bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Stenosis Grading in Magnetic Resonance Imaging Using Deep Convolutional Neural Networks
Authors: Won Dongkyu , Lee Hyun-Joo , Lee Suk-Joong , Park Sang Hyun
Published: January 2020

Study Design.

Retrospective magnetic resonance imaging grading with comparison between experts and deep convolutional neural networks (CNNs).

Objective.

This study aims to verify the feasibility of a computer-assisted spine stenosis grading system by comparing the diagnostic agreement between two experts and the agreement between the experts and trained artificial CNN classifiers.

Summary of Background Data.

Spinal stenosis grading is important; however, it is tedious job to check the MR images slide by slide to classify patient grades often having different opinions regarding the final diagnosis.

Methods.

For 542 L4-5 axial MR images, two experts independently localized the center position of the spine canal and graded the status. Two CNN classifiers each trained with the grading label made by the two experts were validated using 10-fold cross-validation. Each classifier consisted of a CNN detection model responsible for the localization of patches near the canal and a classification CNN model to predict the spinal stenosis status in the localized patches. Faster R-CNN was used for the detection model whereas VGG network was used for the classification model. A comparison in grading agreement was carried out between the two experts as well as that of the experts and the prediction results generated by the CNN models.

Results.

Grading agreement between the experts was 77.5% and 75% in terms of accuracy and F1 scores. The agreement between the first expert and the model trained with the labels of the first expert was 83% and 75.4%, respectively. The agreement between the second expert and the model trained with the labels of the second expert was 77.9% and 74.9%. The differences between the two experts were significant, whereas the differences between each expert and the trained models were not significant.

Conclusion.

We indeed confirmed that automatic diagnosis using deep learning may be feasible for spinal stenosis grading.

Level of Evidence: 4
Characterization of Sagittal Spine Alignment With Reference to the Gravity Line and Vertebral Slopes
Authors: Hey Hwee Weng Dennis , Tan Kimberly-Anne , Thadani Vishaal Nanik , Liu Gabriel Ka-Po , Wong Hee-Kit
Published: January 2020

Mini

Spinal sagittal realignment necessitates a reference posture, and thus far this has only been defined for an “averaged” curve via horizontal offsets from the gravity line (GL). This prospective study of 169 healthy subjects demonstrates normative sagittal spatial orientation of each vertebra, for all Roussouly curve types, using vertebral slopes and horizontal offsets from the GL.

Study Design.

Prospective study.

Objective.

To map the healthy standing alignment of the adult spine, grouped according to Roussouly curve types, using both horizontal offset distance from the gravity line (GL), as well as vertebral slope measurements.

Summary of Background Data.

Spinal sagittal realignment requires a reference posture, and this has been defined in the literature via horizontal offsets from the GL. While useful, this does not provide information on the orientation of each vertebral segment, or distinguish between the various physiological curve types.

Methods.

A total of 169 consecutive young adult subjects with healthy spines were recruited over a year. (EOS Imaging, Paris, France) whole body radiographs were performed. Radiographic measurements collected included sagittal vertical axis (SVA), T1-slope, global cervical angle (GCA), global thoracic angle (GTA), global lumbar angle (GLA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), apical and inflection vertebrae. Outcome measures comprised slope measurements, and distance offsets relative to the GL for individual vertebrae from T3 to S1.

Results.

GLA, PI, PT, SS, apex of lordosis, and inflection vertebra were significantly different across groups, while SVA, T1-slope, GCA, GTA, and apex of kyphosis were not. Mean PI to LL discrepancy for Type I to IV groups were 8.0°, 2.3°, 4.8°, and 3.0°, respectively. Between groups, T3, T7 to T12, and L2 to S1 slopes and T9 to L3 offset distances from GL were significantly different, while the distance of the hip center from the GL was not. GLA was significantly different between curve types except between Type 1 and 2 curves, while the inflection vertebrae were not significantly different between Type 1 and 2 curves, as well as Type 3 and 4 curves.

Conclusion.

This study demonstrates normative sagittal spatial orientation of each vertebra in healthy adults, for each Roussouly type. Comparison across groups suggests the possibility of further refining the sagittal curve patterns described by Roussouly.

Level of Evidence: 3
Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus
Authors: Gao Chang , Wang Yeming , Gu Xiaoying , Shen Xinghua , Zhou Daming , Zhou Shujun , Huang Jian-an , Cao Bin , Guo Qiang ,   for the Community-Acquired Pneumonia–China Network
Published: January 2020

Objectives:

To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus.

Design:

Retrospective cohort study.

Setting:

A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus–infected patients between January 22, 2015, and June 16, 2017.

Patients:

A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis.

Interventions:

None.

Measurements and Main Results:

Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower Pao
2/Fio
2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31–3.24) during hospitalization.

