bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the left medial temporal gyrus and adjacent brain areas during affective theory of mind processing correlates with trait schizotypy in a nonclinical population
Authors: Vucurovic Ksenija , Raucher-Chéné Delphine , Obert Alexandre , Gobin Pamela , Henry Audrey , Barrière Sarah , Traykova Martina , Gierski Fabien , Portefaix Christophe , Caillies Stéphanie , Kaladjian Arthur
Published: September 2022

Schizophrenia, a severe psychiatric disorder, is associated with abnormal brain activation during theory of mind (ToM) processing. Researchers recently suggested that there is a continuum running from subclinical schizotypal personality traits to fully expressed schizophrenia symptoms. Nevertheless, it remains unclear whether schizotypal personality traits in a nonclinical population are associated with atypical brain activation during ToM tasks. Our aim was to investigate correlations between fMRI brain activation during affective ToM (ToMA) and cognitive ToM (ToMC) tasks and scores on the Schizotypal Personality Questionnaire (SPQ) and the Basic Empathy Scale in 39 healthy individuals. The total SPQ score positively correlated with brain activation during ToMA processing in clusters extending from the left medial temporal gyrus (MTG), lingual gyrus and fusiform gyrus to the parahippocampal gyrus (Brodmann area: 19). During ToMA processing, the right inferior occipital gyrus, right MTG, precuneus and posterior cingulate cortex negatively correlated with the emotional disconnection subscore and the total score of self-reported empathy. These posterior brain regions are known to be involved in memory and language, as well as in creative reasoning, in nonclinical individuals. Our findings highlight changes in brain processing associated with trait schizotypy in nonclinical individuals during ToMA but not ToMC processing.
NDR1/HIN1-Like Protein 13 Interacts with Symbiotic Receptor Kinases and Regulates Nodulation in Lotus japonicus
Authors: Yamazaki Akihiro , Battenberg Kai , Shimoda Yoshikazu , Hayashi Makoto
Published: September 2022

Lysin-motif receptor-like kinases (LysM-RLKs) are involved in the recognition of microbe-associated molecular patterns to initiate pattern-triggered immunity (PTI). LysM-RLKs are also required for recognition of microbe-derived symbiotic signal molecules upon establishing mutualistic interactions between plants and microsymbionts. A LysM-RLK CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) plays central roles both in chitin-mediated PTI and in arbuscular mycorrhizal symbiosis, suggesting the overlap between immunity and symbiosis, at least in the signal perception and the activation of downstream signal cascades. In this study, we screened for the interacting proteins of Nod factor Receptor1 (NFR1), a CERK1 homolog in the model legume Lotus japonicus, and obtained a protein orthologous to NONRACE-SPECIFIC DISEASE RESISTANCE1/HARPIN-INDUCED1-LIKE13 (NHL13), a protein involved in the activation of innate immunity in Arabidopsis thaliana, which we named LjNHL13a. LjNHL13a interacted with NFR1 and with the symbiosis receptor kinase SymRK. LjNHL13a also displayed positive effects in nodulation. Our results suggest that NHL13 plays a role both in plant immunity and symbiosis, possibly where they overlap.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Tumor Volume Predicts for Pathologic Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation
Authors: Yang Fan , Hill Jordan , Abraham Aswin , Ghosh Sunita , Steed Tanner , Kurtz Clay , Joseph Kurian , Yun Jihyun , Warkentin Brad , Thai JoAnn , Nijjar Tirath , Severin Diane , Tankel Keith , Fairchild Alysa , Usmani Nawaid
Published: September 2022

Objectives:

Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM.

Materials and Methods:

In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis. Tumor volumes were derived from pretreatment MRI. Clinical parameters such as tumor volume, stage, and location were analyzed by univariate and multivariate analysis, against pCR. A receiver operator characteristic curve was generated to identify a tumor volume cut-off with the highest clinically relevant Youden index for predicting pCR.

Results:

Seventy-five of 412 patients (18%) achieved pCR. A tumor volume threshold of 37.3 cm3 was identified as predictive for pCR. On regression analysis, a tumor volume >37.3 cm3 was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV <37.3 cm3 [odds ratio (OR)=3.7, P<0.0001] was significantly associated with an increased pCR rate, whereas tumor length > 4.85 cm was associated with pCR on univariate (OR=3.03, P<0.01) but not on multivariate analysis (OR=1.45, P=0.261). Other clinical parameters did not impact pCR rates.

Conclusions:

A tumor volume threshold of 37.3 cm3 was identified as predictive for pCR in locally advanced rectal cancer patients receiving neoadjuvant chemoradiation. Tumors above this volume threshold corresponded to a greater than 78% probability of not achieving pCR. This information will be helpful at diagnosis for clinicians who are considering potential candidates for NOM.
Oleander-Associated Keratitis and Uveitis
Authors: Tailor Prashant D. , Farazdaghi Marybeth K. , Patel Sanjay V. , Baratz Keith H.
Published: September 2022

Purpose:

Oleander is a poisonous plant with extensively documented systemic side effects; however, oleander's ophthalmic side effects have not been detailed in the literature. We report a case of oleander-associated keratitis with subsequent corneal edema and anterior uveitis.

