bluuebunny/crossref_metadata_2025 huggingface dataset:
Using two “V” shaped flaps in penile torsion treatment
Authors: Mirsadeghi Seyed Amin , Aghaii Maryam , Aghamir Seyed Mohammad Kazem
Published: September 2020

Introduction:

Penile torsion is a congenital malformation that causes a rotational deformity of the penile shaft. Several techniques have been considered for penile torsion repair. In this study, we described our experience using two separate “V” dartos flaps, which leads to a more satisfying result.

Patient and methods:

Two young men with severe penile torsion aged 24 and 28 years old were candidates for surgery. During our novel method for penile torsion repair, we degloved the penis and dissected the dartos fascia from the penis shaft, then cut it distally from the sub-coronal region with a longitudinal cut to make two dartos flaps in a “V” shape. With these two flaps, we corrected penile torsion in a more satisfying way without crossing the urethra.

Results:

Penile torsion and concurrent chordee were completely corrected after surgery. Urine culture was sterile and uroflowmetry indicated a maximal urinary flow of 12 ml/s 3 months after the operation. Both patients were satisfied with ejaculation and their follow-up indicated complete resolution of penile torsion.

Conclusions:

Penile torsion is a challenging congenital anomaly. We used a two “V” shaped flap passage method to complete penile rotation and chordee correction without performing any plication techniques. Our penile torsion correction procedure resulted in the successful repair of torsion and excellent outcomes.

Level of evidence:

Not applicable for this multicenter audit.
Utilizing a novel unified healthcare model to compare practice patterns between telemedicine and in-person visits
Authors: Norden Justin G , Wang Jonathan X , Desai Sumbul A , Cheung Lauren
Published: September 2020

Objective

Telemedicine practice has been shown to vary from clinical guidelines. Variations in practice patterns may be caused by disruptions in the continuity of care between traditional and telemedicine providers. This study compares virtual and in-person visits in Stanford’s ClickWell Care (CWC) – where patients see the same provider for both visit modalities.

Methods

Clinical data for two years of patient encounters at CWC from January 2015–2017 (5772 visits) were obtained through Stanford STRIDE. For the 20 most common visit categories, including 17 specific diagnoses, we compared the frequency of prescriptions, labs, procedures, and images ordered, as well as rates of repeat visits.

Results

For the 17 specific diagnoses, there are no differences in labs ordered. Two diagnoses show differences in images ordered, and four differences in prescriptions. Overall, there are more labs (0.16 virtual, 0.33 in-person p < 0.0001) and images ordered (0.07 virtual, 0.16 in-person, p < 0.0001) for in-person visits – due mainly to general medical exam visits. Repeat visits were more likely after in-person visits (19% virtual, 38% in-person, p < 0.0001), 10 out of 17 specific diagnoses showed differences in visit frequency between visit modalities. Visits for both anxiety (5.3x, p < 0.0001) and depression (5.1x, p < 0.0001) were much more frequent in the virtual setting.

Conclusions

Prescriptions, labs, and images ordered were similar between in-person and virtual visits for most diagnoses. Overall however, for in-person visits we find increased orders for labs and images, primarily from general medical exams. Finally, for anxiety and depression patients show clear preferences for virtual visits.
Influence of Surface Conditioning on the Repair Strength of Bioactive Restorative Material
Authors: Awad Mohamed Moustafa , Almutairi Nader , Alhalabi Feras , Robaian Ali , Vohra Fahim Ahmed , Ozcan Mutlu , Maawadh Ahmed , Alrahlah Ali
Published: September 2020

Objective:

To evaluate the effects of surface treatment and repair material on the repair shear bond strength (SBS) of the bioactive restorative material.

Methods:

A total of 240 Activa BioActive Restorative (Activa) discs were prepared, aged, and polished, and divided randomly into eight groups ( n = 30). Groups 1–4 discs were repaired with bulk-fill flowable resin-based composite (Bulk-RBC), and Groups 5–8 discs with Activa. Surface treatment used for each repair material type were air abrasion with silica-coated 30-m Al2O3 particles (air abrasion) (Groups 2 & 6), Air abrasion with universal primer (Groups 3 & 7), and Air abrasion with universal adhesive (Groups 4 & 8). Groups 1 and 5 were controls without surface treatment. SBS test was performed, and the failure mode and surface topography were assessed.

