bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a model to estimate the risk of acute ischemic stroke in geriatric patients with primary hypertension
Authors: Zheng Xifeng , Fang Fang , Nong Weidong , Feng Dehui , Yang Yu
Published: August 2021

Objectives

This study aimed to construct and validate a prediction model of acute ischemic stroke in geriatric patients with primary hypertension.

Methods

This retrospective file review collected information on 1367 geriatric patients diagnosed with primary hypertension and with and without acute ischemic stroke between October 2018 and May 2020. The study cohort was randomly divided into a training set and a testing set at a ratio of 70 to 30%. A total of 15 clinical indicators were assessed using the chi-square test and then multivariable logistic regression analysis to develop the prediction model. We employed the area under the curve (AUC) and calibration curves to assess the performance of the model and a nomogram for visualization. Internal verification by bootstrap resampling (1000 times) and external verification with the independent testing set determined the accuracy of the model. Finally, this model was compared with four machine learning algorithms to identify the most effective method for predicting the risk of stroke.

Results

The prediction model identified six variables (smoking, alcohol abuse, blood pressure management, stroke history, diabetes, and carotid artery stenosis). The AUC was 0.736 in the training set and 0.730 and 0.725 after resampling and in the external verification, respectively. The calibration curve illustrated a close overlap between the predicted and actual diagnosis of stroke in both the training set and testing validation. The multivariable logistic regression analysis and support vector machine with radial basis function kernel were the best models with an AUC of 0.710.

Conclusion

The prediction model using multiple logistic regression analysis has considerable accuracy and can be visualized in a nomogram, which is convenient for its clinical application.
Severity-associated markers and assessment model for predicting the severity of COVID-19: a retrospective study in Hangzhou, China
Authors: Qi Jianjiang , He Di , Yang Dagan , Wang Mengyan , Ma Wenjun , Cui Huaizhong , Ye Fei , Wang Fei , Xu Jinjian , Li Zhijian , Liu Chuntao , Wu Jing , Qi Kexin , Wu Rui , Huang Jinsong , Liu Shourong , Zhu Yimin
Published: August 2021

Background

The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19.

Methods

172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively.

Results

Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values < 0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914–0.943) and 0.827 (95% CI, 0.716–0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845–0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score.

Conclusions

Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.
Molecular study of metallo-β-lactamases and integrons in Acinetobacter baumannii isolates from burn patients
Authors: Nikibakhsh Mahnaz , Firoozeh Farzaneh , Badmasti Farzad , Kabir Kourosh , Zibaei Mohammad
Published: August 2021

Background

Productions of metallo-β-lactamases enzymes are the most common mechanism of antibiotic resistance to all beta-lactam classes (except monobactams) in Acinetobacter baumannii. MBLs are usually associated with gene cassettes of integrons and spread easily among bacteria. The current study was performed to detect the genes encoding MBLs and integron structures in A. baumannii isolates from burn patients.

Methods

This study was performed on 106 non-duplicate A. baumannii isolates from burn patients referred to Shahid Motahari Hospital in Tehran. Antibiotic susceptibility of A. baumannii isolates was performed using disk diffusion and broth microdilution method in accordance with the CLSI guidelines. The presence of class 1 integron and associated gene cassettes as well as MBLs-encoding genes including blaVIM, and blaIMP were investigated using PCR and sequencing techniques.

Results

In this cross-sectional study all (100%) of the A. baumannii isolates examined were multidrug resistant. All isolates were sensitive to colistin and simultaneously all were resistant to imipenem. PCR assays showed the presence of blaVIM and blaIMP genes in 102 (96.2%) and 62 (58.5%) isolates of A. baumannii respectively. In addition, 62 (58.5%) of the A. baumannii isolates carried integron class 1, of which 49 (79.0%) were identified with at least one gene cassette. Three types of integron class 1 gene cassettes were identified including: arr2, cmlA5, qacE1 (2300 bp); arr-2, ereC, aadA1, cmlA7, qacE1 (4800 bp); and aac(3)-Ic, cmlA5 (2250 bp).

Conclusion

A high prevalence of MBLs genes, especially blaVIM, was identified in the studied MDR A. baumannii isolates. In addition, most of the strains carried class 1 integrons. Furthermore, the gene cassettes arrays of integrons including cmlA5 and cmlA7 were detected, for the first time, in A. baumannii strains in Iran.
Characteristics of patients meeting the new definition of pre-capillary pulmonary hypertension (Nice 2018) in a single Japanese pulmonary hypertension center
Authors: Yamamoto Keiko , Tanabe Nobuhiro , Takahashi Yukiko , Naito Akira , Sekine Ayumi , Suda Rika , Jujo Sanada Takayuki , Sugiura Toshihiko , Shigeta Ayako , Sakao Seiichiro , Tatsumi Koichiro
Published: August 2021

Background

The 6th World Symposium on Pulmonary Hypertension (Nice 2018) proposed a new definition of pre-capillary pulmonary hypertension (PH) as a condition with mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure  ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU). The characteristics and prognosis of patients with pre-capillary PH, according to this new definition, is unclear. Therefore, we determined the characteristics and survival of patients with borderline pre-capillary PH.