Methods:

This is a case report and review of relevant literature.

Results:

A 58-year-old woman presented with large corneal epithelial defect after being struck in the eye with an oleander leaf. Despite treatment with topical moxifloxacin, she developed severe corneal edema and anterior uveitis. A diagnosis of oleander-associated ocular inflammation with secondary corneal edema was made, given the temporal relationship, and treatment was initiated with topical prednisolone and cyclopentolate. However, the corneal edema and inflammation continued to progress until oral prednisone and topical difluprednate were initiated. Visual acuity, anterior uveitis, and corneal edema significantly improved with aggressive immunomodulation. Follow-up at 1 month confirmed complete recovery of symptoms, corneal edema and anterior uveitis.

Conclusions:

Severe corneal edema and anterior uveitis can be associated with oleander exposure. Aggressive treatment with oral and topical steroids may be required without persistent sequelae at the 5-month follow-up. Ophthalmologists should consider this inflammatory reaction if patients experience ocular exposure to oleander.
Suicide Risk Among Adolescents With ADHD
Authors: Trivedi Chintan , Nandakumar Aiswarya Lakshmi , Yousefzadehfard Yashar , Goriparthi Tulasi S.K. , Chaudhari Gaurav , Vora Darshini , Mansuri Zeeshan , Jain Shailesh
Published: September 2022

Studies have shown an association between attention deficit hyperactivity disorder (ADHD) and suicide; however, it has not been studied from inpatient hospitalization data among adolescents. For this study, data from the National Inpatient Sample data set were used. Based on the diagnosis of ADHD, the patient sample was stratified into two groups. Study group was composed of patients with ADHD, and control group was selected by propensity score matching (1:1), which composed of patients without ADHD. The primary outcome was suicidal ideation/attempt between the groups. Prevalence of SI was 25.1% in patients with ADHD versus 10.3% among patients without ADHD. Prevalence of SA was also very high (8.0% vs 3.9%) among patient with ADHD compared with non-ADHD group. After controlling for covariates, ADHD was a strong predictor of suicidal ideation/attempt with an odds ratio of 2.18. It is important to screen for suicidality in patient with ADHD given the high prevalence of suicidality.
Continuous Dural Suturing for the Closure of Grade 1 to 2 Cerebrospinal Fluid Leakage After Pituitary Adenoma Removal Using an Endoscopic Endonasal Approach
Authors: Zhou Lv , Wang Bin , Ye Lei , Gao Peng , Cheng Hongwei
Published: September 2022

In this study, we aim at evaluating continuous dural suturing in patients with grade 1 to 2 cerebrospinal fluid (CSF) leakage after pituitary adenoma removal using an endoscopic endonasal approach. The study population comprised 381 pituitary adenoma patients who underwent endoscopic endonasal removal of the tumor. The degree of intraoperative CSF leakage was graded based on Esposito method. Cranial base repair using continuous dural suturing was performed according to the grade of CSF leakage. Intraoperative grade 1 to 2 CSF leakage was identified in 143 patients (37.5%). Continuous dural suturing to repair the cranial base was accepted by 61 patients and refused by 82 patients. Among patients who accepted dural suturing, the incidence of postoperative CSF leakage was reduced and the length of hospital stay was shortened. Patients with low-flow leakage were treated using a reduced vascularized pedicled nasoseptal flap. In conclusion, our graded cranial base repair method using the dural suturing technique is simple and effective.
The Accuracy of Computer-Assisted Surgical Planning in Predicting Soft Tissue Responses After Le Fort I Osteotomy: Retrospective Analysis
Authors: Şenyürek S. Aysima , Ajami Sara , Ruggiero Federica , Van de Lande Lara , Caron Cornelia J.J.M. , Schievano Silvia , Dunaway David J. , Padwa Bonnie , Koudstaal Maarten J. , Borghi Alessandro
Published: September 2022

Purpose:

Mismatch between preoperative planning and surgical outcome in maxillofacial surgery relate to on-table replication of presurgical planning and predictive algorithm inaccuracy: software error was hereby decoupled from planning inaccuracy to assess a commercial software. The hypothesis was that soft tissue prediction error would be minimized if the surgical procedure was replicated precisely as planned and is independent of the extent of bone repositioning.

Materials and Methods:

Cone-beam computed tomography scans of 16 Le Fort I osteotomy patients were collected at Boston Children’s Hospital. Preoperative and postoperative models of bone and soft tissue were constructed and the maxilla repositioning was replicated. Each model was subdivided into 6 regions: mouth, nose, eyes, and cheeks. Soft tissue prediction (performed using Proplan CMF-Materialise) for each patient was compared with the relative postoperative reconstruction and error was determined. P<0.05 was considered significant.

Results:

Le Fort I segment repositioning was replicated within 0.70±0.18 mm. The highest prediction error was found in the mouth (1.49±0.77 mm) followed by the cheeks (0.98±0.34 mm), nose (0.86±0.23 mm), and eyes (0.76±0.32). Prediction error on cheeks correlated significantly with mouth (r=0.63, P< 0.01) and nose (r=0.67, P< 0.01). Mouth prediction error correlated with total advancement (r=0.52, P=0.04).

