bluuebunny/crossref_metadata_2025 huggingface dataset:
New cycle, same old mistakes? Overlapping vs. discrete generations in long-term recurrent selection
Authors: Labroo Marlee R. , Rutkoski Jessica E.
Published: October 2022

Background

Recurrent selection is a foundational breeding method for quantitative trait improvement. It typically features rapid breeding cycles that can lead to high rates of genetic gain. Usually, generations are discrete in recurrent selection, which means that breeding candidates are evaluated and considered for selection for only one cycle. Alternately, generations can overlap, with breeding candidates considered for selection as parents for multiple cycles. With recurrent genomic selection but not phenotypic selection, candidates can be re-evaluated by using genomic estimated breeding values without additional phenotyping of the candidates themselves. Therefore, it may be that candidates with true high breeding values discarded in one cycle due to underestimation of breeding value could be identified and selected in subsequent cycles. The consequences of allowing generations to overlap in recurrent selection are unknown. We assessed whether maintaining overlapping and discrete generations led to differences in genetic gain for phenotypic, genomic truncation, and genomic optimum contribution recurrent selection by stochastic simulation.

Results

With phenotypic selection, overlapping generations led to decreased genetic gain compared to discrete generations due to increased selection error bias. Selected individuals, which were in the upper tail of the distribution of phenotypic values, tended to also have high absolute error relative to their true breeding value compared to the overall population. Without repeated phenotyping, these individuals erroneously believed to have high value were repeatedly selected across cycles, leading to decreased genetic gain. With genomic truncation selection, overlapping and discrete generations performed similarly as updating breeding values precluded repeatedly selecting individuals with inaccurately high estimates of breeding values in subsequent cycles. Overlapping generations did not outperform discrete generations in the presence of a positive genetic trend with genomic truncation selection, as individuals from previous breeding cycles typically had truly lower breeding values than candidates from the current generation. With genomic optimum contribution selection, overlapping and discrete generations performed similarly, but overlapping generations slightly outperformed discrete generations in the long term if the targeted inbreeding rate was extremely low.

Conclusion

Maintaining discrete generations in recurrent phenotypic selection leads to increased genetic gain, especially at low heritabilities, by preventing selection error bias. With genomic truncation selection and genomic optimum contribution selection, genetic gain does not differ between discrete and overlapping generations assuming non-genetic effects are not present. Overlapping generations may increase genetic gain in the long term with very low targeted rates of inbreeding in genomic optimum contribution selection.
Gamma-glutamyl transpeptidase to platelet and gamma-glutamyl transpeptidase to lymphocyte ratio in a sample of Chinese Han population
Authors: Chen Weijie , Hong Danmian , Chen Zeliang , Dai Xiaoqing , Cao Jing , Yu Min , Li Liping
Published: October 2022

Background

Gamma-glutamyl transpeptidase to platelet ratio (GPR) and gamma-glutamyl transpeptidase to lymphocyte ratio (GLR) are assumed to be prognostic factors in liver fibrosis, cirrhosis and hepatocellular carcinoma. However, the reference values of GPR and GLR were not known.

Objectives

The study aimed to investigate the reference ranges of GPR and GLR in Chinese Han population in Chaoshan region in South China.

Methods

A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. 2400 healthy adults aged 20~79 years were included. GPR and GLR were determined.

Results

Of 2400 healthy adults, 1200 men and 1200 women were included. The median GPR and GLR for men were 0.22 and 11.28, for women were 0.18 and 7.86, respectively. The 95% reference range of GPR in normal male and female are 0.09~0.54 and 0.08~0.55, GLR are 4.55~29.64 and 3.52~23.08, respectively. The male had a higher GPR at age 20~49 than the female while the GPR at age 60~79 was higher in the female than in the male. The GPR was affected by age, decreased with aging in male and increased in female. The GLR was higher in the male than in the female and varied with aging in the female but not in the male.

Conclusion

The study provides reference data on GPR and GLR from different age and sex groups in South China. GPR and GLR varied with age and sex.
Personalized targeted therapy prescription in colorectal cancer using algorithmic analysis of RNA sequencing data
Authors: Sorokin Maxim , Zolotovskaia Marianna , Nikitin Daniil , Suntsova Maria , Poddubskaya Elena , Glusker Alexander , Garazha Andrew , Moisseev Alexey , Li Xinmin , Sekacheva Marina , Naskhletashvili David , Seryakov Alexander , Wang Ye , Buzdin Anton
Published: October 2022

Background:

Overall survival of advanced colorectal cancer (CRC) patients remains poor, and gene expression analysis could potentially complement detection of clinically relevant mutations to personalize CRC treatments.

Methods:

We performed RNA sequencing of formalin-fixed, paraffin-embedded (FFPE) cancer tissue samples of 23 CRC patients and interpreted the data obtained using bioinformatic method Oncobox for expression-based rating of targeted therapeutics. Oncobox ranks cancer drugs according to the efficiency score calculated using target genes expression and molecular pathway activation data. The patients had primary and metastatic CRC with metastases in liver, peritoneum, brain, adrenal gland, lymph nodes and ovary. Two patients had mutations in NRAS, seven others had mutated KRAS gene. Patients were treated by aflibercept, bevacizumab, bortezomib, cabozantinib, cetuximab, crizotinib, denosumab, panitumumab and regorafenib as monotherapy or in combination with chemotherapy, and information on the success of totally 39 lines of therapy was collected.

