bluuebunny/crossref_metadata_2025 huggingface dataset:
Klebsiella pneumoniae pneumonia in patients with rheumatic autoimmune diseases: clinical characteristics, antimicrobial resistance and factors associated with extended-spectrum β-lactamase production
Authors: Liu Yang , Liu Yecheng , Dai Jiayuan , Liu Anlei , Li Yi , Xu Jun , Yu Xuezhong , Liu Jihai , Zhu Huadong
Published: April 2021

Background

Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum β-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department.

Methods

We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected.

Results

Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing.

Conclusions

K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.
Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study
Authors: Kjældgaard Anne-Lene , Pilely Katrine , Olsen Karsten Skovgaard , Jessen Anders Hedegaard , Lauritsen Anne Øberg , Pedersen Stephen Wørlich , Svenstrup Kirsten , Karlsborg Merete , Thagesen Helle , Blaabjerg Morten , Theódórsdóttir Ásta , Elmo Elisabeth Gundtoft , Møller Anette Torvin , Bonefeld Lone , Berg Mia , Garred Peter , Møller Kirsten
Published: April 2021

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials.

Objective

This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort.

Methods

The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis.

Results and conclusions

Both ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.
Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers
Authors: Lan Aihua , Ren Chunxia , Wang Xiaoling , Tong Guoqing , Yang Gong
Published: April 2021

Background

Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG.

Methods

RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID).

Results

Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers.

Conclusion

Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).
Effects of once-yearly zoledronic acid on bone density and incident vertebral fractures in nonmetastatic castration-sensitive prostate cancer patients with osteoporosis
Authors: Watanabe Daisuke , Kimura Takahiro , Watanabe Ken , Takano Hiromitsu , Uehara Yuko , Minowa Tadaaki , Yamashita Akemi , Yoshikawa Seiichiro , Mizushima Akio
Published: April 2021

Background

Androgen deprivation therapy (ADT) is the effective treating prostate cancer but is often accompanied by cancer treatment-induced bone loss (CTIBL), which impairs the patient’s quality of life. In patients with nonmetastatic castration-sensitive prostate cancer (M0CSPC) who already have osteoporosis before starting ADT, appropriate bone-modifying agent intervention must be performed in parallel, as the patient has a high risk of future fracture. However, little is known about therapeutic interventions aimed at preventing the progression of CTIBL and new fractures. The present study explored the effect of once-yearly zoledronic acid 5 mg (ZOL 5 mg) on bone mineral density (BMD) and new vertebral fractures (VFs) in M0CSPC patients with coexisting osteoporosis before starting ADT.

Methods

We conducted a retrospective, multi-institutional, cohort study involving 42 M0CSPC patients with osteoporosis who had undergone ADT with/without a single intravenous infusion of ZOL 5 mg at the start of ADT (ZOL 5 mg group, n = 26; control group, n = 16). The association of the ZOL 5 mg with changes in the BMD from baseline to 12 months and the incidence of VFs were evaluated.

Results

Prevalent VFs were found in 47.6% of all patients at baseline. ZOL 5 mg significantly increased the lumbar spine BMD (LS-BMD) (mean rate of change: + 4.02%, p < 0.0001) and significantly decreased the TRACP-5b (mean rate of change: − 52.1%, p < 0.0001) at 12 months after starting ADT. Incident VFs were identified in 19.0% of all patients at 12 months after starting ADT. After adjusting for the age, BMI, and changes in the LS-BMD, ZOL 5 mg was not significantly associated with incident VFs (odds ratio 0.66, 95% confidence interval 0.04–11.3, p = 0.7774).

Conclusion

ZOL 5 mg significantly increased the LS-BMD 12 months after starting ADT, and our short-term results showed that ZOL 5 mg was not significantly correlated with the suppression of incident vertebral fractures.
Psychosocial characteristics and HIV-related sexual behaviors among cisgender, transgender, and gender non-conforming MSM in China
Authors: Duan Zhizhou , Wang Liyin , Guo Menglan , Ding Changmian , Huang Danqin , Yan Hong , Wilson Amanda , Li Shiyue
Published: April 2021

Background

While a growing number of studies focus on men who have sex with men (MSM), they typically ignore the heterogeneity of gender minorities within the MSM population. The recognition of new sub-groups among gender minorities (i.e., transgender and gender non-conforming), who also identify as MSM, play a considerable role in new HIV infections in China. Information on the psychosocial factors and HIV-related sexual behaviors require further consideration to understand the prevalence of HIV infection among MSM within these gender minority sub-groups.

