bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific proteome changes in platelets from individuals with GATA1-, GFI1B-, and RUNX1-linked bleeding disorders
Authors: Van Bergen M. G. J. M. , Marneth A. E. , Hoogendijk A. J. , Van Alphen F. P. J. , Van den Akker E. , Laros-Van Gorkom B. A. P. , Hoeks M. , Simons A. , De Munnik S. A. , Janssen J. J. W. M. , Martens J. H. A. , Jansen J. H. , Meijer A. B. , Van der Reijden B. A.
Published: March 2021

Mutations in the transcription factors GATA binding factor 1 (GATA1), growth factor independence 1B (GFI1B), and Runt-related transcription factor 1 (RUNX1) cause familial platelet and bleeding disorders. Mutant platelets exhibit common abnormalities including an α-granule reduction resulting in a grayish appearance in blood smears. This suggests that similar pathways are deregulated by different transcription factor mutations. To identify common factors, full platelet proteomes from 11 individuals with mutant GATA1R216Q, GFI1BQ287*, RUNX1Q154Rfs, or RUNX1TD2-6 and 28 healthy controls were examined by label-free quantitative mass spectrometry. In total, 2875 platelet proteins were reliably quantified. Clustering analysis of more than 300 differentially expressed proteins revealed profound differences between cases and controls. Among cases, 44 of 143 significantly downregulated proteins were assigned to platelet function, hemostasis, and granule biology, in line with platelet dysfunction and bleedings. Remarkably, none of these proteins were significantly diminished in all affected cases. Similarly, no proteins were commonly overrepresented in all affected cases compared with controls. These data indicate that the studied transcription factor mutations alter platelet proteomes in distinct largely nonoverlapping manners. This work provides the quantitative landscape of proteins that affect platelet function when deregulated by mutated transcription factors in inherited bleeding disorders.
Vacuolization of hematopoietic precursors: an enigma with multiple etiologies
Authors: Gurnari Carmelo , Pagliuca Simona , Durkin Lisa , Terkawi Laila , Awada Hassan , Kongkiatkamon Sunisa , Zawit Misam , Hsi Eric D. , Carraway Hetty E. , Rogers Heesun J. , Visconte Valeria , Maciejewski Jaroslaw P.
Published: March 2021

Cytoplasmic vacuoles in precursors can be seen in a number of clinical settings, including copper deficiency, zinc toxicity, alcohol abuse, antibiotic treatment, myelodysplasia, and VEXAS syndrome. Gurnari et al asked how common VEXAS syndrome is in patients whose bone marrow aspirates show this distinctive feature, finding 2 diagnoses of VEXAS among 24 cases with vacuoles.
Correction to: Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head
Authors: Yin Yukun , Ding Lixiang , Hou Yu , Jiang Haoran , Zhang Ji , Dai Zhong , Zhang Genai
Published: March 2021

After publication of the original article [1], the authors flagged that their article had published with an incomplete version of affiliation ‘1’.
Genome-wide analysis of spatiotemporal expression patterns during rice leaf development
Authors: Miya Masayuki , Yoshikawa Takanori , Sato Yutaka , Itoh Jun-Ichi
Published: March 2021

Background

Rice leaves consist of three distinct regions along a proximal-distal axis, namely the leaf blade, sheath, and blade-sheath boundary region. Each region has a unique morphology and function, but the genetic programs underlying the development of each region are poorly understood. To fully elucidate rice leaf development and discover genes with unique functions in rice and grasses, it is crucial to explore genome-wide transcriptional profiles during the development of the three regions.

Results

In this study, we performed microarray analysis to profile the spatial and temporal patterns of gene expression in the rice leaf using dissected parts of leaves sampled in broad developmental stages. The dynamics in each region revealed that the transcriptomes changed dramatically throughout the progress of tissue differentiation, and those of the leaf blade and sheath differed greatly at the mature stage. Cluster analysis of expression patterns among leaf parts revealed groups of genes that may be involved in specific biological processes related to rice leaf development. Moreover, we found novel genes potentially involved in rice leaf development using a combination of transcriptome data and in situ hybridization, and analyzed their spatial expression patterns at high resolution. We successfully identified multiple genes that exhibit localized expression in tissues characteristic of rice or grass leaves.

Conclusions

Although the genetic mechanisms of leaf development have been elucidated in several eudicots, direct application of that information to rice and grasses is not appropriate due to the morphological and developmental differences between them. Our analysis provides not only insights into the development of rice leaves but also expression profiles that serve as a valuable resource for gene discovery. The genes and gene clusters identified in this study may facilitate future research on the unique developmental mechanisms of rice leaves.
Integrated microRNA and transcriptome profiling reveal key miRNA-mRNA interaction pairs associated with seed development in Tartary buckwheat (Fagopyrum tataricum)
Authors: Li Hongyou , Meng Hengling , Sun Xiaoqian , Deng Jiao , Shi Taoxiong , Zhu Liwei , Lv Qiuyu , Chen Qingfu
Published: March 2021

Background

Tartary buckwheat seed development is an extremely complex process involving many gene regulatory pathways. MicroRNAs (miRNAs) have been identified as the important negative regulators of gene expression and performed crucial regulatory roles in various plant biological processes. However, whether miRNAs participate in Tartary buckwheat seed development remains unexplored.