Results:

Surface treatment with air abrasion significantly improved the SBS for repair using both Activa and Bulk-RBC. Repair SBS using Activa was significantly higher compared with Bulk-RBC. Cohesive failure in substrate and mixed failures were most common in the surface-treated groups (2–4, 6–8). Air abrasion produced prominent surface topography changes compared with polishing.

Conclusion:

Air abrasion enhances the repair SBS of aged bioactive restorative material. The use of the same material (Activa) for repair affords a higher bond strength compared with the use bulk-RBC.
How time pressure is associated with both work engagement and emotional exhaustion: The moderating effects of resilient capabilities at work
Authors: Kunzelmann Arian , Rigotti Thomas
Published: September 2020

Resilience in the organizational context is a fruitful concept for understanding employees’ success in dealing with workplace adversity. Through a diary study, we have examined the interaction effects of time pressure and different work-related capabilities of resilience (i.e. emotional coping, comprehensive planning, positive reframing, and focused action) on emotional exhaustion and work engagement of employees. A sample of 79 employees (54.4% male) responded to two daily surveys (after work and before bedtime) for a period of five consecutive workdays. Results show that time pressure had a positive association with emotional exhaustion. Further, time pressure showed a positive association with work engagement, but only when considering additional personal resources. Positive reframing was positively related to work engagement on the day-level but did not moderate the link between time pressure and the outcomes. Emotional coping as well as focused action decreased sensitivity to time pressure. The results underpin the impact of different work-related capabilities of resilience and provide novel theoretical and practical implications.
Intentional and unintentional nonadherence to hydroxyurea among people with sickle cell disease: a qualitative study
Authors: Hodges Jason R. , Phillips Shannon M. , Norell Sarah , Nwosu Chinonyelum , Khan Hamda , Luo Lingzi , Badawy Sherif M. , King Allison , Tanabe Paula , Treadwell Marsha , Rojas Smith Lucia , Calhoun Cecelia , Hankins Jane S. , Porter Jerlym
Published: September 2020

Hydroxyurea is an efficacious treatment for sickle cell disease (SCD), but adoption is low among individuals with SCD. The objective of this study was to examine barriers to patients’ adherence to hydroxyurea use regimens by using the intentional and unintentional medication nonadherence framework. We interviewed individuals with SCD age 15 to 49.9 years who were participants in the Sickle Cell Disease Implementation Consortium (SCDIC) Needs Assessment. The intentional and unintentional medication nonadherence framework explains barriers to using hydroxyurea and adds granularity to the understanding of medication adherence barriers unique to the SCD population. In total, 90 semi-structured interviews were completed across 5 of the 8 SCDIC sites. Among interviewed participants, 57.8% (n = 52) were currently taking hydroxyurea, 28.9% (n = 26) were former hydroxyurea users at the time of the interview, and 13.3% (n = 12) had never used hydroxyurea but were familiar with the medication. Using a constructivist grounded theory approach, we discovered important themes that contributed to nonadherence to hydroxyurea, which were categorized under unintentional (eg, Forgetfulness, External Influencers) and intentional (Negative Perceptions of Hydroxyurea, Aversion to Taking Any Medications) nonadherence types. Participants more frequently endorsed adherence barriers that fell into the unintentional nonadherence type (70%) vs intentional nonadherence type (30%). Results from this study will help SCD health care providers understand patient choices and decisions as being either unintentional or intentional, guide tailored clinical discussions regarding hydroxyurea therapy, and develop specific, more nuanced interventions to address nonadherence factors.
Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models
Authors: Alig Stefan , Jurinovic Vindi , Shahrokh Esfahani Mohammad , Haebe Sarah , Passerini Verena , Hellmuth Johannes C. , Gaitzsch Erik , Keay William , Tahiri Natyra , Zoellner Anna , Rosenwald Andreas , Klapper Wolfram , Stein Harald , Feller Alfred , Ott German , Staiger Annette M. , Horn Heike , Hansmann Martin L. , Pott Christiane , Unterhalt Michael , Schmidt Christian , Dreyling Martin , Alizadeh Ash A. , Hiddemann Wolfgang , Hoster Eva , Weigert Oliver
Published: September 2020

High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months–prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.
Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population
Authors: Medjani Somia , Chellat-Rezgoune Djalila , Kezai Taher , Chidekh Mohammed , Abadi Noureddine , Satta Dalila
Published: September 2020

Background

Prostate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namelycytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1(GSTM1) andGST theta 1 (GSTT1).