Results:

Oncobox drug efficiency score was effective biomarker that could predict treatment outcomes in the experimental cohort (AUC 0.77 for all lines of therapy and 0.91 for the first line after tumor sampling). Separately for bevacizumab, it was effective in the experimental cohort (AUC 0.87) and in 3 independent literature CRC datasets, n = 107 (AUC 0.84–0.94). It also predicted progression-free survival in univariate (Hazard ratio 0.14) and multivariate (Hazard ratio 0.066) analyses. Difference in AUC scores evidences importance of using recent biosamples for the prediction quality.

Conclusion:

Our results suggest that RNA sequencing analysis of tumor FFPE materials may be helpful for personalizing prescriptions of targeted therapeutics in CRC.
Can the level of HbA1C predict diabetic retinopathy among type II diabetic patients?
Authors: Setareh Javad , Hoseinzade Ghazale , Khoundabi Batoul , Kamali Mahsa , Ebrahimi Ata , Fazlollahpour-Naghibi Andarz , Zareei Mohammad , Mohamaditabar Mona , Makaremi Ali
Published: October 2022

Background

Hemoglobin A1C (HbA1C) test is the best care evaluation measurement due to a strong correlation between the test results and diabetic complications. So, this cross-sectional study aimed to assess whether the level of HbA1C can predict Diabetic Retinopathy (DR) among Type 2 diabetes mellitus (T2DM) in the Iranian population.

Method

One hundred sixty-eight diabetic patients were selected via the convenience sampling method. Data were collected by research made questionnaire scale and laboratory test had been done. To estimate the cut off point for some variables statistical tests, formal measures of classification performance, model evaluation criteria and a decision Tree were used.

Results

The prevalence of DR was 29.8%. The Receiver Operating Characteristic (ROC) curve and decision tree showed the optimal cut-off point for the HbA1C variable that separates the patient with and without DR is HbA1C = 8.15.

Conclusion

Current study showed an appropriate cutoff point for detecting the development of DR among diabetic patients. So, this cutoff point can be used as guide evidence in several clinical judgments on the Iranian population.
Association of metabolic comorbidity with myocardial infarction in individuals with a family history of cardiovascular disease: a prospective cohort study
Authors: An Seokyung , Moon Sungji , Park Sue K.
Published: October 2022

Background

The association between metabolic comorbidity and myocardial infarction (MI) among individuals with a family history of cardiovascular disease (CVD) is yet to be elucidated. We aimed to examine the combined effects of metabolic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia, with a family history of CVD in first-degree on the risk of incident MI.

Methods

This cohort study consisted of 81,803 participants aged 40–89 years without a previous history of MI at baseline from the Korean Genome and Epidemiology Study. We performed Cox proportional hazard regression analysis to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for MI and early-onset MI risk associated with metabolic comorbidity in individuals with a family history of CVD.

Results

During a median follow-up of 5 years, 1,075 and 479 cases of total and early-onset MI were reported, respectively. According to the disease score, among individuals who had a positive family history of CVD, the HRs for MI were 1.92 (95% CI: 1.47–2.51) in individuals with one disease, 2.75 (95% CI: 2.09–3.61) in those with two diseases, and 3.74 (95% CI: 2.45–5.71) in those with three diseases at baseline compared to individuals without a family history of CVD and metabolic diseases. Similarly, an increase of the disease score among individuals with a positive family history of CVD was associated with an increase in early-onset MI risk.

Conclusion

Metabolic comorbidity was significantly associated with an increased risk of MI among individuals with a family history of CVD.
Mental and physical health and well-being of Canadian employees who were working from home during the COVID-19 pandemic
Authors: Somasundram Kumara G. , Hackney Amy , Yung Marcus , Du Bronson , Oakman Jodi , Nowrouzi-Kia Behdin , Yazdani Amin
Published: October 2022

Background

The COVID-19 pandemic has drastically changed various aspects of our lives, including how we work. Since the start of the pandemic, numerous organizations in Canada have mandated their employees to work from home (WFH) on a full-time basis. The rapid rise in the number of remote workers and the possibility for WFH continuing in the future signifies the importance of understanding the health and well-being of employees working from home over the course of the pandemic in Canada. We present the findings of two surveys (initial and 6-month follow-up) to examine the health and well-being of WFH employees during the COVID-19 pandemic in Canada. We analyzed the changes in mental and physical health and well-being of employees who were working from home between two time points during the pandemic.

Methods

Initial survey was completed between October 2020 and December 2020 (n = 1617); follow-up survey was completed between May 2021 and June 2021 (n = 382). We calculated the frequencies for survey questions involving demographics, WFH preferences, workstation setup training, employment situation, provision of hardware technologies, provision and usage of software technologies, and organization’s return to work plan. We conducted Wilcoxon signed-rank tests to analyze the within-individual changes in mental and physical health and well-being of the 382 respondents who completed both the initial and follow-up surveys.

Results

Our analyses showed significant changes in various aspects of employee mental and physical health and well-being. Burnout, stress, general mental health, and job insecurity levels significantly decreased between the two time periods. Work-related sedentary behaviour reduced over time; however, the average proportion of time spent sitting during work hours was more than 80% in both surveys. Employees received more help and feedback from their colleagues and experienced a better sense of community with their co-workers over time.