Methods

From September 2017 to January 2018, MSM without HIV were recruited in Wuhan, Nanchang, and Changsha cities in China. Participants were asked to fill out a structured self-administered questionnaire to assess depression, perceived social support, resilience, identity concealment, and HIV-related risky sexual behaviors.

Results

A total of 715 MSM completed the structured questionnaire, the number of MSM identifying as gender minorities were 63 and accounted for 8.8% of the population. Compared to the cisgender MSM population, transgender MSM were more likely to have a one-night stand/occasional partner (AOR = 3.49, 95% CI =1.02–11.98), to have sex after drug use in the past 6 months (AOR = 2.57, 95%CI =1.05–6.29), and to have reported a significantly lower likelihood of identity concealment (mean difference = − 3.30, 95%CI = -5.86, − 0.74, P = 0.01).

Conclusions

The findings highlight the significance of providing targeted interventions for different gender minorities within the MSM population. Research is required to further understand the relationship between gender identity, mental health, and HIV-related sexual behaviors.
COVID-19 pandemic-related changes in wellness behavior among older Americans
Authors: Harrison Elgloria , Monroe-Lord Lillie , Carson Andrew D. , Jean-Baptiste Anne Marie , Phoenix Janet , Jackson Phronie , Harris B. Michelle , Asongwed Elmira , Richardson Matthew L.
Published: April 2021

Background

COVID-19 has taken its toll on citizens in all 50 states of the United States. The United States (U.S.) leads the world with 30,291,863 confirmed reported cases and 549,664 deaths as of March 29, 2021 compared to globally confirmed cases at 127,442,926 and 2,787,915 deaths as of March 29, 2021. The U.S. federal government primarily left the response to the virus to individual states, and each implemented varying measures designed to protect health of citizens and the state’s economic well-being. Unintended consequences of the virus and measures to stop its spread may include decreased physical activity and exercise, shifting access and consumption of food, and lower quality-of-life. Therefore, our primary goal was to quantify the impact of COVID-19 on health and well-being by measuring changes in physical activity, mental health-quality of life, food security and nutrition in adults ages 40 and older. We believed shifts in health behaviors would be more prevalent in minorities, less educated, lower socio-economic status, older adults, and those with underlying health conditions, so a secondary goal was to determine the impact of COVID-19 on these sub-populations.

Methods

We conducted an online survey with 9969 adults 40 years and older between 9 August and 15 September 2020 in urban areas across the four U.S. census regions. The survey included questions about demographic variables, pre-existing health conditions, physical activity, access to food, quality-of-life, and nutritional food status and asked participants to respond with information from pre-pandemic and pandemic conditions. We used paired-sample t-tests to detect changes in variables after the start of the pandemic and Cohen’s d to determine effect sizes.

Results

Our main findings showed a decrease in physical activity since the onset of COVID-19 for minorities and non-minorities. Food security also slightly increased for minorities during the pandemic, but we found no other changes in food security, quality-of-life indicators, or nutritional status of those who responded to this survey.

Conclusions

It is concerning that physical activity declined. Such activity helps maintain physical and mental health, and it is also an important time to socialize for many older adults. In many ways, our data indicate that the older adult population in U.S. cities may be more resilient than expected during the pandemic. However, the pandemic could have negative impacts that we did not detect, either due to the survey instrument or the timing of our survey, so the health and well-being of older adults should continue to be monitored in order to mitigate potential negative impacts.
Magnitude and predictors of hospital admission, readmission, and length of stay among patients with type 2 diabetes at public hospitals of Eastern Ethiopia: a retrospective cohort study
Authors: Regassa Lemma Demissie , Tola Assefa
Published: April 2021

Background

Type 2 Diabetes (T2D) represents one of the leading causes for hospital admissions and outpatient visits. Hence, T2D continuously imposes a significant burden to healthcare systems. The aim of this study was to assess predictors of hospital admission, readmission rates, and length of hospital stay among T2D patients in government hospitals of Eastern Ethiopia from 2013 to 2017.