Methods

We retrospectively enrolled 683 patients who underwent their first right heart catheterization at Chiba University, Japan. Among them, 489 patients met the pre-capillary PH requirement with mPAP ≥ 25 mmHg (conventional pre-capillary PH group), while 22 patients met the borderline pre-capillary PH criteria (borderline pre-capillary PH group). Additionally, 16 patients with a mean PAP of 20–25 and PVR of 2–3 WU were also examined.

Results

The borderline pre-capillary PH group comprised 4.3% of the total patients with pre-capillary PH, and the majority was in Group 3 (40.9%) or 4 (45.5%). The survival of the borderline pre-capillary PH group tended to be better than that of the conventional pre-capillary PH group. The prognosis of Group3 PH was the worst among the patients with borderline precapillary PH. There was no significant difference in survival between the borderline pre-capillary PH group with PVR ≥ 3 WU and that with PVR of 2–3 2WU, although none of the patients in the latter group died due to right heart failure.

Conclusions

This is the first study conducted in a PH center in an Asian country to reveal the characteristics of patients with pre-capillary PH, according to the Nice 2018 definition. They comprised 4.3% of the total population with pre-capillary PH, and the majority of the pre-capillary PH cases were in either Group3 or 4. The prognosis may be affected by the patients’ underlying diseases. Further prospective studies are needed to determine whether the new definition, including the PVR cut-off, is beneficial in clinical practice.
Combined serum and synovial C-reactive protein tests: a valuable adjunct to the diagnosis of chronic prosthetic joint infection
Authors: Wang Hai , Qin Leilei , Wang Jiawei , Hu Ning , Huang Wei
Published: August 2021

Background

Diagnosis of periprosthetic joint infection (PJI), especially chronic PJI, is very confusing and challenging. The value of C-reactive protein (CRP) in infectious diseases has been recognized, but the diagnostic value of CRP in chronic PJI is unknown. Our aim was to investigate the diagnostic value of synovial CRP in chronic PJI and to explore the role of combined serum and synovial CRP in distinguishing chronic PJI from aseptic failure after knee and hip arthroplasties.

Methods

We prospectively enrolled patients scheduled to have a revision surgery for chronic PJI or aseptic loosening from January 2019 to December 2020, in which synovial CRP was additionally measured along with routine preoperative diagnostic serum ((ESR, CRP) and synovial (PMN%) biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy.

Results

There were no statistically significant differences between the infection (n = 39) and aseptic (n = 58) groups, including 61 hips and 36 knees. The synovial CRP levels were significantly higher in the infection group than in the aseptic group (median: 9.93 mg/l vs 3.58 mg/l; p < .001). The optimal cut-off value for detecting chronic PJI of Synovial fluid (SF) CRP was of 7.26 mg/l with a sensitivity of 84.62%, a specificity of 93.10%. The combined model I (Serum CRP > 10.2 mg/l OR SF CRP > 7.26 mg/l) had a negative predictive value (NPV) of 96.67%, and a sensitivity of 97.44%. The combined model II (Serum CRP > 10.2 mg/l AND Synovial CRP > 7.26 mg/l) led to a specificity of 1, and a positive predictive value (PPV) of 1.

Conclusions

The present study demonstrated that the combination of serum and synovial CRP can be used as an adjunct to the diagnosis of chronic PJI.
Silicate/zinc-substituted strontium apatite coating improves the osteoinductive properties of β-tricalcium phosphate bone graft substitute
Authors: Sugimoto Hironori , Inagaki Yusuke , Furukawa Akira , Kira Tsutomu , Kawasaki Sachiko , Uchihara Yoshinobu , Akahane Manabu , Tanaka Yasuhito
Published: August 2021

Background

β-Tricalcium phosphate (β-TCP) is a popular synthetic bone graft substitute with excellent osteoconductive properties and bioabsorbability. However, its osteoinductive properties are inferior to those of autologous or allogeneic bone. Trace elements such as strontium (Sr), silica (Si), and zinc (Zn) have been reported to promote osteogenesis in materials. In this study, we aimed to determine whether a Si/Zn-substituted Sr apatite coating of β-TCP could enhance osteoinductive properties.

Methods

The apatite-coated β-TCP disks were prepared using nanoparticle suspensions of silicate-substituted Sr apatite (SrSiP) or silicate- and Zn-co-substituted Sr apatite (SrZnSiP).

Bone marrow mesenchymal cells (BMSCs) from rat femur were cultured and subsequently seeded at a density of 1.0 × 106/cm2onto apatite-coated and non-coated β-TCP disks.