Conclusion

The findings can inform workers and organizations on the changes in mental and physical health and well-being of employees working from home during the pandemic. By understanding the changes in worker health and well-being, employers can develop effective strategies and implement policies that help protect employees’ health and well-being.
Association between sociodemographic status and cardiovascular risk factors burden in community populations: implication for reducing cardiovascular disease burden
Authors: Cai Anping , Nie Zhiqiang , Ou Yanqiu , Wang Jiabin , Chen Yanshuang , Lu Zhisheng , Liang Yanhua , Zhou Yingling , Feng Yingqing
Published: October 2022

Background:

We aimed to evaluate the burden of cardiovascular (CV) risk factors in the community populations of Guangdong Province and its association with sociodemographic status (SDS).

Method:

The data were from the community populations of Guangdong Province who have participated in the China PEACE Million Persons Project between 2016 and 2020 (n = 102,358, women 60.5% and mean age 54.3 years). The prevalence of CV risk factors (smoking, drinking, overweight/obesity, hypertension, dyslipidemia and diabetes mellitus) and its association with SDS (age, sex and socioeconomic status [SES]) was evaluated cross-sectionally.

Results:

The prevalence of overweight/obesity was 48.9%, hypertension 39.9%, dyslipidemia 18.6%, smoking 17.2%, diabetes mellitus 16.1% and drinking 5.3%. Even in young adults (aged 35–44), nearly 60% had at least 1 CV risk factor. Overweight/obesity often coexisted with other risk factors, including smoking, hypertension, dyslipidemia and diabetes mellitus. The proportion of people with no risk factor decreased with increasing age. Women were more likely than men to have no CV risk factor (29.4% vs. 12.7%). People with ≥ high school degree were more likely than those with < high school to have no risk factor (28.5% vs. 20.4%), and farmers were less likely than non-farmers to have no risk factor (20.8% vs. 23.1%).

Conclusion:

The burden of CV risk factors is high and varied by SDS in the community populations of Guangdong Province. Cost-effective and targeted interventions are needed to reduce the burden of CV risk factors at the population level.
Preoperative plasma D-Dimer level is correlated with peritoneal cancer index of patients with pseudomyxoma peritonei
Authors: Feng Jing , Qi Changhai , Lu Yiyan , Wei Hongjiang , Liang Guowei , Ma Ruiqing , Bai Mingjian
Published: October 2022

Purpose

Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients.

Methods

A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI < 28) subgroups. The D-Dimer and tumor markers were compared between the two subgroups. The correlation between the abovementioned biomarkers and PCI will be calculated, and further compared with each other. Two-sided P value less than 0.05 is considered statistically significant.

Results

The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p < 0.001. The Spearman correlation between D-Dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), CA 19 − 9 and PCI were 0.487, 0.509, 0.469, and 0.499, respectively (all p < 0.001). The correlation coefficients were compared with each other according to Meng, Rosenthal and Rubin’s method, however, there was no significant difference.

Conclusion

Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.
Improving midwifery educators’ capacity to teach emergency obstetrics and newborn care in Kenya universities: a pre-post study
Authors: Shikuku Duncan N , Jebet Joyce , Nandikove Peter , Tallam Edna , Ogoti Evans , Nyaga Lucy , Mutsi Hellen , Bashir Issak , Okoro Dan , Bar Zeev Sarah , Ameh Charles
Published: October 2022

Background:

International Confederation of Midwives and World Health Organization recommend core competencies for midwifery educators for effective theory and practical teaching and practice. Deficient curricula and lack of skilled midwifery educators are important factors affecting the quality of graduates from midwifery programmes. The objective of the study was to assess the capacity of university midwifery educators to deliver the updated competency-based curriculum after the capacity strengthening workshop in Kenya.

Methods:

The study used a quasi-experimental (pre-post) design. A four-day training to strengthen the capacity of educators to deliver emergency obstetrics and newborn care (EmONC) within the updated curriculum was conducted for 30 midwifery educators from 27 universities in Kenya. Before-after training assessments in knowledge, two EmONC skills and self-perceived confidence in using different teaching methodologies to deliver the competency-based curricula were conducted. Wilcoxon signed-rank test was used to compare the before-after knowledge and skills mean scores. McNemar test was used to compare differences in the proportion of educators’ self-reported confidence in applying the different teaching pedagogies. P-values < 0.05 were considered statistically significant.

Findings:

Thirty educators (7 males and 23 females) participated, of whom only 11 (37%) had participated in a previous hands-on basic EmONC training – with 10 (91%) having had the training over two years beforehand. Performance mean scores increased significantly for knowledge (60.3% − 88. %), shoulder dystocia management (51.4 – 88.3%), newborn resuscitation (37.9 − 89.1%), and overall skill score (44.7 − 88.7%), p < 0.0001. The proportion of educators with confidence in using different stimulatory participatory teaching methods increased significantly for simulation (36.7 – 70%, p = 0.006), scenarios (53.3 – 80%, p = 0.039) and peer teaching and support (33.3 – 63.3%, p = 0.022). There was improvement in use of lecture method (80 – 90%, p = 0.289), small group discussions (73.3 – 86.7%, p = 0.344) and giving effective feedback (60 – 80%, p = 0.146), although this was not statistically significant.

