bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic syndrome in type 2 diabetic patients: a review of current evidence
Authors: Regufe Virgínia M.G. , Pinto Cristina M.C.B. , Perez Pedro M.V.H.C.
Published: December 2020

The metabolic syndrome (MS) is a set of metabolic disturbances, represented by various cardiovascular risk factors which are generally associated with the central accumulation of fat and the resistance to insulin. Inadequate changes in eating behaviours and weight loss, which are associated to taking part in regular physical activity, are considered to be primary and first choice therapies for the treatment of MS, as they assist in the reduction of the abdominal girth and visceral fat, improve the sensibility to insulin and reduce the plasmatic concentrations of glucose and triglycerides, raise the values of high density lipoproteins and, consequently decrease the risk factors which contribute to the development of type 2 diabetes. The MS is a current discussion theme in the health field as it is related to illnesses/diseases, which not only cause a worldwide high mortality rate but show increasing incidence. Type 2 diabetes is characterised by a deregulation of the carbohydrates, lipids and proteins found in the metabolism and result in diminished secretion of insulin, resistance to insulin or a combination of both. Type 2 diabetes is the most form of diabetes of the first 3 types of diabetes, representing 90% of all cases. Diabetes is a chronic and complex disease which requires a strict medical follow-up so as to reduce the risks and obtain strategies for its control. The fast-epidemiological global evolution which has been registered in the last few years, leads to it being considered one of the pandemics of the 21st century. In this non-systematic and advanced review of the MS in type 2 diabetic patients, several articles were consulted, and some recently published studies were analysed.
Psychometric Properties and Factorial Structure of Vietnamese Version of the Hypertension Self-care Profile Behavior Scale
Authors: Van Truong Pham , Lin Mei-Yu , Chiu Hsiao-Yean , Hou Wen-Hsuan , Tsai Pei-Shan
Published: December 2020

Background

The Hypertension Self-care Profile Behavior (HTN-SCPB) scale is a self-report instrument with which a patient's self-care behavior can be assessed. However, its psychometric properties for adult patients with hypertension in Vietnam require clarification.

Objective

The aim of this study was to translate the HTN-SCPB scale into Vietnamese and to assess its psychometric properties.

Methods

The study included 220 adult patients with hypertension. To evaluate test-retest reliability, 133 participants were tested twice with a 3-week interval between tests. For construct validity, exploratory factor analysis was used to assess factor structure, and confirmatory factor analysis was used to evaluate the structural model fit of the scale.

Results

Reliability was confirmed by internal consistency (Cronbach α = 0.79) and test-retest reliability (intraclass correlation coefficient, 0.88). The Kaiser-Meyer-Olkin value was 0.75, and Bartlett's test of sphericity was significant (P < .001) and adequate for exploratory factor analysis. A 5-factor structure was obtained, and the factors were named as follows: “advanced self-management skills,” “adverse health behaviors,” “medication adherence,” “diet-related knowledge regarding hypertension,” and “information skills.” Confirmatory factor analysis revealed that the model fit indices were acceptable (root-mean-square error of approximation, 0.07) or slightly less than the good fit values (comparative fit index, 0.85; incremental fit index, 0.85; goodness-of-fit index, 0.88; adjusted goodness-of-fit index, 0.84; and Tucker-Lewis index, 0.82).

Conclusions

The Vietnamese HTN-SCPB scale had satisfactory validity and reliability for assessing self-care behaviors in patients with hypertension in Vietnam.
Mindfulness, Posttraumatic Stress Symptoms, and Posttraumatic Growth in Aid Workers
Authors: Wen Xue , An Yuanyuan , Zhou Yuyang , Du Jiaxuan , Xu Wei
Published: December 2020

Objective: The risk for aid workers to develop posttraumatic mental problems highlights the importance of reducing the harm of posttraumatic stress symptoms (PTSS) and promoting the benefits of posttraumatic growth (PTG). This study examined the negative relationship between mindfulness and PTSS, and the positive relationship between mindfulness and PTG, and further explored the mediating roles of self-acceptance, intrusive rumination, and deliberate rumination. Methods: Aid workers from the Red Cross Organization (N = 298) were recruited in the study. They completed a series of questionnaires assessing mindfulness, self-acceptance, rumination, posttraumatic stress disorder (PTSD), and PTG. Results: Results showed that mindfulness was significantly and negatively associated with PTSD through positively predicting self-acceptance and negatively predicting intrusive rumination. Mindfulness was significantly and positively associated with PTG, although the mediating effect did not exist because the path between self-acceptance and deliberate rumination was impassable. Conclusion: The mechanisms between mindfulness, PTSD, and PTG were further explored. Limitations and implications for trauma intervention and future research were discussed.
The Effects of Maintenance Electroconvulsive Therapy on Hospitalization Rates
Authors: Kocamer Şahin Şengül , Demir Bahadır , Elboğa Gülçin , Altındağ Abdurrahman , Elmalı Enes
Published: December 2020

