bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen Coating Improves In Vitro Tenocyte Interaction With Suture Tape for Ligament Augmentation
Authors: Brouwer Haley , Matuska Andrea , Kadakia Anish R.
Published: May 2022

InternalBrace ligament augmentation is a recent advancement in the treatment of ligament instability, with demonstrated safety and clinical effectiveness for lateral ligament reconstruction. There are multiple commercially available suture tapes made of a variety of materials whose biological properties have not been well evaluated. These properties may affect the quality of reparative tissue given the intimate apposition of the ligament to the augment. This study explores tenocyte viability, adhesion, and proliferation to 4 suture tapes. Four suture tapes were studied: 1 with a collagen coating, 1 with a silicone coating, and 2 uncoated. The sutures were seeded with tenocytes and viability, adhesion and proliferation were evaluated over a 14-day period (n=12). Initial viability was highest on the collagen-coated suture tape (96.7±3.6%) and lowest on the silicone coated (54.7±23.0%). The highest live cell density after 14 days was observed on the collagen-coated suture tape (64.0±24.9 cells/mm2), while the lowest was observed on silicone-coated (5.0±5.1 cells/mm2). The collagen-coated and both uncoated suture tapes similarly supported 3.6- to 4.2-fold cell proliferation over 14 days, significantly more than observed on the silicone-coated tape (2.5±0.8-fold). The composition and coatings of suture tape may have biological consequences for ligament repair.

Level of Evidence: Diagnostic in vitro study. See Instructions for Authors for a complete description of levels of evidence.
Religious Sisters in Healthcare
Authors: Beach Patricia Ringos , White Beth E. Heinzeroth
Published: May 2022

To better understand the impact Roman Catholic religious sisters have had on healthcare in the United States, the authors initiated the Religious Sisters in Health Care: The Conspicuous Love of Jesus project, recording sisters' stories of service, obedience, and leadership that point to their foundational work of making the healing presence of Jesus central to Catholic healthcare identity. The sisters' counsel for nurses and all staff in Catholic healthcare was to focus on Jesus' love in all work and to keep each person's healing ministry alive through regular rejuvenating opportunities.
Evaluation of efficiency and safety of combined loratadine and budesonide in patients with anaphylactic rhinitis
Authors: Zhang Jing , Kan Dan
Published: May 2022

Background:

Among the most prevalent allergic conditions that affect children is anaphylactic rhinitis (AR). It is capable of leading to physical as well as mental health issues. Concomitant use of loratadine and budesonide may improve symptoms of AR more than treatment with either drug alone. To assess the efficacy and safety of combined loratadine and budesonide for patients experiencing AR is the aim of this study.

Methods:

We will apply 2 independent authors in six databases, including EMBASE, Pub Med, Web of Science, China National Knowledge Infrastructure, WanFang Database, Chinese Scientific Journal Database (VIP database). Studies evaluating the efficacy and safety of combined loratadine and budesonide in patients with AR will include studies published between inception and Dec 2021. Accordingly, the data will have to be in English and Chinese. For the selection of data extraction, the studies and risk of bias assessment will be completed by 2 independent authors. Accordingly, data synthesis will be conducted through RevMan 5.3 software. The study will establish heterogeneity using the I
2 test. Without correct data or information, there is a need for Publication bias, which is assessed by performing the Begg and Egger test and generating a funnel plot.

Results:

The study provides a trustable clinical foundation for loratadine and budesonide for AR treatment.

OSF registration number: DOI 10.17605/OSF.IO/M2RFG

Ethics and dissemination: Because the present study is founded on existing studies, it does not require ethics approval.
Making Time and Being Present
Authors: Slabaugh Kristen , Elliott Brenda
Published: May 2022

The COVID-19 pandemic has placed significant strain on home healthcare clinicians, shifting the focus of care to essential physical care needs. Spiritual care needs have always been present, but the pandemic has heightened recognition of the importance of spiritual care in home care. The goals of spiritual care include promoting physical healing, improving quality of life, and enhancing patient and family wellbeing. The use of a standardized spiritual assessment tool can increase provider awareness and patient expression of spiritual care needs. Spiritual care activities consist of obtaining a spiritual history, compassionate presence, mindful listening, interprofessional collaboration, and the provision of space for spiritual practices. This article provides a conceptual overview and strategies for application of spiritual care competencies.
Assessment and Management Tools for Advancing Disease
Authors: Stober Mary J. , Hager Kathy , Rinker Gwendolyn
Published: May 2022