Results

In this study, we first identified 26 miRNA biosynthesis genes in the Tartary buckwheat genome and described their phylogeny and expression profiling. Then we performed small RNA (sRNA) sequencing for Tartary buckwheat seeds at three developmental stages to identify the miRNAs associated with seed development. In total, 230 miRNAs, including 101 conserved and 129 novel miRNAs, were first identified in Tartary buckwheat, and 3268 target genes were successfully predicted. Among these miRNAs, 76 exhibited differential expression during seed development, and 1534 target genes which correspond to 74 differentially expressed miRNAs (DEMs) were identified. Based on integrated analysis of DEMs and their targets expression, 65 miRNA-mRNA interaction pairs (25 DEMs corresponding to 65 target genes) were identified that exhibited significantly opposite expression during Tartary buckwheat seed development, and 6 of the miRNA-mRNA pairs were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) and ligase-mediated rapid amplification of 5′ cDNA ends (5′-RLM-RACE). Functional annotation of the 65 target mRNAs showed that 56 miRNA-mRNA interaction pairs major involved in cell differentiation and proliferation, cell elongation, hormones response, organogenesis, embryo and endosperm development, seed size, mineral elements transport, and flavonoid biosynthesis, which indicated that they are the key miRNA-mRNA pairs for Tartary buckwheat seed development.

Conclusions

Our findings provided insights for the first time into miRNA-mediated regulatory pathways in Tartary buckwheat seed development and suggested that miRNAs play important role in Tartary buckwheat seed development. These findings will be help to study the roles and regulatory mechanism of miRNAs in Tartary buckwheat seed development.
Strengthened workplace relationships facilitate recovery at work – qualitative experiences of an intervention among employees in primary health care
Authors: Ejlertsson Lina , Heijbel Bodil , Andersson Ingemar H , Troein Margareta , Brorsson Annika
Published: March 2021

Background

The literature on workplace interventions focusing on recovery is scarce; hence this study intends to expand that knowledge. An intervention was run for one year, aiming at increasing the experience of recovery during the workday among primary health care employees. During the intervention, different forms of recovery activities were integrated into the daily work at six primary health care centres. The aim of this study was to explore the intervention process and its effects.

Methods

After completion of an intervention, 39 employees in seven focus groups were interviewed about their experiences of the intervention. A semi-structured interview guide was used, and the qualitative analysis was conducted by systematic text condensation.

Results

Despite different conditions and attitudes when the project was launched, the participants portrayed a positive outcome of the intervention at all six workplaces. Four promoting factors for intervention success were identified: support, legitimacy, customization, and simplicity. Also, three areas of improvement during the intervention period were described: the workplace climate, employee well-being, and recovery awareness, which in turn became promoting factors.

Conclusions

An intervention aiming at increasing workplace recovery can be promoted by support, legitimacy, customization, and simplicity. By using these promoting factors, health care workplaces can implement activity models which could increase employees’ experiences of recovery during the workday. Positive effects on workplace climate and employee well-being can also be achieved.
Does self-reported symptom questionnaire play a role in nonadherence to colonoscopy for risk-increased population in the Tianjin colorectal cancer screening programme?
Authors: Zhao Lizhong , Zhang Xiaorui , Chen Yongjie , Wang Yuan , Zhang Weihua , Lu Wenli
Published: March 2021

Background

A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population.

Methods

Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012–2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors.

Results

A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29–2.41, no FIT: OR, 1.27; 95% CI, 1.24–1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ.

Conclusion

In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.
Liver transplantation in adult polycystic liver disease: the Ontario experience
Authors: Alsager Mohammed , Neong Shuet Fong , Gandhi Radhika , Teriaky Anouar , Tang Ephraim , Skaro Anton , Qumosani Karim , Lilly Les , Galvin Zita , Selzner Nazia , Bhat Mamatha Pallavi , Puka Klajdi , Brahmania Mayur
Published: March 2021

Background

Liver transplantation (LT) remains the curative treatment for symptomatic Polycystic Liver Disease (PCLD) patients and is associated with excellent survival rates. The aim of the study is to review the Ontario experience in LT for PCLD.

Methods

A retrospective study was performed from pre-existing LT databases from the LT Units at Toronto General Hospital and London Health Sciences Center, which are the two LT programs in Ontario, Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for PCLD. Data was extracted for patients who underwent LT between January 2000–April 2017 and included follow up until December 31st, 2018.