Conclusions:

ProPlan CMF is a useful outcome prediction tool; however, accuracy decreases with the extent of maxillary advancement even when errors in surgical replication are minimized.
Patient Support Program and Healthcare Resource Utilization in Patients Using Clean Intermittent Catheterization for Bladder Management
Authors: Hasan Shaquib Al , Neal-Herman Levi , Norman Holly S. , Zhao Julie Z. , Carlson Angeline
Published: September 2022

PURPOSE:

The primary purpose of this study was to evaluate the impact of a patient-centered, chronic care self-management support program of clean intermittent catheterization (CIC) on emergency department (ED) visits and hospitalizations within the first 30 days of starting CIC. Secondary research objectives were to compare reuse of catheters, adherence to healthcare provider–instructed frequency of CIC, and reasons for nonadherence.

DESIGN:

A correlational survey design with 2 respondent groups.

SUBJECTS AND SETTING:

Four hundred forty-five respondents met inclusion criteria for this study; 321 respondents enrolled in an intermittent catheter manufacturer–supported CIC support program, and 124 respondents were not enrolled in a support program (comparison group).

METHODS:

Participants completed a 37-item online questionnaire designed for purposes of this study. Chi-square test was used to assess differences in the proportions of patients with ED visits and overnight hospital admissions comparing respondents enrolled in the patient support program to those not enrolled. Regression analyses were performed to estimate the effect of the CIC support program on ED visit events and on hospital overnight stays.

RESULTS:

Within the first month of CIC initiation, 16.1% and 10.2% of the respondents in the comparison group reported at least 1 ED visit and at least 1 overnight hospital stay, respectively. Respondents participating in the CIC support program experienced a 47% decrease in ED visits (adjusted rate ratio: 0.53; 95% confidence interval: 0.30-0.94, P = .036) and a 77% decrease (adjusted rate ratio: 0.24; 95% confidence interval: 0.10-0.62, P = .002) in hospital overnight stays within the first month of CIC initiation, while controlling for age, sex, education, duration of CIC use, region, health insurance status, and medical conditions necessitating CIC. Respondents in the CIC support program group reported an 8% higher adherence rate with the healthcare provider–instructed frequency of CIC usage compared to the comparison group (88% vs 80%, P = .039).

CONCLUSIONS:

The burden of CIC-related complications within the first month of CIC initiation is significant. A patient-centered, chronic care self-management program for CIC was associated with fewer ED visits and overnight hospital stays during the first month of CIC and improved adherence to prescribed frequency of CIC use.
Treatment of Pediatric Pyoderma Gangrenosum With Modified Negative Pressure Wound Therapy and Intralesional Corticosteroids
Authors: Barker Catherine S. , Santa Lucia Gabriella , Brunette Glenda , Wine Lee Lara
Published: September 2022

BACKGROUND:

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease; its etiology is unknown, though it is often associated with autoimmune diseases. Pyoderma gangrenosum results in significant morbidity and exquisite pain that affects health-related quality of life. Wound healing is delayed, and patients often experience relapse. Pyoderma gangrenosum is susceptible to pathergy and deterioration with surgical intervention or other trauma; therefore, treatment includes atraumatic wound care, infection management, and local or systemic immunosuppression.

CASE:

We describe the use of modified negative pressure wound therapy (NPWT) with intralesional and topical steroids for the treatment of PG in a 15-year-old female patient with ulcerative colitis and a staged J-pouch ileoanal reconstruction. The patient and her family refused all systemic therapy due to prior steroid-associated weight gain. She was unable to tolerate conscious dressing changes, further complicating the treatment plan. Procedural interventions such as NPWT have been used previously for PG; however, they can cause wound pathergy and subsequent wound deterioration. Modified NPWT in conjunction with topical and intralesional steroids induced wound healing without producing pathergy.

CONCLUSION:

Timely recognition of PG is crucial to appropriate delivery of care. Modified NPWT and localized corticosteroid treatment were key to promoting wound healing in this case of pediatric PG.
Incontinence Management and Pressure Injury Rates in US Acute Care Hospitals
Authors: Koloms Kimberly , Cox Jill , VanGilder Catherine A. , Edsberg Laura E.
Published: September 2022

PURPOSE:

The purpose of this study was to identify and describe the prevalence of incontinence (urinary and/or fecal) and incontinence management practices among patients in US adult acute care settings, with and without hospital-acquired pressure injuries (HAPIs), using the data from the 2018/2019 International Pressure Ulcer Prevalence™ (IPUP) survey.

DESIGN:

Observational, cohort study with cross-sectional data collection and retrospective data analysis.

SUBJECTS AND SETTING:

The sample comprised 296,014 patients hospitalized in 1801 acute care facilities in the United States that participated in 2018 and/or 2019 IPUP survey. Of these, 192,852 (65%) patients had information recorded in the survey on incontinence status and were included in the analytical sample.