Methods

This study utilized retrospective data from a cohort of T2D patients following their treatment in government hospitals in Harari regional state of Ethiopia. Predictor of hospital admission was determined using parametric survival analysis methods. The readmission rate and length of hospital stay were determined by Poisson regression and mixed effect Poisson regression, respectively. All association were performed at 95% confidence level. Significance of association with determinants was reported using the hazard rate for hospital admission, and the incidence rate for readmission and length of hospital stay. Optimal model for each outcome was selected by using information criteria after fitness was checked.

Results

The hospital admission rate for T2D patients was 9.85 (95%CI: 8.32, 11.66) per 1000-person-year observation. Alcohol drinking, inactive lifestyle, being a rural resident, history of comorbidities, and experiencing chronic diabetes complications were predictors of hospital admission. Seventy-one (52.2%) of the admitted patients had a history of readmission. Readmission rate was increased by being female, duration of disease, inactive lifestyle, having BMI greater than 29.9 kg/m2, and higher blood glucose. The median time of hospital stay for admitted patients was 18 (IQR:7). The length of hospital stay was longer among females, patients with the history of insulin administration, and higher blood glucose.

Conclusion

Multiple and complex factors were contributing for high diabetes admission and readmission rates as well as for longer in-hospital duration among T2D patients in Harari regional state. Socio-demographic characteristics (sex, place of residence), behavioral factors (alcohol intake, lifestyle), and medical conditions (longer duration of disease, comorbidities, chronic diabetes complications, higher blood glucose level, and treatment modality) were significant determinants of hospital admission, readmission and longer hospital stay among T2D patients.
Harmful alcohol use among mothers of under-five child: findings from the Panel Study on Korean Children
Authors: Kim Seulgi , Choe Seung-Ah , Cho Sung-Il
Published: April 2021

Background

Harmful alcohol use in young mothers as a primary caregiver has a profound impact on their own health and interaction with the child. We studied the epidemiology of harmful alcohol use among Korean mothers and their partners of under-five children.

Methods

We used a longitudinal data of 2,150 Korean mothers of the Panel Study on Korean Children (PSKC). We assessed temporal trend and risk factors for harmful alcohol use in mothers using generalized estimating equation (GEE) model. To estimate the impact of maternal harmful alcohol use on the child, the association between neurodevelopment of the child measured by the Korean-Ages & Stages Questionnaire (K-ASQ) and maternal harmful alcohol use was analyzed using GEE and generalized linear mixed model. We included mother’s age, education, preterm, year of the survey and time-varying covariates (including maternal working status, monthly household income, plan for additional childbirth, psychological stress related with childcare, current smoking, and partner’s harmful alcohol use) in the model.

Results

Mean age of mothers at the baseline was 31.3 years. Annual prevalence of harmful alcohol use increased from 0.7% in the 1st year to 2.6% in the 4th year (P for linear trend < 0.001). Prevalence of harmful alcohol use increased by 48% per year among the mothers (adjusted odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.22, 1.78). Lower education than college or university graduation was associated with higher odds of harmful alcohol use (2.52, 95% CI: 1.43, 4.45). Current smoking (7.44, 95% CI: 3.00, 18.45), harmful use of alcohol of partner (2.66, 95% CI: 1.57, 4.49) were associated with higher risk of harmful alcohol use in mothers. The association between low K-ASQ score and maternal harmful alcohol use was toward positive which did not reach statistical significance.

Conclusions

In a cohort of Korean mothers participating in the PKSC, risk of harmful alcohol use increases over time and is associated with harmful alcohol use of their partners. We suggest an approach targeting both parents can be more effective in controlling the harmful alcohol use of mothers.
Risk factors associated with physician trainee concern over missed educational opportunities during the COVID-19 pandemic
Authors: Lou Sunny S. , Goss Charles W. , Evanoff Bradley A. , Duncan Jennifer G. , Kannampallil Thomas
Published: April 2021

Background

The COVID-19 pandemic resulted in a transformation of clinical care practices to protect both patients and providers. These changes led to a decrease in patient volume, impacting physician trainee education due to lost clinical and didactic opportunities. We measured the prevalence of trainee concern over missed educational opportunities and investigated the risk factors leading to such concerns.