Conclusion:

Training improved midwifery educators’ knowledge, skills and confidence to deliver the updated EmONC-enhanced curriculum. To ensure that midwifery educators maintain their competence, there is need for structured regular mentoring and continuous professional development. Besides, there is need to cascade the capacity strengthening to reach more midwifery educators for a competent midwifery workforce.
Public-access defibrillation and favorable neurological outcome after out-of-hospital cardiac arrest during the COVID-19 pandemic in Japan
Authors: Matsuyama Tasuku , Kiyohara Kosuke , Kitamura Tetsuhisa , Nishiyama Chika , Kiguchi Takeyuki , Iwami Taku
Published: October 2022

Background

Early public-access defibrillation (PAD) effectively improves the outcomes of out-of-hospital cardiac arrests (OHCA), but several strategies implemented to prevent the spread of coronavirus disease 2019 (COVID-19) could decrease the availability of PAD and worsen outcomes after OHCA. Previous studies have reported conflicting findings, and there is a paucity of nationwide observations. This study aims to investigate the impact of COVID-19 on PAD and OHCA outcomes using a nationwide OHCA registry in Japan, where PAD is well-documented.

Methods

This secondary analysis of the All-Japan Utstein Registry, a prospective population-based nationwide registry of OHCA patients, included patients aged ≥ 18 years with bystander-witnessed OHCA and an initial shockable rhythm who were transported to medical facilities between January 1, 2005, and December 31, 2020. The analytical parameters of this study were the proportion of patients who underwent PAD and patients with one-month survival with favorable neurological outcomes, defined as a cerebral performance category score of 1 or 2. We compared the data between 2019 and 2020 using a multivariable logistic regression analysis.

Results

During the study period, 1,930,273 OHCA patients were registered; of these, 78,302 were eligible for the analysis. Before the COVID-19 pandemic, the proportion of OHCA patients who underwent PAD and demonstrated favorable neurological outcomes increased gradually from 2005 to 2019 (P for trend < 0.001). The proportion of patient who had PAD were 17.7% (876/4959) in 2019 and 15.1% (735/4869) in 2020, respectively. The proportion of patient who displayed favorable neurological outcomes were 25.1% (1245/4959) in 2019 and 22.8% (1109/4869) in 2020, respectively. After adjusting for potential confounders, a significant reduction in the proportion of PAD was observed compared to that in 2019 (adjusted odds ratio [AOR], 0.86; 95% confidence interval [CI], 0.76–0.97), while no significant reduction was observed in favorable neurological outcomes (AOR, 0.97; 95% CI 0.87–1.07).

Conclusion

The proportion of PAD clearly decreased in 2020, probably due to the COVID-19 pandemic in Japan. In contrast, no significant reduction was observed in favorable neurological outcomes.
Association of haemoglobin glycation index with outcomes in patients with acute coronary syndrome: results from an observational cohort study in China
Authors: Li Jiayu , Xin Yanguo , Li Jingye , Zhou Li , Qiu Hui , Shen Aidong , Chen Hui , Li Hongwei
Published: October 2022

Background

The hemoglobin glycation index (HGI) is the difference between measured and estimated glycation of hemoglobin. However, there is limited evidence to investigate the HGI and the clinical outcomes of acute coronary syndrome patients. This study aimed to evaluate the association between HGI and the clinical outcomes of acute coronary syndrome (ACS) in a China cohort.

Method

This single-center retrospective study was carried out in the Cardiovascular Center of Beijing Friendship Hospital, a total of 11004 consecutive patients with ACS from Dec 2012–Dec 2020 were enrolled in this study. Patients were divided into quintiles according to their HGI levels. The incidence of major adverse cardiac and cerebrovascular events (MACCEs) was recorded.

Result

HGI were divided into five quintiles quintiles: −0.906 (−7.188, −0.663), −0.491 (−0.663, −0.343), −0.196 (−0.342, −0.039), 0.170 (−0.039, 0.485), and 1.156 (0.485, 7.875), respectively.

Competing risk regression revealed that HGI was positively related to all-cause death, CV death, and composite MACCEs. Multivariate Cox proportional hazards regression analysis indicated that hypertension (HR:1.109, P = 0.013), previous stroke (HR:1.208, P < 0.001), past PCI (HR: 1.268, P < 0.001), age (HR: 1.011, P < 0.001), BMI (HR: 0.987, P = 0.012), heart rate (HR: 1.004, P = 0.001), NSTEMI (HR: 1.205, P < 0.001), WBC (HR: 1.020, P = 0.008), eGFR (HR: 0.993, P < 0.001), HDL-C (HR: 0.809, P = 0.002), LVEF (HR:0.240, P < 0.001), LM/three-vessel or proximal LAD involved (HR: 1.208 P < 0.001; HR:0.914, P = 0.019, respectively), and antiplatelet agents during hospitalization (HR:0.806, P = 0.020) independently predicted the incidence of MACCEs in ACS patients. Restricted cubic spline indicated a U-shaped association between the HGI and risk of MACCEs.