This study aimed to study the effect of maintenance electroconvulsive therapy (mECT) on hospitalization rates in patients who had been readmitted after acute courses of electroconvulsive therapy (ECT), and determine the most frequently used treatment schedules in mECT. Patients who had undergone mECT treatment for the last 5 years were retrospectively reviewed. Seventy patients were included in the study. The control group of 70 patients was selected from patients who received only acute ECT. Of the patients in the mECT group, 55.8% (39) were female, and 41.4% (29) were diagnosed with major depressive disorder. The mean number of patients hospitalized who received mECT after acute ECT was 0.55 ± 0.87, whereas it was 1.13 ± 1.31 in patients who received only pharmacotherapy after ECT in a covariant analysis adjusted for age and diagnosis. The most commonly used initial treatment protocol of mECT was weekly × 4, biweekly × 2, and monthly × 6. mECT is more effective in reducing hospitalization after acute ECT treatments than using psychotropic drugs alone for maintenance therapy.
Exploring the Association Between Organizational Safety Climate, Failure to Rescue, and Mortality in Inpatient Surgical Units
Authors: Bacon Cynthia Thornton , McCoy Thomas P. , Henshaw Daryl S.
Published: December 2020

OBJECTIVE

To examine the association between organizational safety climate (OSC), in-hospital mortality (IM), and failure to rescue (FTR) in 2 hospitals, 1 with and 1 without crew-resource-management training.

BACKGROUND

OSC is 1 of the most important organizational factors that promotes safety at work; however, there is a lack of research examining the relationship between OSC and patient deaths in hospitals.

METHODS

We utilized a matched 2-group comparison of surgical patients and surveyed surgical staff to assess the relationship between OSC, FTR, and IM.

RESULTS

The OSC assessment was completed by 261 surgical team members. A total of 1764 patients had at least 1 FTR complication; however, there was no association between OSC with FTR or IM for either hospital.

CONCLUSIONS

Nurse leaders should remain vigilant in building work teams with strong hospital safety climates. More research is needed to explore the relationship between OSC and patient outcomes.
Evaluation of a Bed Reaggregation Initiative at an Urban Academic Medical Center
Authors: Kuczero Jennifer L. , Staffileno Beth A. , Grenier Jennifer M.
Published: December 2020

BACKGROUND

Hospital flow disruptions have been linked to treatment delays, longer length of stay (LOS), poor patient outcomes, and overburdened staff leading to disengagement.

OBJECTIVE

This project was designed to evaluate and determine if the bed reaggregation was successful at meeting its goals.

METHODS

Donabedian's framework guided the following evaluation points: 1) patient placement accuracy, 2) LOS variance, 3) emergency department (ED) boarding times, 4) hospital bypass hours, 5) operational declination rates, 6) patient satisfaction, and 7) RN engagement. Data were analyzed using pre-post percent change and χ
2 analysis.

RESULTS

Primary placement of patients, LOS variance, and operational declinations improved. Hours on bypass and ED boarding times were not reduced. RN engagement scores varied widely with significant decreases on 2 of the reaggregated units. Patient satisfaction scores varied, but overall did not decrease.

CONCLUSION

Further consideration is needed for improving hospital bypass, ED boarding times, and RN engagement.
An Exploration of Characteristics and Behavioral Traits of DAISY Honorees and Nominees
Authors: Nair Julie McCulloh , Merring Paige , Jones Bradley , Guney Senem
Published: December 2020

BACKGROUND

In the literature, an abundance of stories exist describing patient situations and caregiver actions, but only 2 studies were identified that outline DAISY honorees' actions and behavioral characteristics.

OBJECTIVE

This study utilized patient nomination data and DAISY honoree insight to identify and gain better understanding of the characteristics and behavioral traits of DAISY nurses.

METHODS

A grounded theory approach and purposive sample were used in this study, which was conducted in 2 phases using 2 different data sets. In phase 1, the NarrativeDx AI platform generated insights from DAISY nomination comments. In phase 2, a survey was administered to DAISY honorees collecting descriptive data that were analyzed in SPSS, whereas insights on DAISY nurses were collected via open-ended responses and analyzed using NVivo software.

RESULTS

Three themes emerged in phase 1 from DAISY nomination data: caring, knowledge/skills, and reliability. A total of 37 DAISY honorees participated in phase 2. Most participants were bachelor's degree–prepared and worked day shift in the emergency department, critical care units, or medical-surgical units; some entered leadership roles post award, and 34% cited nursing as a 2nd career. Four themes emerged from their open-ended responses: engaging in care, environment of care, dedicated to care, and competence of care. Subthemes emerged in both analyses.

CONCLUSIONS

The essence of caring was noted continuously in both nomination and honoree data. Further research aimed at discovering the characteristics and behaviors of DAISY honorees is recommended as examination of these factors may provide a deeper understanding of this exemplary group of nurses. Insights could be incorporated into training and practice programs aimed at increasing patient and nursing satisfaction.
Development of a Mobile Hospital for Disaster Relief
Authors: Neely Robyn , Haynes Kristy , Miller Greg
Published: December 2020

Mobile supplemental hospitals were an important asset to community response in preparing for the recent pandemic. MED-1 is a Mobile Emergency Department that has adapted and evolved to the changing needs of communities in times of disaster and nondisaster. An overview of the asset (MED-1), the operations, and use is provided to demonstrate how mobile supplemental hospitals can effectively meet a range of healthcare needs. Innovative utilization of MED-1 has secured its future as an effective resource averaging 100 days of deployment per year.
Suicide and Suicide Attempts on Veterans Affairs Medical Center Outpatient Clinic Areas, Common Areas, and Hospital Grounds
Authors: Rajendran Sreevaishali , Mills Peter D. , Watts Bradley V. , Gunnar William
Published: December 2020

Objectives

Few studies have analyzed suicide deaths and attempts occurring outside inpatient units on other hospital locations. We aimed to quantify and analyze suicide deaths and attempts occurring on Department of Veterans Affairs medical center outpatient clinic areas, common areas, and hospital grounds including parking lots to determine whether a relationship with access to mental health care exists and to elucidate potential mitigation strategies.