In vitro, the β-TCP disks were then placed in osteogenic medium, and lactate dehydrogenase (LDH) activity was measured from supernatants after culture for 2 days. Additionally, after culture for 14 days, the mRNA expression of genes encoding osteocalcin (OC), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was evaluated by qRT-PCR.In vivo, the β-TCP disks were transplanted subcutaneously into rats that were sacrificed after 4 weeks. Then, the harvested disks were evaluated biochemically (ALP activity, OC content, mRNA expression of OC, ALP, BMP-2, and VEGF measured by qRT-PCR), radiologically, and histologically.

Results

Significantly higher mRNA expression of almost all evaluated osteogenic and angiogenic genes was observed in the SrZnSiP and SrSiP groups than in the non-coated group, with no significant cytotoxicity elicited by the apatite coating in vitro. Moreover, in vivo, the SrZnSiP and SrSiP groups showed significantly higher osteogenic and angiogenic gene expression and higher ALP activity and OC content than the non-coated group (P < 0.05). Radiological and histopathological findings revealed abundant bone formation in the apatite-coated group.

Conclusions

Our findings indicate that apatite coating of β-TCP improves osteoinductive properties without inducing significant cytotoxicity.
Prognostic value of preoperative body mass index for diabetic patients with non-metastasis gastric cancer: a single center experience
Authors: Ye Zaisheng , Wei Shenghong , Zeng Yi , Wang Yi , Lin Zhitao , Chen Shu , Xie Yunqing , Zheng Qiuhong , Chen Luchuan
Published: August 2021

Aim

This study was designed to investigate the prognostic effect of preoperative body mass index (BMI) for Type 2 diabetes mellitus (T2DM) patients with non-metastasis gastric cancer (GC) who underwent D2 gastrectomy.

Methods

T2DM patients with pT1–4bN0–3bM0 GC were retrospectively collected in Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital from January, 2000 to December, 2010. These patients underwent D2 radical resection of the stomach combined with regional lymphadenectomy. Chi-square test was used to analyze unordered categorical variables and ranked data, followed by Kaplan–Meier analysis as well as Cox regression models to detect risk factors for survival outcomes. In addition, the cut-off point was determined by the X-tile program. All analyses were carried out using survival package of R and SPSS Software.

Results

A total of 302 T2DM patients with pT1–4bN0–3bM0 GC were collected and analyzed. The cut-off points of BMI, identified by the X-tile program, was 19 kg/m2. Patients with low BMI (< 19 kg/m2) had a higher percentage of advanced T stage (T4a and T4b), more advanced TNM stage (stage IIIA, IIIB and IIIC), and more elevated level of serum carcinoembryonic antigen (CEA), compared to those with high BMI (> 19 kg/m2) (all P < 0.05). In the low BMI subgroup, the 5-year overall survival rate was 39.02%, which was as high as 58.11% in the high BMI subgroup (P < 0.05). In the multivariate Cox regression model revealed that IIIC stage (OR = 3.101), N3b stage (OR = 3.113) were the most important prognostic indicators, followed by pretreatment BMI (OR = 2.136).

Conclusion

Low preoperative BMI (< 19 kg/m2) was a poor prognostic marker for T2DM patients with pT1–4bN0–3bM0 GC.
Learnings from the design and acceptance of the German COVID-19 tracing app for IS-driven crisis management: a design science research
Authors: Behne Alina , Krüger Nicolai , Beinke Jan Heinrich , Teuteberg Frank
Published: August 2021

Background

This article investigates the research problem of digital solutions to overcome the pandemic, more closely examining the limited effectiveness and scope of the governmental COVID-19 tracing apps, using the German COVID-19 tracing app (Corona-Warn-App) as an example. A well-designed and effective instrument in the technological toolbox is of utmost importance to overcome the pandemic.

Method

A multi-methodological design science research approach was applied. In three development and evaluation cycles, we presented, prototyped, and tested user-centered ideas of functional and design improvement. The applied procedure contains (1) a survey featuring 1993 participants from Germany for evaluating the current app, (2) a gathering of recommendations from epidemiologists and from a focus group discussion with IT and health experts identifying relevant functional requirements, and (3) an online survey combined with testing our prototype with 53 participants to evaluate the enhanced tracing app.

Results

This contribution presents 14 identified issues of the German COVID-19 tracing app, six meta-requirements, and three design principles for COVID-19 tracing apps and future pandemic apps (e.g., more user involvement and transparency). Using an interactive prototype, this study presents an extended pandemic app, containing 13 potential front-end (i.e., information on the regional infection situation, education and health literacy, crowd and event notification) and six potential back-end functional requirements (i.e., ongoing modification of risk score calculation, indoor versus outdoor). In addition, a user story approach for the COVID-19 tracing app was derived from the findings, supporting a holistic development approach.