Conclusion

Both low HGI and high HGI was associated with an increased risk of adverse outcomes in patients with acute coronary syndrome, compared with moderate HGI.
Genome-wide DNA methylation analysis of extreme phenotypes in the identification of novel epigenetic modifications in diabetic retinopathy
Authors: Yang Shaopeng , Guo Xiao , Cheng Weijing , Seth Ishith , Bulloch Gabriella , Chen Yifan , Shang Xianwen , Zhu Zhuoting , Huang Wenyong , Wang Wei
Published: October 2022

Background

Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design.

Methods/results

Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case–control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates.

Conclusions

Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.
Exponential stability for a class of set dynamic equations on time scales
Authors: Jia Keke , Hong Shihuang , Cao Xiaoyu , Yue Jieqing
Published: October 2022

We first present a new definition for some form of exponential stability of solutions, including H-exponential stability, H-exponentially asymptotic stability, H-uniformly exponential stability, and H-uniformly exponentially asymptotic stability for a class of set dynamic equations on time scales. Employing Lyapunov-like functions on time scales, we provide the sufficient conditions for the exponential stability of the trivial solution for such set dynamic equations.
Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p
Authors: Yang Xiaoqi , Wang Shuhua , Zhang Xianjun , Gao Xiangbin , Xu Pengfei
Published: October 2022

Background

Circ-NT5C2 has been confirmed to be highly expressed and associated to the progression of osteosarcoma (OS). However, the behind mechanism of circ-NT5C2 involvement in OS remains unclear.

Methods

The expression of circ-NT5C2, miR-488-3p and FZD4 was measured by quantitative real-time PCR, and the protein expression of E-cadherin, N-cadherin and FZD4 was detected by western blot. Cell counting kit 8 assay, colony formation assay and 5-ethynyl-2-deoxyuridine assay were performed to assess the cell proliferation. The cell apoptosis was measured by flow cytometry and Caspase3/Caspase9 Activity Assay Kits. Cell migration and invasion were detected by transwell assay. Dual-luciferase reporter assay and RIP assay were carried out to determine the binding relation among circ-NT5C2, miR-488-3p and FZD4. Animal experiment and immunohistochemistry analysis were conducted to explore the role of circ-NT5C2 in tumor growth in vivo.

Results

Comparing with controls, the expression of circ-NT5C2 and FZD4 was upregulated and miR-488-3p expression was downregulated in OS tumor tissues and cells. Circ-NT5C2 overexpression facilitated the cell proliferation and motility and induced cell apoptosis of OS cells, whereas circ-NT5C2 knockdown had the opposite effect. Besides, we also found and confirmed that circ-NT5C2 regulated cell malignant behaviors via modulating miR-488-3p/FZD4 axis in OS. Moreover, circ-NT5C2 silencing repressed the growth of xenografts in vivo.

Conclusion

Circ-NT5C2 upregulated FZD4 expression via sponging miR-488-3p, thus facilitating cell malignant behaviors in OS.
Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor
Authors: Jabbar Shaima , Mathews Parker , Wang Xiaobei , Sundaramoorthy Pasupathi , Chu Emily , Piryani Sadhna O. , Ding Shengli , Shen Xiling , Doan Phuong L. , Kang Yubin
Published: October 2022

Background

Thioredoxin-1 (TXN1) is one of the major cellular antioxidants in mammals and is involved in a wide range of physiological cellular responses. However, little is known about the roles and the underlying molecular mechanisms of TXN1 in the regulation of hematopoietic stem/progenitor cells (HSPCs).

Methods

TXN1 conditional knockout mice (ROSA-CreER-TXN1fl/fl) and TXN1fl/fl control mice were used. The mice were treated with tamoxifen and the number and biological functions of HSPCs were measured by flow cytometry, PCR and western blot. Limiting dilution competitive transplantation with sorted HSCs and serial transplantations were performed to assess the effects of TXN1 knockout on HSC self-renewal and long-term reconstitutional capacity. RNA sequencing (RNA-seq) was performed to investigate the downstream molecular pathways of TXN1 deletion in murine HSPCs. CRISPR/Cas9 knockout experiments were performed in vitro in EML murine hematopoietic stem/progenitor cell line to investigate the effects of TXN1 and/or TP53 deletion on cell survival, senescence and colony forming units. TP53 protein degradation assay, CHiP PCR and PGL3 firefly/renilla reporter assay were performed. The effects of TXN1 on various molecular pathways relevant to HSC radiation protection were examined in vitro and in vivo.

Results

TXN1-TP53 tumor suppressor axis regulates HSPC biological fitness. Deletion of TXN1 in HSPCs using in vivo and in vitro models activates TP53 signaling pathway, and attenuates HSPC capacity to reconstitute hematopoiesis. Furthermore, we found that knocking out of TXN1 renders HSPCs more sensitive to radiation and treatment with recombinant TXN1 promotes the proliferation and expansion of HSPCs.