Methods

We conducted a retrospective review of patient safety report (n = 3,186), root cause analysis (n = 234), and issue brief (n = 2,064) national databases between January 1, 2015, and December 31, 2018, to identify occurrences of suicides and attempts. Correlation between mental health access times and hospital-specific rates of suicides and attempts was assessed. Qualitative analyses of root causes and mitigation strategies were conducted.

Results

Of 192 reports meeting our location criteria, 42 suicides or attempts occurred in outpatient clinic areas, 39 in common spaces, and 111 on outdoor facility areas. Forty-four reports (23%) pertained to suicides, and 148 (77%) pertained to attempts. The predominate methods were death by firearms (64%) and attempt by drug overdose (38%). We identified a weak yet significant relationship between mental health access times for established patients and rates of on-campus suicides and attempts (r = 0.279, P = 0.0013).

Conclusions

Clinical changes including environmental assessments and interventions, staff training on identifying suicide risk characteristics, policy changes toward improving contraband search techniques, and medications risk assessment, as well as timely access to care may be effective mitigation strategies toward preventing suicides of this nature.
Qualitative Perceptions of Dapivirine VR Adherence and Drug Level Feedback Following an Open-Label Extension Trial
Authors: Naidoo Kalendri , Mansoor Leila E. , Katz Ariana W. K. , Garcia Morgan , Kemigisha Doreen , Morar Neetha S. , Zimba Chifundo C. , Chitukuta Miria , Reddy Krishnaveni , Soto-Torres Lydia , Naidoo Sarita , Montgomery Elizabeth T.
Published: December 2020

Background:

There continues to be a need for HIV prevention options that women can initiate and use autonomously. The dapivirine vaginal ring (VR) has been shown to have a favorable safety profile and reduce the risk of HIV-1 acquisition. We report on women's experiences with VR adherence during the MTN-025/HIV Open-label Prevention Extension (HOPE) study and responses to Residual Drug Level (RDL) results.

Setting:

Ten women at each of the 6 HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were randomly selected (n = 60).

Methods:

After confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented.

Results:

Many women with low RDL release measurements deflected blame onto other factors (the ring, the drug, and faulty testing machines) and distrust of the testing method. The disclosure of RDL results enabled some users to discuss their challenges experienced (fear of partner objections, perceived side effects, and removals during menses). Consistent users reported important motivators (support from others, protection from HIV, and enhanced sexual experiences from the VR).

Conclusion:

The VR provided a sense of security for some women; however, adherence was still challenging for others regardless of it being a female controlled, long-acting HIV prevention technology. Adherence measurements may not be sustainable in the real-world implementation of the VR, although they can be seen as a benefit as they provide a better understanding of actual product use and provide women with a platform to discuss their experiences.
Steadily Increasing Inversion Time Improves Blood Suppression for Free-Breathing 3D Late Gadolinium Enhancement MRI With Optimized Dark-Blood Contrast
Authors: Holtackers Robert J. , Gommers Suzanne , Van De Heyning Caroline M. , Mihl Casper , Smink Jouke , Higgins David M. , Wildberger Joachim E. , ter Bekke Rachel M.A.
Published: December 2020

Objectives

Free-breathing 3-dimensional (3D) late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) techniques with high isotropic resolution and dark-blood contrast may optimize the delineation of myocardial scar patterns. The extended acquisition times required for such scans, however, are paralleled by a declining contrast agent concentration. Consequently, the optimal inversion time (TI) is continuously increasing. We hypothesize that a steadily increasing (dynamic) TI can compensate for this effect and can lead to improved blood nulling to optimize the dark-blood contrast.

Materials and Methods

Fifty consecutive patients with previous cardiac arrhythmias, scheduled for high-resolution 3D LGE MRI, were prospectively enrolled between October 2017 and February 2020. Free-breathing 3D dark-blood LGE MRI with high isotropic resolution (1.6 × 1.6 × 1.6 mm) was performed using a conventional fixed TI (n = 25) or a dynamic TI (n = 25). The average increase in blood nulling TI per minute was obtained from Look-Locker scans before and after the 3D acquisition in the first fixed TI group. This average increment in TI was used as input to calculate the dynamic increment of the initial blood nulling TI value as set in the second dynamic TI group. Regions of interest were drawn in the left ventricular blood pool to assess mean signal intensity as a measure for blood pool suppression. Overall image quality, observer confidence, and scar demarcation were scored on a 3-point scale.

Results

Three-dimensional dark-blood LGE data sets were successfully acquired in 46/50 patients (92%). The calculated average TI increase of 2.3 ± 0.5 ms/min obtained in the first fixed TI group was incorporated in the second dynamic TI group and led to a significant decrease of 72% in the mean blood pool signal intensity compared with the fixed TI group (P < 0.001). Overall image quality (P = 0.02), observer confidence (P = 0.02), and scar demarcation (P = 0.01) significantly improved using a dynamic TI.