Methods

All residents and fellows at a large academic medical center were invited to participate in a web-based survey in May of 2020. Participants responded to questions regarding demographic characteristics, specialty, primary assigned responsibility during the previous 2 weeks (clinical, education, or research), perceived concern over missed educational opportunities, and burnout. Multivariable logistic regression was used to assess the relationship between missed educational opportunities and the measured variables.

Results

22% (301 of 1375) of the trainees completed the survey. 47% of the participants were concerned about missed educational opportunities. Trainees assigned to education at home had 2.85 [95%CI 1.33–6.45] greater odds of being concerned over missed educational opportunities as compared with trainees performing clinical work. Trainees performing research were not similarly affected [aOR = 0.96, 95%CI (0.47–1.93)]. Trainees in pathology or radiology had 2.51 [95%CI 1.16–5.68] greater odds of concern for missed educational opportunities as compared with medicine. Trainees with greater concern over missed opportunities were more likely to be experiencing burnout (p = 0.038).

Conclusions

Trainees in radiology or pathology and those assigned to education at home were more likely to be concerned about their missed educational opportunities. Residency programs should consider providing trainees with research or at home clinical opportunities as an alternative to self-study should future need for reduced clinical hours arise.
A 4-gene-based hypoxia signature is associated with tumor immune microenvironment and predicts the prognosis of pancreatic cancer patients
Authors: Ding Jianfeng , He Xiaobo , Cheng Xiao , Cao Guodong , Chen Bo , Chen Sihan , Xiong Maoming
Published: April 2021

Background

Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood.

Methods

The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score.

Results

We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor.

Conclusions

In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.
Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS
Authors: Jäkel Bianka , Kedor Claudia , Grabowski Patricia , Wittke Kirsten , Thiel Silvia , Scherbakov Nadja , Doehner Wolfram , Scheibenbogen Carmen , Freitag Helma
Published: April 2021

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease accompanied by muscular fatigue and pain. A functional measure to assess muscle fatigability of ME/CFS patients is, however, not established in clinical routine. The aim of this study is to evaluate by assessing repeat maximum handgrip strength (HGS), muscle fatigability as a diagnostic tool and its correlation with clinical parameters.

Methods

We assessed the HGS of 105 patients with ME/CFS, 18 patients with Cancer related fatigue (CRF) and 66 healthy controls (HC) using an electric dynamometer assessing maximal (Fmax) and mean force (Fmean) of ten repetitive measurements. Results were correlated with clinical parameters, creatinine kinase (CK) and lactate dehydrogenase (LDH). Further, maximum isometric quadriceps strength measurement was conducted in eight ME/CFS patients and eight HC.

Results

ME/CFS patients have a significantly lower Fmax and Fmean HGS compared to HC (p < 0.0001). Further, Fatigue Ratio assessing decline in strength during repeat maximal HGS measurement (Fmax/Fmean) was higher (p ≤ 0.0012). The Recovery Ratio after an identical second testing 60 min later was significantly lower in ME/CFS compared to HC (Fmean2/Fmean1; p ≤ 0.0020). Lower HGS parameters correlated with severity of disease, post-exertional malaise and muscle pain and with higher CK and LDH levels after exertion.

Conclusion

Repeat HGS assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.
Chemotherapy-induced CDA expression renders resistant non-small cell lung cancer cells sensitive to 5′-deoxy-5-fluorocytidine (5′-DFCR)
Authors: Gao Yanyun , Zens Philipp , Su Min , Gemperli Camila Anna , Yang Haitang , Deng Haibin , Yang Zhang , Xu Duo , Hall Sean R. R. , Berezowska Sabina , Dorn Patrick , Peng Ren-Wang , Schmid Ralph Alexander , Wang Wenxiang , Marti Thomas Michael
Published: April 2021

Background

Pemetrexed (MTA) plus cisplatin combination therapy is considered the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, in advanced NSCLC, the 5-year survival rate is below 10%, mainly due to resistance to therapy. We have previously shown that the fraction of mesenchymal-like, chemotherapy-resistant paraclone cells increased after MTA and cisplatin combination therapy in the NSCLC cell line A549.

