bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous total occlusion due to spasm of 2 main coronary arteries: A case report
Authors: Wang Yajing , Si Ganggang , Li Xiangbing , Li Jianjun , Zhang Ruxia , Pan Sancong
Published: January 2023

Rationale:

Coronary artery spasm (CAS) defined by severe reversible focal or diffuse vasoconstriction, plays an essential role in the pathophysiology of acute coronary syndrome but is not very common in the clinic. Due to its transience, it is difficult to diagnose CAS directly, many patients are diagnosed by clinical experience. Here, we report the diagnosis and treatment of a rare case of simultaneous total occlusion due to spasm of the two main coronary arteries by coronary angiography (CAG).

Patient concerns:

A 47-year-old man with no medical history was admitted to our emergency room complaining of sudden-onset chest pain lasting 3 hours. Emergency CAG showed total occlusion of the proximal left anterior descending artery and right coronary artery.

Diagnoses:

Acute myocardial infarction caused by CAS was diagnosed, according to CAG findings and test results.

Interventions:

Intracoronary injection of nitroglycerin and anti-spasm medication.

Outcomes:

The patient was discharged on the 8th day with complete resolution of symptoms and normalization of the electrocardiography findings. No ischemic events occurred during a follow-up for 27 months.

Lessons:

This case highlights the significance of identifying CAS in patients with acute myocardial infarction and avoiding blind interventional stent therapy, which requires closer attention from clinicians.
Case series: Montgomery T-tube placement for subglottic tracheal stenosis: a report of 3 cases
Authors: Hong Ping-Yang , Huang Mao-Hong , Zhan Feng-Fu , Lin Yi-Li , Qiu Shao-Zhao , Zhang Xiao-Bin
Published: January 2023

Rationale:

Subglottic tracheal stenosis is stenosis of the trachea between the vocal cords and the lower margin of the cricoid cartilage. The Montgomery T-tube is used as a tracheostomy tube and a combined tracheal stent to avoid postoperative tracheal stenosis.

Patient concerns:

Because the stenosis is close to the glottis, surgical treatment is complex, and many complications may arise.

Diagnoses:

Subglottic tracheal stenosis.

Interventions:

The patients underwent endotracheal intubation or tracheotomy because of acute pancreatitis, laryngeal malignancy, or cerebral hemorrhage after endotracheal intubation or tracheotomy and presented with varying degrees of tracheal stenosis and dyspnea. We relieved airway stenosis and improved dyspnea in these 3 patients by placing a Montgomery T-tube.

Outcomes:

None of the 3 patients had intraoperative complications. In 2 of the cases, airway secretions were stored after surgery.

Lessons:

Montgomery T-tube placement is safe and effective for patients with complex subglottic tracheal stenosis.
Case report of intracranial large vessel occlusion in glioblastoma multiforme patient after radiation therapy
Authors: Chien-Tung Yang , Chen Chun-Chung
Published: January 2023

Introduction:

Vasculopathy of the large arteries is a prominent complication of radiotherapy. Radiation-induced cerebral vasculopathy can cause arterial stenosis/occlusion, cerebral hemorrhage, and aneurysm formation. We report a cases of glioblastoma multiforme (GBM) with occlusive radiation vasculopathy (ORV).

Case presentation:

This 28-year-old patient who suffered from GBM had surgery for cytoreduction and received postoperative CCRT. We adopted the radiotherapy and oncology group radiation guideline. This patient had cerebrovascular accident episodes without any known risk. Therefore, ORV was highly suspected and vascular stenosis was confirmed using magnetic resonance angiography (MRA) or digital subtraction angiography. Extracranial-intracranial bypass was performed and patency was confirmed. The patient had not suffered from recurrent symptoms of transient ischemic attack or ischemic stroke for 1.5 years.

Discussion:

This is the first article to report bypass surgery for GBM patients. Although the median survival rate of GBM is approximately 15 months, the short survival time may be sufficient for occlusive vasculopathy to occur. Regular follow-up magnetic resonance imaging assessments are recommended, as is MRA as a screening tool for the early diagnosis of ORV.

The Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial focused on atherosclerotic intracranial arterial stenosis, revealing that aggressive medical management was superior to stenting for secondary stroke prevention; however, it did not mention radiation-induced vasculopathy. Bypass surgery has yielded some positive outcomes. In the absence of contraindications, antiplatelet or anticoagulation agents could be added, and bypass surgery could be performed because there was no stent in the distal intracranial arteries.