Conclusion

Throughout this study, practical relevant findings can be directly transferred to the German and other international COVID-19 tracing applications. Moreover, we apply our findings to crisis management theory—particularly pandemic-related apps—and derive interdisciplinary learnings. It might be recommendable for the involved decision-makers and stakeholders to forego classic application management and switch to using an agile setup, which allows for a more flexible reaction to upcoming changes. It is even more important for governments to have a well-established, flexible, design-oriented process for creating and adapting technology to handle a crisis, as this pandemic will not be the last one.
Are male nurses sexually harassed? A cross-sectional study in the Greek Health System
Authors: Papantoniou Panagiotis
Published: August 2021

Background

The #MeToo and #Times Up movements have put a global spotlight on the phenomenon of sexual harassment in healthcare. Yet, most studies have explored sexual harassment among female professionals. This study departs from current research practices and investigates the frequency of sexual harassment in male nurses working in the Greek NHS and the reasons for not reporting their experiences.

Methods

A cross-sectional study was conducted using the Sexual Experiences Questionnaire (SEQ) to collect data from 507 male nurses working in Greece's various settings during October and February 2021. The electronic survey was sent to male nurses (n=3,091 registered with the Hellenic Association of Nurses. Survey items were consent form, demographics, three-dimensions of sexual harassment, silencing and negative consequences. Questions were measured using five-point Likert scales, binary scale and multiple-choice questions. ANOVA and T-tests were used to investigate whether specific groups more frequently dealt with sexual harassment. Multiple regression analyses were conducted to investigate the association between independent variables (sexually harassing behaviours) and the dependent variable (participants' negative physical, mental, and job-related outcomes).

Results

40% of male nurses have experienced sexual harassment at least once in their working lives, and the most common form of sexual harassment faced was gender harassment, followed by unwanted sexual attention. Male doctors and male nurses were the most common perpetrators. Private and younger male nurses with up to 5 years of experience experienced more frequent sexual harassment. 30% did not report sexual harassment due to the fear that no one would believe them, and because of beliefs, no action would be taken against the wrongdoer. Multiple regression analyses showed that unwanted sexual attention and sexual coercion were associated with physical and job-related outcomes. Cronbach Alpha was 0.91.

Conclusion

A high proportion of male nurses have experienced sexual harassment during their careers. Being younger with limited working experience and working in the private sector were positively associated with sexual harassment. Policymakers and health managers should focus on sexual harassment prevention strategies and report-enabling policies.
Peanut components measured by ISAC: comparison with ImmunoCap and clinical relevance in peanut allergic children
Authors: Brand H. K. , Schreurs M. W. J. , Emons J. A. M. , Gerth van Wijk R. , de Groot H. , Arends N. J. T.
Published: August 2021

Background

Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy.

Methods

In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard.

Results

Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p < 0.01).

Conclusion

Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.
The impact of gender and the social determinants of health on the clinical course of people living with HIV in Myanmar: an observational study
Authors: Nyein Phyo Pyae , Aung Eithandee , Aung Ne Myo , Kyi Mar Mar , Boyd Mark , Lin Kyaw Swar , Hanson Josh
Published: August 2021

Background

There is a growing recognition of the impact of gender and the social determinants of health on the clinical course of people living with HIV (PLHIV). However, the relative contribution of these factors to clinical outcomes of PLHIV is incompletely defined in many countries. This study was performed to gain a greater understanding of the non-clinical determinants of prognosis of PLHIV in Myanmar.

Methods

Selected demographic, behavioural and socioeconomic characteristics of outpatients at two specialist HIV hospitals and one general hospital in Yangon, Myanmar were correlated with their subsequent clinical course; a poor outcome was defined as death, hospitalisation, loss to follow-up or a detectable viral load at 6 months of follow-up.

Results

221 consecutive individuals with advanced HIV commencing anti-retroviral therapy (ART) were enrolled in the study; their median CD4 T-cell count was 92 (44–158) cells/mm3, 138 (62.4%) were male. Socioeconomic disadvantage was common: the median (interquartile range (IQR) monthly per-capita income in the cohort was US$48 (31–77); 153 (69.9%) had not completed high school. However, in a multivariate analysis that considered demographic, behavioural, clinical factors and social determinants of health, male gender was the only predictor of a poor outcome: odds ratio (95% confidence interval): 2.33 (1.26–4.32, p = 0.007). All eight of the deaths and hospitalisations in the cohort occurred in males (p = 0.03).

