bluuebunny/crossref_metadata_2025 huggingface dataset:
Partnering With a Purpose: Promoting Equity and Justice for Black Children With Autism Spectrum Disorder
Authors: Castelin Stephanie , Okorodudu Josselyn , Smith Teresa
Published: July 2024

Objective:

Black children with autism and their families face disparities within clinical care and services, leading to inequitable health outcomes. However, there is limited research centering the voices of the Black autism community in understanding how to address these inequities. In this study, researchers explored the perspectives of caregivers of Black children with autism regarding barriers to equitable care and recommendations for improved services.

Methods:

Community leaders from an autism advocacy group and researchers from a large academic medical center partnered to conduct a Group Level Assessment with 31 Black families of children with autism. During a three-hour research event, participants discussed their experiences within community, school, and clinical services, collectively coded and interpreted the data, and generated action steps to improve services.

Results:

The findings revealed 6 areas of need regarding the services Black children with autism and their caregivers receive. Black caregivers recommended that systems of care improve access to culturally responsive care, integrate caregiver priorities within their care, and engage in collaborative decision-making with caregivers. Providers should also equip caregivers with an accessible roadmap for navigating their child's services and connect them to care management professionals and resources for mental health support.

Conclusion:

The findings of this study address a critical gap in the literature by partnering with the Black autism community to identify solutions to address their needs; these recommendations can be used as a foundation for service providers to reduce disparities and improve outcomes for Black children with autism and their families.
Associations Among Race, Ethnicity, and Clinical Profiles of Young Children Evaluated for Autism in the Primary Care Setting
Authors: Martin Ann Marie , Keehn Brandon , Paxton Angela , Ciccarelli Mary R. , McNally Keehn Rebecca
Published: July 2024

Objective:

Despite long-standing racial and ethnic disparities in autism spectrum (AS) diagnosis, recent research suggests that overall, greater numbers of Black and Latine children are now diagnosed with AS as compared with non-Latine White (NLW) children in some US regions. However, gaps remain in the equitable detection of Black and Latine children with AS without significant developmental impairment. The objective of this study was to determine whether the clinical profiles of young children evaluated for AS across a statewide system of early autism diagnosis in Indiana vary by race and ethnicity.

Methods:

We examined racial and ethnic differences in: (1) AS symptom severity, (2) developmental functioning, (3) adaptive functioning, and (4) behavior problems in a sample of 147 children, aged 14 to 48 months (M = 2.6 years), referred for AS evaluation.

Results:

Clinical profiles of young children evaluated differed significantly by race and ethnicity, with Black and Latine children exhibiting lower developmental (p = 0.008) and adaptive abilities (p = 0.01) and higher AS symptoms (p = 0.03) as compared with NLW children.

Conclusion:

Potential explanations for findings include racial and ethnic differences in family and community awareness and knowledge about AS and follow-through on evaluation referral, both driven by social determinants of health (SDOH) affecting minoritized children. Bias in screening and assessment instruments and clinician surveillance, screening, and referral practices may also underlie differences in clinical profiles of children evaluated. Future research is needed to understand the SDOH that influence AS detection and diagnosis to improve equitable access to early diagnosis and intervention.
Characterizing the Association Between Traumatic Brain Injury and Discontinuation of Medications for Opioid Use Disorder in a Commercially Insured Adult Population
Authors: Morgan Jake R. , Reif Sharon , Stewart Maureen T. , Larochelle Marc R. , Adams Rachel Sayko
Published: July 2024

Objective:

Extending prior research that has found that people with traumatic brain injury (TBI) experience worse substance use treatment outcomes, we examined whether history of TBI was associated with discontinuation of medication to treat opioid use disorder (MOUD), an indicator of receiving evidence-based treatment.

Setting:

We used MarketScan claims data to capture inpatient, outpatient, and retail pharmacy utilization from large employers in all 50 states from 2016 to 2019.

Participants:

We identified adults aged 18 to 64 initiating non-methadone MOUD (ie, buprenorphine, injectable naltrexone, and oral naltrexone) in 2016-2019. The exposure was whether an individual had a TBI diagnosis in the 2 years before initiating MOUD. During this period, there were 709 individuals with TBI who were then matched with 709 individuals without TBI.

Design:

We created a retrospective cohort of matched individuals with and without TBI and used quasi-experimental methods to identify the association between TBI status and MOUD use. We estimated propensity scores by TBI status and created a 1:1 matched cohort of people with and without TBI who initiated MOUD. We used a Cox proportional hazards model to identify the association between TBI and MOUD discontinuation.

Main Measure:

The outcome was discontinuation of MOUD (ie, a gap of 14 days or more of MOUD).

Results:

Among those initiating MOUD, the majority were under 26 years of age, male, and living in an urban setting. Nearly 60% of individuals discontinued medication by 6 months. Adults with TBI had an elevated risk of MOUD discontinuation (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.01-1.27) compared to those without TBI. Additionally, initiating oral naltrexone was associated with a higher risk of discontinuation (HR 1.63; 95% CI, 1.40-1.90).