Conclusions

A steadily increasing dynamic TI improves blood pool suppression for optimized dark-blood contrast and increases observer confidence in free-breathing 3D dark-blood LGE MRI with high isotropic resolution.
A Deep-Learning Diagnostic Support System for the Detection of COVID-19 Using Chest Radiographs
Authors: Fontanellaz Matthias , Ebner Lukas , Huber Adrian , Peters Alan , Löbelenz Laura , Hourscht Cynthia , Klaus Jeremias , Munz Jaro , Ruder Thomas , Drakopoulos Dionysios , Sieron Dominik , Primetis Elias , Heverhagen Johannes T. , Mougiakakou Stavroula , Christe Andreas
Published: December 2020

Objectives

The aim of this study was to compare a diagnosis support system to detect COVID-19 pneumonia on chest radiographs (CXRs) against radiologists of various levels of expertise in chest imaging.

Materials and Methods

Five publicly available databases comprising normal CXR, confirmed COVID-19 pneumonia cases, and other pneumonias were used. After the harmonization of the data, the training set included 7966 normal cases, 5451 with other pneumonia, and 258 CXRs with COVID-19 pneumonia, whereas in the testing data set, each category was represented by 100 cases. Eleven blinded radiologists with various levels of expertise independently read the testing data set. The data were analyzed separately with the newly proposed artificial intelligence–based system and by consultant radiologists and residents, with respect to positive predictive value (PPV), sensitivity, and F-score (harmonic mean for PPV and sensitivity). The χ2 test was used to compare the sensitivity, specificity, accuracy, PPV, and F-scores of the readers and the system.

Results

The proposed system achieved higher overall diagnostic accuracy (94.3%) than the radiologists (61.4% ± 5.3%). The radiologists reached average sensitivities for normal CXR, other type of pneumonia, and COVID-19 pneumonia of 85.0% ± 12.8%, 60.1% ± 12.2%, and 53.2% ± 11.2%, respectively, which were significantly lower than the results achieved by the algorithm (98.0%, 88.0%, and 97.0%; P < 0.00032). The mean PPVs for all 11 radiologists for the 3 categories were 82.4%, 59.0%, and 59.0% for the healthy, other pneumonia, and COVID-19 pneumonia, respectively, resulting in an F-score of 65.5% ± 12.4%, which was significantly lower than the F-score of the algorithm (94.3% ± 2.0%, P < 0.00001). When other pneumonia and COVID-19 pneumonia cases were pooled, the proposed system reached an accuracy of 95.7% for any pathology and the radiologists, 88.8%. The overall accuracy of consultants did not vary significantly compared with residents (65.0% ± 5.8% vs 67.4% ± 4.2%); however, consultants detected significantly more COVID-19 pneumonia cases (P = 0.008) and less healthy cases (P < 0.00001).

Conclusions

The system showed robust accuracy for COVID-19 pneumonia detection on CXR and surpassed radiologists at various training levels.
Management of Pediatric Orbital Fractures
Authors: Wolff Amir , Ohayon Chaim , Emodi Omri , Sviri Gill E. , Shapira Vladimir , Rachmiel Adi
Published: December 2020

Introduction:

Although uncommon in children, orbital fractures can be devastating to both vision and appearance. Due to the scarce information in the literature, the authors here present our experience and management with all pediatric orbital fracture patients.

Material and methods:

A 6-years retrospective study was conducted on pediatric patients presented with orbital wall fracture (OFx). All patients (n = 43) were grouped for comparison based on the treatment method. The cohorts were analyzed for demographics data, location of fracture, type of material used for reconstruction, complication rate and follow up length. Data was analyzed utilizing SPSS for χ
2 test.

Results:

The majority of patients were male (86%) and the mean age of patients was 12.09 ± 4 years. Mean follow-up time was 237 ± 72 days. Most of Patients 31 (72%) underwent surgical intervention. A higher rate of complications was observed in the surgically treated group (32%) compared to the conservative group (8%) regardless to the defect size. Subgroup analysis of the surgery treated group revealed that large size defect had inferior outcome compared to small size defect.

Conclusion:

The consequences of treatment on long-term growth and development must be a cornerstone when choosing the optimal therapeutic method. Conservative management should be considered first in the absence of significant clinical pathologies. In addition, when surgery is indicated the least invasive procedure should be applied. The use of autogenous bone graft is preferable over alloplastic materials, however, when there is insufficient bone quantity the use of alloplastic materials is not contraindicated for reconstruction.
Prominent Ear Repair Surgery: Long-Term Results
Authors: Toplu Gaye , Altinel Dincer
Published: December 2020

Purpose:

Prominent ear is common in the white population at a rate of 5%. Many surgical incision and suture techniques have been described for its correction. The purpose of this article was to report the results of the prominent ear surgeries applied in our clinic for the last 5 years and to show the details of the surgical technique, to evaluate long-term results, complications, revisions and to compare them with previously published studies.

Materials and Methods:

A total of 27 patients were included in the study. The patient age ranged from 7 to 60 at the time of surgery (mean age: 18.7). Of the 27 patients, 13 were female (48.2%) and 14 were male (51.8%). The procedure was bilateral in 19 cases (70.4%) and unilateral in 8 cases (29.6%). The patients were treated with the same technique by three surgeons. Aesthetic results were evaluated by patient and surgeon surveys.