Conclusions

Men starting ART in Myanmar have a poorer prognosis than women. Expanded implementation of gender-specific management strategies is likely to be necessary to improve outcomes.
Dynamically adjusted strategy in response to developments in the COVID-19 pandemic as a new normal
Authors: Shen Weifeng
Published: August 2021

Presently, the developments of COVID-19 situation in different countries and regions have clearly differentiated. Due to differences in resources, infrastructure, and awareness of epidemic prevention and control, capabilities for COVID-19 prevention and control in various regions have also shown a significant imbalance as the COVID-19 epidemic is entering a new normal. The objectives of this study are to provide dynamically adjusted strategies in response to developments in the COVID-19 pandemic as a new normal. In the face of the new normal, one key is normalizing epidemic prevention and control. As part of this, we should implement precise policies based on the dynamics of the COVID-19 epidemic and particular response needs. In ongoing COVID-19 prevention and control, we must pay attention to new vulnerabilities and new features in the dynamics of the epidemic. In this study, health and government officials can benefit from insights of preparing ourselves for long-term challenges and both certainties and uncertainties in a future facing COVID-19.
Characterization of an ETV6-NTRK3 rearrangement with unusual, but highly significant FISH signal pattern in a secretory carcinoma of the salivary gland: a case report
Authors: Wagner Florian , Greim Ralf , Krebs Kathrin , Luebben Finn , Dimmler Arno
Published: August 2021

Background

Fusions of neurotrophic tropomyosin receptor kinase genes NTRK1, NTRK2 and NTRK3 with various partner genes occur in both common and rare tumours and are of paramount predictive value due to the availability of very effective pan-Trk inhibitors like Larotrectinib and Entrectinib. Detection of NTRK fusions is mainly performed by fluorescence in situ hybridization (FISH) and next generation sequencing (NGS). The case described here showed a very unusual, but highly significant FISH signal pattern with an NTRK3 break apart probe, indicative of a functional NTRK3 rearrangement.

Case presentation

We describe here the case of a male patient who was originally diagnosed with an adenocarcinoma of the parotid gland without evidence of metastases. After the development of multiple lung metastases, an extensive immunohistochemical and molecular examination of archived tumour tissue including analysis of NTRK was performed. NTRK expression was detected by immunohistochemistry (IHC) and then comprehensively analysed further by FISH, quantitative reverse transcription PCR (RT-qPCR), and NGS. NTRK3 break apart FISH showed multiple and very faint single 3′ signals in addition to fusion signals. Quantitative reverse transcription PCR and NGS confirmed an ETV6:exon5-NTRK3:exon15 fusion. Diagnosis was therefore revised to metastatic secretory carcinoma of the salivary gland, and the patient subsequently treated with Larotrectinib, resulting in persisting partial remission.

Conclusions

Our findings underline the importance to be aware of non-canonical signal patterns during FISH analysis for detection of NTRK rearrangements. Very faint single 3′ signals can indicate a functional NTRK rearrangement and therefore be of high predictive value.
FDG-PET/CT versus bone marrow biopsy in bone marrow involvement in newly diagnosed paediatric lymphoma: a systematic review and meta-analysis
Authors: Li Zhizhuo , Li Chengxin , Chen Bingrong , Shi Lijun , Gao Fuqiang , Wang Peixu , Sun Wei
Published: August 2021

Background

Bone marrow infiltration (BMI) is a devastating stage of paediatric lymphoma. Prompt diagnosis of BMI in newly diagnosed paediatric lymphoma patients is critical but can be very challenging at present.

Methods

We systematically retrieved studies from PubMed, EMBASE, and the Cochrane Library. Data extraction and quality assessment were performed by two reviewers independently. A total of nine eligible studies were included in the quantitative analysis.

Results

The pooled sensitivity and specificity of FDG-PET/CT for diagnosing BMI in newly diagnosed paediatric lymphoma patients were 0.97 (95% confidence interval [CI], 0.93 to 0.99) and 0.99 (95% CI, 0.98 to 0.99), respectively. The pooled PLR, NLR, and DOR were 79.9 (95% CI, 42.7 to 149.6), 0.03 (95% CI, 0.01 to 0.17), and 2414.6 (95% CI, 989.6 to 5891.4), respectively. The AUC of FDG-PET/CT for BMI was 1.00 (95% CI, 0.99 to 1.00). Compared with FDG-PET/CT, BMB had a lower pooled sensitivity (0.44, 95% CI, 0.34 to 0.55) and comparable pooled specificity (1.00, 95% CI, 0.92 to 1.00).