Conclusion:

MRA is a potential screening tool for ORV in GBM patients and bypass surgery could be performed to improve brain perfusion. Bypass surgery could help patient with occlusive radiation vasculopathy
Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study
Authors: Lou Zheng , Huang Yizhou , Lan Yibing , Li Chunming , Chu Ketan , Chen Peiqiong , Xu Wenxian , Ma Linjuan , Zhou Jianhong
Published: January 2023

Lipid alteration in postmenopausal women is commonly due to hormonal changes. This study aimed to explore the association between the years since menopause and lipid profiles in postmenopausal women. In this cross-sectional study, a total of 1033 postmenopausal women were recruited from the Women’s Hospital of Zhejiang University in China between 2015 and 2022. Each participant was interviewed using questionnaires regarding sociodemographic and reproductive data. Anthropometric measurements, lipid profiles, and reproductive hormone levels were assessed. Participants were divided into 3 groups based on the length of time since menopause: 2, 2 to 5.9, and 6 years. Differences in lipid profiles and reproductive hormones among the groups were compared. Logistic and linear regression analyses were used to examine the relationship between years after menopause and lipid profile. High-density lipoprotein cholesterol (HDL-C) and luteinizing hormone levels were significantly lower in postmenopausal women with time since menopause of ≥6 years than those <2 years (P < .05), whereas low-density lipoprotein cholesterol levels were significantly higher (P < .05). A longer time after menopause was independently associated with lower HDL-C levels (β, −0.059, standard error, 0.023, P = .01) after adjustment for age, body mass index, and other confounders. Compared to women who had menopause for <2 years, those who were postmenopausal for >6 years had lower HDL-C levels after adjustment for age, body mass index, and other covariates (β, −0.123, 95% confidence interval, [−0.221, −0.014], P = .014). Longer time since menopause was associated with an atherogenic lipid profile with appreciably low levels of HDL-C subfraction. Future multicenter studies are necessary to examine postmenopausal population and determine how differences in lipids influence the risk of cardiovascular disease in this group.
Randomized Controlled Study of Self-Managed Music-Guided Exercise Intervention Following Intensive Care
Authors: Liang Zhan , Munro Cindy , Yip Hilary , Ji Ming , Moore Kimberly Sena , Ferreira Tanira , Signorile Joseph F. , Pan Yue
Published: January 2023

Background

Patients who are discharged from ICU (ICU survivors) often experience persistent physical impairment.

Objective

To explore the effects of a self-managed, music-guided exercise intervention on physical outcomes and adherence rates among ICU survivors.

Methods

A randomized controlled design was used. Following ICU discharge, participants admitted to the ICU for at least 5 days were randomly assigned to a music group (n = 13) or active control group (n = 13). Activity counts were measured using an Actiwatch, and physical health score was measured using the Patient-Reported Outcomes Measurement Information System global health subscale. Adherence to exercise was documented daily. Independent t-tests were used for data analysis.

Results

Data were analyzed for 26 participants. The mean age was 62.8 ± 13.8 years, 53.8% were male, 65.4% were White, and mean Acute Physiology and Chronic Health Evaluation severity of illness score was 59 ± 23.4. Global health physical scores were significantly higher in the music group than in the active control group. Although not significantly different, music group participants tended to be more active and had higher physical activity and adherence rates compared to those in the active control group.

Conclusion

A self-managed, music-guided exercise intervention demonstrated positive benefits on physical outcomes. Future clinical trials with a larger sample size should be conducted to examine the effects of this tailored, cost-effective, innovative, self-managed exercise intervention among ICU survivors.
Head and Neck Mesenchymal Tumors with Kinase Fusions
Authors: Xu Bin , Suurmeijer Albert J.H. , Agaram Narasimhan P. , Antonescu Cristina R.
Published: January 2023