Results

A total of 3560 patients underwent LT, of whom 51 (1.4%) had PCLD and met inclusion criteria. 43 (84%) of these patients were female. The median physiologic Model for End Stage Liver Disease (MELD-Na) score at time of referral was 13 (IQR = 7–22), however all patients required MELD-Na exception points to receive LT. The median age of transplant was 62 years (IQR = 59–64) for male vs. 52 (IQR = 45–56) for female patients. 33 (65%) of our cohort had PCLD while 9 (17.5%) had ADPKD and 9 (17.5%) had both diseases. 39 (76%) had LT due to symptoms of mass effect, while 8 (16%) had portal hypertensive complications. After a median follow-up of 6.3 (IQR = 2.9–12.5) years, the probability of survival was 96% (95% CI: 90%, 100%). Log-rank test, comparing survival analysis between males and females did not show a statistically significant difference (p = 0.26).

Conclusion

Most patients underwent LT for PCLD due to symptoms of mass effect with women being more likely than men to undergo LT. LT for PCLD had excellent long-term survival.
Association between body mass index and severe infection in older adults with microscopic polyangiitis: a retrospective cohort in Japan
Authors: Sugiyama Hirokazu , Yamaguchi Makoto , Katsuno Takayuki , Iwagaitsu Shiho , Nobata Hironobu , Kinashi Hiroshi , Banno Shogo , Ando Masahiko , Kubo Yoko , Ishimoto Takuji , Ito Yasuhiko
Published: March 2021

Background

Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV.

Methods

This single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P <  0.05.

Results

During the median follow-up period of 19 (6–53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14–3.52, per 10 years; P =  0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5–23.0 kg/m2], adjusted HR =  2.63, 95% CI: 1.11–6.19; P =  0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07–5.76; P =  0.034) were found to be significant predictors of severe infection.

Conclusions

Low BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.
The effect of comorbidities on survival in persons with Alzheimer’s disease: a matched cohort study
Authors: Rajamaki Blair , Hartikainen Sirpa , Tolppanen Anna-Maija
Published: March 2021

Background

Alzheimer’s disease (AD) is one of the leading causes of death world-wide, but little is known on the role of comorbidities on mortality among people with AD. We studied how comorbidities and age at AD diagnosis impact the survival of people with AD.

Methods

The Medication Use and Alzheimer’s disease (MEDALZ) cohort study included 70,718 community-dwelling persons in Finland with AD diagnosis from 2005 to 2011 and were matched 1:1 (age, gender, and hospital district) to people without AD (mean age 80 years, 65% women, and the mean follow-up 4.9 and 5.6 years, respectively). Covariates (age, gender, and socioeconomic position), comorbidities (cardiovascular disease, stroke, diabetes, asthma/ chronic obstructive pulmonary disease (COPD), hip fracture, cancer treatment, and mental or behavioral disorders excluding dementia) and survival data were obtained from nationwide registers. Cox proportional hazard models were used to compare risk of death between people with and without AD.

Results

During the follow-up period a greater proportion of the AD cohort died compared to the non-AD cohort (63% versus 37%).In both cohorts, older age, male gender, lower socioeconomic position, and history of comorbidities were associated with shorter survival and higher risk of death. The associations of comorbidities with survival is weaker in the older age groups and people with AD. Hip fracture (adjusted HR 1.35, 95% CI 1.30–1.41), stroke (1.30, 1.27–1.34), and recent cancer treatment (1.29, 1.26–1.32) had the strongest associations in the AD cohort. Age modified the associations in both cohorts (weaker associations among older people).

Conclusion

Alzheimer’s disease is the major factor affecting survival, but comorbidities further decrease survival also in individuals with Alzheimer’s disease. Therefore, appropriate management of care of these comorbidities might affect not only survival but also the wellbeing of this vulnerable population.
The prevalence and clinical significance of Presymptomatic COVID-19 patients: how we can be one step ahead in mitigating a deadly pandemic
Authors: Tan Juen Kiem , Leong Dalleen , Munusamy Hemalatha , Zenol Ariffin Nor Hazwani , Kori Najma , Hod Rozita , Periyasamy Petrick
Published: March 2021

Background

Presymptomatic COVID-19 patients have been identified as a major stumbling block in efforts to break the chain of transmission. Studies on temporal dynamics of its shedding suggests it peaks 1–2 days prior to any symptom onset. Therefore, a large proportion of patients are actively spreading the disease unknowingly whilst undetected. However, lengthy lockdowns and isolation leads to a host of socioeconomic issues and are impractical. Conversely, there exists no study describing this group and their clinical significance despite their key role in disease transmission.

Methods

As a result, we devised a retrospective study to look at the prevalence of presymptomatic patients with COVID-19 from data sourced via our medical records office. Subsequently, we identify early indicators of infection through demographic information, biochemical and radiological abnormalities which would allow early diagnosis and isolation. In addition, we will look into the clinical significance of this group and their outcome; if it differs from asymptomatic or symptomatic patients. Descriptive statistics were used in addition to tabulating the variables and corresponding values for reference. Variables are compared between the presymptomatic group and others via Chi-square testing and Fisher’s exact test, accepting a p value of < 0.05 as significant.