Conclusion:

We found evidence of reduced MOUD retention among people with TBI. Differences in MOUD retention may reflect health care inequities, as there are no medical contraindications to using MOUD for people with TBI or other disabilities.
Surgical techniques for optimal lens management of posterior segment metallic intraocular foreign body removal: a case series
Authors: Moon Jade Y. , Looysen Tyler , Monsalve Pedro , Simmons Michael , Khundkar Tahsin , Naravane Ameay , Sather Richard , Johnston Richard , Nazari Hossein , Koozekanani Dara , Montezuma Sandra R.
Published: July 2024

Purpose:

We describe three different approaches for lens management in cases of metallic IOFBs involving the posterior segment.

Methods:

All consecutive posterior segment metallic IOFB cases from 2012 to 2023 at a single institution were included in this retrospective case series. Surgical outcomes and surgical videos are presented.

Results:

A total of 25 metallic IOFB cases were included. In 9 cases, there was no significant lens involvement, therefore not requiring lens extraction at the time of IOFB removal. In 8 cases with traumatic cataract, lens extraction sparing the anterior lens capsule was performed with IOFB removal. In 8 cases, both lens extraction and lens capsule removal were required at the time of IOFB removal.

Conclusion:

We demonstrate our algorithm to capsular management in patients who present with IOFB with good visual outcomes in follow-up.
INVESTIGATION OF THE PATHOPHYSIOLOGY OF EPIRETINAL MEMBRANE FOVEOSCHISIS
Authors: Matoba Ryo , Kanzaki Yuki , Morita Tetsuro , Masuda Yuki , Kimura Shuhei , Hosokawa Mio M. , Shiode Yusuke , Morizane Yuki
Published: July 2024

Purpose:

To analyze the pathophysiology of epiretinal membrane foveoschisis (FS) by evaluating the longitudinal changes in visual function and several optical coherence tomography parameters.

Methods:

The medical records of 33 consecutive patients (35 eyes) with untreated epiretinal membrane foveoschisis were retrospectively reviewed. Best-corrected visual acuity, M-CHARTS score, and optical coherence tomography parameters including epiretinal membrane area, maximum depth of retinal folds, FS area, and FS circularity were evaluated.

Results:

A wide range of FS area changes was observed at the final follow-up visit (59.68%–240.45% of the baseline FS area). In the FS enlargement group, best-corrected visual acuity and mean M-CHARTS scores significantly worsened and maximum depth of retinal folds significantly increased over time, whereas in the FS non-enlargement group, no significant change was observed in the best-corrected visual acuity, mean M-CHARTS scores, or maximum depth of retinal folds during the follow-up period. Multivariate logistic regression analyses revealed that maximum depth of retinal folds (odds ratio: 1.05, 95% confidence interval: 1.00–1.10, P = 0.048) and FS circularity (odds ratio: 0.91, 95% confidence interval: 0.83–1.00, P = 0.043) were significantly associated with FS enlargement.

Conclusion:

Epiretinal membrane foveoschisis encompasses diverse pathophysiologies. Since visual functions do not worsen in some cases, monitoring the changes in visual functions and retinal morphology over time is recommended to determine surgical indications.
THE GENETIC BASIS OF CLINICALLY SUSPECTED ACHROMATOPSIA IN THE UNITED ARAB EMIRATES
Authors: Khan Arif O.
Published: July 2024

Purpose:

Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically suspected ACHM in the United Arab Emirates.

Methods:

Retrospective case series (January 2016–December 2023) of patients with (1) clinically suspected ACHM or (2) mutations in ACHM-associated genes (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, AT6).

Results:

Twenty-two clinically suspected patients (19 probands) were identified. Biallelic disease genes and the number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Some mutant alleles were recurrent across different families. Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP-related bradyopsia and CNNM4-related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review—one each related to PDE6C, to AT6, and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM.

Conclusion:

CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Recurrent mutant alleles may represent founder effects. Macular discoloration on presentation can occur in PDE6C-related disease, AT6-related disease, and triallelic CNGB3/CNGA3-related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.
Ozaki technique versus Ross operation for complex aortic valve diseases in children: a retrospective cohort study
Authors: Wang Guan-Xi , Zhang Sen , Ma Kai , Pang Kun-Jing , Wang Xu , Yang Ke-Ming , Zhang Ben-Qing , Yang Yang , Li Shou-Jun
Published: July 2024

Background:

The Ozaki technique demonstrated promising results in adults, but few studies reported on pediatric patients with limited follow-up time. This study aimed to evaluate the mid-term results of Ozaki technique compared with Ross operation for complex aortic valve diseases in children.

Materials and methods:

One hundred and seventeen children underwent either Ozaki (n=64) or Ross (n=53) operation from January 2017 to December 2023. The primary endpoint was incidence of moderate or severe regurgitation/stenosis (AR/AS) post procedure.