Mesenchymal tumors harboring various kinase fusions were recently recognized as emerging entities mainly in the soft tissues. We herein investigate the clinicopathologic and molecular characteristics of head and neck mesenchymal tumors harboring kinase fusions. The study cohort included 15 patients with a median age of 13 years (ranging from congenital to 63 y). The kinase genes involved in descending order were NTRK1 (n=6), NTRK3 (n=5), BRAF (n=2), and 1 each with MET, and RET. The anatomic locations were broad involving all tissue planes, including skin (n=4), intraosseous (n=4), major salivary glands (n=2), sinonasal tract (n=2), soft tissue of face or neck (n=2), and oral cavity (n=1). The histologic spectrum ranged from benign to high grade, in descending order including tumors resembling malignant peripheral nerve sheath tumor (MPNST)-like, fibrosarcoma (infantile or adult-type), lipofibromatosis-like neural tumor (LPFNT), inflammatory myofibroblastic tumor-like, and a novel phenotype resembling myxoma. Perivascular hyalinization/stromal keloid-like collagen bands and staghorn vasculature were common features in MPNST-like and LPFNT-like tumors. Two tumors (1 each with NTRK1 or BRAF rearrangement) were classified as high grade. By immunohistochemistry, S100 and CD34 positivity was noted in 71% and 60%, frequently in MPNST-like and LPFNT-like phenotypes. Pan-TRK was a sensitive marker for NTRK-translocated tumors but was negative in tumor with other kinase fusions. One patient with a high-grade tumor developed distant metastasis. Molecular testing for various kinase fusions should be considered for S100+/CD34+ spindle cell neoplasms with perivascular hyalinization and staghorn vessels, as pan-TRK positivity is seen only in NTRK fusions.
Changes in the Diagnoses of Breast Core Needle Biopsies on Second Review at a Tertiary Care Center
Authors: Calle Catarina , Zhong Elaine , Hanna Matthew G. , Ventura Katia , Friedlander Maria A. , Morrow Monica , Cody Hiram , Brogi Edi
Published: January 2023

Core needle biopsy (CNB) of breast lesions is routine for diagnosis and treatment planning. Despite refinement of diagnostic criteria, the diagnosis of breast lesions on CNB can be challenging. At many centers, including ours, confirmation of diagnoses rendered in other laboratories is required before treatment planning. We identified CNBs first diagnosed elsewhere that were reviewed in our department over the course of 1 year because the patients sought care at our center and in which a change in diagnosis had been recorded. The outside and in-house CNB diagnoses were then classified based on Breast WHO Fifth Edition diagnostic categories. The impact of the change in diagnosis was estimated based on the subsequent surgical management. Findings in follow-up surgical excisions (EXCs) were used for validation. In 2018, 4950 outside cases with CNB were reviewed at our center. A total of 403 CNBs diagnoses were discrepant. Of these, 147 had a change in the WHO diagnostic category: 80 (54%) CNBs had a more severe diagnosis and 44 (30%) a less severe diagnosis. In 23 (16%) CNBs, the change of diagnostic category had no impact on management. Intraductal proliferations (n=54), microinvasive carcinoma (n=18), and papillary lesions (n=35) were the most disputed diagnoses. The in-house CNB diagnosis was confirmed in most cases with available excisions. Following CNB reclassification, 22/147 (15%) lesions were not excised. A change affecting the surgical management at our center occurred in 2.5% of all CNBs. Our results support routine review of outside breast CNB as a clinically significant practice before definitive treatment.
Risk of Developmental Coordination Disorder in 8- and 9-Year-Olds Following Newborn Cardiac and Non–Cardiac Surgery
Authors: Fairbairn Natalie , Badawi Nadia , Galea Claire , Hodge Antoinette , Loughran-Fowlds Alison , Novak Iona
Published: January 2023

Purpose:

To investigate the risk of developmental coordination disorder (DCD) and motor impairment for children aged 8 to 9 years following newborn surgery.

Methods:

Prospective longitudinal cohort study. Motor proficiency and risk of DCD were assessed using the Movement Assessment Battery for Children (second edition) for children born 37 weeks of gestation and older who had undergone newborn cardiac surgery (CS) or non–cardiac surgery (NCS).

Results:

Children who had undergone CS were 3.0 times more likely than controls and 1.7 times more likely than children who had undergone NCS to score below the 15th centile on MABC-2 and have increased risk of DCD. Children who had undergone CS were 1.9 times more likely than controls and 1.4 times more likely than children who had undergone NCS to score below the fifth centile on MABC-2.