As the population of the United States has aged, the number of home care patients with multiple chronic diseases has also increased. A review of the literature suggested that layering palliative care principles on traditional home healthcare could improve outcomes for patients with advancing disease. The purpose of this quality improvement project was to educate home care staff on the use of assessment and management tools to identify symptoms and provide symptom control, prevent unnecessary hospitalizations, and reduce healthcare costs in patients with advancing disease. This project took place at eight offices of a national home care agency in Kentucky and Indiana. Nurses, social workers, and therapists attended mandatory education sessions over 5 months on integrating palliative care principles into care planning for home care patients and using the Edmonton Symptom Assessment Scale (ESAS) and state-specific end-of-life planning tools. Symptoms were tracked and managed. A paired-samples t-test was used to analyze ESAS scores. Hospitalization and rehospitalization rates and costs were compared and benchmarked. Some symptoms worsened from beginning to end of the episode of care, suggesting a need for additional staff training about symptom management. The wide range of symptoms and symptom worsening suggest the need for individualized care, possibly extended home healthcare, and the inclusion of a more formal palliative care course for staff on symptom management.
Osteonectin/SPARC Expression in Head and Neck Squamous Cell Carcinoma: A Tissue Microarray Study
Authors: Lewis James S. , Thorstad Wade L. , Hussaini Mohammad
Published: May 2022

Background:

Some studies have correlated secreted protein acidic and rich in cysteine (SPARC) expression with more aggressive behavior in head and neck squamous cell carcinoma (SCC). We investigated the impact of SPARC expression on patient outcomes in a large cohort of SCCs.

Materials and Methods:

Patients with SCC were identified by searching institutional databases. A tissue microarray of paraffin-embedded tumor specimens was constructed, and SPARC immunohistochemistry was performed. Cellular and stromal SPARC expression were quantitated and correlated with clinicopathologic features.

Results:

Of 191 cases, 171 were adequate for SPARC evaluation. A total of 112 (65%) cases showed SPARC tumor cell staining, and 167 (98%) cases showed stromal staining. Increased SPARC stromal expression was correlated with poorer overall survival (OS) [mean (SD) survival, 64.3 (3.25) vs. 42.8 (3.25) mo; P=0.0015] and poorer disease-specific survival (DSS) [mean (SD) survival, 51.1 (1.58) vs. 38.3 (1.832) mo; P=0.0381]. Human papillomavirus–positive status correlated with both stromal and tumor SPARC expression (P=0.0047 and 0.0408, respectively). SPARC staining did not correlate with OS or DSS in multivariate analyses. Among nonchemotherapy patients, SPARC stromal expression was associated with poorer OS and DSS (P=0.0074 and 0.033, respectively). In multivariate analyses, increased stromal SPARC expression was associated with a longer disease-free interval [P=0.0170 (hazard ratio, 1.384)].

Conclusions:

SPARC expression is frequently present in tumoral stroma of head and neck SCCs. In contravention to prior studies, we found that SPARC expression did not correlate with survival overall. This suggests that previously reported associations may not, in fact, exist highlighting the need to meticulously adjust for confounding variables in novel biomarker studies. However, subgroup analysis showed that stromal SPARC expression is associated with better disease-free survival among patients who are not treated with chemotherapy.
PRAME Expression in Endometrioid and Serous Endometrial Carcinoma: A Potential Immunotherapeutic Target and Possible Diagnostic Pitfall
Authors: Coppock Joseph D. , Gradecki Sarah E. , Mills Anne M.
Published: May 2022

Preferentially expressed antigen in melanoma (PRAME) is a cancer testes antigen initially employed as a diagnostic marker for melanoma. Although negative in most normal tissues, its expression has been reported in benign endometrial glands. Additionally, PRAME expression has been identified in a growing list of solid and hematologic malignancies and is of interest as a predictive biomarker, as cancer vaccination strategies and adoptive T-cell transfer targeting this molecule are under clinical investigation; additionally, PRAME may identify candidates for retinoid therapy. However, expression of PRAME has not been well-studied in endometrial cancers. We herein evaluate PRAME expression in endometrial carcinomas to better characterize its limitations as a diagnostic melanoma marker as well as its potential as a predictive biomarker in endometrial carcinomas. PRAME expression was evaluated in 256 endometrioid (n=235) and serous (n=21) endometrial carcinomas via tissue microarray. In all, 89% (227/256) demonstrated some degree of nuclear PRAME expression, including 88% (207/235) of endometrioid carcinomas and 95% (20/21) of serous carcinomas. Diffuse (>50%) expression was observed in 70% (179/256) of all cases, including 69% (163/235) of endometrioid carcinomas and 76% (16/21) of serous carcinomas. There was no association between degree of expression and grade, mismatch repair protein status, or stage. The widespread expression of PRAME in endometrial carcinomas suggests this marker should not be interpreted as specific for melanoma in this context. However PRAME may have utility as a predictive biomarker in endometrial cancer, and expansion of testing of PRAME-based therapies to endometrioid and serous endometrial carcinomas may lead to new therapeutic options for these endometrial cancer subtypes.
Anastomosing Hemangioma of the Ovary With Leydig Cell Hyperplasia: A Clinicopathologic Study of 12 Cases
Authors: McHenry Austin , Buza Natalia
Published: May 2022