Results:

No significant difference was observed in age (6.5±3.4 vs. 7.9±4.3 years) and weight (25.9±15.5 vs. 31.0±25.9 kgs) at surgery. The Ozaki group had significantly more patients in heart failure (20.3 vs. 1.9%, P = 0.003) before surgery and more patients needed ECMO installation (6.3% vs. 0, P=0.125) after surgery. The Ozaki group were in worse status with more patients occurred heart failure (20.3 vs. 1.9%, P = 0.003) before surgery and needed ECMO installation (6.3 vs. 0, P = 0.125) after surgery. During follow-up (20.4±17.3 vs. 22.7±22.8 months, P=0.526), five patients (7.8%) in Ozaki group but no patients in Ross group required reoperations. The incidence of moderate or severe AR (28.1 vs. 3.1%) and AS (31.3 vs. 5.7%) were significantly higher than Ross group. Multivariate analysis identified lower age [HR: 1.282 (95% CI: 1.075–1.529), P=0.006] and ECMO installation [HR: 0.126 (0.018–0.887), P=0.037] to be risk factors for moderate or severe AR, and higher aortic transvalvular gradient before discharge was confirmed as the only risk factor for moderate or severe AS (≥36 mmHg) at follow-up in Ozaki group.

Conclusion:

Ozaki technique may be used as a palliative procedure for complex aortic valve diseases in children, but its’ mid-term results were not durable as Ross surgery, especially younger patients.
The evaluation of risk factors in fascia dehiscence after abdominal surgeries
Authors: Parsa Hossein , Haji Maghsoudi Leila , Mohammadzadeh Alireza , Hosseini Maryam
Published: July 2024

Background:

Despite the advances in surgical techniques and risk control practices in recent years, open wounds following abdominal laparotomy still have a high prevalence. The purpose of this study is to investigate the risk factors of fascia dehiscence (FD) in abdominal surgery patients.

Methods:

In this observational study, a total of 60 emergency and elective laparotomy patients were enrolled. For all patients, with (treatment) or without (control) wound dehiscence, a checklist was used to extract data from medical records regarding underlying diseases, suturing method, emergency or elective surgical procedure, duration of surgery less than 180 min, intraoperative bleeding, wound closure method, hernia repair, age, sex, smoking history, comorbidities, type of surgery, colostomy placement, wound complications, re-operation, mortality, wound complications including wound infection, wound dehiscence, incisional hernia, and anastomotic leak, and preoperative readiness assessments such as laboratory tests including C-reactive protein (CRP), Albumin (Alb), etc., were completed, and then comparisons were made.

Results:

Patients were examined in two groups: 14 patients (70%) in wound dehiscence with age 40–60 and 6 patients (30%) in non-wound dehiscence with age 60–75. Eight patients (40%) underwent elective surgery, and 12 patients (60%) underwent emergency surgery (P=0.2). Fourteen patients (70%) experienced mortality (P<0.001) and 13 patients (65%) had Alb less than 3 (P<0.001). Fourteen patients (70%) had drain installation (P=0.02). It was determined that the increase in CRP levels (compared to pre-dehiscence levels) was observed in 17 out of 20 cases, with the highest difference being CRP=91 and an average increase of 30. None of the patients suspected of anastomotic leakage were confirmed to have it. Dehiscence was typically diagnosed between the 4th and 7th days post-surgery. The colon and rectum were significantly more associated with dehiscence, while the stomach had the lowest association among surgical sites.

Conclusion:

Based on this study, FD is more common in patients treated in the emergency room than in elective procedures. Mortality occurred more in patients with FD, and there is a significant relationship between FD with albumin less than 3 and drain placement.
Nursing Quality Indicators in Emergency Nursing
Authors: Mustonen Meeri , Ameel Maria , Ritmala Marita , Leino-Kilpi Helena
Published: July 2024

Background:

Nursing quality indicators (NQIs) are essential for evaluating and managing care, yet few validated NQIs exist for emergency nursing. The dynamic nature of this field demands specific, validated indicators.

Purpose:

The purpose of this review was to identify NQIs in adult emergency nursing using Donabedian’s quality categories (structure, process, outcome) and explore their validation.

Methods:

A scoping review was conducted including articles from 2010 to February 2023, using the Cumulative Index to Nursing and Allied Health Literature and Medline (Ovid) databases.

Results:

Among 936 screened articles, 18 were included, identifying 85 NQIs across structure (n = 14), process (n = 45), and outcome (n = 26) in emergency nursing. However, the validation of these NQIs was limited.