Conclusions:

Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.
A Qualitative Exploration of Simulation as a Tool for Learning in Physical Therapist Education
Authors: Donlan Pamela , Greenwood Kristin , Kiami Sheri
Published: January 2020

Background:

Physical therapists must be able to practice in acute care environments, integrate complex information to ensure patient safety, and effectively adapt to the changing medical needs of patients. Simulation-based learning experiences (SBLEs) have been found to be useful teaching methods to prepare clinicians for high-risk acute care experiences. While research has examined the use of SBLE in physical therapist education, a clear focus has not been given to SBLE in the neurologic curriculum, where students must incorporate knowledge of critical care medical management with neurorehabilitation expertise. The purpose of this study was to understand how SBLE, within a neurorehabilitation curriculum, contributes to physical therapist students' learning.

Methods:

Using the reflective practitioner theory as a framework for inquiry, qualitative data were gathered from 2 focus groups and analyzed through conventional content analysis.

Results:

An analysis of transcripts yielded 3 major themes: (1) promotes advanced clinical performance through reflection; (2) promotes authenticity without high risk; and (3) highlights the value of teamwork. Participants conveyed that synthesis of neurologic management content material in conjunction with skill execution was uniquely able to promote higher order learning. Additionally, they underscored the importance of designing the activity to enhance learning rather than using it solely for assessment. Further, participants highlighted how collaboration during a simulation activity advances clinical performance and communication.

Conclusion:

Consideration should be given to designing specific neurorehabilitation scenarios that mimic real life, include interprofessional or group collaboration, and provide an opportunity for post-SBLE reflection.
Reducing Hospital Length of Stay for Total Joint Arthroplasty Patients: Effects of Extended Physical Therapy Staffing and Day of Surgery Evaluations
Authors: Phillips Elizabeth A. , Dalton Jennifer R. , Childress Ryan E. , Heidel Robert E.
Published: January 2020

Purpose:

The Rehabilitation Department at the University of Tennessee Medical Center in Knoxville, Tennessee, changed its staffing model in an effort to increase efficiency and reduce hospital length of stay (LOS) without compromising safety for patients undergoing total joint arthroplasty (TJA). This study was designed to reveal effects of extended physical therapy (PT) coverage on TJA patient safety and LOS at our hospital.

Methods:

Our study is a retrospective chart review including 775 patients. After a staffing change involving the addition of an evening PT shift, we gathered data on patients with TJA in 2 groups: (1) before staffing change and (2) after staffing change. We examined the percentage of patients in each group who received a day of surgery (DOS) PT evaluation and tracked each group's incidence of adverse events and hospital LOS. We then compared outcomes between groups.

Results:

The percentage of Patients who received a DOS PT evaluation increased from 64.5% prestaffing change to 97.0% poststaffing change. Hospital LOS decreased from 2.30 days (SD = 0.9) in the prestaffing change group to 2.16 days (SD = 0.8) in the poststaffing change group, with no difference in incidence of adverse events between groups. The frequency of adverse events tracked in this study was only 6.6% in each group, indicating that the greater frequency of DOS PT evaluations did not increase the incidence of adverse events or compromise patients' safety.

Conclusions:

A staffing change involving extended PT evening coverage resulted in a higher percentage of patients with TJA receiving a DOS PT evaluation, no increase of adverse events, and a statistically significant decrease in hospital LOS.
Emergency Department Ergonomic Redesign Improves Team Satisfaction in Cardiopulmonary Resuscitation Delivery: A Simulation-Based Quality Improvement Approach
Authors: Ehmann Michael R. , Kane Erin M. , Arciaga Zakk , Duval-Arnould Jordan , Saheed Mustapha
Published: January 2020

Background:

Delivering high-quality cardiopulmonary resuscitation (CPR) requires teams to administer highly choreographed care. The American Heart Association recommends audiovisual feedback for real-time optimization of CPR performance. In our Emergency Department (ED) resuscitation bays, ZOLL cardiac resuscitation device visibility was limited.

Objective:

To optimize the physical layout of our resuscitation rooms to improve cardiac resuscitation device visibility for real-time CPR feedback.

Methods:

A simulated case of cardiac arrest with iterative ergonomic modifications was performed four times. Variables included the locations of the cardiac resuscitation device and of team members. Participants completed individual surveys and provided qualitative comments in a group debriefing. The primary outcome of interest was participants' perception of cardiac resuscitation device visibility.

Results:

The highest scoring layout placed the cardiac resuscitation device directly across from the compressor and mirrored the device screen to a television mounted at the head of the bed. Comparing this configuration to our standard configuration on a five-point Likert scale, cardiac resuscitation device visibility increased 46.7% for all team members, 150% for the team leader, and 179% for team members performing chest compressions.

