantian , Jin Weilin , Chen Jinnan , Wu Chengsi , Wang Mingrong , Liu Yizhen
Published: August 2020

Background

The platinum-based chemotherapy is the first-line regimen for the treatment of Non-small cell lung cancer (NSCLC). However, the therapeutic efficiency is largely limited by tenacious chemo-insensitivity that results in inferior prognosis in a cohort of patients. It has been known that KIAA1522 is aberrantly expressed and implicated in several types of solid tumors including NSCLC. Nowadays, knowledge about this gene is quite limited. Here, we aimed to identify the role of KIAA1522 in lung adenocarcinomas, and the molecular events that underlie KIAA1522-mediated chemoresistance to the platinum.

Methods

Immunohistochemistry were used to detect KIAA1522 expression in clinical NSCLC samples. Then, the survival analyses were performed to assess the link between KIAA1522 expression and overall survival or therapeutic outcome. In vivo depletion of KIAA1522 in adenocarcinoma cells were achieved by adeno-associated virus-mediated sgRNA/Cre delivery into the conditional KrasG12D/Cas9 expressed mice, which were designated to identify the roles of KIAA1522 in tumorigenesis and/or chemotherapy responses. The effects of KIAA1522 and downstream molecular events were studied by pharmacology in mice model and assays using in vitro cultured cells. The clinical relevance of our findings was examined by data-mining of online datasets from multiple cohorts.

Results

The clinical evidences reveal that KIAA1522 independently predicts both the overall survival and the outcome of platinum-based chemotherapy in lung adenocarcinomas. By using a KrasG12D-driven murine lung adenocarcinoma model and performing in vitro assays, we demonstrated that KIAA1522 is a critical positive regulator of lung adenocarcinoma and a modulator of cisplatin response. KIAA1522 potentiates the TNFα-TNFR2-NFκB signaling which in turn intensifies recalcitrance to cisplatin treatment. These results were further manifested by integrative bioinformatic analyses of independent datasets, in which KIAA1522 is tightly associated with the activity of TNFα-NFκB pathway and the cisplatin-resistant gene signatures. More strikingly, overexpression of KIAA1522 counteracts the cisplatin-induced tumor growth arrest in vivo, and this effect can be remarkably diminished by the disruption of NFκB activity.

Conclusion

High expression of KIAA1522 is turned out to be an indicator of dismal effectiveness of platinum-based therapy in lung adenocarcinomas. KIAA1522 hyperactivates TNFα-NFκB signaling to facilitate resistance to platinum reagents. Targeting NFκB signaling through small molecule inhibitors may be a rational strategy to conquer chemoresistance and synergize platinum-based chemotherapy in KIAA1522 overexpressed lung adenocarcinomas.
A systematic evaluation of single-cell RNA-sequencing imputation methods
Authors: Hou Wenpin , Ji Zhicheng , Ji Hongkai , Hicks Stephanie C.
Published: August 2020

Background

The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to address the increased sparsity observed in single-cell data. Although many imputation methods have been developed, there is no consensus on how methods compare to each other.

Results

Here, we perform a systematic evaluation of 18 scRNA-seq imputation methods to assess their accuracy and usability. We benchmark these methods in terms of the similarity between imputed cell profiles and bulk samples and whether these methods recover relevant biological signals or introduce spurious noise in downstream differential expression, unsupervised clustering, and pseudotemporal trajectory analyses, as well as their computational run time, memory usage, and scalability. Methods are evaluated using data from both cell lines and tissues and from both plate- and droplet-based single-cell platforms.

Conclusions

We found that the majority of scRNA-seq imputation methods outperformed no imputation in recovering gene expression observed in bulk RNA-seq. However, the majority of the methods did not improve performance in downstream analyses compared to no imputation, in particular for clustering and trajectory analysis, and thus should be used with caution. In addition, we found substantial variability in the performance of the methods within each evaluation aspect. Overall, MAGIC, kNN-smoothing, and SAVER were found to outperform the other methods most consistently.
The effect of psychoeducational intervention, based on a self-regulation model on menstrual distress in adolescents: a protocol of a randomized controlled trial
Authors: Asgari Somayeh , Alimoardi Zainab , Soleimani Mohammad Ali , Allen Kelly-Ann , Bahrami Nasim
Published: August 2020

Introduction

Menstrual distress caused by primary dysmenorrhea is associated with physical and psychological symptoms—before, after, and during menstruation. Leventhal’s self-regulation educational model is based on the cognitive and emotional experiences of threat responses to symptoms and relates to coping responses. This study aims to investigate the effect of the implementation of a psychoeducational intervention, based on the self-regulation model of menstrual distress in adolescents.