METHODS:

Data from the 2018/2019 IPUP database were analyzed to evaluate the prevalence of incontinence (urinary [UI], fecal [FI], and dual [DI]), and the use of incontinence and moisture management strategies. Incontinence prevalence was analyzed between 3 groups of patients: (1) those without pressure injuries; (2) patients with stage 1 and 2 HAPIs; and (3) those with severe HAPIs (stage 3, 4, unstageable, deep tissue pressure injury). Analysis of the subgroups within acute care was also undertaken and included medical-surgical, critical care, and step-down units.

RESULTS:

Incontinent patients were older (mean age 69-74 years depending on type of incontinence as compared to 62 years for continent patients) and had lower Braden Scale scores (range, 14.7-16.7, compared to 19.4 for continent patients). Half of the patients were female, 49.6% male, and 0.4% were unknown. Incontinence was identified in 32% of patients. Among patients with incontinence, 33% had UI, 12% had FI, and 55% had DI. Hospital-acquired pressure injuries were present in 27.4% of continent patients and 72.6% of incontinent patients, with DI having the highest rate of HAPIs. Analysis revealed a higher proportion of incontinent patients with unstageable HAPIs than continent patients (14.9% vs 9.6%, P = .00), as well as a higher proportion of incontinent patients with deep tissue HAPIs as compared to continent patients (27.0% vs 22.1%, P = .00). Significantly more incontinent patients regardless of HAPI status were using a bowel or bladder management system (P = .00).

CONCLUSION:

Results of this study support the importance of incontinence as a risk factor in HAPI development. The prevalence of all types of incontinence was 31.7% for the entire sample. Almost three-fourths (72.6%) of patients with HAPI had UF, FI, or DI. A standardized definition of both UI and FI is needed, given that over 70% of all critical care unit patients with a urinary catheter for incontinence management were still classified as urinary incontinent.
Interactive Evidence-Based Pressure Injury Education Program for Hospice Nursing
Authors: Seton Jacinta M. , Hovan Holly M. , Bogie Kath M. , Murray Maudie M. , Wasil Bridgette , Banks Patricia G. , Burant Christopher J. , Miller Charman , Vogt Marjorie
Published: September 2022

PURPOSE:

The purpose of this quality improvement (QI) project was to develop and implement an interactive, evidence-based pressure injury (PI) education program and evaluate the impact on frontline hospice nursing staff knowledge and practice.

PARTICIPANTS AND SETTING:

The QI setting was a 12-bed inpatient hospice unit in a tertiary care Veterans Affairs (VA) Medical Center in Cleveland, Ohio. Nineteen licensed and unlicensed hospice nursing staff participated in this pre-/postworkshop project.

APPROACH:

Chart audit determined baseline PI incidence and prevalence on the inpatient hospice unit. Interviews with key leaders informed the need to develop and implement innovative PI education opportunities. A literature review determined existing standards regarding the benefits of PI education for nursing staff but did not reveal measurable targets in hospice settings. We developed a PI education intervention based on Kolcaba's Theory of Comfort framework and a Plan-Do-Study-Act (PDSA) performance improvement model. Education was delivered in 7 workshops, lasting 2 hours each. Knowledge, practice, and comfort for inpatient hospice nursing staff were evaluated at baseline and 8 weeks following the final refresher visit. Workshop satisfaction was collected once using standard program evaluation forms after final workshop delivery.

OUTCOMES:

We observed a significant improvement in staff PI knowledge (P = .001) and practice (P = .001) after initial workshop attendance and repeat engagement (P = .001). There was a large magnitude of effect for overall knowledge change (d = 1.04); similarly PI care planning and practice showed a large magnitude of effect and significant improvement (P = .001, d = 2.64). Staff comfort with job duties was stable with low effect size (mean 4.52, d = 0.04), and satisfaction with the workshop education was high (100% agreement with trainer effectiveness).

IMPLICATIONS FOR PRACTICE:

We found that frontline hospice nursing staff knowledge and practice improved after attendance at our evidence-based PI education program. Results of this QI project have stimulated ongoing discussion on how to sustain this program in our hospice setting.
Open Retromuscular Lateral Abdominal Wall Hernia Repair: Algorithmic Approach and Long-Term Outcomes at a Single Center
Authors: Montelione Katherine C , Petro Clayton C , Krpata David M , Lau Braden , Shukla Priya , Olson Molly A , Tamer Robert , Rosenblatt Steven , Rosen Michael J , Prabhu Ajita S
Published: September 2022

BACKGROUND:

Lateral abdominal wall hernias are relatively rare and present unique challenges to repair. Our group has developed an algorithm for repair based on several anatomic characteristics identified on preoperative imaging. Herein, we report our algorithm and outcomes of a large series of open retromuscular lateral abdominal wall hernia repairs.

STUDY DESIGN:

Open retromuscular lateral abdominal wall hernia repairs performed at our institution from August 2014 through April 2021 were identified in the Abdominal Core Health Quality Collaborative. Hernia characteristics, etiology, operative techniques, postoperative outcomes, and long-term patient-reported outcomes were extracted from the Abdominal Core Health Quality Collaborative database, chart review, and telephone follow-up.