Conclusion

Compared with BMB, FDG-PET/CT was a more valuable diagnostic method for evaluating BMI in paediatric Hodgkin and non-Hodgkin lymphoma patients with extremely high diagnostic accuracy.
Treatment-induced arteriolar revascularization and miR-126 enhancement in bone marrow niche protect leukemic stem cells in AML
Authors: Zhang Bin , Nguyen Le Xuan Truong , Zhao Dandan , Frankhouser David E. , Wang Huafeng , Hoang Dinh Hoa , Qiao Junjing , Abundis Christina , Brehove Matthew , Su Yu-Lin , Feng Yuxin , Stein Anthony , Ghoda Lucy , Dorrance Adrianne , Perrotti Danilo , Chen Zhen , Han Anjia , Pichiorri Flavia , Jin Jie , Jovanovic-Talisman Tijana , Caligiuri Michael A. , Kuo Calvin J. , Yoshimura Akihiko , Li Ling , Rockne Russell C. , Kortylewski Marcin , Zheng Yi , Carlesso Nadia , Kuo Ya-Huei , Marcucci Guido
Published: August 2021

Background

During acute myeloid leukemia (AML) growth, the bone marrow (BM) niche acquires significant vascular changes that can be offset by therapeutic blast cytoreduction. The molecular mechanisms of this vascular plasticity remain to be fully elucidated. Herein, we report on the changes that occur in the vascular compartment of the FLT3-ITD+ AML BM niche pre and post treatment and their impact on leukemic stem cells (LSCs).

Methods

BM vasculature was evaluated in FLT3-ITD+ AML models (MllPTD/WT/Flt3ITD/ITD mouse and patient-derived xenograft) by 3D confocal imaging of long bones, calvarium vascular permeability assays, and flow cytometry analysis. Cytokine levels were measured by Luminex assay and miR-126 levels evaluated by Q-RT-PCR and miRNA staining. Wild-type (wt) and MllPTD/WT/Flt3ITD/ITD mice with endothelial cell (EC) miR-126 knockout or overexpression served as controls. The impact of treatment-induced BM vascular changes on LSC activity was evaluated by secondary transplantation of BM cells after administration of tyrosine kinase inhibitors (TKIs) to MllPTD/WT/Flt3ITD/ITD mice with/without either EC miR-126 KO or co-treatment with tumor necrosis factor alpha (TNFα) or anti-miR-126 miRisten.

Results

In the normal BM niche, CD31+Sca-1high ECs lining arterioles have miR-126 levels higher than CD31+Sca-1low ECs lining sinusoids. We noted that during FLT3-ITD+ AML growth, the BM niche lost arterioles and gained sinusoids. These changes were mediated by TNFα, a cytokine produced by AML blasts, which induced EC miR-126 downregulation and caused depletion of CD31+Sca-1high ECs and gain in CD31+Sca-1low ECs. Loss of miR-126high ECs led to a decreased EC miR-126 supply to LSCs, which then entered the cell cycle and promoted leukemia growth. Accordingly, antileukemic treatment with TKI decreased the BM blast-produced TNFα and increased miR-126high ECs and the EC miR-126 supply to LSCs. High miR-126 levels safeguarded LSCs, as shown by more severe disease in secondary transplanted mice. Conversely, EC miR-126 deprivation via genetic or pharmacological EC miR-126 knock-down prevented treatment-induced BM miR-126high EC expansion and in turn LSC protection.

Conclusions

Treatment-induced CD31+Sca-1high EC re-vascularization of the leukemic BM niche may represent a LSC extrinsic mechanism of treatment resistance that can be overcome with therapeutic EC miR-126 deprivation.

Graphic abstract
Characterizing alternative and emerging tobacco product transition of use behavior on Twitter
Authors: Bardier Cortni , Yang Joshua S. , Li Jiawei , Mackey Tim K.
Published: August 2021

Objective

The objective of this study was to develop an inductive coding approach specific to characterizing user-generated social media conversations about transition of use of different tobacco and alternative and emerging tobacco products (ATPs).

Results

A total of 40,206 tweets were collected from the Twitter public API stream that were geocoded from 2018 to 2019. Using data mining approaches, these tweets were then filtered for keywords associated with tobacco and ATP use behavior. This resulted in a subset of 5718 tweets, with 657 manually annotated and identified as associated with user-generated conversations about tobacco and ATP use behavior. The 657 tweets were coded into 9 parent codes: inquiry, interaction, observation, opinion, promote, reply, share knowledge, use characteristics, and transition of use behavior. The highest number of observations occurred under transition of use (43.38%, n = 285), followed by current use (39.27%, n = 258), opinions about use (0.07%, n = 46), and product promotion (0.06%, n = 37). Other codes had less than ten tweets that discussed these themes. Results provide early insights into how social media users discuss topics related to transition of use and their experiences with different and emerging tobacco product use behavior.
Using point-of-care diagnostic testing for improved antibiotic prescription: an economic model
Authors: Antoñanzas F. , Juárez-Castelló C. A. , Rodríguez-Ibeas R.
Published: August 2021

Background

Antibiotics have been overprescribed to treat infectious diseases and have generated antimicrobial resistances that reduce their effectiveness. Following the rationale behind the new paradigm of personalized medicine, point-of-care diagnostic testing (POCT) has been proposed to improve the quality of antibiotic prescription with the aim of reducing antimicrobial resistances.