Methods

The current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping ofCYP1A1 T3801Cpolymorphisms andGSTM1/GSTT-nullwas made, respectively, by PCR-RFLP and multiplex PCR.

Results

No significantly positive associations were found for theCYP1A1 T3801C[p = 0.71, OR = 1.23 (0.56–2.72)] andGSTM1-null[p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association betweenGSTT1-nullgenotype [p = 0.03, OR = 2.03 (1.06–3.99)],GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa.

Conclusions

The risk of developing prostate cancer in Algeria does not appear to be associated withCYP1A1 T3801Cgenotypes andGSTM1-null, butGSTT1-nullandGSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.
Computationally identifying hot spots in protein-DNA binding interfaces using an ensemble approach
Authors: Pan Yuliang , Zhou Shuigeng , Guan Jihong
Published: September 2020

Background

Protein-DNA interaction governs a large number of cellular processes, and it can be altered by a small fraction of interface residues, i.e., the so-calledhot spots, which account for most of the interface binding free energy. Accurate prediction of hot spots is critical to understand the principle of protein-DNA interactions. There are already some computational methods that can accurately and efficiently predict a large number of hot residues. However, the insufficiency of experimentally validated hot-spot residues in protein-DNA complexes and the low diversity of the employed features limit the performance of existing methods.

Results

Here, we report a new computational method for effectively predicting hot spots in protein-DNA binding interfaces. This method, calledPreHots(the abbreviation ofPredictingHotspots), adopts an ensemble stacking classifier that integrates different machine learning classifiers to generate a robust model with 19 features selected by a sequential backward feature selection algorithm. To this end, we constructed two new and reliable datasets (one benchmark for model training and one independent dataset for validation), which totally consist of 123 hot spots and 137 non-hot spots from 89 protein-DNA complexes. The data were manually collected from the literature and existing databases with a strict process of redundancy removal. Our method achieves a sensitivity of 0.813 and an AUC score of 0.868 in 10-fold cross-validation on the benchmark dataset, and a sensitivity of 0.818 and an AUC score of 0.820 on the independent test dataset. The results show that our approach outperforms the existing ones.

Conclusions

PreHots, which is based on stack ensemble of boosting algorithms, can reliably predict hot spots at the protein-DNA binding interface on a large scale. Compared with the existing methods,PreHotscan achieve better prediction performance. Both the webserver ofPreHotsand the datasets are freely available at:http://dmb.tongji.edu.cn/tools/PreHots/.
Multi-omics profiling reveals microRNA-mediated insulin signaling networks
Authors: Lin Yang-Chi-Dung , Huang Hsi-Yuan , Shrestha Sirjana , Chou Chih-Hung , Chen Yen-Hua , Chen Chi-Ru , Hong Hsiao-Chin , Li Jing , Chang Yi-An , Chiew Men-Yee , Huang Ya-Rong , Tu Siang-Jyun , Sun Ting-Hsuan , Weng Shun-Long , Tseng Ching-Ping , Huang Hsien-Da
Published: September 2020

Background

MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells.

Results

We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network.

Conclusions

In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes.
A multiple T cell epitope comprising DNA vaccine boosts the protective efficacy of Bacillus Calmette–Guérin (BCG) against Mycobacterium tuberculosis
Authors: Maurya Sudeep Kumar , Aqdas Mohammad , Das Deepjyoti Kumar , Singh Sanpreet , Nadeem Sajid , Kaur Gurpreet , Agrewala Javed Naim
Published: September 2020

Background

Approximately 80% - 90% of individuals infected with latentMycobacterium tuberculosis (Mtb)remain protected throughout their life-span. The release of unique, latent-phase antigens are known to have a protective role in the immune response againstMtb. Although the BCG vaccine has been administered for nine decades to provide immunity againstMtb, the number of TB cases continues to rise, thereby raising doubts on BCG vaccine efficacy. The shortcomings of BCG have been associated with inadequate processing and presentation of its antigens, an inability to optimally activate T cells againstMtb, and generation of regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latentMtbinfection. With these facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes ofMtbexpressed during latent, acute, and chronic stages of infection and engineered a multi-epitope-based DNA vaccine (C6).