Results

Our analysis shows a higher proportion of presymptomatic patients with atypical symptoms like chest pain while symptomatic patients commonly present with respiratory symptoms like cough and shortness of breath. Besides that, there were more females presenting as presymptomatic patients compared to males (p = 0.019) and these group of patients were likely to receive treatment (p < 0.001). Otherwise, we were not able to identify other statistically significant markers suggesting a patient is presymptomatic.

Conclusion

As we have little means of identifying these silent spreaders, it highlights further the importance of general measures implemented to stop COVID-19 transmission like social distancing, face mask, and widespread testing.
Identification and validation of a five-lncRNA prognostic signature related to Glioma using bioinformatics analysis
Authors: Zhang Chunyu , Liu Haitao , Xu Pengfei , Tan Yinqiu , Xu Yang , Wang Long , Liu Baohui , Chen Qianxue , Tian Daofeng
Published: March 2021

Background

To accurately predict the prognosis of glioma patients.

Methods

A total of 541 samples from the TCGA cohort, 181 observations from the CGGA database and 91 samples from our cohort were included in our study. Long non-coding RNAs (LncRNAs) associated with glioma WHO grade were evaluated by weighted gene co-expression network analysis (WGCNA). Five lncRNA features were selected out to construct prognostic signatures based on the Cox regression model.

Results

By weighted gene co-expression network analysis (WGCNA), 14 lncRNAs related to glioma grade were identified. Using univariate and multivariate Cox analysis, five lncRNAs (CYTOR, MIR155HG, LINC00641, AC120036.4 and PWAR6) were selected to develop the prognostic signature. The Kaplan-Meier curve depicted that the patients in high risk group had poor prognosis in all cohorts. The areas under the receiver operating characteristic curve of the signature in predicting the survival of glioma patients at 1, 3, and 5 years were 0.84, 0.92, 0.90 in the CGGA cohort; 0.8, 0.85 and 0.77 in the TCGA set and 0.72, 0.90 and 0.86 in our own cohort. Multivariate Cox analysis demonstrated that the five-lncRNA signature was an independent prognostic indicator in the three sets (CGGA set: HR = 2.002, p < 0.001; TCGA set: HR = 1.243, p = 0.007; Our cohort: HR = 4.457, p = 0.008, respectively). A nomogram including the lncRNAs signature and clinical covariates was constructed and demonstrated high predictive accuracy in predicting 1-, 3- and 5-year survival probability of glioma patients.

Conclusion

We established a five-lncRNA signature as a potentially reliable tool for survival prediction of glioma patients.
Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer
Authors: He Ping , Cheng Shihuan , Hu Feng , Ma Zhanchuan , Xia Yan
Published: March 2021

Background

Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression. A growing number of evidences showed that elevated expression of DGAT1 in cancer tissue indicated a poor outcome in cancer patients. However, the relationship between DGAT1 and gastric cancer is still unclear. Thus, Transcriptomic analysis and in vitro experiments were performed to investigate the role of DGAT1 in gastric cancer, as well as the potential therapy target in gastric cancer treatment.

Methods

We screened the public cancer datasets to identify the expression and function of DGAT1 in gastric cancer and tumor infiltrating lymphocytes. Then we testified the DGAT1 expression and function after sodium oleate treatment in AGS and MKN45 cell line. Finally, we analyzed ration of apoptosis, necrosis in gastric cancer cells by using flow cytometry after administration of DGAT1 inhibitor.

Results

Our results showed a highly expression of DGAT1 in gastric cancer tissues (n = 5, p = 0.0004), and tumor-infiltrating macrophages with elevated DGAT1 expression is associated with poor overall survival in gastric cancer patients. In addition, gastric cell lines AGS (n = 3, p < 0.05) and MKN45 (n = 3, p < 0.01) expressed higher level of DGAT1 than human gastric mucosal epithelial cell line GES-1. Administration of DGAT1 inhibitor effectively suppressed functional factors expression and induced cell death in MKN45.

Conclusion

The findings of this research provide an in-depth insight into the potential role and influences involved in DGAT1 in the gastric cancer patients. And higher expression of DGAT1 leads to lower overall survival (OS) rate in patients with poorly differentiated gastric cancer. Our findings suggest a potential role for DGAT1 in the gastric cancer progression and inhibiting DGAT1 might be a promising strategy in gastric cancer treatment.
Knowledge, attitude, and practice of patients with type 2 diabetes mellitus with regard to their disease: a cross-sectional study among Palestinians of the West Bank
Authors: Shawahna Ramzi , Samaro Saed , Ahmad Zaid
Published: March 2021

Background

In Palestine, type 2 diabetes mellitus (T2DM) is a rapidly growing health concern. This study evaluated knowledge, attitude, and practice of patients with T2DM with regard to their disease. The study also investigated association and correlation between knowledge, attitude, and practice with sociodemographic and clinical characteristics of the patients. Predictors of higher knowledge, positive attitude, and good practice were also identified.