Conclusions:

NQIs evaluate emergency nursing quality, primarily in process assessment. Future work should validate the NQIs identified in this review for adult emergency nursing and search for potential new ones.
Trajectories in Intensity of Medical Interventions at the End of Life: Clustering Analysis in a Pediatric, Single-Center Retrospective Cohort, 2013–2021*
Authors: Liesse Kelly M. , Malladi Lakshmee , Dinh Tu C. , Wesp Brendan M. , Kam Brittni N. , Turturice Benjamin A. , Pyke-Grimm Kimberly A. , Char Danton S. , Hollander Seth A.
Published: July 2024

OBJECTIVE:

Pediatric deaths often occur within hospitals and involve balancing aggressive treatment with minimization of suffering. This study first investigated associations between clinical/demographic features and the level of intensity of various therapies these patients undergo at the end of life (EOL). Second, the work used these data to develop a new, broader spectrum for classifying pediatric EOL trajectories.

DESIGN:

Retrospective, single-center study, 2013–2021.

SETTING:

Four hundred sixty-one bed tertiary, stand-alone children’s hospital with 112 ICU beds.

PATIENTS:

Patients of age 0–26 years old at the time of death.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 1111 included patients, 85.7% died in-hospital. Patients who died outside the hospital were older. Among the 952 in-hospital deaths, most occurred in ICUs (89.5%). Clustering analysis was used to distinguish EOL trajectories based on the presence of intensive therapies and/or an active resuscitation attempt at the EOL. We identified five simplified categories: 1) death during active resuscitation, 2) controlled withdrawal of life-sustaining technology, 3) natural progression to death despite maximal therapy, 4) discontinuation of nonsustaining therapies, and 5) withholding/noninitiation of future therapies. Patients with recent surgical procedures, a history of organ transplantation, or admission to the Cardiovascular ICU had more intense therapies at EOL than those who received palliative care consultations, had known genetic conditions, or were of older age.

CONCLUSIONS:

In this retrospective study of pediatric EOL trajectories based on the intensity of technology and/or resuscitation discontinued at the EOL, we have identified associations between these trajectories and patient characteristics. Further research is needed to investigate the impact of these trajectories on families, patients, and healthcare providers.
Brief Report: Aging With HIV: An Epidemiological Profile of Persons With Diagnosed HIV Aged 50 Years and Older in New York State, 2012–2021
Authors: Wang Zhengyan , Patterson Wendy , Rajulu Deepa T.
Published: July 2024

Background:

Advanced antiretroviral treatment has led to a growing population of older persons with HIV. To understand the characteristics of persons aging with HIV, this analysis examines epidemiological profiles of persons with diagnosed HIV through 2021 aged 50 years and older in New York State.

Methods:

Persons diagnosed with HIV and reported to the NYS HIV registry by December 31, 2021, were included in the analysis. Characteristics of persons aged 50 years and older were compared with persons younger than 50 years.

Results:

Persons diagnosed with HIV and aged 50 years and older more often reported heterosexual transmission risk and were more often females than individuals diagnosed with HIV younger than 50 years. Among new diagnoses in 2021, persons aged 50 years and older were more likely to have a stage 3 HIV diagnosis. By the end of 2021, 57% of persons living with diagnosed HIV were aged 50 years and older. There was an upward trend of deaths with cardiovascular disease as an underlying cause of death among persons aged 50 years and older.

Conclusions:

More females diagnosed with HIV and a higher percentage of persons who reported heterosexual transmission risk among persons aged 50 years and older suggest a need for enhanced clinician education and sexual health discussions with this adult population. A greater rate of stage 3 HIV diagnoses in persons aged 50 years and older emphasizes the need for specialized HIV testing and treatment, care for comorbidities, and social supports for this aging population.
Practical Reconstructive Techniques Using the Transoral Approach to Segmental Mandibulectomy With Cosmofix: Technical Report
Authors: Kurosawa Yusuke , Yoshizawa Kunio , Moroi Akinori , Ueki Koichiro
Published: July 2024

This paper introduces a new, less invasive, aesthetic, and functional reconstructive method using a transorally inserted, custom-made Cosmofix fixation plate. Two medication-related cases with stage 3 osteonecrosis of the jaw (MRONJ) are presented. Both procedures required a segmental mandibulectomy as the osteonecrosis had progressed to the mandibular inferior margin and was reconstructed by a transoral approach with a good prognosis. The reconstructed sites were satisfactorily restored with good occlusal conditions and with dentures. No esthetic or functional problems were evident >1 year after surgery. Compared to traditional reconstructive surgery involving facial skin incisions, this technique takes less time, is minimally invasive, is not associated with aesthetic complications, and does not cause facial nerve palsy. Therefore, this procedure may be safely performed in patients with advanced MRONJ who are in poor general condition or older patients.
Scalable Bioreactor-based Suspension Approach to Generate Stem Cell–derived Islets From Healthy Donor-derived iPSCs
Authors: Verhoeff Kevin , Cuesta-Gomez Nerea , Maghera Jasmine , Dadheech Nidheesh , Pawlick Rena , Smith Nancy , O’Gorman Doug , Razavy Haide , Marfil-Garza Braulio , Young Lachlan G. , Thiesen Aducio , MacDonald Patrick E. , Shapiro A. M. James
Published: July 2024

Background.

Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety.

Methods.

Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation. Protocol yield and costs are assessed to determine scalability.

Results.

Differentiation was capable of generating 90.4% PDX1+/NKX6.1+ pancreatic progenitors and 100% C-peptide+/NKX6.1+ iPSC islet cells. However, 82.1%, 49.6%, and 0.9% of the cells expressed SOX9 (duct), SLC18A1 (enterochromaffin cells), and CDX2 (gut cells), respectively. Explanted grafts contained mature monohormonal islet-like cells, however, CK19+ ductal tissues persist. Using this protocol, semi-planar differentiation using 150 mm plates achieved 5.72 × 104 cells/cm2 (total 8.3 × 106 cells), whereas complete suspension differentiation within 100 mL Vertical-Wheel bioreactors significantly increased cell yield to 1.1 × 106 cells/mL (total 105.0 × 106 cells), reducing costs by 88.8%.

Conclusions.

This study offers a scalable suspension-based approach for iPSC islet differentiation within Vertical-Wheel bioreactors with thorough characterization of the ensuing product to enable future protocol comparison and evaluation of approaches for off-target cell elimination. Results suggest that bioreactor-based suspension differentiation protocols may facilitate scalability and clinical implementation of iPSC islet therapies.
Organ Utilization From Donors Following Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review of Graft and Recipient Outcome
Authors: Rajsic Sasa , Treml Benedikt , Rugg Christopher , Innerhofer Nicole , Eckhardt Christine , Breitkopf Robert
Published: July 2024

Background.

The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR.

Methods.

We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024.

Results.

From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%).

Conclusions.

Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool.
Electroconvulsive Therapy and Akathisia
Authors: Mukai Hiroo , Kageyama Sayaka , Miura Gentaro , Takeuchi Hiroyoshi
Published: July 2024

This review aimed to investigate the effects of electroconvulsive therapy (ECT) on akathisia. We systematically searched MEDLINE and Embase and included case reports on akathisia caused by or treated with ECT. We identified and included 9 articles. Seven articles, representing 10 cases, reported that akathisia improved after ECT. Most cases (7 cases) were diagnosed with a mood disorder, and all 10 cases were treated with antipsychotics. Akathisia was regarded as tardive (3 cases) and severe (4 cases). Although treatments for akathisia, such as adjusting antipsychotics and adding medication for akathisia, were tried before ECT, ultimately none were effective. In all 10 cases, akathisia showed significant improvement after ECT, and nonantipsychotic psychotropics or low-dose antipsychotics were administered as post-ECT treatment. Two articles (5 cases) reported that akathisia occurred after ECT. Three of these cases were diagnosed with a mood disorder, and all 5 cases were treated with perphenazine and tricyclic antidepressants. Akathisia occurred multiple times after ECT, but it was transient. Despite attempts to manage the akathisia, including discontinuation of psychotropics, addition of medication for akathisia, and adjustment of stimulation electrode positions, the outcomes of the interventions were inconsistent. Nonetheless, no persistent akathisia was observed after the end of the ECT course. Although the effects of ECT on akathisia remain unclear because of the paucity of high-quality studies, ECT could be considered particularly for treatment-resistant, tardive, and/or severe akathisia comorbid with mood disorders. Conversely, clinicians should keep in mind that transient akathisia can develop following ECT.
Alterations in secondary structure and binding affinity from mutations in the interleukin-1 receptor antagonist
Authors: Pillai Joshua
Published: July 2024

Abstract

Deficiency of Interleukin-1 receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory disorder that occurs during the neonatal period, manifesting a spectrum of symptoms including but not limited to osteomyelitis and pustulosis. This disease results from loss-of-function mutations in theIL1RNgene, encoding the IL-1 receptor antagonist (IL-1Ra). The dysfunction of IL-1Ra may arise from two mechanisms: (i) disruptions in the folding of its secondary structure, and (ii) impaired binding to its receptor, IL-1 receptor type 1. However, limited information exists detailing broad alterations in structure and binding affinity of known IL-1Ra variants. Herein, we used a validated protein prediction model to visualize 15 unique variants, and subsequently performed a structural analysis to elucidate the mutational impacts on secondary structure and binding affinity. Our analyses revealed reduced affinity at the 5 critical binding sites (W16, Q20, Y34, Q36, and Y147) along with missing secondary structures (β-sheets, α-helices) among the variants.

Highlights

Structural analyses revealed reduced binding affinity resulting from impacts in critical binding sites of IL-1Ra.

This is the first study broadly evaluating the mutational impacts on structure and binding affinity of IL-1Ra.