Anastomosing hemangioma is a recently described vascular neoplasm, initially identified in the male genitourinary tract. Since its first description, it has been reported at multiple anatomic sites, including rare cases in the female genital tract, most in the ovary. Herein we report the largest series to date of 12 ovarian anastomosing hemangiomas identified at our institution over a 15-yr period. The patients’ age at the time of resection ranged from 50 to 76 yr (median: 62 yr), 3 patients presented with symptomatic pelvic masses, 3 tumors were identified by imaging studies, and the remaining 6 were incidentally discovered in ovaries removed for other indications. All tumors were unilateral, occurred at the ovarian hilum, and contained a vaguely lobulated architecture with sinusoidal-like vessels lined by hobnail endothelial cells with minimal to no cytologic atypia. A rim of luteinized/Leydig cells with abundant, eosinophilic cytoplasm and round, centrally placed nuclei surrounding the hemangioma was present in 9/12 tumors. Reinke crystals were observed in 3 of these 9 tumors. The volume of luteinized cells relative to the vascular proliferation ranged from 2% to 30%. All tumors with luteinized/Leydig cells also displayed numerous small eosinophilic, globular intracytoplasmic inclusions within the endothelial cells. The 3 tumors without luteinized/Leydig cells were exclusively intravascular lesions. Despite the frequent presence of luteinization/Leydig cells none of the patients experienced hormonal manifestations. Awareness of this rare benign ovarian entity is important, as its association with luteinized cells/Leydig cell hyperplasia (often exuberant) may be misinterpreted as a steroid cell tumor, Leydig-cell tumor, or as a mixed stromal-vascular tumor.
THE ROLE OF KINESIOTHERAPY IN THE PREVENTION OF HETEROTOPIC OSSIFICATION: A SYSTEMATIC REVIEW
Authors: Vasileiadis George Ioannis , Balta Apostolia A. , Zerva Aikaterini , Kontogiannopoulos Vasileios , Varvarousis Dimitrios N , Dimakopoulos Georgios , Ploumis Avraam
Published: May 2022

Objective

The role of kinesiotherapy in heterotopic ossification (HO) remains unclear. The goal of this study is to revisit the literature on the preventive role of kinesiotherapy against HO formation and maturation.

Design

A systematic review was performed in MEDLINE, OVID, SCOPUS and Cochrane databases.

Results

A high-quality clinical trial is missing from the literature. Out of 9617 studies primarily identified, 9 studies offered the proper data and were included. They infer that satisfactory results on neurogenic HO prevention were achieved with passive exercises, including continuous passive motion (CPM), that were initiated early and at a painless range of motion (ROM). On the contrary, for elbow post-traumatic HO and major joints burn-associated HO, active ROM is indicated as early as possible.

Conclusion

Due to the very low quality of the studies included in this review, firm conclusions cannot be drawn about the effectiveness of kinesiotherapy. Nevertheless, it is recommended that controlled passive ROM (PROM) exercises (especially CPM) be applied early and pain-free especially in the neurogenic HO patients while active ROM in painless limits is beneficial in the HO prevention of traumatic elbows or burn joints.
Functional Rehabilitation: An Integrated Treatment Model for Patients With Complex Physical and Psychiatric Conditions
Authors: Orme William H. , Fowler J. Christopher , Bradshaw Major R. , Carlson Marianne , Hadden Julia , Daniel Jelani , Flack James N. , Freeland Diana , Head John , Marder Kate , Weinstein Benjamin L. , Madan Alok
Published: May 2022

The health care delivery system in the United States, structured to provide single-disease care, presents unique challenges for patients with complex physical and psychiatric comorbidities. Patients in these populations are often referred to multiple specialty clinics, encounter little continuity of care or collaboration among their providers, incur high health care costs, and experience poor treatment outcomes. Given these barriers, questions remain about the extent to which siloed and fragmented care, as opposed to the complex nature of the illnesses themselves, contribute to poor outcomes. If given the opportunity to receive well-integrated, consistent, and personalized care, can patients with historically difficult-to-treat comorbid medical and mental illnesses make progress? This article describes an innovative model of care called functional rehabilitation that is designed to address existing barriers in treatment. The functional rehabilitation program seeks to disrupt the escalating effects of interacting comorbidities by offering highly collaborative treatment from a small team of clinicians, personalized interventions using a shared decision-making framework, multipronged treatment options, colocation in a large hospital system, and significant 1:1 time with patients. The article includes a case example with longitudinal outcome data that illustrates how progress can be made with appropriate programmatic supports. Future research should examine the cost-effectiveness of this model of care.
Afterword: Beyond Diagnosis to Mourning and the Meaning of Symptoms
Authors: Plakun Eric M.
Published: May 2022

Reports of destructive behavior by military personnel after demobilization have become more frequent; however, the pathways that might lead these individuals to commit such acts are not clear enough. This column presents the case of a retired soldier who reported the onset of pyromania after military service, and the relationship between dissociation and reenactment of the trauma is discussed. The main conclusions are that psychotherapy of traumatized patients should focus on helping them create a verbal representation of the trauma and that integrating ceremonies and rituals into treatment is a possible and significant option.
Association Between Mild Neurocognitive Disorder Due to Alzheimer’s Disease and Possible Attention-deficit/Hyperactivity Disorder: A Case Report
Authors: Carrillo Pablo , Rey Romain , Padovan Catherine , Herrmann Mathieu , Dorey Jean-Michel
Published: May 2022