Cytidine deaminase (CDA) and thymidine phosphorylase (TYMP) are key enzymes of the pyrimidine salvage pathway. 5′-deoxy-5-fluorocytidine (5′-DFCR) is a cytidine analogue (metabolite of capecitabine), which is converted by CDA and subsequently by TYMP into 5-fluorouracil, a chemotherapeutic agent frequently used to treat solid tumors. The aim of this study was to identify and exploit chemotherapy-induced metabolic adaptations to target resistant cancer cells.

Methods

Cell viability and colony formation assays were used to quantify the efficacy of MTA and cisplatin treatment in combination with schedule-dependent addition of 5′-DFCR on growth and survival of A549 paraclone cells and NSCLC cell lines. CDA and TYMP protein expression were monitored by Western blot. Finally, flow cytometry was used to analyze the EMT phenotype, DNA damage response activation and cell cycle distribution over time after treatment. CDA expression was measured by immunohistochemistry in tumor tissues of patients before and after neoadjuvant chemotherapy.

Results

We performed a small-scale screen of mitochondrial metabolism inhibitors, which revealed that 5′-DFCR selectively targets chemotherapy-resistant A549 paraclone cells characterized by high CDA and TYMP expression. In the cell line A549, CDA and TYMP expression was further increased by chemotherapy in a time-dependent manner, which was also observed in the KRAS-addicted NSCLC cell lines H358 and H411. The addition of 5′-DFCR on the second day after MTA and cisplatin combination therapy was the most efficient treatment to eradicate chemotherapy-resistant NSCLC cells. Moreover, recovery from treatment-induced DNA damage was delayed and accompanied by senescence induction and acquisition of a hybrid-EMT phenotype. In a subset of patient tumors, CDA expression was also increased after treatment with neoadjuvant chemotherapy.

Conclusions

Chemotherapy increases CDA and TYMP expression thereby rendering resistant lung cancer cells susceptible to subsequent 5′-DFCR treatment.
Ovarian sex cord stromal tumours: analysis of the clinical and sonographic characteristics of different histopathologic subtypes
Authors: Jiang Mei-jiao , Le Qian , Yang Bo-wen , Yuan Fei , Chen Hui
Published: April 2021

Background

Ovarian sex cord stromal tumours (OSCSTs) are rare ovarian tumours and include different histopathologic subtypes. This study aimed to analyse the clinical and sonographic characteristics of different histopathologic OSCST subtypes.

Methods

A total of 63 patients with surgically proven OSCSTs were enrolled in this retrospective study to analyse their clinical and sonographic features. Ultrasound examinations and predictive models were performed before surgery. The clinical and sonographic findings were compared according to the type of OSCST based on the histopathological diagnosis.

Results

The mean age of 63 patients was 52.17 years (range: 17–78 years). Eighteen patients experienced irregular vaginal bleeding (28.57% 18/63), 7 patients exhibited abnormal body hair (11.11%). 2 patients (3.17%) showed an increased level of CA125, and 25 patients (39.68%, 25/63) showed an increased level of testosterone. Forty-two patients had ovarian thecoma-fibroma groups (OTFGs). Six patients had Sertoli-Leydig cell tumours (S-LCTs), 4 patients had Leydig cell tumours (LCTs), 8 patients had ovarian granulosa cell tumours (OGCTs), 2 patients had ovarian steroid cell tumours, not otherwise specified (OSCTs-NOS), and one patient had sclerosing stromal tumours (SSTs). The mean diameter of the tumour was 47.9 mm (range: 10–258 mm). Forty-seven masses were hypoechoic (74.60%). Twenty-eight masses had posterior echo attenuation, 22 masses exhibited abundant Doppler flow signals (34.92%), and one patient had ascites (1.59%). The diagnostic accuracy of the Simple Rules (SR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in distinguishing benign and malignant OSCSTs was 44% (30/63) and 84% (53/63), respectively. The diagnostic accuracy of the SR for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 47.6% (20/42), 16.67% (2/12), 100% (8/8), and 0% (0/1), respectively. The diagnostic accuracy of the ADNEX model for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 93% (31/42), 58.33% (7/12), 75% (6/8), and 100% (1/1), respectively.