Methods

In order to understand whether this recommendation is valid, we create a theoretical economic model to determine under which conditions the expected benefits of using POCT to guide antibiotic prescription are greater than for empiric prescription, where we define the expected benefits as the difference between the economic value of health and the costs of the treatment. We consider the interaction of a group of physicians who express differing levels of uncertainty when prescribing with a firm selling a diagnostic device, and analyse the firm’s pricing policy and the physicians’ prescribing decisions. We allow the physicians to internalize the external costs of antimicrobial resistances.

Results

We find that the use of POCT reduces the number of antibiotic prescriptions. The reduction in antibiotic prescriptions is higher when physicians internalise the costs of antimicrobial resistances. Physicians with relatively high levels of uncertainty use POCT as they are uncertain about the right treatment for a large proportion of patients. Physicians with low levels of uncertainty prefer to prescribe empirically. The segmentation in the population of physicians regarding the uptake of POCT depends on the distribution of levels of uncertainty across physicians. For each test, the firm charges the marginal production costs of the inputs needed to administer the test, and makes its profit from the sales of the testing devices.

Conclusions

From a theoretical perspective, our findings corroborate the fact that POCT improve the quality of antibiotic prescription and reduce the number of prescriptions. Nevertheless, their use is not always recommended as empiric therapy may be preferred when uncertainty is low.
A novel machine learning-based approach for the computational functional assessment of pharmacogenomic variants
Authors: Pandi Maria-Theodora , Koromina Maria , Tsafaridis Iordanis , Patsilinakos Sotirios , Christoforou Evangelos , van der Spek Peter J. , Patrinos George P.
Published: August 2021

Background

The field of pharmacogenomics focuses on the way a person’s genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient’s genome, hence rendering its incorporation into clinical routine practice a realistic possibility.

Methods

This study exploited thoroughly characterized in functional level SNVs within genes involved in drug metabolism and transport, to train a classifier that would categorize novel variants according to their expected effect on protein functionality. This categorization is based on the available in silico prediction and/or conservation scores, which are selected with the use of recursive feature elimination process. Toward this end, information regarding 190 pharmacovariants was leveraged, alongside with 4 machine learning algorithms, namely AdaBoost, XGBoost, multinomial logistic regression, and random forest, of which the performance was assessed through 5-fold cross validation.

Results

All models achieved similar performance toward making informed conclusions, with RF model achieving the highest accuracy (85%, 95% CI: 0.79, 0.90), as well as improved overall performance (precision 85%, sensitivity 84%, specificity 94%) and being used for subsequent analyses. When applied on real world WGS data, the selected RF model identified 2 missense variants, expected to lead to decreased function proteins and 1 to increased. As expected, a greater number of variants were highlighted when the approach was used on NGS data derived from targeted resequencing of coding regions. Specifically, 71 variants (out of 156 with sufficient annotation information) were classified as to “Decreased function,” 41 variants as “No” function proteins, and 1 variant in “Increased function.”

Conclusion

Overall, the proposed RF-based classification model holds promise to lead to an extremely useful variant prioritization and act as a scoring tool with interesting clinical applications in the fields of pharmacogenomics and personalized medicine.
Strategic actions of urban development to define the intervention policies of slums
Authors: Ragheb Amany , El-Ashmawy Rasha
Published: August 2021

The problem of slums is one of the most imperative problems experienced by many developing countries as well as some developed countries. The random gatherings shape real disruption in the economic and social development plans of the concerned countries. The importance of the research lies in conducting a field study for Ezbet El-Shahatin area in Mansoura city, given that it is the largest unplanned informal area in Dakahlia Governorate in terms of area. Geographic information systems were used to make enter data to form a coordinated database. In addition, policy intervention matrix in slums was used to make the appropriate decision regarding the development of the area. The study concludes to specifying several recommendations to deal with slums and set a model for integrated urban development in low-income areas that can be repeated in other similar locations.
Interaction between phloretin and insulin: a spectroscopic study
Authors: Yanti Sahri , Wu Zhong-Wen , Agrawal Dinesh Chandra , Chien Wei-Jyun
Published: August 2021