Conclusion:

The surgical population should be considered at an increased risk of DCD.
Type D Personality as a Risk Factor for Adverse Outcome in Patients With Cardiovascular Disease: An Individual Patient-Data Meta-analysis
Authors: Lodder Paul , Wicherts Jelte M. , Antens Marijn , Albus Christian , Bessonov Ivan S. , Condén Emelie , Dulfer Karolijn , Gostoli Sara , Grande Gesine , Hedberg Pär , Herrmann-Lingen Christoph , Jaarsma Tiny , Koo Malcolm , Lin Ping , Lin Tin-Kwang , Meyer Thomas , Pushkarev Georgiy , Rafanelli Chiara , Raykh Olga I. , Schaan de Quadros Alexandre , Schmidt Marcia , Sumin Alexei N. , Utens Elisabeth M.W.J. , van Veldhuisen Dirk J. , Wang Yini , Kupper Nina
Published: January 2023

Objective

Type D personality, a joint tendency toward negative affectivity and social inhibition, has been linked to adverse events in patients with heart disease, although with inconsistent findings. Here, we apply an individual patient-data meta-analysis to data from 19 prospective cohort studies (N = 11,151) to investigate the prediction of adverse outcomes by type D personality in patients with acquired cardiovascular disease.

Method

For each outcome (all-cause mortality, cardiac mortality, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiac event, any adverse event), we estimated type D’s prognostic influence and the moderation by age, sex, and disease type.

Results

In patients with cardiovascular disease, evidence for a type D effect in terms of the Bayes factor (BF) was strong for major adverse cardiac event (BF = 42.5; odds ratio [OR] = 1.14) and any adverse event (BF = 129.4; OR = 1.15). Evidence for the null hypothesis was found for all-cause mortality (BF = 45.9; OR = 1.03), cardiac mortality (BF = 23.7; OR = 0.99), and myocardial infarction (BF = 16.9; OR = 1.12), suggesting that type D had no effect on these outcomes. This evidence was similar in the subset of patients with coronary artery disease (CAD), but inconclusive for patients with heart failure (HF). Positive effects were found for negative affectivity on cardiac and all-cause mortality, with the latter being more pronounced in male than female patients.

Conclusion

Across 19 prospective cohort studies, type D predicts adverse events in patients with CAD, whereas evidence in patients with HF was inconclusive. In both patients with CAD and HF, we found evidence for a null effect of type D on cardiac and all-cause mortality.
Small-Fiber Polyneuropathy Is Prevalent in Patients With Interstitial Cystitis/Bladder Pain Syndrome
Authors: Wolff Dylan T. , Xu Raymond , Overholt Tyler , Bassett E. Hadley , Ahn Christine , Simon Trang , Lee Peyton , Badlani Gopal , Matthews Catherine A. , Evans Robert J. , Walker Stephen J.
Published: January 2023

Importance

The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is imperfectly understood. Recent studies reported that small-fiber polyneuropathy (SFPN) is common in fibromyalgia, a condition commonly comorbid with IC/BPS.

Objective

The objective of this study was to determine the prevalence of SFPN in a large cohort of IC/BPS patients.

Methods

Adults diagnosed with IC/BPS scheduled to undergo either therapeutic hydrodistention (n = 97) or cystectomy with urinary diversion (n = 3) were prospectively recruited to this study. A skin biopsy obtained from the lower leg was used for intraepidermal nerve fiber density measurement. Small-fiber polyneuropathy (+/−) status was determined by comparing linear intraepidermal nerve fiber density (fibers/mm2) with normative reference values. Demographic information, medical history, and diagnoses for 14 conditions (both urologic and nonurologic) known to co-occur with IC/BPS were documented from self-report and electronic medical record.

Results

In this large cohort of patients with IC/BPS, 31% (31/100) were positive for SFPN. Intraepidermal nerve fiber density was below the median for age and sex in 81% (81/100) of patients. Approximately one-third (31%) of SFPN+ patients reported co-occurring chronic fatigue syndrome, compared with 10.6% of the SFPN− group (P = 0.034). Small-fiber polyneuropathy–positive patients reported significantly fewer allergies than SFPN− patients (37.9% vs 60.6%; P = 0.047). There were no significant differences in bladder capacity or Hunner lesion status between the SFPN+ and SFPN− subgroups.