RESULTS:

Of 464 patients who underwent hernia repair, 121 with isolated lateral abdominal wall hernias (L1–4) and mean follow-up of 34 ± 24 months had a clinical recurrence rate of 0.9% (n = 1) and bulge rate of 37% (n = 42). The median Hernia-Related Quality of Life Survey and PROMIS pain intensity scores improved 37 and 9 points, respectively. Another 343 patients with lateral (L1–4) and midline (M1–5) abdominal wall hernias and mean follow-up of 29 ± 21 months had a clinical recurrence rate of 6% (n = 20) and bulge rate of 35% (n = 117). The median Hernia-Related Quality of Life Survey and PROMIS pain intensity scores improved by 43 and 16 points, respectively.

CONCLUSION:

We present an algorithm for open retromuscular lateral abdominal wall hernia repair with relatively low anatomic recurrence rates and substantial improvement in patient-reported quality of life and pain. Notably, postoperative bulging is commonly reported by patients, likely due to underlying denervation injuries from the original incision.
Factors Associated with Cutaneous Colonization of Mucormycetes in Diabetic and Non-Diabetic Individuals
Authors: Saud Bhuvan , Chand Kajal , Amatya Neetu , Paudel Govinda , Adhikari Saroj , Shrestha Vikram
Published: September 2022

To access factors associated with cutaneous colonization of mucormycetes in diabetic and non-diabetic individuals. From 200 participants (100 diabetics and 100 non-diabetics) 800 swab samples collected from four different body sites (forehead, nasal, hand and feet). Fungal isolation, identification and sensitivity tests performed. Overall, 12.0% of people had mucormycetes colonization, with diabetics having an 11 times greater colonization rate than non-diabetics. The most typical fungal isolates were Mucor spp. and Rhizopus spp. The majority of the isolates were resistant to Itraconazole; however, Amphotericin B was sensitive to all isolates. Between participant occupation and fungal colonization, a statistically significant difference (p<0.05) was found. A larger risk of colonization demonstrated by additional factors such older age, lower middle class position, and maximal contact with soil. Therefore, it is urgently required to have a proper awareness of risk factors for prevention of mucormycosis in diabetes patients.
The Effect of Intradialytic Exercise on Dialysis Patient Survival: A Randomized Controlled Trial
Authors: Tabibi Mohammad Ali , Cheema Bobby , Salimian Nasrin , Corrêa Hugo , Ahmadi Saghar
Published: September 2022

Introduction

Patients with kidney failure have a high mortality rate. This study aimed to evaluate the effect of intradialytic exercise on survival in patients receiving hemodialysis (HD).

Methods

In this randomized controlled trial conducted in a HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 minutes) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcome was survival rate at 12 months. Secondary outcomes were serum albumin, hemoglobin, hematocrit, red blood cell count, serum calcium, serum phosphorous, parathyroid hormone, physical function (6-minute walk test) and nutritional status (Geriatric Nutritional Risk Index) during the first 6 months. The trial follow-up period was 12 months.

Results

The study included 74 participants randomized to intervention (n=37) or control (n=37). Compared with controls, 1-year survival was higher in the intervention group compared with the control group (94% vs 73%, P=0.01). The hazard ratio on univariate analysis in intervention group was 0.17 (95% CI 0.04-0.8; P =0.02) compared to that in control group. During the 6-month intervention period, significant between-group changes were observed in all secondary outcomes between the intervention and control groups.

Conclusion

Intradialytic exercise performed for at least 60 minutes during thrice weekly dialysis sessions improves survival in adult patients receiving HD. This effect may be mediated by exercise-related improvements in bone mineral metabolism, anemia, physical function or nutritional status.

Trial registration

ClinicalTrials.gov Identifier: NCT04898608, Registered on May 21st,2021. Registered trial name: The Effect of Intradialytic Exercise on Dialysis Patients Survival.
Differences in Motivators, Barriers, and Incentives between Black and White Older Adults for Participation in Alzheimer’s Disease Biomarker Research
Authors: Eliacin Johanne , Polsinelli Angelina J. , Epperson Francine , Gao Sujuan , Van Heiden Sarah , Westmoreland Glenda , Richards Ralph , Richards Mollie , Campbell Chris , Hendrie Hugh , Risacher Shannon L. , Saykin Andrew J. , Wang Sophia
Published: September 2022

Introduction

The study aimed to identify strategies to increase older Black adults’ participation in Alzheimer’s disease (AD) biomarker research studies.

Methods

399 community-dwelling Black and White older adults (age ≥ 55) who had never participated in AD research completed a survey about their perceptions of AD research involving blood draw, MRI, and PET.

Results

Although most participants expressed interest in AD biomarker research (Black participants: 63.0%, White participants: 80.6%), Black participants were significantly more hesitant than White participants (28.9% vs 15.1%), were more concerned about study risks, (30.8% vs. 11.1%) and perceived multiple barriers to participating in brain scans. Lack of information was perceived as a barrier to participation across groups (45.8%) and return of study results was perceived as a participation incentive (78.9-85.7%) (Ps < .05).