Conclusions

Our findings suggest that TXN1-TP53 axis acts as a regulatory mechanism in HSPC biological functions. Additionally, our study demonstrates the clinical potential of TXN1 for enhancing hematopoietic recovery in hematopoietic stem cell transplant and protecting HSPCs from radiation injury.
Anti-SEZ6L2 antibodies in paraneoplastic cerebellar syndrome: case report and review of the literature
Authors: Kather Annika , Holtbernd Florian , Brunkhorst Robert , Hasan Dimah , Markewitz Robert , Wandinger Klaus-Peter , Wiesmann Martin , Schulz Jörg B. , Tauber Simone C.
Published: October 2022

Seizure Related 6 Homolog Like 2 (SEZ6L2) protein has been shown to have implications in neuronal and especially motor function development. In oncology, overexpression of SEZ6L2 serves as a negative prognostic marker in several tumor entities. Recently, few cases of anti-SEZ6L2 antibody mediated cerebellar syndromes were reported. In this article, we present a case of a 70-year-old woman with subacute onset of gait disturbance, dysarthria and limb ataxia. Serum anti-SEZ6L2 antibodies were markedly increased, and further diagnostic workup revealed left sided breast cancer. Neurological symptoms and SEZ6L2 titer significantly improved after curative tumor therapy. This is a very rare and educationally important report of anti-SEZ6L2 autoimmune cerebellar syndrome with a paraneoplastic etiology. Additionally, we performed a review of the current literature for SEZ6L2, focusing on comparing the published cases on autoimmune cerebellar syndrome.
18F-FDG PET–CT dual-time imaging in detection and characterization of recurrent lesions in patients with testicular cancer
Authors: Nasr Ibrahim Mansour , Talaat Omnia Mohamed , Rezk Mahmoud Aly , Ali Ismail Mohamed
Published: October 2022

Background

Testicular cancer is the second most frequent form of male genital tumors. Globally, testicular malignancy has risen over the last forty years. Among malignant testicular tumors, germ cell tumors represent approximately 95% of all tumors. They are classified into seminomatous and non-seminomatous tumors as they differ in clinical features, therapy, and prognosis. Despite the increasing value of whole-body fluorodeoxyglucose positron emotion tomography/computerized tomography (18FDG-PET/CT) for all malignancies, the practical function of this imaging method in testicular germ cell tumors is still unknown. We aim to assess the diagnostic performance of18FDG-PET/CT dual-time-point imaging (DTPI) in the detection and characterization of recurrent testicular cancer lesions.

Results

18FDG-PET/CT DTPI showed higher specificity (SP) in lesions' delectability and characterization for local, nodal, and distant lesions than the single-time-point imaging (STPI) (97.6%, 93.8%, and 97% versus 95.2%, 68.8%, and 84.8%, respectively) and higher sensitivity (SN) for nodal and distant lesions (97% and 93.8% versus 87.8% and 87.5%, respectively). The mean SUVmaxD and the RI values—not the SUVmaxE—of the malignant lesions were significantly greater than the benign lesions (p 0.001*).

Conclusions

18FDG-PET/CT DTPI and its related indices (SUVmaxD and the RI) are more accurate, sensitive, and specific than the STPI in the characterization of recurrent lesions in testicular cancer patients.
Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer
Authors: Sadik Helen , Pritchard Daryl , Keeling Derry-Mae , Policht Frank , Riccelli Peter , Stone Gretta , Finkel Kira , Schreier Jeff , Munksted Susanne
Published: October 2022

PURPOSE

Personalized medicine presents new opportunities for patients with cancer. However, many patients do not receive the most effective personalized treatments because of challenges associated with integrating predictive biomarker testing into clinical care. Patients are lost at various steps along the precision oncology pathway because of operational inefficiencies, limited understanding of biomarker strategies, inappropriate testing result usage, and access barriers. We examine the impact of various clinical practice gaps associated with diagnostic testing-informed personalized medicine strategies on the treatment of advanced non–small-cell lung cancer (aNSCLC).

METHODS

Using Diaceutics' Data Repository, a multisource database including commercial and Medicare claims and laboratory data from over 500,000 patients with non–small-cell lung cancer in the United States, we analyzed the number of patients with newly diagnosed aNSCLC who could have, but did not, benefit from a personalized treatment. The analysis focuses on the independent and cumulative impacts of gaps occurring during seven steps of the precision oncology pathway, from diagnosis to treatment.

RESULTS

For every 1,000 patients in the study cohort, 497 (49.7%) are lost to precision oncology because of factors associated with getting biomarker test results. Among the 503 of 1,000 patients who did receive results from a biomarker test, 147 (29.2%) did not receive appropriate targeted treatments. Thus, approximately 64% of potentially eligible patients with aNSCLC are not benefiting from precision oncology therapies appropriate for their disease.

CONCLUSION

Most patients with aNSCLC eligible for precision oncology treatments do not benefit from them because of clinical practice gaps. This finding is likely reflective of similar gaps in other cancer types. An increased understanding of the impact of each practice gap can inform strategies to improve the delivery of precision oncology, helping to fully realize the promise of personalized medicine.
Data Mining Framework for Discovering and Clustering Phenotypes of Atypical Diabetes
Authors: Parikh Hemang M , Remedios Cassandra L , Hampe Christiane S , Balasubramanyam Ashok , Fisher-Hoch Susan P , Choi Ye Ji , Patel Sanjeet , McCormick Joseph B , Redondo Maria J , Krischer Jeffrey P
Published: October 2022

Context

Some individuals present with forms of diabetes that are “atypical” (AD), which do not conform to typical features of either type 1 diabetes (T1D) or type 2 diabetes (T2D). These forms of AD display a range of phenotypic characteristics that likely reflect different endotypes based on unique etiologies or pathogenic processes.