Methods

This cross-sectional study was conducted in primary healthcare facilities frequently visited by patients with T2DM across the West Bank of Palestine in the period of October 2018 to January 2019. An interviewer administered questionnaire was used to determine knowledge, attitude and practice of patients with T2DM with regard to their disease.

Results

Out of 300 patients invited, 220 (73.3%) patients responded. In this study, the median age was 57.0 years (51.0, 65.0), the median time elapsed since diagnosis with T2DM was 7.0 years (4.0, 14.0), the median fasting blood glucose was 150.0 mg/dL (128.8, 180.0), the median postprandial glucose was 230.0 mg/dL (200.0, 270.0), the median HbA1c was 7.8% (7.0, 8.53), and the median BMI was 28.8 kg/m2 (25.5, 33.1). The median knowledge score was 6.0/13.0 (4.5/13.0, 7.5/13.0), the median attitude score was 3.0/4.0 (2.0/4.0, 4.0/4.0), and the median practice score was 3.0 (1.0/5.0, 4.0/5.0). Having university education was strongly associated with having higher knowledge scores (p-value = 0.001). Additionally, having attended an educational program on diabetes was moderately associated with higher practice scores (p-value = 0.026).

Conclusions

Findings of this study highlighted the need for appropriately designed interventions to increase knowledge about T2DM among patients with low educational level. Well-designed educational programs might promote healthy practice among patients with T2DM. Future studies are still needed to assess if such interventions could be effective in improving health outcomes and quality of life of patients with T2DM in Palestine.
Insulin resistance and high molecular weight adiponectin in obese and non-obese patients with Polycystic Ovarian Syndrome (PCOS)
Authors: Shirazi Farnaz Kamali Haghighi , Khodamoradi Zohre , Jeddi Marjan
Published: March 2021

Background

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy among young women. Insulin resistance is a key feature in the pathogenesis of PCOS; also high molecular weight adiponectin is a marker of insulin resistance. The aim of this study was to evaluate the insulin resistance, metabolic and androgenic profiles and high molecular weight adiponectin in obese and non-obese PCOS patients.

Methods

In this cross-sectional study in outpatient endocrinology clinics of Shiraz University of Medical Sciences, 80 women aged 17–43 years old with PCOS were enrolled. Biochemical and hormonal assay was done on fasting blood sample on the third day of follicular phase.

Results

The individuals had a mean age of 28.39 ± 6.56 years, mean weight of 65.41 ± 12.59 Kg, mean BMI of 25.5 ± 4.9, and mean waist circumference of 88.0 ± 13.1 cm. Of all individuals 20% had frank insulin resistance with HOMA-IR > 3.8. Although the obese PCOS patients had lower levels of high molecular weight adiponectin (P = 0.03) than the normal weight PCOS individuals, the level of insulin and insulin resistance was not different in them (P = 0.13, 0.13). Patients with classic PCOS phenotype significantly had higher levels of insulin resistance and free androgen index (P < 0.001, 0.001). We found a significant correlation between the insulin level and free androgen index (correlation coefficient: 0.266 and P = 0.018) after adjusting for BMI.

Conclusion

This cross-sectional study showed a high incidence of insulin resistance in PCOS patients independent of obesity, and determined BMI related lower level of high molecular weight adiponectin in obese PCOS individuals. More detailed studies are warranted for evaluation of insulin resistance and its pathophysiologic role in PCOS.
MicroRNA related prognosis biomarkers from high throughput sequencing data of kidney renal clear cell carcinoma
Authors: Huang Minjiang , Zhang Ti , Yao Zhi-Yong , Xing Chaoqung , Wu Qingyi , Liu Yuan-Wu , Xing Xiao-Liang
Published: March 2021

Background

Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC.

Methods

All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.

Results

We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year.

Conclusion

The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.
Pyridoxal-5′-phosphate-dependent enzyme GenB3 Catalyzes C-3′,4′-dideoxygenation in gentamicin biosynthesis
Authors: Zhou Shaotong , Chen Xiaotang , Ni Xianpu , Liu Yu , Zhang Hui , Dong Min , Xia Huanzhang
Published: March 2021

Background

The C-3′,4′-dideoxygenation structure in gentamicin can prevent deactivation by aminoglycoside 3′-phosphotransferase (APH(3′)) in drug-resistant pathogens. However, the enzyme catalyzing the dideoxygenation step in the gentamicin biosynthesis pathway remains unknown.