Methods/design

In this randomized controlled trial, 120 adolescent girls with moderate to severe menstrual pain (based on visual analog scale (VAS) ≥ 4) from twelve randomly selected high schools in Qazvin City will be enrolled in the study and will be randomly assigned to either a 3-session psychoeducational intervention (n = 60) or control (n = 60) groups. The sessions will be between 60 and 90 min apiece, and they will run for three consecutive weeks (one session per week). The data collection tools will include questionnaire eliciting menstrual information and demographics, the VAS, the Moos Menstrual Distress Questionnaire, and the illness perception questionnaire. One month prior to the intervention, both groups will participate in an initial assessment to assess the severity of their pain and level of menstrual distress. Finally, all questionnaires will be completed for three consecutive months after the intervention is completed.

Discussion

It is anticipated that findings of this study will provide evidence for the effectiveness of the Leventhal self-regulation model. Implications for improved practice, understanding, and treatment for menstrual distress may also arise.

Ethical considerations

The research protocol will be reviewed by the ethics committee, which is affiliated with the Qazvin University of Medical Sciences (Decree code: IR.QUMS.REC.1398.043).

Trial registration

IRCT20190625044002N1. Registration date: 2019-09-03.
Rivaroxaban compared to no treatment in ER-negative stage I–III early breast cancer patients (the TIP Trial): study protocol for a phase II preoperative window-of-opportunity study design randomised controlled trial
Authors: Castle John , Blower Emma , Bundred Nigel J. , Harvey James R. , Thachil Jecko , Marshall Andrea , Cox Karina , Cicconi Silvia , Holcombe Chris , Palmieri Carlos , Kirwan Cliona C.
Published: August 2020

Background

Breast cancer patients are at a four-fold increased risk of developing a venous thromboembolism (VTE), a major cause of death in this group. Conversely, coagulation factors promote tumour growth and metastasis. This has been evidenced in preclinical models, with an inhibitory effect of anticoagulants on cancer growth through proliferative, angiogenic, apoptotic, cancer stem cell and metastatic processes. The extrinsic clotting pathway is also more upregulated in patients in the relatively poorer prognosis oestrogen receptor (ER)-negative breast cancer subgroup, with increased tumour stromal expression of the coagulation factors Tissue Factor and thrombin.

Rivaroxaban (Xarelto®, Bayer AG, Leverkusen, Germany) is a direct oral anticoagulant (DOAC). It is a Factor Xa inhibitor that is routinely prescribed for the prevention of stroke in non-valvular atrial fibrillation and for both VTE prophylaxis and treatment. This trial will assess the anti-proliferative and other anti-cancer progression mechanisms of Rivaroxaban in ER-negative early breast cancer patients.

Methods

This UK-based preoperative window-of-opportunity phase II randomised control trial will randomise 88 treatment-naïve early breast cancer patients to receive 20 mg OD Rivaroxaban treatment for 11 to 17 days or no treatment. Treatment will be stopped 24 h (range 18–36 h) prior to surgery or repeat core biopsy. All patients will be followed up for 2 weeks following surgery or repeat core biopsy.

The primary endpoint is change in tumour Ki67. Secondary outcome measures include tumour markers of apoptosis and angiogenesis, extrinsic clotting pathway activation and systemic markers of metastasis, tumour load and coagulation.

Discussion

Laboratory evidence supports an anti-cancer role for anticoagulants; however, this has failed to translate into survival benefit when trialled in patients with metastatic disease or poor prognosis cancers, such as lung cancer. Subgroup analysis supported a potential survival benefit in better prognosis advanced disease patients. This is the first study to investigate the anti-cancer effects of anticoagulants in early breast cancer.

Trial registration

UK National Research Ethics Service (NRES) approval 15/NW/0406, MHRA Clinical Trials Authorisation 48380/0003/001-0001. The sponsor is Manchester University NHS Foundation Trust, and the trial is co-ordinated by Cancer Research UK Liverpool Cancer Trials Unit (LCTU). EudraCT2014-004909-33, registered 27 July 2015.ISRCTN14785273.
Acupressure therapy and Liu Zi Jue Qigong for pulmonary function and quality of life in patients with severe novel coronavirus pneumonia (COVID-19): a study protocol for a randomized controlled trial
Authors: Zhang Shuaipan , Zhu Qingguang , Zhan Chao , Cheng Wei , Mingfang Xiao , Fang Min , Fang Lei
Published: August 2020

Background

In December 2019, pneumonia associated with the 2019 novel coronavirus (COVID-19) emerged in Wuhan, China. The number of cases has increased rapidly. Patients with severe disease have a poor prognosis, and there are no effective therapies for COVID-19. Only rapid advice guidelines for symptomatic supportive care have been used. A traditional Chinese medicine rehabilitation (TCMR) program consisting of acupressure therapy and Liu Zi Jue Qigong can be used as a complementary therapy for COVID-19. Hence, we designed a randomized trial to evaluate the efficacy and advantages of TCMR for treating patients with severe COVID-19.