Conclusion:

An iterative, multidisciplinary, simulation-based approach can improve team satisfaction with important clinical care factors when caring for patients suffering cardiac arrest in the ED.
Myocardial perfusion abnormalities in Eisenmenger syndrome
Authors: Gupta Anunay , Patel Chetan , Gupta Saurabh Kumar , Ramakrishnan S. , Saxena Anita , Kothari Shyam S.
Published: January 2020

Background

Compared to primary pulmonary hypertension (PPH), the right ventricular (RV) contractile function is preserved for a long time in patients with Eisenmenger syndrome and is likely the most important determinant of relatively higher survival. The differences in myocardial perfusion have been purported to explain this discrepancy. The exact prevalence of myocardial perfusion abnormalities in Eisenmenger syndrome is not known. We sought to examine the prevalence of myocardial perfusion abnormalities in patients with Eisenmenger syndrome.

Methods

In this prospective study, 20 consecutive adult patients with Eisenmenger syndrome were subjected to clinical assessment, six-minute walk test and echocardiography. Myocardial perfusion was assessed using one day stress-rest Gated Technetium-99 m Sestamibi single-photon emission computed tomography.

Results

Nineteen (95%) patients were in New York Heart Association functional class I or II. All patients had RV hypertrophy. Five (25%) patients had RV systolic dysfunction. Left ventricular systolic function was normal in all except in three patients. Two (10%) patients had perfusion defects in the RV and 4 (20%) patients had perfusion defects in the left ventricle (LV).

Conclusion

Myocardial perfusion defects, both in RV and LV, occur even in asymptomatic or mildly symptomatic patients with Eisenmenger syndrome.
Exposure to Suicide in the Family
Authors: Campos Rui C. , Holden Ronald R. , Spínola Joana , Marques Diandra , Santos Sara
Published: January 2020

The aims of the present study were to compare a sample of individuals exposed to suicide in their families with a control group, on suicidal ideation, and to test possible potentiating effects for unmet interpersonal needs. Three hundred eighty-six young Portuguese adults participated. Two groups were defined: a group exposed to suicide in the family (n = 38) and a control group (n = 335). Groups differed significantly on suicidal ideation, on depressive symptoms, and on perceived burdensomeness and tended to differ on thwarted belongingness. Results from a hierarchical multiple regression analysis demonstrated that having lost a family member by suicide and perceived burdensomeness each provided a significant unique contribution to explaining variance in suicidal ideation when controlling for levels of depressive symptoms and having had a psychiatric diagnosis. The interaction between group membership and perceived burdensomeness provided a further enhancement to the statistical prediction of suicidal ideation.
The Relationship Between Nurse-Reported Safety Culture and the Patient Experience
Authors: Abrahamson Kathleen , Hass Zach , Morgan Kristopher , Fulton Bradley , Ramanujam Rangaraj
Published: January 2020

OBJECTIVE:

The purpose of this study was to better understand the relationship between nurse-reported safety culture and the patient experience in a multistate sample of nurses and patients, matched by hospital unit/service line and timeframe of care delivery.

BACKGROUND:

Nurses play a key role in the patient experience and patient safety. A strong safety culture may produce positive spillover effects throughout the nurse caregiving experience, resulting in patient perception of a high-quality experience.

METHODS:

Multivariate mixed-effects regression models were specified using data from a multistate sample of hospital units that administered both the Agency for Healthcare Research and Quality (AHRQ) staff safety culture survey and the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient satisfaction survey over a 12-month period. Survey response variables are measured at the unit (service line) and hospital level.

RESULTS:

Key variables in the HCAHPS and AHRQ surveys were significantly correlated. Findings highlight the relationship between 3 safety culture domains: teamwork, adequate staffing, and organizational learning on the achievement of a positive patient experience.

CONCLUSION:

Modifiable aspects of hospital culture can influence the likelihood of achieving high HCAHPS top box percentages in the nursing and global domains, which directly impact hospital reimbursement.
Three-Generation Academic Mentoring Teams
Authors: Webber Elaine , Vaughn-Deneen Tanya , Anthony Maureen
Published: January 2020

Background

New faculty are often not prepared for a career in academia, and the transition can be challenging. They often come from practice environments where work expectations are clearly delineated.

Problem

Traditional mentoring programs typically pair new with experienced faculty members who are expected to provide guidance and advice. Results of the hierarchical dyad method have been mixed.

Approach

Three generations of faculty formed a team composed of a tenured, a midcareer, and a new faculty member. The midcareer educator was better suited to help the novice prepare to teach, as they had recently been through the process, whereas the tenured faculty member was able to provide scholarship support to both.