A validatedin silicoprotocol was used to predict structural alterations of the IL-1Ra variants.
Proteostasis modulates gene dosage evolution in antibiotic-resistant bacteria
Authors: Jena Chinmaya , Chinnaraj Saillesh , Deolankar Soham , Matange Nishad
Published: July 2024

Evolution of gene expression frequently drives antibiotic resistance in bacteria. We had previously (Patel and Matange,eLife, 2021) shown that, inEscherichia coli, mutations at themgrBlocus were beneficial under trimethoprim exposure and led to overexpression of dihydrofolate reductase (DHFR), encoded by thefolAgene. Here, we show that DHFR levels are further enhanced by spontaneous duplication of a genomic segment encompassingfolAand spanning hundreds of kilobases. This duplication was rare in wild typeE. coli. However, its frequency was elevated in alon-knockout strain, altering the mutational landscape early during trimethoprim adaptation. We then exploit this system to investigate the relationship between trimethoprim pressure andfolAcopy number. During long-term evolution,folAduplications were frequently reversed. Reversal was slower under antibiotic pressure, first requiring the acquisition of point mutations in DHFR or its promoter. Unexpectedly, despite resistance-conferring point mutations, some populations under high trimethoprim pressure maintainedfolAduplication to compensate for low abundance DHFR mutants. We find that evolution of gene dosage depends on expression demand, which is generated by antibiotic and exacerbated by proteolysis of drug-resistant mutants of DHFR. We propose a novel role for proteostasis as a determinant of copy number evolution in antibiotic-resistant bacteria.
COLLAGE: COnsensus aLignment of muLtiplexing imAGEs
Authors: Antoranz Asier , Arnould Alexandre , Andhari Madhavi Dipak , Nazari Pouya , Shankar Gautam , Moor Bart De , De Smet Frederik , Bosisio Francesca Maria , Pey Jon
Published: July 2024

Multiplexed immunohistochemistry (mIHC) enables the high-dimensional single-cell interrogation of pathological tissue samples. mIHC is commonly based on the collection of high-resolution images from repeated staining cycles of the same tissue sample. Images of individual cycles typically consist of smaller tiles that need to be stitched into larger composite images, while images from serial rounds require alignment in a shared set of coordinates to enable pixel-perfect data integration. Current algorithms for stitching and registration require solving a single large puzzle consisting of billions of pixels making them computationally expensive but moreover forcing them to introduce errors to close the puzzle, which significantly impact the downstream results and the single-cell profiles. Here, we present the development and evaluation of COLLAGE (COnsensus aLignment of muLtiplexing imAGEs), an innovative stitching and registration method that leverages on the complementarity of these two steps in a ‘divide and conquer’ approach: in contrast to other algorithms, COLLAGE breaks the process down into thousands of small puzzles, enabling extensive parallelisation and not forcing errors in its solution. Because COLLAGE also includes AlgnQC, a novel deep-learning-based evaluation metric of registration quality, the quality of the resulting image stacks is consistently maximised, while images with errors are flagged in an automated way. COLLAGE is available viawww.disscovery.org.

Abstract Figure
Fine-Scale Models of Bee Species Diversity and Habitat in New York State
Authors: Buckner Mark A. , White Erin L. , Howard Timothy G. , Schlesinger Matthew D. , Danforth Bryan N.
Published: July 2024

Anthropogenic drivers of global change threaten bee diversity and the ecosystem services bees provide. Despite their importance, the conservation of bee pollinators is complicated by limited and often heavily biased occurrence data. A recent state-wide survey of insect pollinators across New York, United States generated a large spatial dataset of bee species occurrence records from community scientists, historical collections, and survey efforts. Using a combination of the state survey records with occurrence data from across the contiguous United States, we applied an ensemble modeling approach using balanced random forest and small bivariate generalized linear models to predict the distributions of most of the state’s bee species. We predicted the spatial distribution of bee species richness using a stacked species distribution model with climate, land cover, and soil covariates. To inform bee diversity conservation, we predicted spatial variation for each species and groups of species sharing similar life history traits. We also estimated statewide distribution of range-size rarity, ecological uniqueness, and climate exposure. We found that the richness of modeled species is high across the state, with the greatest richness in regions with low soil clay content and intermediate forest cover. The fine spatial scale and extent of our gridded data layers match the scale of conservation action in the state, providing an opportunity to incorporate wild bee diversity into broader statewide conservation planning. Conserving New York State’s bee pollinators is not straightforward, and decisions should be based on broader conservation priorities that incorporate bee biodiversity indicators into decision-making. Here, we encourage the inclusion of these vital pollinators in conservation decisions by leveraging the best available data and methods robust to small sample sizes to provide spatially explicit data products representing the distribution of bee diversity across the state of New York.
Clade-specific long-read sequencing increases the accuracy and specificity of the gyrB phylogenetic marker gene
Authors: Nichols Robert G , Davenport Emily R
Published: July 2024