Methods/design

This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. A total of 128 patients with COVID-19 aged from 20 to 80 years will be recruited and assigned randomly into a guideline therapy group and a guideline therapy plus TCMR group at a 1:1 ratio. Patients in both groups will receive guideline therapy. The patients in the intervention group will perform acupressure therapy and Liu Zi Jue Qigong exercises in addition to conventional treatments twice a day and will be persistent from admission to discharge. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Activities of Daily Living Barthel Index Scale, Patient Health Questionnaire-9 Scale, and the Respiratory Symptoms Scale. The assessments of the clinical scales will be performed at three points (before treatment, the 7th day during hospitalization, and the discharge day). Adverse events will be noted and recorded for the safety evaluation.

Discussion

This trial will provide high-quality evidence of the value of TCMR, which consists of acupressure therapy and Liu Zi Jue Qigong exercises, for treating patients with severe COVID-19.

Trial registration

Chinese Clinical Trial RegistryChiCTR2000029994. Registered on 18 February 2020
Efficacy of Hwangryunhaedok-tang (Huang-lian-jie-du-tang, Oren-gedoku-to) for patients with hyperlipidemia: a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated clinical trial
Authors: Lee Boram , Han Kyungsun , Park Hyo-Ju , Kim Ae-Ran , Kwon O-Jin , Yang Changsop , Cho Chung-Sik
Published: August 2020

Background

The prevalence of hyperlipidemia continues to increase due to aging and lifestyle changes. Statins are currently used as the first choice for treating hyperlipidemia, but are limited by adverse reactions. Hwangryunhaedok-tang (HHT) has received attention as a promising intervention for hyperlipidemia through a few experimental and clinical trials. This study aims to explore the feasibility, effectiveness, and safety of HHT for hyperlipidemia treatment.

Methods

This is a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated, pilot clinical trial held in Daejeon, Republic of Korea. Thirty patients with hyperlipidemia will be randomly allocated to HHT or placebo granule groups in equal proportions. Participants will be administered HHT or placebo granules three times per day for 8 weeks and followed up for another 4 weeks. The primary outcome is low-density lipoprotein cholesterol at 8 weeks from the commencement of treatment. Other blood lipid parameters, biomarkers of atherosclerosis, the degree of arteriosclerosis, blood glucose parameters, blood pressure, anthropometric parameters, health-related quality of life, and the changes in the general symptoms of cold and hot patterns will be measured as secondary outcomes. Adverse events and laboratory test results will be investigated to assess the safety. Changes in the gut microbiome before and after intervention will also be assessed as an exploratory outcome through next-generation sequencing. Data will be recorded in electronic case report forms and analyzed using SAS® Version 9.4.

Discussion

This is a rigorously designed pilot clinical trial to explore the effect and safety of Hwangryunhaedok-tang compared to placebo control for patients with hyperlipidemia, thereby potentially facilitating better management of hyperlipidemia. The results of this pilot study could form the foundation for a future large-scale, confirmatory clinical trial.

Trial registration

Clinical Research Information ServiceKCT0004564. Registered on December 18, 2019
Zmo0994, a novel LEA-like protein from Zymomonas mobilis, increases multi-abiotic stress tolerance in Escherichia coli
Authors: Yang Jungwoo , Kim Ha Eun , Jung Young Hoon , Kim Jungyeon , Kim Do Hyoung , Walmsley Adrian R. , Kim Kyoung Heon
Published: August 2020

Background

Pretreatment processes and subsequent enzymatic hydrolysis are prerequisites to utilize lignocellulosic sugar for fermentation. However, the resulting hydrolysate frequently hinders fermentation processes due to the presence of inhibitors and toxic products (e.g., ethanol). Thus, it is crucial to develop robust microbes conferring multi-stress tolerance.

Results

Zmo0994, a functionally uncharacterized protein from Zymomonas mobilis, was identified and characterized for the first time. A major effect of Zmo0994 was a significant enhancement in the tolerance to abiotic stresses such as ethanol, furfural, 5′-hydroxymethylfurfural and high temperature, when expressed in Escherichia coli. Through transcriptome analysis and in vivo experiments, the cellular mechanism of this protein was revealed as due to its ability to trigger genes, involved in aerobic respiration for ATP synthesis.