Discussion

Strategies to increase Black older adult participation in AD research may include disseminating additional study information and return of results.

Declaration of Interest

None of the investigators have a conflict of interest. JE receives support from VA IK HX002283, NIA P30AG072976, and NIA P30AG010133. AJP receives support from NIA (NIA U01 AG057195) and Alzheimer’s Association (LDRFP-21-818464). SW receives support from multiple NIA grants (K23AG062555, P30AG072976, P30AG010133, and R21AG074179) and the VA for clinical services. She receives book royalties from APPI and DSMB consultant fees (total less than $2000/year). AJS receives support from multiple NIH grants (P30 AG010133, P30 AG072976, R01 AG019771, R01 AG057739, U01 AG024904, R01 LM013463, R01 AG068193, T32 AG071444, and U01 AG068057 and U01 AG072177). He has also received support from Avid Radiopharmaceuticals, a subsidiary of Eli Lilly (in kind contribution of PET tracer precursor); Bayer Oncology (Scientific Advisory Board); Eisai (Scientific Advisory Board); Siemens Medical Solutions USA, Inc. (Dementia Advisory Board); Springer-Nature Publishing (Editorial Office Support as Editor-in-Chief, Brain Imaging and Behavior).
Immunization Opportunities for Hospitalized Adolescents
Authors: Wurster William R. , Foster Byron A. , Walston James M. , Gardner Tiffany A. , Benchbani Hanae , Austin Jared
Published: September 2022

Introduction

Adolescents seek routine healthcare, including immunizations, less frequently than any other age group. Hospitalizations are an opportunity to provide immunizations to this vulnerable population. The aims of this study were to assess the accuracy of provider documentation of immunization status and evaluate the prevalence of delayed immunization status in this population.

Methods

A retrospective chart review of adolescents discharged from July 2017 to June 2018 from the pediatric hospitalist service of a tertiary care academic children’s hospital was conducted. Provider documentation of immunization status was compared to the immunization registry ALERT Immunization Information System (ALERT IIS) linked to the electronic medical record using descriptive statistics.

Results

Provider documentation of up-to-date on all immunizations had a sensitivity of 60% and specificity of 55%, with 84% of patients needing at least one immunization despite 48% of patients being documented as up-to-date by providers. Provider documentation of the immunization status for the HPV, MCV and Tdap immunizations displayed a low sensitivity (10-11%) but a high specificity (97-100%) while documentation of the influenza immunization was associated with high sensitivity (86%) and low specificity (26%). Provider documentation of immunization status for the HPV, MCV, Tdap and influenza immunizations had positive likelihood ratios of 3.5, 8.5, infinity, and 1.2 with negative likelihood ratios of 0.9, 0.9, 0.9 and 0.53, respectively.

Conclusions

Providers inaccurately documented the immunization status for adolescent patients in the inpatient setting. Hospitalizations may provide opportunities to improve immunization rates in adolescents, especially when using state immunization registries.
The impact of COVID-19 on population cancer screening programs in Australia: modelled evaluations for breast, bowel and cervical cancer
Authors: Nickson Carolyn , Smith Megan A , Feletto Eleonora , Velentzis Louiza S , Broun Kate , Deij Sabine , Grogan Paul , Hall Michaela , He Emily , St John D James , Lew Jie-Bin , Procopio Pietro , Simms Kate T. , Worthington Joachim , Mann G Bruce , Canfell Karen
Published: September 2022

Background

Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel and cervical cancer screening programs on cancer outcomes and cancer services.

Methods

We used the Policy1 modelling platforms to estimate outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9 and 12 months. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts.

Results

We estimated that a 12-month screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020-2021) and colorectal cancer (up to 12·1% reduction over 2020-21), and increase cervical cancer diagnoses (up to 3·6% over 2020-2022), with upstaging expected for these cancer types.

Conclusions

Findings illustrate that maintaining screening participation is critical to sustaining a reduced cancer burden. We provide program-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programs, and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.

Funding

Australian Government Department of Health
A Detector Block-Pairwise Dead Time Correction Method for Improved Quantitation with a Dedicated BrainPET Scanner
Authors: Issa Ahlam Said Mohamad , Scheins Jürgen , Tellmann Lutz , Lopez-Montes Alejandro , Herraiz Joaquin L , Brambilla Cláudia Régio , Herzog Hans , Neuner Irene , Shah N. Jon , Lerche Christoph
Published: September 2022