Phylogenetic marker gene sequencing is often used as a quick and cost-effective way of evaluating microbial composition within a community. While 16S rRNA gene sequencing (16S) is commonly used for bacteria and archaea, other marker genes are preferable in certain situations, such as when 16S sequences cannot distinguish between taxa within a group. Another situation is when researchers want to study cospeciation of host taxa that diverged much more recently than the slowly evolving 16S rRNA gene. For example, the bacterial gyrase subunit B (gyrB) gene has been used to investigate cospeciation between the microbiome and various hominid species. However, to date only primers that generate short-read Illumina MiSeq-length amplicons exist to investigate gyrB of the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families. Here, we update this methodology by creating gyrB primers for the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families for long-read PacBio sequencing and characterize them against established short-read gyrB primer sets. We demonstrate both bioinformatically and analytically that these longer amplicons offer more sequence space for greater taxonomic resolution, lower off-target amplification rates, and lower error rates with PacBio CCS sequencing versus established short-read sequencing. The availability of these long-read gyrB primers will prove to be integral to the continued analysis of cospeciation between bacterial members of the gut microbiome and recently diverging host species.
Classification of dinosaur footprints using machine learning
Authors: Jones Michael , Lallensack Jens N. , Jarman Ian , Falkingham Peter , Siekmann Ivo
Published: July 2024

Fossilised dinosaur footprints enable us to study the behaviour of individual dinosaurs as well as interactions between dinosaurs of the same or different species. There are two principal groups of three-toed dinosaurs, ornithopods and theropods. Determining if a footprint is from an ornithopod or a theropod is a challenging problem. Based on a data set of over 300 dinosaur footprints we train several machine learning models for classifying footprints as either ornithopods or theropods. The data are provided in the form of 20 landmarks for representing each footprint which are derived from images. Variable selection using logistic forward regression demonstrates that the selected landmarks are at locations that are intuitively expected to be especially informative locations, such as the top or the bottom of a footprint. Most models show good accuracy but the recall of ornithopods, of which fewer samples were contained in the data set, was generally lower than the recall of theropods. The Multi-Layer Perceptron (MLP) stands out as the model which did best at dealing with the class imbalance. Finally, we investigate which footprints were misclassified by the majority of models. We find that some misclassified samples exhibit features that are characteristic of the other class or have a compromised shape, for example, a middle toe that points to the left or the right rather than straight ahead.
SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies
Authors: Wong Theresa , Qiu Zhen , Notman Beverly , Tavares Adriana , Smith Colin , Grant Seth G.N.
Published: July 2024

Synapse pathology is a feature of most brain diseases and there is a pressing need to monitor the onset and progression of this pathology using brain imaging in living patients. A major step toward this goal has been the development of small-molecule radiotracers that bind to synaptic vesicle glycoprotein 2A (SV2A) for use in positron emission tomography (PET). Changes in SV2A radiotracer binding in PET are widely interpreted to report differences in the density of all synapses throughout brain regions. Here, we analyse the expression of SV2A at single-synapse resolution across regions of adult mouse and human brain. We find that SV2A is expressed in fewer than 50% of excitatory and inhibitory synapses and that the density of SV2A-positive synapses differs between brain regions. Furthermore, individual synapses differ in their amounts of SV2A. These findings have important implications for the interpretation of PET imaging studies in a clinical setting and point to the need for a detailed understanding of SV2A synaptome architecture in both healthy brain and disease cases where PET imaging is being applied.
Automatic dendritic spine segmentation in widefield fluorescence images reveal synaptic nanostructures distribution with super-resolution imaging
Authors: Zhang Jiahao , Vaidya Rohit , Chung Hee Jung , Selvin Paul R.
Published: July 2024

Dendritic spines are the main sites for synaptic communication in neurons, and alterations in their density, size, and shapes occur in many brain disorders. Current spine segmentation methods perform poorly in conditions with low signal-to-noise and resolution, particularly in the widefield images of thick (⍰ 10 μm) brain slices. Here, we combined two open-source machine-learning models to achieve automatic 3D spine segmentation in widefield diffraction-limited fluorescence images of neurons in thick brain slices. We validated the performance by comparison with manually segmented super-resolution images of spines reconstructed from direct stochastic optical reconstruction microscopy (dSTORM). Lastly, we show an application of our approach by combining spine segmentation from diffraction-limited images with dSTORM of synaptic protein PSD-95 in the same field-of-view. This allowed us to automatically analyze and quantify the nanoscale distribution of PSD-95 inside the spine. Importantly, we found the numbers, but not the average sizes, of synaptic nanomodules and nanodomains increase with spine size.
Simultaneous acclimation to nitrogen and iron scarcity in open ocean cyanobacteria revealed by sparse tensor decomposition of metatranscriptomes
Authors: Blaskowski Stephen , Roald Marie , Berube Paul M. , Braakman Rogier , Virginia Armbrust E.
Published: July 2024

Microbes respond to changes in their environment by adapting their physiology through coordinated adjustments to the expression levels of functionally related genes. To detect these shifts in situ, we developed a sparse tensor decomposition method that derives gene co-expression patterns from inherently complex whole community RNA-sequencing data. Application of the method to metatranscriptomes of the abundant marine cyanobacteriaProchlorococcusandSynechococcusidentified responses to scarcity of two essential nutrients, nitrogen and iron, including increased transporter expression, restructured photosynthesis and carbon metabolism, and mitigation of oxidative stress. Further, expression profiles of the identified gene clusters suggest that both cyanobacteria populations experience simultaneous nitrogen and iron stresses in a transition zone between North Pacific oceanic gyres. The results demonstrate the power of our approach to infer organism responses to environmental pressures, hypothesize functions of uncharacterized genes, and extrapolate ramifications for biogeochemical cycles in a changing ecosystem.