Result

BALB/c mice vaccinated with the C6 construct along with a BCG vaccine exhibited an expansion of both CD4 and CD8 T cell memory populations and augmented IFN-γ and TNF-α cytokine release. Furthermore, enhancement of dendritic cell and macrophage activation was noted. Consequently, illustrating the elicitation of immunity that helps in the protection againstMtbinfection; which was evident by a significant reduction in theMtbburden in the lungs and spleen of C6 + BCG administered animals.

Conclusion

Overall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.
Infection-provoked reversible posterior leukoencephalopathy syndrome in an adult with nephrotic syndrome: a case report
Authors: Li Kuan-Ying , Chien Ching-Fang , Tsai Chin-Ling , Chen Huang-Chi , Wu Meng-Ni , Lai Chiou-Lian , Liou Li-Min
Published: September 2020

Background

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare and heterogeneous clinico-neuroradiological syndrome characterized by headache, altered mental status, seizures, and visual disturbances. Hypertension and immunosuppression are two of the main factors that predispose an individual to RPLS. However, RPLS can develop when no major risk factors are present. RPLS has been reported in pediatric nephrotic patients, but rarely in adults.

Case presentation

A 42-year-old Asian woman with nephrotic syndrome presented with seizures, headaches, and nausea. Her blood pressure was controlled, and no immunosuppressants had been prescribed. All symptoms and tests indicated RPLS following infection with pneumonia, which was successfully treated by immediate administration antibiotic and anti-epileptic medications. Seizures did not recur during a 2-year follow-up period.

Conclusions

When patients with nephrotic syndrome have an infection, RPLS symptoms should be investigated thoroughly. With early diagnosis and appropriate treatment of RPLS, morbidity and mortality can be prevented.
Relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy and conventional fractionation radiotherapy in non-small cell lung Cancer
Authors: Li Lin , Yue Hong Cheng , Han Yun Wei , Liu Wei , Xiong Liang Geng , Zhang Jian Wen
Published: September 2020

Background

The effect of brachytherapy on lymphocytes and cytokines in the tumor microenvironment is unclear. This study aimed to analyze the relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy (SBHFRT) and conventional fractionation radiotherapy (CFRT) in non-small cell lung cancer (NSCLC).

Methods

Lewis tumor-bearing mice were randomly divided into control, CFRT, and SBHFRT groups. On days 7 and 14 after radiation, the expression levels of CD86+, CD4+, CD8+, and Foxp3+ cells, and levels of Ki-67+ protein were detected by immunohistochemistry, and the tumor necrosis rate was calculated. Following this, the levels of interleukin-10 (IL-10), IL-12, and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. The apoptosis rate was evaluated via flow cytometry. The tumor volume and tumor growth inhibition rate (TGIR) were calculated on day 14. Tumor metabolism was assessed via 18F-FDG micropositron emission tomography/computer tomography.

Results

The tumor volume reduced by 22.0% and TGIR increased by 92.2% (p < 0.05) in the SBHFRT group. Further, on days 7 and 14 after radiation, tumor metabolism, Ki-67+ and Foxp3+ expression levels, and IL-10 levels were lower, and tumor necrosis and apoptosis rates; CD86+, CD4+, and CD8+ expression levels; and IL-12 and IFN-γ levels were higher in the SBHFRT group than in the CFRT group, particularly on day 7.

Conclusion

SBHFRT could lead to more accumulation of dendritic cells, anti-tumor lymphocytes, and cytokines, and further reduce the aggregation of immunosuppressive lymphocytes and cytokines in the tumor microenvironment compared with CFRT, and the difference was the most obvious on day 7 after radiation. The clinical significance of the findings remains to be further verified.
Effect of the electrode array-retina gap distance on visual function in patients with the Argus II retinal prosthesis
Authors: Naidu Abhishek , Ghani Nimra , Yazdanie Mohammad Saad , Chaudhary Khurram
Published: September 2020

Background

Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis.

Methods

Five patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session.

Results

Three patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold.