Conclusions

These findings have significant implications that might lead to the development of robust microbes for the highly efficient industrial fermentation processes.
Survival rates of head and neck cancers in Ghana: a retrospective study at the Komfo Anokye Teaching Hospital
Authors: Owusu-Afriyie Osei , Owiredu W. K. B. A. , Oti Alexander Acheampong , Acheampong Emmanuel , Owusu-Danquah Kwabena , Larsen-Reindorf Rita , Fondjo Linda Ahenkorah , Adu Evans Asamoah , Donkor Sampson , Donkor Peter
Published: August 2020

Objective

Data was collected to evaluate the survival rates of head and neck (conjunctiva, oropharyngeal and non-oropharyngeal) squamous cell carcinomas in Ghana.

Data description

We provided data on a retrospective review of 8 years (January 2004 to December 2009) survival rate of head and neck squamous cell carcinomas (HNSCCs) at the Komfo Anokye Teaching Hospital in Ghana. The data consist of patient demographic data and clinicopathological findings which includes tumour site, tumour stage and histological grades of the patients. Clinical outcome measurement was death through to January 2013 on record and confirmed from the hospitals birth and death registry department. More than 85% of death cases were confirmed by gender, age, and folder identification numbers from the birth and death registry.
Immunohistochemical expression of PAX-8 in Sudanese patients diagnosed with malignant female reproductive tract tumors
Authors: Ali Eman T. , Mohamed Nouh S. , Shafig Irene R. , Muneer Mohamed S. , Yosif Abubaker Ahmed , Hassan Lamis Ahmed , Mohamed Areeg M. , Ahmed Ayman , Siddig Emmanuel E.
Published: August 2020

Objectives

Paired box protein-8 (PAX-8) immunohistochemical expression can be used as a diagnostic marker for epithelial cells tumors. This study aimed at investigating the immunohistochemical expression of PAX-8 among Sudanese females diagnosed with cervical, endometrial, and ovarian cancers between December 2017 and May 2019 by studying their Formalin-fixed paraffin embedded blocks.

Results

Sixty patients diagnosed with female reproductive tract cancers were included who aged 58.7 ± 6.9 years (range, 43—71). Cervix was the most common cancer site in 51/60 (85%) patients. Regarding cancer stage, there was 17 (28%) and 14 (23%) of the study population had stage 3B and 2B, respectively. The histopathological diagnosis included 20 (44%), 13 (29%), and 12 (27%) poorly, moderately, and well differentiated cervical squamous cell carcinoma (SCC) as well as 11 (73%), 2 (13%), 1 (7%), and 1 (7%) endometrial adenocarcinoma, metastatic adenocarcinoma, endocervical adenocarcinoma, and ovarian mucinous cyst adenocarcinoma, respectively. PAX-8 was positively expressed in 9 endometrial adenocarcinoma, 1 endocervical adenocarcinoma and 1 ovarian mucinous cyst adenocarcinoma, 2 poorly, and 1 moderately differentiated SCC. All patients diagnosed with well differentiated SCC and metastatic adenocarcinoma showed no expression of PAX-8. A statistically significant was seen for PAX-8 expression and the different histopathological diagnosis, P value < 0.001.
Correction to: Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy
Authors: Guo Kai , Eid Stephanie A. , Elzinga Sarah E. , Pacut Crystal , Feldman Eva L. , Hur Junguk
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-dependent manner in swine neutrophils
Authors: Huang Tinghua , Jiang Caiyun , Yang Min , Xiao Hong , Huang Xiali , Wu Lingbo , Yao Min
Published: August 2020

Neutrophils are the first barriers for resisting the invasion, proliferation, and damage caused by Salmonella Typhimurium. However, the mechanisms that control this resistance are not completely understood. In this study, we established an in vitro Salmonella infection model in porcine neutrophils, and analyzed the cellular transcriptome by deep sequencing and flow cytometry. The results showed that ribosomal gene transcription was inhibited, and two of these genes, RPL39 and RPL9, were related to TRP53 activation. Furthermore, several important innate immunity genes were also inhibited. Knock-down of RPL39 and RPL9 by siRNA caused an approximate fourfold up-regulation of TRP53. Knock-down of RPL39 and RPL9 also resulted in a significant down-regulation of IFNG and TNF, indicating an inhibition of the innate immune response. Silencing of RPL39 and RPL9 also resulted in the up-regulation of FAS, RB1, CASP6, and GADD45A, which play roles in cell cycle arrest and apoptosis. Neutrophils were either first treated with RPL39 siRNA, RPL9 siRNA, TRP53 activator, or TRP53 inhibitor, and then infected with Salmonella. Knock-down of RPL39 and RPL9, or treatment with TRP53 activator, can increase the intracellular proliferation of Salmonella in neutrophils. We speculate that much of the Salmonella virulence can be attributed to the enhancement of cell cycle arrest and the inhibition of the innate immune response, which allows the bacteria to successfully proliferate intracellularly.