Conclusions

Small-fiber polyneuropathy is a common finding in patients with IC/BPS, and SFPN status is significantly correlated with co-occurring chronic fatigue syndrome and negatively correlated with the presence of allergies in this population.
Reduction in Rates of Symptomatic Urinary Tract Infection After Pelvic Reconstructive Surgery: A Quality Improvement Analysis
Authors: Duarte Thibault Mary , Milen Allison , Burns Luke , Tilea Anca , Piehl Kenneth , Morgan Daniel
Published: January 2023

Importance

Urinary tract infections contribute to high health care costs.

Objective

This study aimed to determine if a combination of interventions was successful at reducing the rate of postoperative symptomatic urinary tract infections (SUTIs) in a female pelvic medicine and reconstructive surgery (FPMRS) practice.

Study Design

Observational, retrospective quality improvement analysis looking at the rate of postoperative SUTI within 30 days of surgery in women who underwent gynecologic surgery performed by an FPMRS surgeon from October 2015 to October 2019. Symptomatic urinary tract infection was defined by symptoms and urinalysis, positive urine culture, or treatment for cystitis or urethritis within 30 days of surgery. Interventions were implemented between 2015 and 2016: perioperative cranberry use, intraoperative protocols for catheterization, and postoperative protocols for urinary retention management. In 2018, we added metronidazole to cefazolin for antibiotic prophylaxis. We developed a multivariable logistic regression to determine if postoperative SUTI rates decreased over the study period with adjustment for clustering by surgeons, patient factors, and surgery type.

Results

Of 2,389 procedures performed, 284 (11.8%) involved patients who had an SUTI within 30 days of surgery. The annual infection rate decreased 50% (year 1, 14.7%; year 4, 7.3%). Adjusting for age, race, body mass index, length of stay, surgery type, and surgeon, the odds of SUTI decreased 19% each year (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.72–0.91; P < 0.001). Compared with women who had other gynecologic procedures, those who underwent vaginal prolapse surgery with or without incontinence procedures (OR, 2.75; 95% CI, 1.35–5.54; P = 0.01) or incontinence surgery alone (OR, 2.65; 95% CI, 1.25–5.62; P = 0.01) were more likely to have an SUTI.

Conclusion

Combining interventions can be highly effective in reducing postoperative SUTI rates.
A novel head-fixed assay for social touch in mice uncovers aversive responses in two autism models
Authors: Chari Trishala , Hernandez Ariana , Portera-Cailliau Carlos
Published: January 2023

Social touch, an important aspect of social interaction and communication, is essential to kinship across animal species. How animals experience and respond to social touch has not been thoroughly investigated, in part due to the lack of appropriate assays. Previous studies that examined social touch in freely moving rodents lacked the necessary temporal and spatial control over individual touch interactions. We designed a novel head-fixed assay for social touch in mice, in which the experimenter has complete control to elicit highly stereotyped bouts of social touch between two animals. The user determines the number, duration, context, and type of social touch interactions, while monitoring with high frame rate cameras an array of complex behavioral responses. We focused on social touch to the face because of their high translational relevance to humans. We validated this assay in two different models of autism spectrum disorder (ASD), theFmr1knockout model of Fragile X Syndrome and maternal immune activation mice. We observed increased avoidance, hyperarousal, and more aversive facial expressions to social touch, but not to object touch, in both ASD models compared to controls. Because this new social touch assay for head-fixed mice can be used to record neural activity during repeated bouts of social touch it should be of interest to neuroscientists interested in uncovering the underlying circuits.
Applying joint graph embedding to study Alzheimer’s neurodegeneration patterns in volumetric data
Authors: He Rosemary , Tward Daniel ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2023