Conclusion

Our results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes.
Testing an individualized digital decision assist system for the diagnosis and management of mental and behavior disorders in children and adolescents
Authors: Clausen Carolyn E. , Leventhal Bennett L. , Nytrø Øystein , Koposov Roman , Westbye Odd Sverre , Røst Thomas Brox , Bakken Victoria , Koochakpour Kaban , Thorvik Ketil , Skokauskas Norbert
Published: September 2020

Background

Nearly half of all mental health disorders develop prior to the age of 15. Early assessments, diagnosis, and treatment are critical to shortening single episodes of care, reducing possible comorbidity and long-term disability. In Norway, approximately 20% of all children and adolescents are experiencing mental health problems. To address this, health officials in Norway have called for the integration of innovative approaches. A clinical decision support system (CDSS) is an innovative, computer-based program that provides health professionals with clinical decision support as they care for patients. CDSS use standardized clinical guidelines and big data to provide guidance and recommendations to clinicians in real-time. IDDEAS (Individualised Digital DEcision Assist System) is a CDSS for diagnosis and treatment of child and adolescent mental health disorders. The aim of IDDEAS is to enhance quality, competency, and efficiency in child and adolescent mental health services (CAMHS).

Methods/design

IDDEAS is a mixed-methods innovation and research project, which consists of four stages: 1) Assessment of Needs and Preparation of IDDEAS; 2) The Development of IDDEAS CDSS Model; 3) The Evaluation of the IDDEAS CDSS; and, 4) Implementation & Dissemination. Both qualitative and quantitative methods will be used for the evaluation of IDDEAS CDSS model. Child and adolescent psychologists and psychiatrists (n = 30) will evaluate the IDDEAS` usability, acceptability and relevance for diagnosis and treatment of attention-deficit/hyperactivity disorder.

Discussion

The IDDEAS CDSS model is the first guidelines and data-driven CDSS to improve efficiency of diagnosis and treatment of child and adolescent mental health disorders in Norway. Ultimately, IDDEAS will help to improve patient health outcomes and prevent long-term adverse outcomes by providing each patient with evidence-based, customized clinical care.

Trial registration

ISRCTN, ISRCTN12094788. Ongoing study, registered prospectively 8 April 2020 10.1186/ISRCTN12094788
Qualitative analysis of clinicians’ perspectives on the use of a computerized decision aid in the treatment of psychotic disorders
Authors: Roebroek Lukas O. , Bruins Jojanneke , Delespaul Philippe , Boonstra Albert , Castelein Stynke
Published: September 2020

Background

Clinical decision aids are used in various medical fields to support patients and clinicians when making healthcare decisions. Few attempts have been made to implement such tools in psychiatry. We developed Treatment E-Assist (TREAT); a routine outcome monitoring based computerized clinical decision aid, which generates personalized treatment recommendations in the care of people with psychotic disorders. The aim of this study is to investigate how TREAT is used and evaluated by clinicians and how this tool can be improved.

Methods

Clinicians working with TREAT during a clinical trial were asked to participate in semi-structured interviews. The Unified Theory of Acceptance and Use of Technology (UTAUT) was used as a sensitizing theory to structure a part of the interview questions. The transcripts were analyzed using inductive thematic analysis to uncover the main themes.

Results

Thirteen clinicians (mean age: 49) of which eight psychiatrists and five nurse practitioners, participated in this study. Eight clinicians experienced TREAT as beneficial, whereas five experienced no additional benefits. Thematic analysis revealed five themes surrounding usage and evaluation of TREAT, views on TREAT’s graphic representation of routine outcome monitoring results, guideline based treatment recommendations, contextual factors, effects on patients and effects on shared decision-making. Performance and effort expectancy were perceived as high by clinicians. The facilitating conditions were optimal and perceived social influence was low.

Conclusion

This article presents a qualitative evaluation by clinicians of a computerized clinical decision aid in psychosis care. TREAT was viewed by most clinicians as beneficial during their consultations. The graphic representation of routine outcome monitoring results was well-appreciated and provided input to discuss treatment planning with patients. The treatment recommendations did not change most treatment decisions but supported clinical reasoning. However, some clinicians were unconvinced about TREAT’s benefits. The delivery, applicability and the availability of resources require improvement to increase TREAT’s efficacy. Not all patients responded well to TREAT but the observed facilitation of shared decision-making is promising. All four predictors of the Unified Theory of Acceptance and Use of Technology were positively evaluated by the majority of clinicians.
Increased frequency of intentional weight loss associated with reduced mortality: a prospective cohort analysis
Authors: Willis Erik A. , Huang Wen-Yi , Saint-Maurice Pedro F. , Leitzmann Michael F. , Salerno Elizabeth A. , Matthews Charles E. , Berndt Sonja I.
Published: September 2020