Results

Here, we report that GenP catalyzes 3′ phosphorylation of the gentamicin biosynthesis intermediates JI-20A, JI-20Ba, and JI-20B. We further demonstrate that the pyridoxal-5′-phosphate (PLP)-dependent enzyme GenB3 uses these phosphorylated substrates to form 3′,4′-dideoxy-4′,5′-ene-6′-oxo products. The following C-6′-transamination and the GenB4-catalyzed reduction of 4′,5′-olefin lead to the formation of gentamicin C. To the best of our knowledge, GenB3 is the first PLP-dependent enzyme catalyzing dideoxygenation in aminoglycoside biosynthesis.

Conclusions

This discovery solves a long-standing puzzle in gentamicin biosynthesis and enriches our knowledge of the chemistry of PLP-dependent enzymes. Interestingly, these results demonstrate that to evade APH(3′) deactivation by pathogens, the gentamicin producers evolved a smart strategy, which utilized their own APH(3′) to activate hydroxyls as leaving groups for the 3′,4′-dideoxygenation in gentamicin biosynthesis.
Label-free quantitative proteomic analysis of the inhibition effect of Lactobacillus rhamnosus GG on Escherichia coli biofilm formation in co-culture
Authors: Song Huiyi , Lou Ni , Liu Jianjun , Xiang Hong , Shang Dong
Published: March 2021

Background

Escherichia coli (E. coli) is the principal pathogen that causes biofilm formation. Biofilms are associated with infectious diseases and antibiotic resistance. This study employed proteomic analysis to identify differentially expressed proteins after coculture of E. coli with Lactobacillus rhamnosus GG (LGG) microcapsules.

Methods

To explore the relevant protein abundance changes after E. coli and LGG coculture, label-free quantitative proteomic analysis and qRT-PCR were applied to E. coli and LGG microcapsule groups before and after coculture, respectively.

Results

The proteomic analysis characterised a total of 1655 proteins in E. coli K12MG1655 and 1431 proteins in the LGG. After coculture treatment, there were 262 differentially expressed proteins in E. coli and 291 in LGG. Gene ontology analysis showed that the differentially expressed proteins were mainly related to cellular metabolism, the stress response, transcription and the cell membrane. A protein interaction network and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated that the differentiated proteins were mainly involved in the protein ubiquitination pathway and mitochondrial dysfunction.

Conclusions

These findings indicated that LGG microcapsules may inhibit E. coli biofilm formation by disrupting metabolic processes, particularly in relation to energy metabolism and stimulus responses, both of which are critical for the growth of LGG. Together, these findings increase our understanding of the interactions between bacteria under coculture conditions.
High concentrations of illicit stimulants and cutting agents cause false positives on fentanyl test strips
Authors: Lockwood Tracy-Lynn E. , Vervoordt Alexandra , Lieberman Marya
Published: March 2021

Background

The opioid epidemic has caused an increase in overdose deaths which can be attributed to fentanyl combined with various illicit substances. Drug checking programs have been started by many harm reduction groups to provide tools for users to determine the composition of their street drugs. Immunoassay fentanyl test strips (FTS) allow users to test drugs for fentanyl by either filling a baggie or cooker with water to dissolve the sample and test. The antibody used in FTS is very selective for fentanyl at high dilutions, a characteristic of the traditional use of urine testing. These street sample preparation methods can lead to mg/mL concentrations of several potential interferents. We tested whether these concentrated samples could cause false positive results on a FTS.

Methods

20 ng/mL Rapid Response FTS were obtained from BTNX Inc. and tested against 4 different pharmaceuticals (diphenhydramine, alprazolam, gabapentin, and naloxone buprenorphine) and 3 illicit stimulants [cocaine HCl, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA)] in concentrations from 20 to 0.2 mg/mL. The FTS testing pad is divided into 2 sections: the control area and the test area. Control and test area signal intensities were quantified by ImageJ from photographs of the test strips and compared to a threshold set by fentanyl at the FTS limit of detection.

Results

False positive results indicating the presence of fentanyl were obtained from samples of methamphetamine, MDMA, and diphenhydramine at concentrations at or above 1 mg/mL. Diphenhydramine is a common cutting agent in heroin. The street sample preparation protocols for FTS use suggested by many online resources would produce such concentrations of these materials. Street samples need to be diluted more significantly to avoid interference from potential cutting agents and stimulants.

Conclusions

Fentanyl test strips are commercially available, successful at detecting fentanyl to the specified limit of detection and can be a valuable tool for harm reduction efforts. Users should be aware that when drugs and adulterants are in high concentrations, FTS can give a false positive result.
Determination of wheat spike and spikelet architecture and grain traits using X-ray Computed Tomography imaging
Authors: Zhou Hu , Riche Andrew B. , Hawkesford Malcolm J. , Whalley William R. , Atkinson Brian S. , Sturrock Craig J. , Mooney Sacha J.
Published: March 2021

Background

Wheat spike architecture is a key determinant of multiple grain yield components and detailed examination of spike morphometric traits is beneficial to explain wheat grain yield and the effects of differing agronomy and genetics. However, quantification of spike morphometric traits has been very limited because it relies on time-consuming manual measurements.