Conclusions

Providing new faculty with 2 mentors in a constellation format, along with the opportunity to network during structured mentoring meetings, contributed to a smooth onboarding of new faculty and provided scholarship support for the midcareer faculty member.
Predictors of Sexually Transmitted Infection Positivity Among Substance-Using Native American Adults
Authors: Chambers Rachel Strom , Littlepage Shea , Rompalo Anne , Lee Angelita , Slimp Anna , Melgar Laura , Craig Mariddie , Gaydos Charlotte , Tingey Lauren
Published: January 2020

Background

Sexually transmitted infections (STIs) are a public health crisis with Native Americans suffering a high burden of disease. Studies across gender and racial/ethnic groups have found varying risk factors associated with STI positivity. Understanding how risk factors are associated with STI positivity can help design interventions for those most at risk.

Methods

Participants were Native American binge substance using adults enrolled in a randomized controlled trial evaluating a brief intervention to increase STI screening and reduce sexual risk-taking behaviors. Participants completed a self-report assessment at baseline that included questions about sexual risk factors and STI testing behaviors and diagnosis. This analysis includes those who had ever completed an STI test at baseline. Bivariate and multivariate analyses using logistical regression were utilized to identify associations between risk factors and past STI diagnosis.

Results

A total of 193 people were included in the analysis. Over half (50.6%) of the participants had ever been diagnosed with an STI. Risk behaviors varied by gender. More women with a self-reported history of STI reported having sex with someone they thought had an STI, past experience of physical/sexual violence, and having passed out from drinking. Men with a self-reported history of STI were more likely to report past marijuana and other drug use. Among women with a self-reported history of STI, having sex with someone they thought had an STI was associated with STI positivity, whereas other drug use was associated with STI positivity among men with a self-reported history of STI.

Conclusions

Findings provide information for those working to reduce STIs in Native Communities to better identify and design programs for those at highest risk for STIs. Additional studies examining gender dynamics and sexual risk taking among native adults are warranted.
Darunavir Pharmacokinetics With an Increased Dose During Pregnancy
Authors: Eke Ahizechukwu C. , Stek Alice M. , Wang Jiajia , Kreitchmann Regis , Shapiro David E. , Smith Elizabeth , Chakhtoura Nahida , Capparelli Edmund V. , Mirochnick Mark , Best Brookie M. ,   IMPAACT P1026s Protocol Team
Published: January 2020

Background:

This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.

Methods:

Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.

Results:

Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24–2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17–2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0–12 was lower during the third trimester [GMR 0.65 (IQR 0.52–0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22–1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.

Conclusions:

Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.
Closed Incisional Negative Pressure Wound Therapy Sponge Width and Tension Off-Loading
Authors: Googe Benjamin , Davidson John Clayton , Arnold Peter B. , Medina Abelardo
Published: January 2020

Closed incisional negative pressure wound therapy (ciNPWT) has become commonplace in surgery. One mechanism ciNPWT may prevent incision site complications is by off-loading tension. This study aimed to find what width sponge using ciNPWT provides the most tension off-loading.

A model was designed to test tension off-loading of a wound using ciNPWT. An incision was made in an anatomy model and closed with single stitch at the central axis. Force was applied tangentially using a force gauge at a steady rate until the wound dehisced at a peak force indicated by the 5-0 suture breaking. This was repeated 10 times for the following 4 trials: no ciNPWT and ciNPWT sponges cut a 3-, 6-, and 9-cm widths with 125 mm Hg of negative pressure.

The mean peak force to dehisce the wound without ciNPWT was the lowest, 28.7 N. The mean force for the ciNPWT trials was 43.0, 38.7, and 36.4 N for V.A.C. sponges of 3, 6, and 9 cm in width, respectively. There was a statically significant difference among all the trials using one-way analysis of variance with Tukey posttest analysis with a P value of less than 0.0001.

Closed incisional negative pressure wound therapy was shown to increase peak force required to dehisce an incision of up to 49.7% compared with closure without. There is an inverse relationship with sponge width and tension off-loading. The smaller the sponge, the more tension is off-loaded across the incision. Closed incisional negative pressure wound therapy with a 3-cm-wide sponge required the greatest peak force for dehiscence.
Relationship between exterior environment and quality characteristics of the traditional Gochujang produced in 2018 by eight regions in Korea
Authors: Baek Seung-Yeon , Gil Na-Young , Han Myeong-Hui , Kang Heui-Yun , Lee Ha-Yeon , Yoon Hyang-Sik , Lee Jeong , Song Young-Eun , Lee Sun-Kyung , Ryu Jung-A , Kim Hyeon-Young , Yeo Soo-Hwan , Kim So-Young
Published: January 2020