Background

Due to the high prevalence of obesity and the difficulty in maintaining weight loss, repeated bouts of weight loss are a common occurrence. However, there are inconsistencies in epidemiological studies regarding repetitive weight fluctuations being associated with increased risk of mortality. Therefore, the purpose of this prospective cohort analysis was to determine the long-term association of the frequency of weight loss attempts on mortality.

Methods

This prospective cohort study used data collected from adult AARP members living in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania) or 2 metropolitan areas (Atlanta, Georgia, or Detroit, Michigan) and participating in the National Institutes of Health–AARP Diet and Health Study between 2004 and 2006. Self-reported data were analyzed for 161,738 middle-aged adults. During an average 7 years of follow-up, 21,194 deaths were recorded. Hazard ratios of all-cause, cardiovascular, and cancer mortality were estimated adjusting for demographic, lifestyle, and behavioral risk factors.

Results

Increased frequency of weight loss attempts of at least five pounds was associated with lower mortality (ptrend < 0.010). Multivariate hazard ratios (95% confidence intervals) for all-cause death among individuals who successfully attempted weight loss compared with those who did not make any attempts were 0.94 (0.90–0.98) for 1–2 attempts, 0.96 (0.91–1.01) for 3–4 attempts, 0.91 (0.85–0.96) for 5–6 attempts, 0.91 (0.85–0.98) for 7–8 attempts, 0.87 (0.80–0.95) for 9–10 attempts, and 0.88 (0.82–0.94) for 11+ attempts. Similar results were noted for men and women, participants with healthy weight and overweight/obesity, and even among those who gained weight over time. Protective associations were also observed for deaths due to cardiovascular disease and cancer.

Conclusions

Increased frequency of intentionally losing at least five pounds in mid-life was associated with a lower risk of future death. Repeated attempts with moderate amounts of weight loss may provide benefit in terms of longevity.

Trial registration number

ClinicalTrials.gov number, NCT00340015
Influence of obesity on remodeling of lung tissue and organization of extracellular matrix after blunt thorax trauma
Authors: Xu Pengfei , Gärtner Fabian , Gihring Adrian , Liu Congxing , Burster Timo , Wabitsch Martin , Knippschild Uwe , Paschke Stephan
Published: September 2020

Background

Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet.

Methods

This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h).

Results

Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%.

Conclusions

In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.
The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR
Authors: Tan Biqin , Dong Rong , Zhang Bo , Yan Youyou , Li Qingyu , Wang Fei , Lin Nengming
Published: September 2020

Background

Radiotherapy is one of the main treatments for pancreatic cancer, but radiation resistance limits its clinical application. As a result, novel therapeutic agents to improve radiosensitivity are urgently needed. This study aimed to investigate the effect of Ibr-7 (a derivative of ibrutinib) on the radiosensitivity of human pancreatic cancer cells.

Methods

The effect of Ibr-7 on pancreatic cancer cell proliferation was detected by CCK-8 assays. Radiosensitivity was assessed by clonogenic formation assays. Cell cycle and cell apoptosis were analysed by flow cytometry. DNA damage was evaluated by immunofluorescence analysis. The expression levels of PARP, Cleaved caspase 3, p-EGFR and EGFR were determined by western blot.

Results

Ibr-7 showed an anti-proliferative effect on PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 μmol/L) enhanced the effect of radiation on PANC-1 and Capan2 cells. Further findings showed that this combination enhanced G2/M phase arrest and increased cell apoptosis. Additional molecular mechanism studies revealed that the expression of p-EGFR was decreased by Ibr-7 alone or in combination with radiation. Overexpression of p-EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in the Ibr-7 plus radiation group.