Results:

The follow-up was between 1 and 5 years (mean: 3 years). The patients very satisfied with the overall appearance of the ears, and the symmetry of the ears was rated as excellent by all patients, parents, and surgeons.

Conclusion:

Regardless of the technique used, patient satisfaction appears to be high. To reduce negative results and prevent recurrence, the authors recommend that the ear is preoperatively evaluated and the treatment algorithm is used accordingly.
The Effect of Medial Sural Artery Perforator Flap on Reconstruction of Soft Tissue Defects: A Meta-Analysis With Multiple Free Soft Flaps
Authors: Xu Qiang , Yin Shou-Cheng , Su Xing-Zhou , Wang Si-Min , Liu Yi-Hao , Xu Zhong-Fei
Published: December 2020

Background:

With the gradual popularity of relatively novel medial sural artery perforator flap (MSAPF), robust studies are needed to compare the surgical outcomes of MSAPF versus multiple free soft flaps (MFSFs) to verify the advantages and disadvantages of MSAPF.

Methods:

The authors searched PubMed, Web of Science, EMBASE, Cochrane Library, Chinese BioMedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) until September, 2020, to identify studies that compared surgical outcomes of MSAPF and MFSFs. Two authors followed the PRISMA guidelines, individually extracted the data and performed the quality assessments. Survival rate of flaps, satisfaction degree of patients in recipient and donor site, skin grafting, and morbidity of recipient and donor site were evaluated.

Results:

A total of 441 cases from 7 studies were included in our analysis. No significant differences were found regarding survival rate of flaps, recipient morbidity, and recipient satisfaction degree between the 2 groups. However, MSAPF group was significantly superior to MFSFs group in terms of skin grafting, morbidity, and satisfaction degree of donor site.

Conclusion:

Our meta-analysis showed that the MSPAF and MFSFs groups were similar in terms of survival rate of flaps, recipient morbidity, and recipient satisfaction degree. Medial sural artery perforator flap group was superior to MFSFs group in terms of morbidity and satisfaction degree of donor site. The results may prove that MSAPF is gaining popularity for a reason and is a good choice for repairing soft tissue defects.
Occlusal Plane and Skeletal Changes After Cervical Headgear Treatment With and Without Lower Utility Arch in Class II Growing Patients
Authors: Sambataro Sergio , Bocchieri Salvatore , Fastuca Rosamaria , Giuntini Veronica , Fiorillo Luca , Cicciù Marco , Caprioglio Alberto
Published: December 2020

The purpose of this study was to investigate skeletal and dental changes affecting occlusal plane inclination after cervical headgear treatment with and without lower utility arch. In order to distinguish the orthodontic changes from natural growth a control group was employed.

The sample of this study consisted by 20 Class II subjects (10 males, 10 females; mean age 8.54) treated by using cervical headgear, 19 class II children (19 males, 9 females; mean age 8.64) treated with cervical headgear and utility arch, and 21 Class II patients (11 males, 10 females; mean age 8.41) who had no therapy.

Lateral head films were studied for all the patients before treatment (T1) and after therapy (T2) for all the treated groups and at the beginning and at the end of observational period for the control group; cephalometric analysis was carried out in order to seek for the modifications between time points and between groups.

Means and standard deviation have been analyzed for all the groups. In order to compare the modification between the time points within the same group the ANOVA test was applied. The ANOVA test was used to compare the mean differences (T2-T1) of 3 groups.

The study revealed that there were significant changes in occlusal plane inclination after the different treatment modalities employed instead control group. The treatment with cervical headgear and utility arch is more effective than cervical headgear alone in lowering occlusal plane posteriorly when it is compared with controls.
Improved Mortality, Morbidity, and Long-Term Outcome After Anatomical Hepatectomy With the Glissonean Pedicle Approach in Patients With Hepatocellular Carcinoma
Authors: Ariizumi Shun-ichi , Katagiri Satoshi , Kotera Yoshihito , Yamashita Shingo , Omori Akiko , Kato Takaaki , Shibuya Go , Egawa Hiroto , Takasaki Ken , Yamamoto Masakazu
Published: December 2020

Objective:

We evaluated the morbidity and mortality after anatomical hepatectomy with the Glissonean pedicle approach, and long-term outcomes in relation to the morbidity in patients with hepatocellular carcinoma (HCC).

Summary Background Data:

The mortality, morbidity, and long-term outcomes were evaluated retrospectively.

Methods:

A total of 1953 patients with HCC underwent various anatomical hepatectomies with the Glissonean pedicle approach between 1985 and 2014. The mortality (30-day and 90-day) and morbidity (Clavien-Dindo class Ilia or higher) were evaluated among six 5-year eras (1985–1989, 1990–1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014).