Objective

To develop an analytical approach to identify and cluster phenotypes of AD.

Methods

We developed Discover Atypical Diabetes (DiscoverAD), a data mining framework, to identify and cluster phenotypes of AD. DiscoverAD was trained against characteristics of manually classified patients with AD among 278 adults with diabetes within the Cameron County Hispanic Cohort (CCHC) (Study A). We then tested DiscoverAD in a separate population of 758 multiethnic children with T1D within the Texas Children's Hospital Registry for New-Onset Type 1 Diabetes (TCHRNO-1) (Study B).

Results

We identified an AD frequency of 11.5% in the CCHC (Study A) and 5.3% in the pediatric TCHRNO-1 (Study B). Cluster analysis identified 4 distinct groups of AD in Study A: cluster 1, positive for the 65 kDa glutamate decarboxylase autoantibody (GAD65Ab), adult-onset, long disease duration, preserved beta-cell function, no insulin treatment; cluster 2, GAD65Ab negative, diagnosed at age ≤21 years; cluster 3, GAD65Ab negative, adult-onset, poor beta-cell function, lacking central obesity; cluster 4, diabetic ketoacidosis (DKA)–prone participants lacking a typical T1D phenotype. Applying DiscoverAD to the pediatric patients with T1D in Study B revealed 2 distinct groups of AD: cluster 1, autoantibody negative, poor beta-cell function, lower body mass index (BMI); cluster 2, autoantibody positive, higher BMI, higher incidence of DKA.

Conclusion

DiscoverAD can be adapted to different datasets to identify and define phenotypes of participants with AD based on available clinical variables.
Microtubule-associated ROP interactors affect microtubule dynamics and modulate cell wall patterning and root hair growth
Authors: Feiguelman Gil , Cui Xiankui , Sternberg Hasana , Hur Eliran Ben , Higa Takeshi , Oda Yoshihisa , Fu Ying , Yalovsky Shaul
Published: October 2022

Rho of plant (ROP) proteins and the interactor of constitutively active ROP (ICR) family member ICR5/MIDD1 have been implicated to function as signaling modules that regulate metaxylem secondary cell wall patterning. Yet, loss-of-function mutants of ICR5 and its closest homologs have not been studied and, hence, the functions of these ICR family members are not fully established. Here, we studied the functions of ICR2 and its homolog ICR5. We show that ICR2 is a microtubule-associated protein that affects microtubule dynamics. Secondary cell wall pits in the metaxylem of Arabidopsis icr2 and icr5 single mutants and icr2 icr5 double mutants are smaller than those in wild-type Col-0 seedlings; however, they are remarkably denser, implying a complex function of ICRs in secondary cell wall patterning. ICR5 has a unique function in protoxylem secondary cell wall patterning, whereas icr2, but not icr5, mutants develop split root hairs, demonstrating functional diversification. Taken together, our results show that ICR2 and ICR5 have unique and cooperative functions as microtubule-associated proteins and as ROP effectors.
Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition
Authors: Destefanis Francesca , Manara Valeria , Santarelli Stefania , Zola Sheri , Brambilla Marco , Viola Giacomo , Maragno Paola , Signoria Ilaria , Viero Gabriella , Pasini Maria Enrica , Penzo Marianna , Bellosta Paola
Published: October 2022

NOC1 is a nucleolar protein necessary in yeast for both transport and maturation of ribosomal subunits. Here, we show that Drosophila NOC1 (annotated CG7839) is necessary for rRNAs maturation and for a correct animal development. Its ubiquitous downregulation results in a dramatic decrease in polysome level and of protein synthesis. NOC1 expression in multiple organs, such as the prothoracic gland and the fat body, is necessary for their proper functioning. Reduction of NOC1 in epithelial cells from the imaginal discs results in clones that die by apoptosis, an event that is partially rescued in a Minute/+ background, suggesting that reduction of NOC1 induces the cells to become less fit and to acquire a ‘loser’ state. NOC1 downregulation activates the pro-apoptotic Eiger–JNK pathway and leads to an increase of Xrp1, which results in the upregulation of DILP8, a member of the insulin/relaxin-like family known to coordinate organ growth with animal development. Our data underline NOC1 as an essential gene in ribosome biogenesis and highlight its novel functions in the control of growth and cell competition.
SCRAP: a bioinformatic pipeline for the analysis of small chimeric RNA-seq data
Authors: Mills William T. , Eadara Sreenivas , Jaffe Andrew E. , Meffert Mollie K.
Published: October 2022

MicroRNAs (miRNAs) are small noncoding RNAs (sncRNAs) that function in post-transcriptional gene regulation through imperfect base pairing with mRNA targets, which results in inhibition of translation and typically destabilization of bound transcripts. Sequence-based algorithms historically used to predict miRNA targets face inherent challenges in reliably reflecting in vivo interactions. Recent strategies have directly profiled miRNA–target interactions by crosslinking and ligation of sncRNAs to their targets within the RNA-induced silencing complex (RISC), followed by high-throughput sequencing of the chimeric sncRNA:target RNAs. Despite the strength of these direct profiling approaches, standardized pipelines for effectively analyzing the resulting chimeric sncRNA:target RNA sequencing data are not readily available. Here we present SCRAP, a robustsmallchimeric RNAanalysispipeline for the bioinformatic processing of chimeric sncRNA:target RNA sequencing data. SCRAP consists of two parts, each of which is specifically optimized for the distinctive characteristics of chimeric small RNA sequencing reads: first, read processing and alignment and second, peak calling and annotation. We apply SCRAP to benchmark chimeric sncRNA:target RNA sequencing data sets generated by distinct molecular approaches, and compare SCRAP to existing chimeric RNA analysis pipelines. SCRAP has minimal hardware requirements, is cross-platform, and contains extensive annotations to broaden accessibility for processing small chimeric RNA sequencing data and enable insights into the targets of small noncoding RNAs in regulating diverse biological systems.
Międzypokoleniowe uczenie się
Authors: Muszynski Marcin
Published: October 2022