Conclusions

Our study indicated the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells.
CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells
Authors: Li Hang , Che Jun , Jiang Mian , Cui Ming , Feng Guoxing , Dong Jiali , Zhang Shuqin , Lu Lu , Liu Weili , Fan Saijun
Published: September 2020

Introduction

Radioresistance is a major challenge in lung cancer radiotherapy, and new radiosensitizers are urgently needed. Estrogen receptor β (ERβ) is involved in the progression of non-small cell lung cancer (NSCLC), however, the role of ERβ in the response to radiotherapy in lung cancer remains elusive. In the present study, we investigated the mechanism underlying ERβ-mediated transcriptional activation and radioresistance of NSCLC cells.

Methods

Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of CLPTM1L, ERβ and other target genes. The mechanism of CLPTM1L in modulation of radiosensitivity was investigated by chromatin immunoprecipitation assay, luciferase reporter gene assay, immunofluorescence staining, confocal microscopy, coimmunoprecipitation and GST pull-down assays. The functional role of CLPTM1L was detected by function assays in vitro and in vivo.

Results

CLPTM1L expression was negatively correlated with the radiosensitivity of NSCLC cell lines, and irradiation upregulated CLPTM1L in radioresistant (A549) but not in radiosensitive (H460) NSCLC cells. Meanwhile, IR induced the translocation of CLPTM1L from the cytoplasm into the nucleus in NSCLC cells. Moreover, CLPTM1L induced radioresistance in NSCLC cells. iTRAQ-based analysis and cDNA microarray identified irradiation-related genes commonly targeted by CLPTM1L and ERβ, and CLPTM1L upregulated ERβ-induced genes CDC25A, c-Jun, and BCL2. Mechanistically, CLPTM1L coactivated ERβ by directly interacting with ERβ through the LXXLL NR (nuclear receptor)-binding motif. Functionally, ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance of NSCLC cells in vitro. CLPTM1L shRNA treatment in combination with irradiation significantly inhibited cancer cell growth in NSCLC xenograft tumors in vivo.

Conclusions

The present results indicate that CLPTM1L acts as a critical coactivator of ERβ to promote the transcription of its target genes and induce radioresistance of NSCLC cells, suggesting a new target for radiosensitization in NSCLC therapy.
Utility of the EULAR Sjögren syndrome disease activity index in Japanese children: a retrospective multicenter cohort study
Authors: Iwata Naomi , Tomiita Minako , Kobayashi Ichiro , Inoue Yusaburo , Nonaka Yukiko , Okamoto Nami , Umebayashi Hiroaki , Hara Ryoki , Ito Yasuhiko , Sato Yasunori , Mori Masaaki
Published: September 2020

Background

The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren’s syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren’s syndrome.

Methods

The medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically.

Results

The study subjects included 31 children (3 boys, 28 girls) with primary Sjögren’s syndrome. Their median age at disease onset was 10 years (interquartile range [IQR], 8–13 years), and their median initial ESSDAI was 7.0 (IQR; 5.0–15.0). ESSDAI-determined disease activity was high in nine patients (29.0%), moderate in 15 (48.4%), and low in seven (22.6%). During the first year after their initial visit, 14 patients (45.2%) were treated with prednisolone (PSL) and six (19.4%) with immunosuppressants. Dose of PSL was significantly associated with ESSDAI score. Median ESSDAI score was significantly higher in patients treated with high/medium- than with no/low-dose PSL (16.5 [IQR 10.5–18.0] vs 5.0 [IQR 3.0–8.5]). Eight (66.7%) of 12 patients administered medium/high-dose PSL and one (5.3%) of 19 administered no/low-dose PSL had high disease activity on ESSDAI.

Conclusion

Disease activity assessed by ESSDAI tended to be consistent with disease activity assessed by pediatric rheumatologists in determining treatment regimens. ESSDAI is useful for assessing disease activity in Japanese children with primary Sjögren’s syndrome.
Clinician-ordered peripheral blood smears have low reimbursement and variable clinical value: a three-institution study, with suggestions for operational efficiency
Authors: Beckman Amy K. , Ng Valerie L. , Jaye David L. , Gaddh Manila , Williams Sarah A. , Yohe Sophia L. , Zhang Lin , Linden Michael A.
Published: September 2020

Background

Peripheral blood smears are performed to evaluate a variety of hematologic and non-hematologic disorders. At the authors’ institutions, clinician requests for pathologist-performed blood smear reviews have increased in recent years. Blood smears may contribute significantly to pathologists’ workloads, yet their clinical value is variable, and professional reimbursement rates are low. This study aimed to identify clinical scenarios in which smear review is likely to provide value beyond automated laboratory testing.