Conclusions

OSCSTs generally appear as a solid mass on ultrasound. Posterior echo attenuation indicates an OTFG. A solid mass with abundant Doppler flow signals indicates an S-LCT, LCT, OSCT-NOS or OGCT. Current predictive models are not very effective, but symptoms, sonographic features and serum hormones are helpful for diagnosis.
Broadly sampled orthologous groups of eukaryotic proteins for the phylogenetic study of plastid-bearing lineages
Authors: Van Vlierberghe Mick , Philippe Hervé , Baurain Denis
Published: April 2021

Objectives

Identifying orthology relationships among sequences is essential to understand evolution, diversity of life and ancestry among organisms. To build alignments of orthologous sequences, phylogenomic pipelines often start with all-vs-all similarity searches, followed by a clustering step. For the protein clusters (orthogroups) to be as accurate as possible, proteomes of good quality are needed. Here, our objective is to assemble a data set especially suited for the phylogenomic study of algae and formerly photosynthetic eukaryotes, which implies the proper integration of organellar data, to enable distinguishing between several copies of one gene (paralogs), taking into account their cellular compartment, if necessary.

Data description

We submitted 73 top-quality and taxonomically diverse proteomes to OrthoFinder. We obtained 47,266 orthogroups and identified 11,775 orthogroups with at least two algae. Whenever possible, sequences were functionally annotated with eggNOG and tagged after their genomic and target compartment(s). Then we aligned and computed phylogenetic trees for the orthogroups with IQ-TREE. Finally, these trees were further processed by identifying and pruning the subtrees exclusively composed of plastid-bearing organisms to yield a set of 31,784 clans suitable for studying photosynthetic organism genome evolution.
Adjunct therapy with probiotics for chronic urticaria in children: randomised placebo-controlled trial
Authors: Bi Xiao-Dong , Lu Bao-Zhen , Pan Xin-Xin , Liu Sha , Wang Jiu-Yao
Published: April 2021

Backgrounds

Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria.

Objective

This study aimed to evaluate the efficacy of the Yimingjia® probiotic formula in the adjuvant treatment of chronic urticaria in children.

Methods

We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia®. Clinical efficacy was evaluated at 1, 2 and 4 weeks.

Results

Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ2 = 4.20, p = 0.04).

Conclusion

Adjunct therapy with Yimingjia® was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.
Flame: an open source framework for model development, hosting, and usage in production environments
Authors: Pastor Manuel , Gómez-Tamayo José Carlos , Sanz Ferran
Published: April 2021

This article describes Flame, an open source software for building predictive models and supporting their use in production environments. Flame is a web application with a web-based graphic interface, which can be used as a desktop application or installed in a server receiving requests from multiple users. Models can be built starting from any collection of biologically annotated chemical structures since the software supports structural normalization, molecular descriptor calculation, and machine learning model generation using predefined workflows. The model building workflow can be customized from the graphic interface, selecting the type of normalization, molecular descriptors, and machine learning algorithm to be used from a panel of state-of-the-art methods implemented natively. Moreover, Flame implements a mechanism allowing to extend its source code, adding unlimited model customization. Models generated with Flame can be easily exported, facilitating collaborative model development. All models are stored in a model repository supporting model versioning. Models are identified by unique model IDs and include detailed documentation formatted using widely accepted standards. The current version is the result of nearly 3 years of development in collaboration with users from the pharmaceutical industry within the IMI eTRANSAFE project, which aims, among other objectives, to develop high-quality predictive models based on shared legacy data for assessing the safety of drug candidates.
Preferences of patients with asthma or COPD for treatments in pulmonary rehabilitation
Authors: Damm Kathrin , Lingner Heidrun , Schmidt Katharina , Aumann-Suslin Ines , Buhr-Schinner Heike , van der Meyden Jochen , Schultz Konrad
Published: April 2021

Introduction

Pulmonary rehabilitation (PR) aims to improve disease control in patients with chronic obstructive pulmonary disease (COPD) and asthma. However, the success of PR-programs depends on the patients’ participation and willingness to cooperate. Taking the patients’ preferences into consideration might improve both of these factors. Accordingly, our study aims to analyze patients’ preferences regarding current rehabilitation approaches in order to deduce and discuss possibilities to further optimize pulmonary rehabilitation.