The objective of this study was to investigate the quality and environment properties of traditional Gochujang produced by 56 rural farms in 8 regions of Korea for evaluating the relationship between the components and environmental factors. Based on the regional means at the initiatory and after fermentation, the ranges of moisture content, salinity, pH, and acidity of Gochujang were determined to be from 46.87±7.09% to 43.80±7.17%, from 7.52±2.21% to 8.53±2.57%, from 5.01±0.30 to 4.63±0.34, and from 1.13±0.50% to 1.43±0.58%, respectively. The mean contents of reducing sugar and amino-type nitrogen were from 16.46±7.63% to 20.48±7.57% and from 140.06±78.00 mg% to 198.68±87.11 mg%, respectively. Hunter color values (L, a, and b) of Gochujang were from 26.16±9.27 to 22.49±9.02, from 21.87±6.31 to 20.14±7.58, and from 19.43±11.94 to 19.18±12.06, respectively. Total aerobic number was increased from 6.50±1.29 log CFU/g to 8.15±0.88 log CFU/g, while the fungal number was steadily decreased after fermentation. Next generation sequencing analysis to investigate the microbial communities revealed that the dominant bacteria in Gochujang belong to the phyla of Firmicutes and Cyanobacteria. Similarly, Aspergillus spp. of the phylum Ascomycota was the predominant fungi in traditional Gochujang. Finally, according to principle component analysis of the relationship between the quality and environmental properties of Gochujang, the contents of amino-type nitrogen, salinity, titratable acidity, and reducing sugar had strong correlations with exterior humidity. These results also suggest that the quality of traditional soybean sauces can be controlled by exterior environmental change.
Vitamin D content analysis of agricultural products and processed foods
Authors: Lim Jong-Soon , Kim Hyun-Jeong , Lee Sang-Hoon , Lee Sam-Pin
Published: January 2020

This study was performed to update the National Standard Food Composition Table (NSFCT), published by the Korean Rural Development Administration, especially focusing on vitamin D content in Korean agricultural products and processed foods. A total of 96 kinds of agricultural products and processed foods were analyzed for vitamin D content by using liquid chromatography–mass spectrometry (LC-MS/MS). The recovery rates of the standard materials SRM 1849a (Infant/Adult Nutritional formula) and BCR-122 (Margarine) were 108.18 % and 96.15 %, respectively. All analyses results were below the control line based on the quality control chart for vitamin D. Vitamin D was detected only in 25 out of the 96 products and foods that were analyzed. The vitamin D content in cereals, potato, nuts, and seeds ranged from 0 to 4.11 μg/100 g. In sugars and sweeteners, pulses, oils, teas, and processed foods, the vitamin D content ranged from 0 to 6.13 μg/100 g, whereas in vegetables and mushrooms, it ranged from 0 to 644.72 μg/100 g. The highest vitamin D content was found to be 644.72 μg/100 g in naturally dried oyster mushroom.
Effect on bone formation of fermented soybeans by combination treatment with high-isoflavone aglycone ratios
Authors: Lee Sun-kyung , Lee You-Seok , Ji Soo-Hyun , Jo Gyeong-Suk , Kang Jeong-Hwa
Published: January 2020

The purpose of this study was to investigate the effect on bone formation of fermented soybeans by combination treatment with a high aglycone ratio of isoflavones, since this compounds are known to prevent osteoporosis caused by aging or menopause. The experimental group (osteoporosis-induced rats, n=20) was divided into four groups, namely the normal group (NC), the OVX group (OVXC), the steamed soybean powder group (SSP), and the fermented soybean powder group (FSP). After 8 weeks of administration, the body weights of the OVX, SSP and FSP groups had increased compared to those of the NC group, while the weight of the uterus had not increased compared to that of NC group, and the weight of the kidney leaf fat had not decreased compared to that of the OVXC group. In addition, serum levels of alkaline phospatase (ALP) and osteocalcin were not significantly different between the different experimental groups. However numerically, the FSP group appeared to exhibit some effect on bone formation. More specifically, the trabecular bone volume of the femur was significantly increased in the FSP group compared to the OVXC (p<0.01), and the trabecular bone mineral density was also significantly increased in the SSP and FSP groups compared to the OVXC group (p<0.05). These results indicate that fermented soybeans were effective in promoting bone formation in terms of increasing the bone volume and bone density of the femur. The consumption of fermented soybeans could therefore be suggested for the prevention rather than the improvement of osteoporosis.
Immunostimulatory effect of sweet potato peel-based plant mixture on RAW264.7 macrophages
Authors: Jeong In-Seon , Kim Eun-Hye , Park Seung Man , Chung Mi Ja
Published: January 2020