Recent literature concerning attention-deficit/hyperactivity disorder (ADHD) underlines the persistence of this neurodevelopmental illness in older patients. Comorbidity with a neurodegenerative disease is thus possible. However, few studies have investigated this topic. To our knowledge, this is the first case report of such a possible association, which raises important questions about clinical presentation, symptoms, diagnosis, and treatment. A 72-year-old man, without any psychiatric history, presented with depression, subjective memory loss, and attention deficit and anxious symptoms, and was diagnosed with mild neurocognitive disorder due to Alzheimer’s disease. However, the patient’s attentional symptoms appeared to have been present since childhood. A formalized diagnostic interview assessing for ADHD did not allow for a clear diagnosis, possibly due to recall bias. The patient’s anxiety symptoms also did not respond well to cognitive behavioral therapy coupled with different antidepressants. We hypothesized the presence of ADHD, with the symptoms balanced until now by the patient’s high cognitive capacities, and we postulated that the onset of a neurogenerative process may have disrupted this balance. In this case report, we discuss symptom dimensionality, the interplay between neurodegenerative and neurodevelopmental diseases, and various treatment options. Attentional deficits and anxiety symptoms are frequent in mild neurocognitive disorders due to neurodegenerative illnesses. It is important to explore the time of onset of such symptoms since neurodegenerative processes can worsen neurodevelopmental conditions. Moreover, identification of a pre-existing neurodevelopmental condition can lead to alternative care and treatment options. In addition, the unexplained worsening of ADHD symptoms should prompt clinicians to assess for a neurodegenerative process.
A Case Report of Scrupulosity Presenting as Catatonia in a Patient With Both OCD and OCPD
Authors: Nikjoo Arya , Wright Chela , Kheriaty Aaron
Published: May 2022

We present the case of a woman in her 40s with a history of hypothyroidism, a differential diagnosis of major depressive disorder with psychotic features versus bipolar I disorder, catatonia, and anorexia nervosa. The patient was admitted to the hospital for poor oral intake, mutism, and social withdrawal. Administration of lorazepam successfully treated these presenting symptoms. However, on subsequent days, she was found to be reading the Bible almost constantly during waking hours, at the expense of engaging in treatment or interacting with others. The patient’s history and presentation supported the idea that her hyper-religiosity stemmed not from bipolar disorder or psychosis, as previously thought, but rather from a subtype of obsessive-compulsive disorder referred to as scrupulosity. This report summarizes the characteristics of scrupulosity and discusses this potentially deceptive mimic of more commonly seen conditions.
An Annotated Bibliography on Human Trafficking for the Mental Health Clinician
Authors: Robitz Rachel , Asera Alex , Nguyen Phuong , Gordon Mollie , Coverdale John , Stoklosa Hanni , Chisolm-Straker Makini
Published: May 2022

Objective:

This annotated bibliography provides an overview of sentinel and influential literature about human trafficking for general mental health practitioners.

Methods:

A modified participatory ranking methodology was used to create the list of articles.

Results:

We identified 25 articles relevant to trafficking and mental health which covered the topics of epidemiology, treatment, identification, policy, and research methodology.

Conclusions:

The articles presented cover a broad range of trafficking types and topics. However, there is a dearth of literature about labor trafficking and the trafficking of men, boys, transgender, and nonbinary people.
Incidence and Predisposing Factors of Postoperative Infection after Rhinoplasty: A Single Surgeon’s 16-Year Experience with 2630 Cases in an East Asian Population
Authors: Tran Khanh Ngoc , Jang Yong Ju
Published: May 2022

Background:

This study evaluated the incidence and clinical characteristics of postoperative infection following rhinoplasty.

Methods:

This article is a retrospective review of 2630 East Asian rhinoplasty cases performed by a single surgeon (Y.J.J.), from July of 2003 to June of 2018. There were 1595 male patients (69.9 percent) and 687 female patients (30.1 percent), and the median age was 31 years. The incidence of infection was compared between primary and revision cases and analyzed according to the materials used. The authors evaluated the organisms cultured and the timeframe of infection development and intervention.

Results:

There were 2134 primary and 496 revision cases. Materials included autologous costal cartilage (413 cases), conchal cartilage (572 cases), homologous fascia lata (829 cases), homologous costal cartilage (102 cases), Gore-Tex (373 cases), and silicone (32 cases). The authors identified 22 cases (0.84 percent) of postoperative infection, 18 of which were revision. Revision surgery had a 19-fold greater infection rate than primary surgery (3.63 percent versus 0.19 percent). Women were 3.6 times as likely to develop an infection (p = 0.002). The infection rate using autologous costal cartilage was 3.39 percent, and that for simultaneous correction of a septal perforation was 8.57 percent. In 11 cases (50 percent), infection developed within 1 month after surgery (12 ± 7 days). Methicillin-resistant Staphylococcus aureus was cultured in eight cases. Infection manifested at the nasal tip in 45 percent and the caudal septum/columella in 32 percent of cases. Twenty cases (90.9 percent) underwent surgical débridement.