Results

In this study, using X-ray Computed Tomography imaging, we proposed a method to efficiently detect the 3D architecture of wheat spikes and component spikelets by clustering grains based on their Euclidean distance and relative positions. Morphometric characteristics of wheat spikelets and grains, e.g., number, size and spatial distribution along the spike can be determined. Two commercial wheat cultivars, one old, Maris Widgeon, and one modern, Siskin, were studied as examples. The average grain volume of Maris Widgeon and Siskin did not differ, but Siskin had more grains per spike and therefore greater total grain volume per spike. The spike length and spikelet number were not statistically different between the two cultivars. However, Siskin had a higher spikelet density (number of spikelets per unit spike length), with more grains and greater grain volume per spikelet than Maris Widgeon. Spatial distribution analysis revealed the number of grains, the average grain volume and the total grain volume of individual spikelets varied along the spike. Siskin had more grains and greater grain volumes per spikelet from spikelet 6, but not spikelet 1–5, compared with Maris Widgeon. The distribution of average grain volume along the spike was similar for the two wheat cultivars.

Conclusion

The proposed method can efficiently extract spike, spikelet and grain morphometric traits of different wheat cultivars, which can contribute to a more detailed understanding of the sink of wheat grain yield.
The most appropriate titanium mesh cage size for anterior spinal reconstruction after single-level lumbar total en bloc spondylectomy: a finite element analysis and cadaveric validation study
Authors: Paholpak Permsak , Sirichativapee Winai , Wisanuyotin Taweechok , Kosuwon Weerachai , Kasai Yuichi , Murakami Hideki
Published: March 2021

Purpose

There is little information available regarding the cage diameter that can provide the most rigid construct reconstruction after total en bloc spondylectomy (TES). The aim of this study was thus to determine the most appropriate titanium mesh cage diameter for reconstruction after spondylectomy.

Methods

A finite element model of the single level lumbar TES was created. Six models of titanium mesh cage with diameters of 1/3, 1/2, 2/3, 3/4, 4/5 of the caudad adjacent vertebra, and 1/1 of the cephalad vertebra were tested for construct stiffness. The peak von Mises stress (MPa) at the failure point and the site of failure were measured as outcomes. A cadaveric validation study also conducted to validate the finite element model.

Results

For axial loading, the maximum stress points were at the titanium mesh cage, with maximum stress of 44,598 MPa, 23,505 MPa, 23,778 MPa, and 16,598 MPa, 10,172 MPa, 10,805 MPa in the 1/3, 1/2, 2/3, 3/4, 4/5, and 1/1 diameter model, respectively. For torsional load, the maximum stress point in each of the cages was identified at the rod area of the spondylectomy site, with maximum stress of 390.9 MPa (failed at 4459 cycles), 141.35 MPa, 70.098 MPa, and 88.972 MPa, 42.249 MPa, 15.827 MPa, respectively. A cadaveric validation study results were coincided with the finite element model results.

Conclusion

The most appropriate mesh cage diameter for reconstruction is 1/1 the diameter of the lower endplate of the adjacent cephalad vertebra, due to its ability to withstand both axial and torsional stress. According to the difficulty of large size cage insertion, a cage diameter of more than half of the upper endplate of the caudad vertebrae is acceptable in term of withstand stress. A cage diameter of 1/3 is unacceptable for reconstruction after total en bloc spondylectomy.
The interoperability between the Spanish version of the International Classification of Diseases and ORPHAcodes: towards better identification of rare diseases
Authors: Rico Juan , Echevarría-González de Garibay Luis Javier , García-López María , Guardiola-Vilarroig Sandra , Maceda-Roldán Luis Alberto , Zurriaga Óscar , Cavero-Carbonell Clara
Published: March 2021

Background

Rare diseases present a wide spectrum of clinical manifestations and severity levels and are often poorly known and underrepresented, making them difficult to classify. Diagnoses are usually coded using the International Classification of Diseases (ICD), with its different versions. In Spain, the ICD-10-ES (stem from the ICD-10-CM–Clinical Modification) is used throughout the National Healthcare System since 2016, indistinctively including rare diseases that often lack a specific code. Orphanet aims to provide high-quality resources on rare diseases. The goal was to interrelate the Orphanet classification with the ICD-10-ES in order to engage a tool to track rare diseases diagnosis and characterize the improvement space for the identification of rare diseases patients in the Spanish Healthcare System.

Methods

5775 disorder level ORPHAcodes were mapped to ICD-10-ES codes by comparing the descriptors associated in both classifications. ORPHAcodes were then clustered based on their assigned ICD-10-ES chapter and the redundancy of each individual ICD-10-ES code was calculated by counting the ORPHAcodes they mapped to. Three groups were established: Group 1 (1 ORPHAcode per ICD-10-ES), Group 2 (between 2–49 ORPHAcodes per ICD-10-ES) and Group 3 (≥ 50 ORPHAcodes per ICD-10-ES).