Dead time correction (DTC) is an important factor in ensuring accurate quantification in PET measurements. This is currently often achieved using a global DTC method, i.e., an average DTC factor is computed. For PET scanners designed to image dedicated organs, e.g., those used in brain imaging or positron emission mammography (PEM), a substantial amount of the administered radioactivity is located outside of the PET field-of-view (FOV). This activity contributes to the dead time (DT) of the scintillation detectors. Moreover, the count rates of the individual scintillation detectors are potentially very inhomogeneous due to the specific irradiation of each detector, especially for combined MR/PET systems, where radiation shields cannot be applied. We have developed a block-pairwise DTC method for our Siemens 3T MR BrainPET insert by extending a previously published method that uses the delayed random coincidence count rate to estimate the DT in the individual scans and planes (i.e., scintillation pixel rings). The method was validated in decay experiments using phantoms with a homogenous activity concentration and with and without out-of-FOV activity. Based on a three-compartment phantom, we compared the accuracy and noise properties of the block-pairwise DTC and the global DTC method. While the currently used global DTC led to a substantial positive bias in regions with high activity, the block-pairwise DTC resulted in substantially less bias. The noise level for the block-pairwise DTC was comparable to the global DTC and image reconstructions without any DTC. Finally, we tested the block-pairwise DTC with a data set obtained from volunteer measurements using the mGlu5R (metabotropic glutamate receptor subtype 5) antagonist [11C]-ABP688, when comparing the time-activity curves (TACs) obtained with the global DTC with the block-pairwise DTC, relative differences in the anterior cingulate cortex (ACC) and the cerebellum of up to 25% were observed during the first 30 minutes of these measurements.
Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection
Authors: Duffy Fergal J , Hertoghs Nina , Du Ying , Neal Maxwell L. , Oyong Damian , McDermott Suzanne , Minkah Nana , Carnes Jason , Schwedhelm Katharine V , McElrath M Juliana , Rosa Stephen C De , Newell Evan , Aitchison John D. , Stuart Ken
Published: September 2022

Identifying immune processes required for liver-stage sterilizing immunity to malaria infection remains an open problem. The IMRAS trial comprised 5x immunizations with radiation-attenuated sporozoites resulting in 55% protection from subsequent challenge. To identify correlates of vaccination and protection, we performed detailed systems immunology longitudinal profiling of the entire trial time course including whole blood transcriptomics, detailed PBMC cell phenotyping and serum antigen array profiling of 11 IMRAS RAS vaccinees at up to 21 timepoints each. RAS vaccination induced serum antibody responses to CSP, TRAP, and AMA1 in all vaccinees. We observed large numbers of differentially expressed genes associated with vaccination response and protection, with distinctly differing transcriptome responses elicited after each immunization. These included inflammatory and proliferative responses, as well as increased abundance of monocyte and DC subsets after each immunization. Increases Vδ2 γδ T cells and MAIT cells were observed in response to immunization over the course of study. Interferon responses strongly differed between protected and non-protected individuals with high interferon responses after the 1stimmunization, but not the 2nd-5th. Blood transcriptional interferon responses were correlated with abundances of different circulating classical and non-classical monocyte populations.

This study has revealed multiple coordinated immunological processes induced by vaccination and associated with protection. Our work represents the most detailed immunological profiling of a RAS vaccine trial performed to date and will guide the design and interpretation of future malaria vaccine trials.
Accelerating Antibody Design with Active Learning
Authors: Seo Seung-woo , Kwak Min Woo , Kang Eunji , Kim Chaeun , Park Eunyoung , Kang Tae Hyun , Kim Jinhan
Published: September 2022

Discovering therapeutic antibody starts by screening antibody library of phage-displayed, transgenic mouse or human B cells. The coverage of those kinds of libraries in the entire antibody sequence space is small; thus, the result highly depends on the quality of the library. Exploring sequence space by mutating a template antibody is also impossible to even with the state-of-the-art screening methods because of the cost. Deep learning helped with its pattern recognition nature to predict target binding, which is only applied to HCDR3 because the number of data deep learning needs increases exponentially. We construct a sequence generation model with transfer learning and active learning to leverage deep learning even in data deficiency. With only six thousands data, the generative model finds nine binding antibody sequences at least per antigen with novel HCDR3.
Multi-population genome-wide association study implicates both immune and non-immune factors in the etiology of pediatric steroid sensitive nephrotic syndrome
Authors: Barry Alexandra , McNulty Michelle T. , Jia Xiaoyuan , Gupta Yask , Debiec Hanna , Luo Yang , Nagano China , Horinouchi Tomoko , Jung Seulgi , Colucci Manuela , Ahram Dina F. , Mitrotti Adele , Sinha Aditi , Teeninga Nynke , Jin Gina , Shril Shirlee , Caridi Gianluca , Bodria Monica , Lim Tze Y , Westland Rik , Zanoni Francesca , Marasa Maddalena , Turudic Daniel , Giordano Mario , Gesualdo Loreto , Magistroni Riccardo , Pisani Isabella , Fiaccadori Enrico , Reiterova Jana , Maringhini Silvio , Morello William , Montini Giovanni , Weng Patricia L. , Scolari Francesco , Saraga Marijan , Tasic Velibor , Santoro Domenica , van Wijk Joanna A.E. , Milošević Danko , Kawai Yosuke , Kiryluk Krzysztof , Pollak Martin R. , Gharavi Ali , Lin Fangmin , Simœs e Silva Ana Cristina , Loos Ruth J.F. , Kenny Eimear E. , Schreuder Michiel F. , Zurowska Aleksandra , Dossier Claire , Ariceta Gema , Drozynska-Duklas Magdalena , Hogan Julien , Jankauskiene Augustina , Hildebrandt Friedhelm , Prikhodina Larisa , Song Kyuyoung , Bagga Arvind , Cheong Hae Il , Ghiggeri Gian Marco , Vachvanichsanong Prayong , Nozu Kandai , Vivarelli Marina , Raychaudhuri Soumya , Tokunaga Katsushi , Sanna-Cherchi Simone , Ronco Pierre , Iijima Kazumoto , Sampson Matthew G.
Published: September 2022