Conclusion:

Revision rhinoplasty in women, requiring the use of costal cartilage or simultaneous correction of septal perforation, showed a higher risk of postrhinoplasty infection, which usually manifested at the nasal tip and caudal septum/columella and needed to be managed by surgical débridement.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Associative Prediction of Carotid Artery Plaques Based on Ultrasound Strain Imaging and Cardiovascular Risk Factors in People Living With HIV and Age-Matched Control Subjects of the CHACS Cohort
Authors: Roy Cardinal Marie-Hélène , Durand Madeleine , Chartrand-Lefebvre Carl , Soulez Gilles , Tremblay Cécile , Cloutier Guy ,   for the Canadian HIV and Aging Cohort Study
Published: May 2022

Background:

There is a need for a specific atherosclerotic risk assessment for people living with HIV (PLWH).

Setting:

A machine learning classification model was applied to PLWH and control subjects with low-to-intermediate cardiovascular risks to identify associative predictors of diagnosed carotid artery plaques. Associations with plaques were made using strain elastography in normal sections of the common carotid artery and traditional cardiovascular risk factors.

Methods:

One hundred two PLWH and 84 control subjects were recruited from the prospective Canadian HIV and Aging Cohort Study (57 ± 8 years; 159 men). Plaque presence was based on clinical ultrasound scans of left and right common carotid arteries and internal carotid arteries. A classification task for identifying subjects with plaque was defined using random forest (RF) and logistic regression models. Areas under the receiver operating characteristic curves (AUC-ROCs) were applied to select 5 among 50 combinations of 4 or less features yielding the highest AUC-ROCs.

Results:

To retrospectively classify individuals with and without plaques, the 5 most discriminant combinations of features had AUC-ROCs between 0.76 and 0.79. AUC-ROCs from RF were statistically significantly higher than those obtained with logistic regressions (P = 0.0001). The most discriminant features of RF classifications in PLWH were age, smoking status, maximum axial strain and pulse pressure (equal weights), and sex and antiretroviral therapy exposure (equal weights). When considering the whole population, the HIV status was identified as a cofactor associated with carotid artery plaques.

Conclusions:

Strain elastography adds to traditional cardiovascular risk factors for identifying individuals with carotid artery plaques.
Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder
Authors: Fields Madeline C. , Marsh Christina , Eka Onome , Johnson Emily A. , Marcuse Lara V. , Kwon Churl-Su , Young James J. , LaVega-Talbott Maite , Kurukumbi Mohankumar , Von Allmen Gretchen , Zempel John , Friedman Daniel , Jette Nathalie , Singh Anuradha , Yoo Ji Yeoun , Blank Leah , Panov Fedor , Ghatan Saadi
Published: May 2022

Purpose:

Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

Methods:

This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis.

Results:

Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported.

Conclusions:

Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD–DRE.
Validation of a Model for Targeted EEG Monitoring Duration in Critically Ill Children
Authors: Fung France W. , Fan Jiaxin , Parikh Darshana S. , Vala Lisa , Donnelly Maureen , Jacobwitz Marin , Topjian Alexis A. , Xiao Rui , Abend Nicholas S.
Published: May 2022

Purpose:

Continuous EEG monitoring (CEEG) to identify electrographic seizures (ES) in critically ill children is resource intense. Targeted strategies could enhance implementation feasibility. We aimed to validate previously published findings regarding the optimal CEEG duration to identify ES in critically ill children.

Methods:

This was a prospective observational study of 1,399 consecutive critically ill children with encephalopathy. We validated the findings of a multistate survival model generated in a published cohort (N = 719) in a new validation cohort (N = 680). The model aimed to determine the CEEG duration at which there was <15%, <10%, <5%, or <2% risk of experiencing ES if CEEG were continued longer. The model included baseline clinical risk factors and emergent EEG risk factors.

Results:

A model aiming to determine the CEEG duration at which a patient had <10% risk of ES if CEEG were continued longer showed similar performance in the generation and validation cohorts. Patients without emergent EEG risk factors would undergo 7 hours of CEEG in both cohorts, whereas patients with emergent EEG risk factors would undergo 44 and 36 hours of CEEG in the generation and validation cohorts, respectively. The <10% risk of ES model would yield a 28% or 64% reduction in CEEG hours compared with guidelines recommending CEEG for 24 or 48 hours, respectively.