Methods and analysis

At the end of a 3 weeks in-house PR, patients’ preferences concerning the proposed therapies were assessed during two different time slots (summer 2015 and winter 2015/2016) in three clinics using a choice-based conjoint analysis (CA). Relevant therapy attributes and their levels were identified through literature search and expert interviews. Inclusion criteria were as follows: PR-inpatient with asthma and/or COPD, confirmed diagnosis, age over 18 years, capability to write and read German, written informed consent obtained. The CA analyses comprised a generalized linear mixed-effects model and a latent class mixed logit model.

Results

A total of 542 persons participated in the survey. The most important attribute was sport and exercise therapy. Rehabilitation preferences hardly differed between asthma and COPD patients. Health-related quality of life (HRQoL) as well as time since diagnosis were found to have a significant influence on patients’ rehabilitation preferences.

Conclusions

Patients in pulmonary rehabilitation have preferences regarding specific program components. To increase the adherence to, and thus, the effectiveness of rehabilitation programs, these results must be considered when developing or optimizing PR-programs.
Dietary fiber in poultry nutrition and their effects on nutrient utilization, performance, gut health, and on the environment: a review
Authors: Jha Rajesh , Mishra Pravin
Published: April 2021

Dietary fiber (DF) was considered an antinutritional factor due to its adverse effects on feed intake and nutrient digestibility. However, with increasing evidence, scientists have found that DF has enormous impacts on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry. It may help maintain the small and large intestine’s integrity by strengthening mucosal structure and functions and increasing the population and diversity of commensal bacteria in the GIT. Increasing DF content benefits digestive physiology by stimulating GIT development and enzyme production. And the inclusion of fiber at a moderate level in diets also alters poultry growth performance. It improves gut health by modulating beneficial microbiota in the large intestine and enhancing immune functions. However, determining the source, type, form, and level of DF inclusion is of utmost importance to achieve the above-noted benefits. This paper critically reviews the available information on dietary fibers used in poultry and their effects on nutrient utilization, GIT development, gut health, and poultry performance. Understanding these functions will help develop nutrition programs using proper DF at an appropriate inclusion level that will ultimately lead to enhanced DF utilization, overall health, and improved poultry growth performance. Thus, this review will help researchers and industry identify the sources, type, form, and amount of DF to be used in poultry nutrition for healthy, cost-effective, and eco-friendly poultry production.
Critical incidents in anorexia nervosa: perspectives of those with a lived experience
Authors: Leppanen Jenni , Tosunlar Lara , Blackburn Rachael , Williams Steven , Tchanturia Kate , Sedgewick Felicity
Published: April 2021

Background

Although social-emotional difficulties are believed play a key role in anorexia nervosa (AN), there is uncertainty regarding what these difficulties might look like. Previous research has largely focused on a “disease model” of social-emotional processing in AN with little attention paid to positive emotions and experiences. Therefore, the aim of the present study was to obtain a fuller picture of critical life events as identified by those with lived AN experience.

Methods

Thirty-four participants aged 16–48 with current or past AN completed an online survey describing self-defined positive and difficult critical events. Thematic analysis was used to assess patterns in participants narrative responses.

Results

Two major themes were identified in the descriptions of positive critical events:Moments of celebrationandUnexpected positive outcomes. These major themes revealed increased external focus and some corrective experiences that challenged the participants pre-existing expectations leading to new positive outcomes. Difficult events clustered into life events that were identified asEating disorder (ED) relatedandNon-ED relatedand included the dimensions of relational conflict and feeling unsupported.

Discussion

The findings suggest that although negative emotionality was identified in the accounts of those with lived experience of AN capacity for “big-picture” thinking with and explicit focus on others was also identified. Moreover, an openness to corrective experiences that worked to challenge negative expectations was evident for some participants. Together these findings have scope as targets for further clinical research and treatment interventions.
A review on the multi-criteria seismic hazard analysis of Ethiopia: with implications of infrastructural development
Authors: Ayele Alemayehu , Woldearegay Kifle , Meten Matebie
Published: April 2021