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cellspecific insights into its molecular drivers.
Internet Delivered Sexually Transmitted Infection and Teen Pregnancy Prevention Program: A Randomized Trial
Authors: Kissinger Patricia J. , Green Jakevia , Latimer Jennifer , Schmidt Norine , Ratnayake Aneeka , Madkour Aubrey Spriggs , Clum Gretchen , Wingood Gina M , DiClemente Ralph J. , Johnson Carolyn
Published: September 2022

Importance

Black teenaged women have disproportionately high rates of unintended pregnancy (UTP) and sexually transmitted infections (STI). Internet-based interventions can be delivered to large groups of people in a relatively inexpensive manner.

Objective

The purpose of this randomized trial was to examine the efficacy of an adaptation of a theory- and evidence-based UTP/STI prevention intervention for older teens and for internet delivery.

Design

A randomized, attention-controlled trial.

Setting

Participants were recruited from minority-serving institutions and community events in New Orleans, Louisiana.

Participants

Black women aged 18-19 who were not pregnant nor seeking to become pregnant were enrolled (n=637).

Main outcomes and measures

Participants were randomized to an 8-session intervention or attention control and were followed at 6- and 12-months post-intervention to determine if the use of reliable contraception, dual methods, intention to use condoms, and intention to use reliable contraception were higher among women in the intervention arm compared to controls. Pregnancy and STI rates were also compared.

Results

Overall, at baseline, reliable contraception was 54.8% and dual protection was 29.4% and the prevalence of STI was 11.1%. Participants were similar by arm. Participation and follow-up rates were excellent (60.9% and 80.3%). At 6 months, all outcomes were improved in intervention compared to control, but this effect waned by 12 months.

Conclusion and Relevance

The intervention was efficacious for increasing self-reported pregnancy and STI prevention behavior and intentions and lower trends for pregnancy and STIs were observed in this group which decreased over time suggesting the need for a booster.

Trial Registration

ClinicalTrial.govNCT01579617
Histology of type 3 macular neovascularization and microvascular anomalies in treated age-related macular degeneration: a case study
Authors: Berlin Andreas , Cabral Diogo , Chen Ling , Messinger Jeffrey D , Balaratnasingam Chandrakumar , Mendis Randev , Ferrara Daniela , Freund K. Bailey , Curcio Christine A
Published: September 2022

Objective/Purpose

To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient.

Design

A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation).

Participants

A white woman in her 90’s treated with numerous intravitreal anti-vascular endothelial growth factor (VEGF) injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).

Intervention(s)/ Methods

Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain optical coherence tomography (OCT), OCT angiography, and fluorescein angiography. Eye tracking, applied to the two preserved donor eyes, enabled correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy.

Main Outcome(s) and Measure(s)

Histologic/ ultrastructural descriptions and diameters of vessels seen in clinical imaging.

Results

Six vascular lesions were histologically confirmed (type 3 MNV, n=3; deep retinal age-related microvascular anomalies (DRAMA), n=3). Pyramidal (n=2) or tangled (n=1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the sub-retinal pigment epithelium (RPE)-basal laminar space or cross Bruch’s membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and non-fenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. DRAMA lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers, without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMA lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes.

Conclusions

Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMA are part of the type 3 MNV progression sequence.
Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis
Authors: Gijs Pieter-Jan , Daccord Cécile , Bernasconi Eric , Brutsche Martin , Clarenbach Christian , Hostettler Katrin , Guler Sabina A. , Mercier Louis , Ubags Niki , Funke-Chambour Manuela , Garnier Christophe von
Published: September 2022

Background

High bacterial burden in lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases and observational studies have shown a positive effect of azithromycin on mortality and hospitalization rate in IPF. However, the effect of AZT on lung microbiota in IPF remain unknown.

Methods

We sought to determine the impact of a three-month course of azithromycin on lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomized controlled cross-over trial of a thrice-weekly 500 mg oral azithromycin. 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARG) were assessed using real-time qPCR.

Results

Azithromycin significantly decreased community diversity with a stronger and more persistent effect in lower airways. During treatment, turnover of airway microbiota decreased in upper and lower airways, resulting in greater similarity between microbiota of the two sites persisting one month after macrolide cessation.

Patients with increased expression of ARG had a lower bacterial load and an enrichment of the genus Streptococcus. In contrast, patients without increased in ARG expression had a higher bacterial load and an enrichment in Prevotella.

Conclusions

We observed that AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.