This study aimed to investigate the immunostimulatory effect of a sweet potato peel-based plant mixture, including Platycodon grandiflorum, Codonopsis lanceolata and corn silk, on RAW264.7 macrophages. We tested the immunostimulatory effect of 12 plant extracts, individually, in terms of nitric oxide (NO) production in RAW264.7 macrophages. NO production of Platycodon grandiflorum, Codonopsis lanceolata, and corn silk extracts (PG, CL, CS) in RAW264.7 macrophages was significantly higher than that of other plant extracts (p<0.05). The cytotoxicity and production of NO and cytokines by PG, CL, CS, and weet potato peel extract (SP) in RAW264.7 macrophages were determined. The production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in PG, CL or CS-treated RAW264.7 macrophages was significantly higher than that of SP-treated ones (p<0.05). Immunostimulatory effect of the extract from plant mixture containing Platycodon grandiflorum, Codonopsis lanceolata, corn silk, and sweet potato peel in the ratio 1:1:0.5:3 (w/w) was significantly higher than that of SP extract alone, and was similar or higher than that of PG, CL, and CS, on RAW264.7 macrophages (p<0.05). Therefore, the extract from plant mixture may be considered as a potential candidate for the development of functional food materials for enhancing immune activity.
Analysis of useful substances from immature peach extracts obtained under different conditions and using them as functional materials
Authors: Kim Ha-Eun , Park Ga-Eun , Jang Min-Jung , Jun Dong-Ha , Kim Han-Hyuk , Jeong Yong-Ha
Published: January 2020

Peaches are one of the most abundant cultivated fruits in Korea. There have been many studies on using it as functional materials; however, there has been few reports on immature peaches collected during the thinning out process. Herein we analyzed useful substances extracted under specific conditions from of thinned-out peaches and tested them for the suitability as cosmetic materials. NMR analysis revealed 3-O-cafffeoyl quinic acid as the major substance in the extracts. At PH-10, it showed positive response similar to ascorbic acid, used as a control, in antioxidant activity tests like DPPH and ABTS+ radical scavenging tests. The elastase and collagenase inhibitory activity tests showed minor wrinkle improvements for all the test groups. No antibacterial response was observed for five germ groups. These results show that immature peaches are applicable as functional materials because the major constituent of its extracts (chlorogenic acid) can act as an antioxidant at high concentrations. It could be of benefit to study immature peach extracts in more detail to potentially reveal further value-adding properties.
Beyond T Staging in the Treat All Era: Capturing the Severity and Heterogeneity of Kaposi’s Sarcoma in East Africa
Authors: Freeman Esther E. , McMahon Devon E. , Semeere Aggrey , Byakwaga Helen , Laker-Oketta Miriam , Wenger Megan , Kasozi Charles , Semakadde Matthew , Bwana Mwebesa , Kanyesigye Michael , Kadama-Makanga Philippa , Rotich Elyne , Kisuya Job , Wools-Kaloustian Kara , Bassett Ingrid , Busakhala Naftali , Martin Jeffrey
Published: January 2020

Background

In the treat-all era of HIV, Kaposi’s sarcoma (KS) remains one of the most incident cancers in sub-Saharan Africa. The majority of patients with KS are diagnosed at advanced disease stage in this setting. Staging systems for KS, specifically the AIDS Clinical Trials Group (ACTG) system, were developed in the pre-ART era, were not meant to guide treatment, and may not fully capture the clinical heterogeneity of advanced disease. There is no international consensus on which KS patients need chemotherapy in addition to antiretroviral therapy (ART). Understanding KS severity of disease in the current era would help to inform prognosis and clarify treatment guidelines.

Methods

We performed rapid case ascertainment (RCA) on people living with HIV ≥18 years old newly diagnosed with biopsy-proven KS from 2016 to 2019 at three clinic sites in Kenya and Uganda. As close as possible to time of diagnosis, we performed a structured interview, physical examination, and collection of laboratory specimens. We reported KS severity using ACTG and WHO staging criteria, as well as detailed measurements not captured in current staging systems.

Results

We enrolled 264 adults newly diagnosed with KS. RCA was performed within 1 month of KS diagnosis for 62% of patients and within 6 months for 73% of patients. Patients were 61% Kenyan, 69% male, and with a median age of 35. Median CD4 count was 239 (IQR 87 to 408), with 72% of patients initiating ART greater than 60 days prior to diagnosis. The majority of patients had advanced stage of disease, with 82% qualifying as ACTG T1 and 64% as WHO Severe/Symptomatic KS. There was marked heterogeneity within advanced KS, with 25% of patients having two ACTG qualifiers and 3% of patients had three or more ACTG qualifiers.

Conclusion

The majority of patients with KS in this study had advanced stage disease at time of diagnosis, highlighting the need to improve early diagnosis of KS. Within this group of advanced stage patients was large clinical heterogeneity, leading to questions about whether all patients with advanced KS require the same treatment strategy.
Potential Test-Negative Design Study Bias in Outbreak Settings: Application to Ebola vaccination in Democratic Republic of Congo
Authors: Pearson Carl A. B. , Edmunds W. John , Hladish Thomas J. , Eggo Rosalind M.
Published: January 2020

Background

Infectious disease outbreaks present unique challenges to study designs for vaccine evaluation. Test-negative design (TND) studies have previously been used to estimate vaccine effectiveness and have been proposed for Ebola virus disease (EVD) vaccines. However, there are key differences in how cases and controls are recruited during outbreaks and pandemics of novel pathogens that have implications for the reliability of effectiveness estimates using this design.