Diabetes is among the top ten deadly diseases in the world. It occurs either when the pancreas does not produce enough insulin (INS) or when the body cannot effectively use the insulin it produces. Phloretin (PHL) has a biological effect that can treat diabetes. A spectroscopic study was carried out to explore the interaction between phloretin and insulin. UV/Vis spectroscopy, fluorescence spectroscopy, and circular dichroism spectropolarimeter were used in the study. UV/Vis spectra showed that the interaction between PHL and INS produced strong absorption at a wavelength of 282 nm. The fluorescence analysis results showed that the excitation and emission occurred at 280-nm and 305-nm wavelengths, respectively. Temperature changes did not affect INS emissions. However, the interaction of PHL–INS caused a redshift at 305 to 317 nm. Temperature affected the binding constant (Ka) and the binding site (n). Ka decreased with increasing temperature and increased the binding site. The thermodynamic parameters such as enthalpy (ΔH0) and entropy (ΔS0) each had a value of − 16,514 kJ/mol and 22.65 J/mol·K. PHL and INS interaction formed hydrogen bonds and hydrophobic interaction. The free energy (ΔG0) recorded was negative. PHL and INS interactions took place spontaneously. The quenching effect was dynamic and static.KDvalues were greater thanKS. The higher the temperature, the less wasKDandKS. The appearance of two negative signals on circular dichroism (CD) spectropolarimeter implies that phloretin could induce regional configuration changes in insulin. The addition of PHL has revealed that the proportion of α-helix in the insulin stabilizes its structure. Phloretin’s stabilization and enhancement of the α-helix structural configuration in insulin indicate that phloretin can improve insulin resistance.
Assertive skills: a comparison of two group interventions with Brazilian university students
Authors: de Sousa Conceição Reis , da Costa Padovani Ricardo
Published: August 2021

The improvement or acquisition of socioemotional skills contributes to the academic and personal adaptation of university students. The way students think about themselves and others influence their social skills and well-being. Considering the importance of social competence for professional practice in the face of new social realities, the university must invest in programs that promote the socio-emotional development of students. This study compared the effects of interventions based on Rational Emotive Behavior Therapy and Psychoeducation on assertive skills and subjective well-being. This study involved 25 undergraduate students of a public university. The students were randomly allocated to three groups, including the Control group, and they were evaluated by means of questionnaires, inventories, scales, and written evaluation of the group process. The program consisted of 10 meetings and a 6-week follow-up. Irrational beliefs were reduced and their assertive skills’ scores increased in the post-intervention and follow-up evaluations, regardless of the group. Only verbal reports from participants indicated an increase in well-being. The students’ written reports after the end of the meetings indicate that the two forms of intervention were evaluated as promoting change by the students. One of the limitations of the study is the size of the groups. Despite the very small sample size, the study highlights that developing a set of flexible beliefs is fundamental to the exercise of assertiveness.
Genomic characterization of three marine fungi, including Emericellopsis atlantica sp. nov. with signatures of a generalist lifestyle and marine biomass degradation
Authors: Hagestad Ole Christian , Hou Lingwei , Andersen Jeanette H. , Hansen Espen H. , Altermark Bjørn , Li Chun , Kuhnert Eric , Cox Russell J. , Crous Pedro W. , Spatafora Joseph W. , Lail Kathleen , Amirebrahimi Mojgan , Lipzen Anna , Pangilinan Jasmyn , Andreopoulos William , Hayes Richard D. , Ng Vivian , Grigoriev Igor V. , Jackson Stephen A. , Sutton Thomas D. S. , Dobson Alan D. W. , Rämä Teppo
Published: August 2021

Marine fungi remain poorly covered in global genome sequencing campaigns; the 1000 fungal genomes (1KFG) project attempts to shed light on the diversity, ecology and potential industrial use of overlooked and poorly resolved fungal taxa. This study characterizes the genomes of three marine fungi:Emericellopsissp. TS7, wood-associatedAmylocarpus encephaloidesand algae-associatedCalycina marina.These species were genome sequenced to study their genomic features, biosynthetic potential and phylogenetic placement using multilocus data.Amylocarpus encephaloidesandC. marinawere placed in theHelotiaceaeandPezizellaceae (Helotiales), respectively, based on a 15-gene phylogenetic analysis. These two genomes had fewer biosynthetic gene clusters (BGCs) and carbohydrate active enzymes (CAZymes) thanEmericellopsissp. TS7 isolate.Emericellopsissp. TS7 (Hypocreales,Ascomycota) was isolated from the spongeStelletta normani. A six-gene phylogenetic analysis placed the isolate in the marineEmericellopsisclade and morphological examination confirmed that the isolate represents a new species, which is described here asE. atlantica. Analysis of its CAZyme repertoire and a culturing experiment on three marine and one terrestrial substrates indicated thatE. atlanticais a psychrotrophic generalist fungus that is able to degrade several types of marine biomass. FungiSMASH analysis revealed the presence of 35 BGCs including, eight non-ribosomal peptide synthases (NRPSs), six NRPS-like, six polyketide synthases, nine terpenes and six hybrid, mixed or other clusters. Of these BGCs, only five were homologous with characterized BGCs. The presence of unknown BGCs sets and large CAZyme repertoire set stage for further investigations ofE. atlantica. ThePezizellaceaegenome and the genome of the monotypicAmylocarpusgenus represent the first published genomes of filamentous fungi that are restricted in their occurrence to the marine habitat and form thus a valuable resource for the community that can be used in studying ecological adaptions of fungi using comparative genomics.