Results:

A total of 460 patients (24%) showed morbidity, and the overall 30-day and 90-day mortality rates were 1.8% and 3.3%, respectively. The 30-day (3.9%, 3.0%, 1.8%, 1.3%, 0.3%, 0.5%: P = 0.0074) and 90-day mortality (6.0%, 4.3%, 3.8%, 2.8%, 2.2%, 1.4%: P = 0.0445) significantly improved over the eras. Blood loss >2 L (odds ratio: 11.808, P = 0.0244) was an independent risk factor for 30-day mortality, and blood loss >2 L (odds ratio: 4.046, P = 0.0271) and bile leakage (odds ratio: 2.122, P = 0.0078) were independent risk factors for 90-day mortality on multivariate analysis. Morbidity was significant independent prognostic factors for overall survival (relative risk: 2.129, P < 0.0001) and recurrence-free survival (relative risk: 1.299, P < 0.0001) in patients with HCC.

Conclusions:

Anatomical hepatectomy with the Glissonean pedicle approach was achieved safely in patients with HCC. For more safety and longer survival, blood loss, bile leakage, and morbidity should be reduced. Longterm outcomes after anatomical hepatectomy with the Glissonean pedicle approach in patients with HCC have been improved over 30 years with gradually less mortality and morbidity due to decreases in blood loss >2 L and bile leakage.
Development and Validation of a Multiplex, Bead-based Assay to Detect Antibodies Directed Against SARS-CoV-2 Proteins
Authors: Bray Robert A. , Lee Jar-How , Brescia Peter , Kumar Deepali , Nong Thoa , Shih Remi , Woodle E. Steve , Maltzman Jonathan S. , Gebel Howard M.
Published: December 2020

Background.

Transplant recipients who develop COVID-19 may be at increased risk for morbidity and mortality. Determining the status of antibodies against SARS-CoV-2 in both candidates and recipients will be important to understand the epidemiology and clinical course of COVID-19 in this population. While there are multiple tests to detect antibodies to SARS-CoV-2, their performance is variable. Tests vary according to their platforms and the antigenic targets which make interpretation of the results challenging. Furthermore, for some assays, sensitivity and specificity are less than optimal. Additionally, currently available serological tests do not exclude the possibility that positive responses are due to cross reactive antibodies to community coronaviruses rather than SARS-CoV-2.

Methods.

This study describes the development and validation of a high-throughput multiplex antibody detection assay.

Results.

The multiplex assay has the capacity to identify, simultaneously, patient responses to 5 SARS-CoV-2 proteins, namely, the full spike protein, 3 individual domains of the spike protein (S1, S2, and receptor binding domain), and the nucleocapsid protein. The antibody response to the above proteins are SARS-CoV-2-specific, as antibodies against 4 common coronaviruses do not cross-react.

Conclusions.

This new assay provides a novel tool to interrogate the spectrum of immune responses to SAR-CoV-2 and is uniquely suitable for use in the transplant setting. Test configuration is essentially identical to the single antigen bead assays used in the majority of histocompatibility laboratories around the world and could easily be implemented into routine screening of transplant candidates and recipients.
Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles
Authors: Tan Jian , Ni Duan , Taitz Jemma , Pinget Gabriela Veronica , Read Mark , Senior Alistair , Wali Jibran Abdul , Nanan Ralph , King Nicholas Jonathan Cole , Grau Georges Emile , Simpson Stephen J. , Macia Laurence
Published: December 2020

Secretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high-protein fed mice produced significantly higher quantities of extracellular vesicles (EV), compared to those of mice fed high-carbohydrate or high-fat diets. These EV activated TLR4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We showed that succinate, produced in high concentrations by microbiota of high-protein fed animals, increased the generation of reactive oxygen species by bacteria, which in turn promoted EV production. This is the first report establishing a causal link between dietary macronutrient composition, gut microbial EV release and host sIgA response.
Single-Shot Lightweight Model For The Detection of Lesions And The Prediction of COVID-19 From Chest CT Scans
Authors: Ter-Sarkisov Aram
Published: December 2020

We introduce a lightweight model based on Mask R-CNN with ResNet18 and ResNet34 backbone models that segments lesions and predicts COVID-19 from chest CT scans in a single shot. The model requires a small dataset to train: 650 images for the segmentation branch and 3000 for the classification branch, and it is evaluated on 21292 images to achieve a 42.45% average precision (main MS COCO criterion) on the segmentation test split (100 images), 93.00% COVID-19 sensitivity and F1-score of 96.76% on the classification test split (21192 images) across 3 classes: COVID-19, Common Pneumonia and Control/Negative. The full source code, models and pretrained weights are available on https://github.com/AlexTS1980/COVID-Single-Shot-Model.
Prediction of Covid-19 spreading and optimal coordination of counter-measures: From microscopic to macroscopic models to Pareto fronts
Authors: Wulkow Hanna , Conrad Tim , Conrad Nataša Djurdjevac , Mueller Sebastian A. , Nagel Kai , Schuette Christof
Published: December 2020