Conclusions:

This model enables implementation of a data-driven strategy that targets CEEG duration based on readily available clinical and EEG variables. This approach could identify most critically ill children experiencing ES while optimizing CEEG use.
A Fast, Provably Accurate Approximation Algorithm for Sparse Principal Component Analysis Reveals Human Genetic Variation Across the World
Authors: Chowdhury Agniva , Bose Aritra , Zhou Samson , Woodruff David P. , Drineas Petros
Published: May 2022

Principal component analysis (PCA) is a widely used dimensionality reduction technique in machine learning and multivariate statistics. To improve the interpretability of PCA, various approaches to obtain sparse principal direction loadings have been proposed, which are termed Sparse Principal Component Analysis (SPCA). In this paper, we present ThreSPCA, a provably accurate algorithm based on thresholding the Singular Value Decomposition for the SPCA problem, without imposing any restrictive assumptions on the input covariance matrix. Our thresholding algorithm is conceptually simple; much faster than current state-of-the-art; and performs well in practice. When applied to genotype data from the 1000 Genomes Project, ThreSPCA is faster than previous benchmarks, at least as accurate, and leads to a set of interpretable biomarkers, revealing genetic diversity across the world.
Change in stroke presentations during COVID-19 pandemic in South-Western Sydney
Authors: Thomas James , Manser David , Thomas Peter , Moore Nicholas , Middleton Paul , Cordato Dennis , Cappelen-Smith Cecilia , McDougall Alan
Published: May 2022

Background

Australia managed relatively well during the global COVID-19 pandemic owing to our swift mandated public health response. During the NSW lockdown restrictions, we noted a decrease in acute stroke presentations at our institution, similar to what was subsequently reported worldwide.

Aims

We aimed to test our hypothesis that (i) the true numbers of ischaemic strokes did not change, however patients were presenting later and (ii) the proportion of TIAs decreased.

Methods

We conducted a retrospective audit of all stroke and TIA presentations in 2020 and compared these with data from 2019. We collected information about stroke subtype, severity, time from stroke/TIA onset to presentation and acute reperfusion therapies.

Results

Between January-February and April-March 2020, there was a 15% drop in acute stroke presentations (128 vs. 109). In the same period “stroke mimic” presentations dropped by 22%. The proportion of patients attending the emergency department within 4.5hrs was only 36% compared with 48% over the similar period in 2019.

Conclusions

Although the raw numbers of ischemic stroke presentations remained stable during NSW Covid lockdown, the proportion of patients presenting within time window for acute reperfusion therapies fell. The number of TIAs similarly fell suggesting COVID-19 discouraged patients from presenting to hospital which placed them at higher risk of disabling stroke. The opportunity cost of lockdown restrictions on stroke outcome should be considered in future policy directives.
BREEDIT: A novel multiplex genome editing strategy to improve complex quantitative traits in maize (Zea mays L.)
Authors: Lorenzo Christian Damian , Debray Kevin , Herwegh Denia , Develtere Ward , Impens Lennert , Schaumont Dries , Vandeputte Wout , Aesaert Stijn , Coussens Griet , de Boe Yara , Demuynck Kirin , Van Hautegem Tom , Pauwels Laurens , Jacobs Thomas B. , Ruttink Tom , Nelissen Hilde , Inzé Dirk
Published: May 2022

Ensuring food security for an ever-growing global population while adapting to climate change is the main challenge for agriculture in the 21st century. Though new technologies are being applied to tackle the problem, we are approaching a plateau in crop improvement using conventional breeding. Recent advances in gene engineering via the CRISPR/Cas technology pave the way to accelerate plant breeding and meet this increasing demand. Here, we present a gene discovery pipeline named ‘BREEDIT’ that combines multiplex genome editing of whole gene families with crossing schemes to improve complex traits such as yield and drought resistance. We induced gene knockouts in 48 growth-related genes using CRISPR/Cas9 and generated a collection of over 1000 gene-edited maize plants. Edited populations displayed, on average, significant increases of 5 to 10% for leaf length and up to 20% for leaf width compared with controls. For each gene family, edits in subsets of genes could be associated with increased traits, allowing us to reduce the gene space needed to focus on for trait improvement. We propose BREEDIT as a gene discovery pipeline which can be rapidly applied to generate a diverse collection of mutants to identify subsets of promising candidates that could be later incorporated in breeding programs.
Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2
Authors: Halliday Alice , Long Anna E , Baum Holly E , Thomas Amy C , Shelley Kathryn L , Oliver Elizabeth , Gupta Kapil , Francis Ore , Kavanagh Williamson Maia , di Bartolo Natalie , Randell Matthew J , Ben-Khoud Yassin , Kelland Ilana , Mortimer Georgina , Ball Olivia , Plumptre Charlie , Chandler Kyla , Obst Ulrike , Secchi Massimiliano , Piemonti Lorenzo , Lampasona Vito , Smith Joyce , Gregorova Michaela , Knezevic Lea , Metz Jane , Barr Rachael , Morales-Aza Begonia , Oliver Jennifer , Collingwood Lucy , Hitchings Benjamin , Ring Susan , Wooldridge Linda , Rivino Laura , Timpson Nicholas , McKernon Jorgen , Muir Peter , Hamilton Fergus , Arnold David , Woolfson Derek N , Goenka Anu , Davidson Andrew D. , Toye Ashley M , Berger Imre , Bailey Mick , Gillespie Kathleen M , Williams Alistair JK , Finn Adam
Published: May 2022