Methods

Blood smear review practices at three institutions were examined, and the indications for and interpretations of clinician-initiated smears were reviewed to determine the percentage of smears with potential added clinical value. A smear review was classified as having added clinical value if the pathologist’s interpretation included a morphologic abnormality that had the potential to impact patient management, and that could not be diagnosed by automated complete blood count with white blood cell differential or automated iron studies alone.

Results

Among 515 consecutive clinician-requested smears performed during the study timeframes, 23% yielded interpretations with potential added clinical value. When sorted by indication, 25, 19, and 13% of smear reviews requested for white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities, respectively, had findings with potential added clinical value. The proportion of smears with potential clinical value differed significantly across these three categories (p = 0.0375).

Conclusions

Smear review ordering practices across three institutions resulted in a minority of smears with potential added clinical value. The likelihood of value varied according to the indication for which the smear was requested. Given this, efforts to improve the utilization and efficiency of smear review are worthwhile. Solutions are discussed, including engaging laboratory staff, educating clinicians, and modifying technology systems.
High throughput profiling of tocochromanols in leaves and seeds of Arabidopsis and Maize
Authors: Bao Yan , Magallenes-Lundback Maria , Deason Nicholas , DellaPenna Dean
Published: September 2020

Background

Tocochromanols are a group of lipid-soluble antioxidants produced by all plants and include the tocopherols, which are ubiquitous in the plant kingdom, and the biosynthetically-related compounds tocotrienols, which along with tocopherols commonly occur in seed of monocots. Most tocochromanols have some level of vitamin E activity, with α-tocopherol being the highest, and as such are essential nutrients in the human diet. Tocochromanols are particularly abundant in seeds and are critical for maintaining seed longevity and proper germination and as seed oils are a major component of the human diet, they are an important source of dietary vitamin E. In vegetative tissues, tocochromanols are important components in plant responses to stressful environments and can accumulate to high levels in response to various stresses including high light, heat, and dark.

Results

We report a robust, high throughput extraction and HPLC analysis method to quantify the levels of tocopherols and tocotrienols in leaves and seeds of plants, using Arabidopsis and maize tissues as examples.

Conclusion

The described method provides a rapid, high-throughput, cost-effective approach to quantifying the composition and content of tocopherols, and if needed simultaneously tocotrienols, in vegetative tissues and seeds. Optimized extraction methods are described for the two tissue types and have been used to study tocochromanol (vitamin E) natural variation in seed of large Arabidopsis and maize diversity panels, to assess gene function in T-DNA and Mu-tagged populations of Arabidopsis and maize, respectfully, and study the impact of environmental stresses, including high light stress, heat stress, and dark on tocopherols content and composition of vegetative tissue.
XMU-MP-1 induces growth arrest in a model human mini-organ and antagonises cell cycle-dependent paclitaxel cytotoxicity
Authors: Mitchell Ellen , Mellor Charlotte E. L. , Purba Talveen S.
Published: September 2020

Background

XMU-MP-1 is an inhibitor of the Hippo pathway kinases MST1/2 and has been shown to promote the downstream activation of the pro-proliferative, pro-regenerative and anti-apoptotic transcriptional regulator YAP1. We tested whether XMU-MP-1 can activate YAP1 in a model human mini-organ, namely the hair follicle, to determine whether it can be pharmacologically exploited to promote regeneration in the hair follicle as a novel strategy to treat pathological hair loss disorders.

Results

XMU-MP-1 treatment inhibited MOB1 phosphorylation but did not increase active YAP1 in the hair follicle. Rather than promote proliferation, XMU-MP-1 serendipitously decreased the number of Ki-67+, EdU+ and phospho histone H3+ hair matrix keratinocytes and antagonised the cytotoxic effects of paclitaxel.

Conclusions

XMU-MP-1 perturbs epithelial cell cycle progression in a model human mini-organ. This may arise as an off-target effect, especially when XMU-MP-1 has been described to strongly inhibit 21 additional kinases beyond MST1/2. Therefore, whilst these effects may be dependent on tissue context, researchers should exercise caution when interpreting the effects of XMU-MP-1, especially in tissues with actively proliferating cell populations.