Results

Equivalences to 1700 ICD-10-ES codes were established for 5664 ORPHAcodes. The ORPHAcodes distribution within the ICD-10-ES showed an aggregation in the “Q” (> 40%), “G” (> 14%), and “E” (12%) chapters. The availability of ICD-10-ES codes to map ORPHAcodes reached its lowest at the “G” and “Q” chapters with less than 0.2 ICD-10-ES codes available per ORPHAcode. Global ICD-10-ES codes redundancy analysis revealed that only 1055 of the equivalences pertain to group 1. Group 2 contained 3358 equivalences with 634 ICD-10-ES codes while 1322 equivalences were group 3 (11 ICD-10-ES). Within ICD-10-ES chapters, “G” and “Q” contained over 30% and 45% of their own equivalences in the highest redundancy level (group 3) respectively, but under 10% one to one equivalences each (group 1).

Conclusions

ICD-10-ES codes have not enough specificity to identify rare diseases. Direct mapping between ICD and ORPHAcodes or the integration of ORPHAcodes at the healthcare system for diagnoses codification would enable better detection and epidemiological analysis of rare diseases.
Correction to: CANPMR syndrome and chromosome 1p32-p31 deletion syndrome coexist in two related individuals affected by simultaneous haplo-insufficiency of CAMTA1 and NFIA genes
Authors: Coci Emanuele G. , Koehler Udo , Liehr Thomas , Stelzner Armin , Fink Christian , Langen Hendrik , Riedel Joachim
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Genetic risk score for ovarian cancer based on chromosomal-scale length variation
Authors: Toh Christopher , Brody James P.
Published: March 2021

Introduction

Twin studies indicate that a substantial fraction of ovarian cancers should be predictable from genetic testing. Genetic risk scores can stratify women into different classes of risk. Higher risk women can be treated or screened for ovarian cancer, which should reduce ovarian cancer death rates. However, current ovarian cancer genetic risk scores do not work that well. We developed a genetic risk score based on variations in the length of chromosomes.

Methods

We evaluated this genetic risk score using data collected by The Cancer Genome Atlas. We synthesized a dataset of 414 women who had ovarian serous carcinoma and 4225 women who had no form of ovarian cancer. We characterized each woman by 22 numbers, representing the length of each chromosome in their germ line DNA. We used a gradient boosting machine to build a classifier that can predict whether a woman had been diagnosed with ovarian cancer.

Results

The genetic risk score based on chromosomal-scale length variation could stratify women such that the highest 20% had a 160x risk (95% confidence interval 50x-450x) compared to the lowest 20%. The genetic risk score we developed had an area under the curve of the receiver operating characteristic curve of 0.88 (95% confidence interval 0.86–0.91).

Conclusion

A genetic risk score based on chromosomal-scale length variation of germ line DNA provides an effective means of predicting whether or not a woman will develop ovarian cancer.
A study protocol for a randomized controlled trial of an anti-inflammatory nutritional intervention in patients with fibromyalgia
Authors: Silva Ana Rita , Bernardo Alexandra , de Mesquita Maria Fernanda , Vaz Patto José , Moreira Pedro , Silva Maria Leonor , Padrão Patrícia
Published: March 2021

Background

This study aims to analyze the effects of a potentially anti-inflammatory nutritional intervention in disease assessment parameters, inflammatory markers, and quality of life of fibromyalgia (FM) patients.

Methods

A sample of 100 female patients diagnosed with FM, followed up at Portuguese Institute of Rheumatology (IPR) in Lisbon, is being randomly allocated in two groups. Patients in the intervention group are adopting an anti-inflammatory diet, characterized by the exemption of the intake of foods containing gluten, dairy, sugar, and ultra-processed foods, during 3 months. During the first month, a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet is implemented, along with the anti-inflammatory diet, followed by the reintroduction of all fruits and vegetables over a consecutive period of 2 months. Patients in the control group are adopting a diet based on general recommendations for healthy eating. The outcomes are pain, fatigue, quality of sleep, quality of life, gastrointestinal symptoms, and inflammation. Before and after the 3 months intervention, and also 1 month after beginning the intervention, the following questionnaires are applied: Revised Fibromyalgia Impact Questionnaire, visual analog pain scale, Brief Pain Inventory,visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM, Short Form 36, Fatigue Severity Survey, and Pittsburg Sleep Quality Index. Ultra-sensitive serum C-reactive protein, eritrocyte sedimentation rate, and interleukin-8 are determined. Age, physical activity, anthropometric parameters, and body composition are being collected. Student’s t test will assess the association between the disease evaluation parameters, the inflammatory markers, and the dietary interventions.

Discussion

The results of this study are expected to determine whether a change in patient nutrition helps to alleviate symptoms, which would optimize medical intervention.

Trial registration

www.ClinicalTrials.gov NCT04007705. Registered on July 5, 2019.