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilised pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID- 19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in- house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterised samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
SARS-CoV-2 neutralizing antibodies in Chile after a vaccination campaign with five different schemes
Authors: Aguilera Ximena , Hormazabal Juan , Vial Cecilia , Cortes Lina Jimena , Gonzalez Claudia , Rubilar Paola , Apablaza Mauricio , Ramirez-Santana Muriel , Icaza Gloria , Nuñez-Franz Loreto , Castillo-Laborde Carla , Ramirez-Riffo Carolina , Perez Claudia , Quezada-Gate Ruben , Said Macarena , Vial Pablo
Published: May 2022

Using levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines technologies and heterologous boosters. In 120 randomly selected seropositive individuals from a population-based study, we conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response.
Development of Molecular Inversion Probes for Soybean Progeny Genomic Selection Genotyping
Authors: Wang Haichuan , Campbell Benjamin , Happ Mary , McConaughy Samantha , Lorenz Aaron , Amundsen Keenan , Song Qijian , Pantalone Vincent , Hyten David
Published: May 2022

Increasing rate of genetic gain for key agronomic traits through genomic selection requires the development of new molecular methods to run genome-wide single nucleotide polymorphisms (SNPs). The main limitation of current methods is the cost is too high to screen breeding populations. Molecular inversion probes (MIPs) is a targeted genotyping-by-sequencing method that could be used for soybeans that is both cost effective, high-throughput, and provides high data quality to screen breeder’s germplasm for genomic selection. A 1K MIP SNP set was developed for soybean with uniformly distributed markers across the genome. The SNPs were selected to maximize the number of informative markers in germplasm being tested in soybean breeding programs located in the North Central and Mid-South regions of the United States. The 1K SNP MIP set was tested on diverse germplasm and a recombinant inbred line population. Targeted sequencing with MIPs obtained an 85% enrichment for the targeted SNPs. MIP’s genotyping accuracy was 93% overall while homozoygous call accuracy was 98% with less than 10% missing data. The accuracy of MIPs combined with its low per sample cost makes it a powerful tool to enable genomic selection within soybean breeding programs.
Testing the link between isoaspartate and Alzheimer’s disease etiology
Authors: Wang Jijing , Guo Cong , Meng Zhaowei , Zwan Marissa D. , Chen Xin , Seelow Sven , Lundström Susanna L. , Rodin Sergey , Teunissen Charlotte E. , Zubarev Roman A.
Published: May 2022

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts the secondary and higher order structures of proteins, damaging their functions and making them prone to aggregation. An association has been suggested between isoAsp and Alzheimer’s Disease (AD). Here we strengthened the link between isoAsp and AD by novel approaches to isoAsp analysis in blood human serum albumin (HSA), the most abundant blood protein, a major carrier of amyloid beta (Aß) peptide and phosphorylated tau (pTau) protein in blood and a key participant in their clearance pathway. We discovered a reduced amount of anti-isoAsp antibodies (P < .0001), an elevated isoAsp level in HSA (P < .001), more HSA aggregates (P < .0001) and increased levels of free Aß (P < .01) in AD blood compared to healthy controls. We also found that deamidation significantly reduces HSA capacity to bind with Aß and pTau (P < .05). These findings support the presence in AD of a bottleneck in clearance of Aß and pTau leading to their increased concentrations in brain and facilitating their aggregations there.

RESEARCH IN CONTEXT

Systematic review:We reviewed the evidence that associates isoaspartate (isoAsp) residue in blood proteins with the etiology of Alzheimer’s disease (AD). However, the link between isoAsp in blood and aggregation of amyloid beta (Aß) peptide and phosphorylated tau (pTau) protein in brain remained unclear.

Interpretation:For the first time we demonstrate that isoAsp-containing human serum albumin (HSA) forms aggregates with reduced binding capacity toward Aß peptide and pTau protein. Using a novel ELISA, we discovered in AD blood elevated levels of isoAsp in HSA, together with reduced endogenous anti-isoAsp antibody levels, suggesting hampered Aß and pTau clearance in AD.

Future directions:As degradation of the innate anti-isoAsp defenses may take years to develop, investigation of the isoAsp role in early stages of AD is warranted. And enrollment of different neurodegenerative disease cohorts will illustrate if isoAsp is AD-specific or universal to diseases related to aging.

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Co-occurrence patterns and habitat selection of the mountain hare, European hare, and European rabbit in urban areas of Sweden
Authors: Bach Henriette , Escoubet Hannah , Mayer Martin
Published: May 2022