Teaser

New analytical approach reveals shifts in gene expression that may help cyanobacteria cope with environmental stressors.
Caregivers’ burden of care during emergency department care transitions among older adults: a mixed methods cohort study
Authors: Germain Nathalie , Jémus-Gonzalez Estephanie , Couture Vanessa , Côté Émilie , Morin Michèle , Toulouse-Fournier Annie , Bert Laetitia , Giguère Raphaëlle , Sinha Samir , Sourial Nadia , Chartier Lucas B. , Witteman Holly O. , Légaré France , Samb Rawane , Turcotte Stéphane , Chandavong Sam , Abrougui Lyna , Robitaille Joanie , Archambault Patrick M.
Published: July 2024

Objective

Improving care transitions for older adults can reduce emergency department (ED) revisits, and the strain placed upon caregivers. We analyzed whether caregivers felt a change in burden following a care transition, and what may be improved to reduce it.

Methods

This mixed-methods observational study nested within LEARNING WISDOM included caregivers of older patients who experienced an ED care transition. Burden was collected with the brief Zarit Burden Interview (ZBI-12), and caregivers commented on the care transition. A qualitative coding scheme of patient care transitions was created to reflect themes important to caregivers. Comments were randomly analyzed until saturation and themes were extracted from the data. We followed both the SRQR and STROBE checklists.

Results

Comments from 581 caregivers (mean age (SD) 64.5 (12.3), 68% women) caring for patients (mean age (SD) 77.2 (7.54), 48% women) were analyzed. Caregivers overwhelmingly reported dissatisfaction and unmet service expectations, particularly with home care and domestic help. Communication and follow-up from the ED emerged as an area for improvement. Caregivers who reported an increased level of burden following a care recipient’s care transition had significantly higher ZBI scores than caregivers who self-reported stable burden levels, but not improved burden levels.

Conclusion

Caregivers with increasing, stable, and improved levels of subjective burden all reported areas for improvement in the care transition process. Themes centering on the capacity to live at home most frequently and may represent serious challenges to caregivers. Addressing these challenges could improve both caregiver burden and care transitions.

Key points

We analyzed caregivers’ thoughts about emergency department care transitions using both qualitative and quantitative tools.

Caregivers reported dissatisfaction and unmet service expectations with home care, domestic help, and coordinating follow-ups.

Variance in self-reported subjective caregiver burden corresponds to Zarit Burden Interview (ZBI) scores.
Molecular profiling of primary renal diffuse large B-cell lymphoma unravels a proclivity for immune-privileged organ-tropism
Authors: Künstner Axel , von Kopylow Vera , Lohneis Philipp , Kümmel Matthias , Witte Hanno M. , Bastian Lorenz , Bernard Veronica , Stölting Stephanie , Kusch Kathrin , Krokowski Manuela , von Bubnoff Nikolas , Steinestel Konrad , Arndt Annette , Merz Hartmut , Busch Hauke , Feller Alfred C. , Gebauer Niklas
Published: July 2024

Primary renal manifestations of diffuse large B-cell lymphoma (PR-DLBCL) represent an exceptionally rare variant of the most common type of non-Hodgkin lymphoma (NHL). Insights into PR-DLBCL pathogenesis have been limited to small case series and methodologically limited approaches. The mechanisms driving lymphomagenesis within an organ lacking an intrinsic lymphatic niche and its proclivity for dissemination to immune-privileged sites, including testes and central nervous system, remain poorly understood. To decode the genetic and transcriptional framework of PR-DLBCL, we utilized whole exome sequencing, array-based somatic copy number alterations analysis, and RNA sequencing. Hereby we characterize the most extensive cohort of PR-DLBCL published, comprising 34 samples from 30 patients. Despite significant mutational heterogeneity with a broad distribution among molecular clusters, we observed a strong unifying enrichment in deleterious MHC class I and II aberrations and loss ofCDKN2Aat a frequency similar to primary large B-cell lymphoma of immune privileged sites (IP-LBCL) alongside significant transcriptional deregulation of interferon signaling and MYC targets in MHC class I-deficient cases.

Our integrative assessment of PR-DLBCL biology expands the molecular understanding of this rare variant including similarities with IP-LBCL as an intriguing explanation for its clinical behavior and tropism. Our observations may inform future risk-adapted therapeutic approaches.