Methods

We use a modelling approach to quantify TND bias for a prophylactic vaccine under varying study and epidemiological scenarios. Our model accounts for heterogeneity in vaccine distribution and for two potential routes to testing and recruitment into the study: self-reporting and contact-tracing. We derive conventional and hybrid TND estimators for this model and suggest ways to translate public health response data into the parameters of the model.

Results

Using a conventional TND study, our model finds biases in vaccine effectiveness estimates. Bias arises due to differential recruitment from self-reporting and contact-tracing, and due to clustering of vaccination. We estimate the degree of bias when recruitment route is not available, and propose a study design to eliminate the bias if recruitment route is recorded.

Conclusions

Hybrid TND studies can resolve the design bias with conventional TND studies applied to outbreak and pandemic response testing data, if those efforts collect individuals’ routes to testing. Without route to testing, other epidemiological data will be required to estimate the magnitude of potential bias in a conventional TND study. Since these studies may need to be conducted retrospectively, public health responses should obtain these data, and generic protocols for outbreak and pandemic response studies should emphasize the need to record routes to testing.

Key Messages

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Conventional Test-Negative Design (TND) studies can be biased when follow-up of cases leads to testing and recruitment, which occurs for example during contact tracing.

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A hybrid TND estimator can eliminate this bias, if individual testing routes are recorded.

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The related bias in the conventional TND estimator can be quantified using epidemiological measures.

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If testing route data is unavailable, bias can be limited by other study measures.
High levels of mild to moderate depression among men who have sex with men and transgender women in Lima, Peru: implications for integrated depression and HIV care
Authors: Galea Jerome T. , Marhefka Stephanie , León Segundo R. , Rahill Guitele , Cyrus Elena , Sánchez Hugo , Zhang Zhiwei , Brown Brandon
Published: January 2020

Depression disproportionally affects people at risk of acquiring or living with HIV and is associated with worse health outcomes; however, depression care is not routinely integrated with HIV prevention and treatment services. Selection of the best depression intervention(s) for integration depends both on the prevalence and severity of depression among potential users. To inform depression care integration in a community-based setting in Lima, Peru, we retrospectively analyzed routinely collected depression screening data from men who have sex with men and transgender women seeking HIV prevention and care services (N=185). Depression was screened for using the Patient Health Questionnaire-9. Prevalence of any depression (PHQ-9 ≥5) was 42% and was significantly associated with the last sexual partner being “casual” (p=0.01). Most (81%) depressive symptoms were mild to moderate (≥5 PHQ-9 ≤14). Integrating depression care with HIV prevention and treatment services in Peru should begin by implementing interventions targeting mild to moderate depression.
High prevalence of Human Papillomavirus (HPV) type 66 in low-grade cervical lesions of Mexican women
Authors: Juárez-González Karina , Paredes-Cervantes Vladimir , Gordillo-Rodríguez Silvia , González-Guzmán Saúl , Moncayo-Valencia Xochilt , Méndez-Martínez Rocío , García-Carrancá Alejandro , Martínez-Ezquerro José Darío , Rivas-Ruiz Rodolfo , Sánchez-Suárez Patricia , Álvarez-Sandoval Paola , Padilla-Arrieta Patricia , Martínez-Salazar Martha , Vázquez-Vega Salvador
Published: January 2020

Background

HPV-16 infections constitute the highest risk for developing uterine cervix cancer. However, the role of other high-risk types is still controversial.

Objective

To analyze HR-HPV prevalence and its possible associations between HPV and risk factors related to cervical lesions among Mexican women.

Methods

Cross sectional study using 362 cervical samples collected between 2016 and 2017. Fourteen HR-HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) were detected by highly sensitive PCR amplification followed by reverse hybridization. Bivariate and multivariate analyses were performed to investigate the association between HPV types and risk factors among lesions.

Results

Most samples were HR-HPV positive (83.43%). HPV-16 was the most prevalent infection among negative for intraepithelial lesions or malignancy (78.6%), high-grade squamous intraepithelial lesions (50%), and cervical cancer (58.2%). HPV-66 showed an unexpected high prevalence in atypical squamous cells of undetermined significance (50%), low-grade squamous intraepithelial (45.7%), and only found in 3.6% of cervical cancers. HPV-16 was significantly prevalent among women between 30-39 years, whereas types 66 and 52 were significantly associated when previously sexually transmitted disease had occurred (p< 0.05).