Assessing the underlying mechanisms of co-occurrence patterns can be challenging as biotic and abiotic causations are hard to disentangle. To date, few studies have investigated co-occurrence patterns within urban areas that constitute novel habitat to numerous wildlife species. Moreover, as urban areas expand and are increasingly used as habitat by wildlife, there is a need for a better understanding of urban ecology to facilitate human-wildlife coexistence. Here, we investigated co-occurrence patterns and habitat selection of the European hare (Lepus europaeus), mountain hare (L. timidus), and European rabbit (Oryctolagus cuniculus) inside urban areas of Sweden, using joint species distribution models and generalized linear mixed models based on citizen science observations. All three species were observed within urban areas, but European hares and rabbits appear to be more successful urban colonizers compared to mountain hares. Overall, our findings suggested that urban occurrence by all three lagomorphs was related to suitable conditions within the distribution of each species (e.g. climate and elevation), rather than by the presence of other lagomorph species or specific land cover types within urban areas. On a finer spatial scale, our findings suggested facilitation of European hares by rabbits, though the mechanism for this remains unclear. European hares and rabbits generally selected for green urban areas and mountain hares for residential gardens, which likely constitute suitable foraging sites. Our findings contribute to the understanding of urban ecology and provide valuable insight for management measures of the three lagomorphs in urban areas of Sweden.
CHRNA5links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s Disease
Authors: Rybnicek Jonas , Chen Yuxiao , Millic Milos , Tio Earvin , McLaurin JoAnne , Hohman Timothy J. , De Jager Philip L , Schneider Julie A , Wang Yanling , Bennett David A , Tripathy Shreejoy , Felsky Daniel , Lambe Evelyn K
Published: May 2022

Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging and dementia. Therefore, we investigate the nicotinic α5 geneCHRNA5and the impact of relevant single nucleotide polymorphisms (SNPs) in prefrontal cortex from 922 individuals with matched genotypic andpost-mortemRNA sequencing in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We find that a genotype robustly linked to increased expression ofCHRNA5(rs1979905A2) predicts significantly reduced cortical β-amyloid load. Intriguingly, co-expression analysis suggestsCHRNA5has a distinct cellular expression profile compared to other nicotinic receptor genes. Consistent with this prediction, single nucleus RNA sequencing from 22 individuals revealsCHRNA5expression is disproportionately-elevated in chandelier neurons, a distinct subtype of inhibitory neuron known for its role in excitatory/inhibitory (E/I) balance. We show that chandelier neurons are enriched in amyloid-binding proteins compared to basket cells, the other major subtype of PVALB-positive interneurons. Consistent with the hypothesis that nicotinic receptors in chandelier cells normally protect against β-amyloid, cell-type proportion analysis from 549 individuals reveals these neurons show amyloid-associated vulnerability only in individuals with impaired function/trafficking of nicotinic α5-containing receptors due to homozygosity of the missenseCHRNA5SNP (rs16969968A2). Taken together, these findings suggest thatCHRNA5and its nicotinic α5 subunit exert a neuroprotective role in aging and Alzheimer’s disease centered on chandelier interneurons.
Hybrid offspring of C57BL/6J mice exhibit improved properties for neurobehavioral research
Authors: Sloin Hadas E. , Bikovski Lior , Levi Amir , Amber-Vitos Ortal , Katz Tomer , Spivak Lidor , Someck Shirly , Gattegno Roni , Sivroni Shir , Sjulson Lucas , Stark Eran
Published: May 2022

C57BL/6 is the most commonly used mouse strain in neurobehavioral research, serving as a background for multiple transgenic lines. However, C57BL/6 exhibit behavioral and sensorimotor disadvantages that worsen with age. We bred FVB/NJ females and C57BL/6J males to generate first-generation hybrid offspring, (FVB/NJ x C57BL/6J)F1. The hybrid mice exhibit reduced anxiety-like behavior, improved learning, and enhanced long-term spatial memory. In contrast to both progenitors, older hybrids maintain sensorimotor performance and exhibit improved long-term memory. The hybrids are larger than C57BL/6J, exhibiting enhanced running behavior on a linear track during freely-moving electrophysiological recordings. Hybrids exhibit typical rate and phase coding of space by CA1 pyramidal cells. Hybrids generated by crossing FVB/NJ females with transgenic males of a C57BL/6 background support optogenetic neuronal control in neocortex and hippocampus. The hybrid mice provide an improved model for neurobehavioral studies combining complex behavior, electrophysiology, and genetic tools readily available in C57BL/6 mice.
Multi-view manifold learning of human brain state trajectories
Authors: Busch Erica L. , Huang Jessie , Benz Andrew , Wallenstein Tom , Lajoie Guillaume , Wolf Guy , Krishnaswamy Smita , Turk-Browne Nicholas B
Published: May 2022

The complexity and intelligence of the brain give the illusion that measurements of brain activity will have intractably high dimensionality, rifewith collection and biological noise. Nonlinear dimensionality reduction methods like UMAP and t-SNE have proven useful for high-throughput biomedical data. However, they have not been used extensively for brain imaging data such as from functional magnetic resonance imaging (fMRI), a noninvasive, secondary measure of neural activity over time containing redundancy and co-modulation from neural population activity. Here we introduce a nonlinear manifold learning algorithm for timeseries data like fMRI, called temporal potential of heat diffusion for affinity-based transition embedding (T-PHATE). In addition to recovering a lower intrinsic dimensionality from timeseries data, T-PHATE exploits autocorrelative structure within the data to faithfully denoise dynamic signals and learn activation manifolds. We empirically validate T-PHATE on three human fMRI datasets, showing that T-PHATE significantly improves data visualization, classification, and segmentation of the data relative to several other state-of-the-art dimensionality reduction benchmarks. These notable improvements suggest many potential applications of T-PHATE to other high-dimensional datasets of temporally-diffuse processes.