Międzypokoleniowe uczenie się może mieć charakter nieformalny oraz pozaformalny. W pierwszym przypadku odbywa się wewnątrz rodziny, jak też i poza nią. Natomiast w drugim przypadku przyjmuje postać różnych edukacyjnych programów międzypokoleniowych. Problematyka podjętych badań dotyczy nieformalnego wymiaru międzypokoleniowego uczenia się. Głównym celem było rozpoznanie pozycji, z jakiej osoby starsze kierują swój przekaz do innych pokoleń, identyfikacja zakresu i siły tego przekazu oraz tego, czym wyróżnia się przekaz międzygeneracyjny w późnej dorosłości. Badanie osadzone zostało w paradygmacie konstrukcjonistycznym i metodologii teorii ugruntowanej. Do gromadzenia danych wykorzystana została technika wywiadu częściowo strukturyzowanego. Materiał empiryczny stanowiło 37 nagranych wywiadów z osobami powyżej siedemdziesiątego roku życia (21 kobiet i 16 mężczyzn). Dobór kolejnych przypadków miał charakter teoretyczny. Wyniki przeprowadzonych analiz wykazały, że osoby starsze kierują swój przekaz do różnych pokoleń z dwóch jakościowo odmiennych pozycji – znaczących innych oraz tradycyjnych autorytetów. W przypadku znaczących innych zakres przekazu jest niewielki, ale za to duża jest siła jego oddziaływania. Przekaz formułowany z pozycji tradycyjnych autorytetów ma relatywnie niski zakres i siłę oddziaływania. Wyniki badań pokazują, że międzypokoleniowe uczenie się może zachodzić w obu kierunkach – od generacji starszej do młodszej i od młodszej do starszej, choć z drugiej strony silnie dokumentuje się zjawisko zaimpregnowania inaczej zamknięcia się na przekaz międzygeneracyjny przez osoby z różnych pokoleń. To, co pojawia się w przekazie osób starszych a jest raczej niespotykane na wcześniejszych etapach życia to komunikaty o uniwersalnym przesłaniu do anonimowego i bezosobowego odbiorcy.
Experiencing culture of everyday life by international exchange students. Perspective of arts-based research
Authors: Pryszmont Martyna , Achremowicz Hanna , Pilawska-Gronostaj Roksana , Wylęgły Kamila
Published: October 2022

The text is an attempt to introduce and initiate a research project which focuses on experiencing the culture of daily living by international exchange students. The authors present major theoretical reflections on the issues of experience and culture of everyday life; they also characterize the community of student– participants of international exchange programs. (Re)cognition and understanding of experience is a methodological challenge, especially in regard to dialogue-oriented intercultural education. The authors decided to explore the issue, using arts-based research. In this model, the role of researchers-facilitators is to introduce the respondents into the research process by inviting them to participate in joint activities focusing on cognitive, artistic, social, and educational objectives. Such participation and cooperation are supposed to result in generating critical knowledge necessary to improve the respondents’ daily life. In the last part of the text, the authors conduct an initial analysis of the selected international exchange programs. The goal of the characteristics of ERASMUS, ISEP, AIESEC, CEEPUS programs is to outline the official objectives and priorities assigned to formal education. In this perspective, when planning their original research, the authors asked the following question: How are these priorities present, as complementary to non-formal education, in experiencing the culture of everyday life by exchange students?
Komunikat z badań realizowanych w ramach międzynarodowego projektu badawczego DANUBE
Authors: Wnęk-Gozdek Joanna , Włoch Anna , Tomczyk Łukasz
Published: October 2022

Dynamiczne zmiany zachodzące we współczesnych społeczeństwach, związane z postępującymi procesami globalizacyjnymi, wymuszają wśród dorosłych konieczność poszerzania i uzupełniania posiadanej wiedzy. Dorośli w europejskich społeczeństwach muszą wykazać się gotowością do uczenia się, stałego podnoszenia własnych kwalifikacji, a niekiedy do przekwalifikowania się i uczenia się czegoś nowego. Inwestowanie w edukację także wśród dorosłych wpisuje się w realizację koncepcji „Europy wiedzy” oraz „uczenia się przez całe życie”. Instytucje Unii Europejskiej, respektując odmienność i niezależność narodowych systemów oświaty, jedyne działania, jakie podejmują w zakresie edukacji, to wspieranie jej rozwoju na wszystkich szczeblach. W ostatniej dekadzie szczególnie istotne okazało się wspieranie ze strony instytucji unijnych edukacji dorosłych w krajach UE.