Conclusions

HPV-66 either in single or co-infection with other HR-HPV types (excluding 16 and 18) might be indicative of non-progressive cancer lesions. HPV-66 prevalence was unusually high in low-grade cervical lesions, predominantly in co-infection with HPV-51, and very low among cervical cancer. This should be addressed to interpret results obtained by methods that group type 66 with other HR-types.
Clinical presentation and differential splicing ofSRSF2, U2AF1andSF3B1mutations in patients with Acute Myeloid Leukaemia
Authors: Bamopoulos Stefanos A. , Batcha Aarif M. N. , Jurinovic Vindi , Rothenberg-Thurley Maja , Janke Hanna , Ksienzyk Bianka , Philippou-Massier Julia , Graf Alexander , Krebs Stefan , Blum Helmut , Schneider Stephanie , Konstandin Nikola , Sauerland Maria Cristina , Görlich Dennis , Berdel Wolfgang E. , Woermann Bernhard J. , Bohlander Stefan K. , Canzar Stefan , Mansmann Ulrich , Hiddemann Wolfgang , Braess Jan , Spiekermann Karsten , Metzeler Klaus H. , Herold Tobias
Published: January 2020

Previous studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukaemia remain largely unexplored. In this study we characterized mutations inSRSF2, U2AF1andSF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline we accurately detected aberrant splicing in splicing factor mutated samples. Mutated samples were characterized predominantly by decreased junction usage. A large proportion of differentially used junctions were novel. Targets of splicing dysregulation included several genes with a known role in leukaemia. InSRSF2(P95H) mutants we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes.
High capacity and dynamic accessibility in associative memory networks with context-dependent neuronal and synaptic gating
Authors: Podlaski William F. , Agnes Everton J. , Vogels Tim P.
Published: January 2020

Biological memory is known to be flexible — memory formation and recall depend on factors such as the behavioral context of the organism. However, this property is often ignored in associative memory models. Here, we bring this dynamic nature of memory to the fore by introducing a novel model of associative memory, which we refer to as the context-modular memory network. In our model, stored memory patterns are associated to one of several background network states, or contexts. Memories are accessible when their corresponding context is active, and are otherwise inaccessible. Context modulates the effective network connectivity by imposing a specific configuration of neuronal and synaptic gating – gated neurons (respectively synapses) have their activity (respectively weights) momentarily silenced, thereby reducing interference from memories belonging to other contexts. Memory patterns are randomly and independently chosen, while neuronal and synaptic gates may be selected randomly or optimized through a process of contextual synaptic refinement. Through signal-to-noise and mean field analyses, we show that context-modular memory networks can exhibit substantially increased memory capacity with random neuronal gating, but not with random synaptic gating. For contextual synaptic refinement, we devise a method in which synapses are gated off for a given context if they destabilize the memory patterns in that context, drastically improving memory capacity. Notably, synaptic refinement allows for patterns to be accessible in multiple contexts, stabilizing memory patterns even for weight matrices that do not contain any information about the memory patterns such as Gaussian random matrices. Lastly, we show that context modulates the relative stability of accessible versus inaccessible memories, thereby confirming that contextual control acts as a mechanism to temporarily hide or reveal particular memories. Overall, our model integrates recent ideas about context-dependent memory organization with classic associative memory models, highlights an intriguing trade-off between memory capacity and accessibility, and carries important implications for the understanding of biological memory storage and recall in the brain.
Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics
Authors: Oesterle Jonathan , Behrens Christian , Schröder Cornelius , Herrmann Thoralf , Euler Thomas , Franke Katrin , Smith Robert G , Zeck Günther , Berens Philipp
Published: January 2020

Multicompartment models have long been used to study the biophysical mechanisms underlying neural information processing. However, it has been challenging to infer the parameters of such models from data. Here, we build on recent advances in Bayesian simulation-based inference to estimate the parameters of detailed models of retinal neurons whose anatomical structure was based on electron microscopy data. We demonstrate how parameters of a cone, an OFF- and an ON-cone bipolar cell model can be inferred from standard two-photon glutamate imaging with simple light stimuli. The inference method starts with a prior distribution informed by literature knowledge and yields a posterior distribution over parameters highlighting parameters consistent with the data. This posterior allows determining how well parameters are constrained by the data and to what extent changes in one parameter can be compensated for by changes in another. To demonstrate the potential of such data-driven mechanistic neuron models, we created a simulation environment for external electrical stimulation of the retina as used in retinal neuroprosthetic devices. We used the framework to optimize the stimulus waveform to selectively target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprothetics. Taken together, this study demonstrates how a data-driven Bayesian simulation-based inference approach can be used to estimate parameters of complex mechanistic models with high-throughput imaging data.