Earthquake is a sudden release of energy due to faults. Natural calamities like earthquakes can neither be predicted nor prevented. However, the severity of the damages can be minimized by development of proper infrastructure which includes microzonation studies, appropriate construction procedures and earthquake resistant designs. The earthquake damaging effect depends on the source, path and site conditions. The earthquake ground motion is affected by topography (slope, hill, valley, canyon, ridge and basin effects), groundwater and surface hydrology. The seismic hazard damages are ground shaking, structural damage, retaining structure failures and lifeline hazards. The medium to large earthquake magnitude (< 6) reported in Ethiopia are controlled by the main Ethiopian rift System. The spatial and temporal variation of earthquake ground motion should be addressed using the following systematic methodology. The general approaches used to analyze damage of earthquake ground motions are probabilistic seismic hazard assessment (PSHA), deterministic seismic hazard assessment (DSHA) and dynamic site response analysis. PSHA considers all the scenarios of magnitude, distance and site conditions to estimate the intensity of ground motion distribution. Conversely, DSHA taken into account the worst case scenarios or maximum credible earthquake to estimate the intensity of seismic ground motion distribution. Furthermore, to design critical infrastructures, DSHA is more valuable than PSHA. The DSHA and PSHA ground motion distributions are estimated as a function of earthquake magnitude and distance using ground motion prediction equations (GMPEs) at top of the bedrock. Site response analysis performed to estimate the ground motion distributions at ground surface using dynamic properties of the soils such as shear wave velocity, density, modulus reduction, and material damping curves. Seismic hazard evaluation of Ethiopia shown that (i) amplification is occurred in the main Ethiopian Rift due to thick soil, (ii) the probability of earthquake recurrence due to active fault sources. The situation of active fault is oriented in the N-S direction. Ethiopia is involved in huge infrastructural development (including roads, industrial parks and railways), increasing population and agricultural activity in the main Ethiopian Rift system. In this activity, socio-economic development, earthquake and earthquake-generated ground failures need to be given attention in order to reduce losses from seismic hazards and create safe geo-environment.
Adult onset Still’s disease in the elderly: a case-based literature review
Authors: Mollaeian Arash , Chen Jingjing , Chan Nina N. , Nizialek Gregory A. , Haas Christopher J.
Published: April 2021

Background

Adult onset Still’s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare.

Case presentation

A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis.

Conclusions

AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.
Conditioning and PPP processing of smartphone GNSS measurements in realistic environments
Authors: Shinghal Ganga , Bisnath Sunil
Published: April 2021

Smartphones typically compute position using duty-cycled Global Navigation Satellite System (GNSS) L1 code measurements and Single Point Positioning (SPP) processing with the aid of cellular and other measurements. This internal positioning solution has an accuracy of several tens to hundreds of meters in realistic environments (handheld, vehicle dashboard, suburban, urban forested, etc.). With the advent of multi-constellation, dual-frequency GNSS chips in smartphones, along with the ability to extract raw code and carrier-phase measurements, it is possible to use Precise Point Positioning (PPP) to improve positioning without any additional equipment. This research analyses GNSS measurement quality parameters from a Xiaomi MI 8 dual-frequency smartphone in varied, realistic environments. In such environments, the system suffers from frequent phase loss-of-lock leading to data gaps. The smartphone measurements have low and irregular carrier-to-noise (C/N0) density ratio and high multipath, which leads to poor or no positioning solution. These problems are addressed by implementing a prediction technique for data gaps and a C/N0-based stochastic model for assigning realistic a priori weights to the observables in the PPP processing engine. Using these conditioning techniques, there is a 64% decrease in the horizontal positioning Root Mean Square (RMS) error and 100% positioning solution availability in sub-urban environments tested. The horizontal and 3D RMS were 20 cm and 30 cm respectively in a static open-sky environment and the horizontal RMS for the realistic kinematic scenario was 7 m with the phone on the dashboard of the car, using the SwiftNav Piksi Real-Time Kinematic (RTK) solution as reference. The PPP solution, computed using the YorkU PPP engine, also had a 5–10% percentage point more availability than the RTK solution, computed using RTKLIB software, since missing measurements in the logged file cause epoch rejection and a non-continuous solution, a problem which is solved by prediction for the PPP solution. The internal unaided positioning solution of the phone obtained from the logged NMEA (The National Marine Electronics Association) file was computed using point positioning with the aid of measurements from internal sensors. The PPP solution was 80% more accurate than the internal solution which had periodic drifts due to non-continuous computation of solution.