The Covid-19 disease has caused a world-wide pandemic with more than 60 million positive cases and more than 1.4 million deaths by the end of November 2020. As long as effective medical treatment and vaccination are not available, non-pharmaceutical interventions such as social distancing, self-isolation and quarantine as well as far-reaching shutdowns of economic activity and public life are the only available strategies to prevent the virus from spreading. These interventions must meet conflicting requirements where some objectives, like the minimization of disease-related deaths or the impact on health systems, demand for stronger counter-measures, while others, such as social and economic costs, call for weaker counter-measures. Therefore, finding the optimal compromise of counter-measures requires the solution of a multi-objective optimization problem that is based on accurate prediction of future infection spreading for all combinations of counter-measures under consideration. We present a strategy for construction and solution of such a multi-objective optimization problem with real-world applicability. The strategy is based on a micro-model allowing for accurate prediction via a realistic combination of person-centric data-driven human mobility and behavior, stochastic infection models and disease progression models including micro-level inclusion of governmental intervention strategies. For this micro-model, a surrogate macro-model is constructed and validated that is much less computationally expensive and can therefore be used in the core of a numerical solver for the multi-objective optimization problem. The resulting set of optimal compromises between counter-measures (Pareto front) is discussed and its meaning for policy decisions is outlined.
The impact of non-pharmaceutical interventions on the prevention and control of COVID-19 in New York City
Authors: Yang Jiannan , Zhang Qingpeng , Cao Zhidong , Gao Jianxi , Pfeiffer Dirk , Zhong Lu , Zeng Daniel Dajun
Published: December 2020

The emergence of coronavirus disease 2019 (COVID-19) has infected more than 37 million people worldwide. The control responses varied across countries with different outcomes in terms of epidemic size and social disruption. In this study, we presented an age-specific susceptible-exposed-infected-recovery-death model that considers the unique characteristics of COVID-19 to examine the effectiveness of various non-pharmaceutical interventions (NPIs) in New York City (NYC). Numerical experiments from our model show that the control policies implemented in NYC reduced the number of infections by 72% (IQR 53-95), and the number of deceased cases by 76% (IQR 58-96) by the end of 2020, respectively. Among all the NPIs, social distancing for the entire population and the protection for the elderly in the public facilities is the most effective control measure in reducing severe infections and deceased cases. School closure policy may not work as effectively as one might expect in terms of reducing the number of deceased cases. Our simulation results provide novel insights into the city-specific implementation of NPIs with minimal social disruption considering the locations and population characteristics.
CellKb Immune: a manually curated database of mammalian hematopoietic marker gene sets for rapid cell type identification
Authors: Patil Ajay , Patil Ashwini
Published: December 2020

Using single-cell RNA sequencing, it is now possible to get the detailed gene expression pattern in each cell for millions of cells in a single experiment under varying conditions. Annotating cells by assigning a type or state to them is important for correct interpretation of results. In spite of current advances in technology, assigning cell types in single-cell datasets remains a bottleneck due to the lack of a comprehensive reference database and an accurate search method in a single tool. CellKb Immune is a knowledgebase of manually collected, curated and annotated marker gene sets representing cell types in the immune response in mouse. It allows users to find matching cell types in literature given a list of genes. We evaluated the contents and search methodology of CellKb Immune using a leave-one-out approach. We further used CellKb Immune to annotate previously defined marker gene sets from a bulk RNA-seq dataset to confirm its accuracy and coverage. CellKb Immune provides an easy-to-use online tool with a reliable method to find matching cell types and annotate cells in single-cell experiments. It is available athttps://www.cellkb.com/immune.
Spatiotemporal Dynamics of Intra-tumoral Dependence on NEK2-EZH2 Signaling in Glioblastoma Cancer Progression
Authors: Wang Jia , Pavliukov Marat S , Yamashita Daisuke , Cheng Peng , Zhang Zhuo , Kim Sung-Hak , Nakano Mayu A , Xie Wanfu , Chen Dongquan , Frett Brendan , Hu Wen-hao , Shin Yong Jae , Lee Yeri , Goidts Violaine , Nam Do-Hyun , Li Hong-yu , Nakano Ichiro
Published: December 2020

The highly lethal brain cancer glioblastoma undergoes dynamic changes in molecular profile and cellular phenotype throughout tumor core establishment and in primary-to-recurrent tumor progression. These dynamic changes allow glioblastoma tumors to escape from multimodal therapies, resulting in patient lethality. Here, we identified the emergence of dependence on NEK2-mediated EZH2 signaling, specifically in therapy-resistant tumor core-located glioblastoma cells. In patient-derived glioblastoma core models, NEK2 was required for in vivo tumor initiation, propagation, and radio-resistance. Mechanistically, in glioblastoma core cells, NEK2 binds with EZH2 to prevent its proteasome-mediated degradation in a kinase-dependent manner. Clinically, NEK2 expression is elevated in recurrent tumors after therapeutic failure as opposed to their matched primary untreated cases, and its high expression is indicative of worse prognosis. For therapeutic development, we designed a novel NEK2 kinase inhibitor CMP3a, which effectively attenuated growth of murine glioblastoma models and exhibited a synergistic effect with radiation therapy. Collectively, the emerging NEK2-EZH2 signaling axis is critical in glioblastoma, particularly within the tumor core, and the small molecule inhibitor CMP3a for NEK2 is a potential novel therapeutic agent for glioblastoma.
Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data
Authors: Lause Jan , Berens Philipp , Kobak Dmitry
Published: December 2020

Background

Standard preprocessing of single-cell RNA-seq UMI data includes normalization by sequencing depth to remove this technical variability, and nonlinear transformation to stabilize the variance across genes with different expression levels. Instead, two recent papers propose to use statistical count models for these tasks: Hafemeister & Satija [1] recommend using Pearson residuals from negative binomial regression, while Townes et al. [2] recommend fitting a generalized PCA model. Here, we investigate the connection between these approaches theoretically and empirically, and compare their effects on downstream processing.

Results

We show that the model of Hafemeister and Satija produces noisy parameter estimates because it is overspecified, which is why the original paper employs post-hoc smoothing. When specified more parsimoniously, it has a simple analytic solution equivalent to the rank-one Poisson GLM-PCA of Townes et al. Further, our analysis indicates that per-gene overdispersion estimates in Hafemeister and Satija are biased, and that the data are in fact consistent with the overdispersion parameter being independent of gene expression. We then use negative control data without biological variability to estimate the technical overdispersion of UMI counts, and find that across several different experimental protocols, the data are close to Poisson and suggest very moderate overdispersion. Finally, we perform a benchmark to compare the performance of Pearson residuals, variance-stabilizing transformations, and GLM-PCA on scRNA-seq datasets with known ground truth.

Conclusions

We demonstrate that analytic Pearson residuals strongly outperform other methods for identifying biologically variable genes, and capture more of the biologically meaningful variation when used for dimensionality reduction.
Cholesterol metabolism is a potential therapeutic target in Duchenne Muscular Dystrophy
Authors: Amor F. , Vu Hong A. , Corre G. , Sanson M. , Suel L. , Blaie S. , Servais L. , Voit T. , Richard I. , Israeli D.
Published: December 2020

Background

Duchenne Muscular Dystrophy (DMD) is a lethal muscle disease detected in approximately 1:5000 male births. DMD is caused by mutations in the DMD gene, encoding a critical protein that link the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. The primary consequence of the disrupted link between the extracellular matrix and the myofiber actin cytoskeleton is thought to involve sarcolemma destabilization, perturbation of Ca+2homeostasis, activation of proteases, mitochondrial damage and tissue degeneration. A recently emphasized secondary aspect of the dystrophic process is a progressive metabolic change of the dystrophic tissue; however, the mechanism and nature of the metabolic dysregulation is yet poorly understood. In this study, we characterized a molecular mechanism of metabolic perturbation in DMD.

Methods

We sequenced plasma miRNA in a DMD cohort, comprising of 54 DMD patients treated or not by glucocorticoid, compared to 27 healthy controls, in three age groups. We developed an original approach for the biological interpretation of miRNA dysregulation, and produced a novel hypothesis concerning metabolic perturbation in DMD. We then used the mdx mouse model for DMD for the investigation of this hypothesis.

Results

We identified 96 dysregulated miRNAs, of which 74 were up- and 22 down-regulated in DMD. We confirmed the dysregulation in DMD of Dystro-miRs, Cardio-miRs and a large number of the DLK1-DIO3 miRNAs. We also identified numerous dysregulated miRNAs, yet unreported in DMD. Bioinformatics analysis of both target and host genes for dysregulated miRNAs predicted that lipid metabolism might be a critical metabolic perturbation in DMD. Investigation of skeletal muscles of the mdx mouse uncovered dysregulation of transcription factors of cholesterol and fatty acid metabolism (SREBP1 and SREBP2), perturbation of the mevalonate pathway, and accumulation of cholesterol. Elevated cholesterol level was also found in muscle biopsies of DMD patients. Treatment of mdx mice with Simvastatin, a cholesterol-reducing agent, normalized these perturbations and partially restored the dystrophic parameters.

Conclusion

This investigation supports that cholesterol metabolism and the mevalonate pathway are potential therapeutic targets in DMD.
RUNX1 controls the dynamics of cell cycle entry of naïve resting B cells by regulating expression of cell cycle and immunomodulatory genes in response to BCR stimulation
Authors: Thomsen Inesa , Kunowska Natalia , de Souza Roshni , Moody Anne-Marie , Crawford Greg , Wang Yi-Fang , Khadayate Sanjay , Strid Jessica , Karimi Mohammad M. , Barr Alexis , Dillon Niall , Sabbattini Pierangela
Published: December 2020

RUNX1 is a transcription factor that plays key roles in haematopoietic development and in adult haematopoiesis and lymphopoiesis. Here we report that RUNX1 is also involved in controlling the dynamics of cell cycle entry of naïve resting B cells in response to stimulation of the B cell receptor (BCR). Conditional knockout ofRunx1in mouse resting B cells resulted in accelerated entry of the cells into S-phase following BCR engagement. Our results indicate that Runx1 regulates the cyclin D2 (Ccnd2) gene, the immediate early genes,Fosl2,Atf3andEgr2, and the Notch effectorRbpj, in B cells, reducing the rate at which transcription of these genes increases following BCR stimulation. RUNX1 interacts with the chromatin remodeller SRCAP, recruiting it to promoter and enhancer regions of theCcnd2gene. BCR-mediated activation triggers switching between binding of RUNX1 and its paralog RUNX3 and between SRCAP and the SWI/SNF remodelling complex member BRG1. We also find that RUNX1 regulates expression of a number of immunomodulatory genes in resting B cells. These include the interferon receptor subunit geneIfnar1, which is upregulated in B cells from lupus patients, thePtpn22gene, which has been identified as a major lupus risk allele, and theLrrk2gene, which is mutated in familial Parkinson’s disease. The hyperresponsiveness of theRunx1knockout B cells to antigen stimulation and its role in regulating a suite of genes that are known to be associated with autoimmune disease suggest that RUNX1 is a major regulator of B cell tolerance and autoimmunity.