Neurodegeneration measured through volumetry in MRI is recognized as a potential Alzheimer’s Disease (AD) biomarker, but its utility is limited by lack of specificity. Quantifying spatial patterns of neurodegeneration on a whole brain scale rather than locally may help address this. In this work, we turn to network based analyses and extend a graph embedding algorithm to study morphometric connectivity from volume-change correlations measured with structural MRI on the timescale of years. We model our data with the multiple random eigengraphs framework, as well as modify and implement a multigraph embedding algorithm proposed earlier to estimate a low dimensional embedding of the networks. Our version of the algorithm guarantees meaningful finite-sample results and estimates maximum likelihood edge probabilities from population-specific network modes and subject-specific loadings. Furthermore, we propose and implement a novel statistical testing procedure to analyze group differences after accounting for confounders and locate significant structures during AD neurodegeneration. Family-wise error rate is controlled at 5% using permutation testing on the maximum statistic. We show that results from our analysis reveal networks dominated by known structures associated to AD neurodegeneration, indicating the framework has promise for studying AD. Furthermore, we find network-structure tuples that are not found with traditional methods in the field.
Individual Variability in the Structural Connectivity Architecture of the Human Brain
Authors: Huang Weijie , Chen Haojie , Liu Zhenzhao , Dong Xinyi , Feng Guozheng , Liu GuangFang , Ma GuoLing , Zhang Zhanjun , Su Li , Shu Ni
Published: January 2023

The human brain shows higher variability in functional connectivity in the heteromodal association cortex but lower variability in the unimodal cortex. As the anatomical substrate of functional connectivity, the temporal-spatial pattern of individual variability in structural connectivity remains largely unknown. In the present study, we depicted the temporal-spatial pattern of individual variability in structural connectivity, which is highest in the limbic regions and lowest in the unimodal sensorimotor regions. With increasing age, the variability in structural connectivity increased. Our results demonstrated that this specific spatial distribution relates to the plasticity of synapses and white matter. We proposed a modified ridge regression model to predict cognition individually and generate idiographic brain mapping. Individual variability in structural connectivity is significantly correlated with idiographic brain mapping. Overall, our study has potential implications for understanding biological and genetic mechanisms of variability in structural connectivity, guiding interventions to promote successful cognitive ageing and interpreting statistical maps in the human connectome.
Neural evidence for boundary updating as the source of the repulsive bias in classification
Authors: Lee Heeseung , Lee Hyang-Jung , Choe Kyoung Whan , Lee Sang-Hun
Published: January 2023

Binary classification, an act of sorting items into two classes by setting a boundary, is biased by recent history. One common form of such biases is repulsive bias, a tendency to sort an item into the class opposite to its preceding items. Sensory-adaptation and boundary-updating are considered as two contending sources of the repulsive bias, yet no neural support has been provided for either source. Here we explored human brains, using fMRI, to find such supports by relating the brain signals of sensory-adaptation and boundary-updating to human classification behavior. We found that the stimulus-encoding signal in the early visual cortex adapted to previous stimuli, yet its adaptation-related changes were dissociated from current choices. Contrastingly, the boundary-representing signals in the inferior-parietal and superior-temporal cortices shifted to previous stimuli and covaried with current choices. Our exploration points to boundary-updating, rather than sensory-adaptation, as the origin of the repulsive bias in binary classification.
Experiences of family caregivers in caring for patients with heart failure at Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania: a qualitative study
Authors: Mcharo Tunzo L. , Iseselo Masunga K. , Kahema Samwel E. , Tarimo Edith AM.
Published: January 2023

Background

Heart failure (HF) continues to be a global health problem with its ramifications more pronounced in underdeveloped countries. Family members play a pivotal part in patient management which may influence the patient’s overall quality of life. Prolonged delay in attendance to health care facilities among patients indicates ineffective support from family caregivers. In the Tanzanian context, there is limited information about the experiences of family caregivers in caring for patients with HF. This study explored family caregivers’ experiences in caring for HF patients.

Methods

A qualitative descriptive study design was conducted at Jakaya Kikwete Cardiac Institute in Dar es Salaam, Tanzania. A purposive sampling technique was used to select the potential participants. A sample size of 10 family caregivers of patients with HF was included in the study. Thematic analysis was used to derive the main theme and sub-themes.

Results

Three major themes were identified: demands for supportive care, new caring role and lifestyle, and professional support in caring for patients with HF. Caregivers needed social and financial support to facilitate the caring process. Learning to provide the required care at the right time was the new role acquired by caregivers while failing to participate in social events and caregiving in an unfavourable environment were reported as challenges in caregiving. However, compliance with instruction and effective interaction among the nurses and caregivers were considered to be positive professional support.

Conclusion

Caregivers need social and financial support to provide effective care to their patients. Caregiving is a learning process that needs continuous educational support to adapt to the new caring roles and challenges. Nurses should conduct regular assessments to explore caregivers’ needs, challenges, and concerns and provide timely counselling that can facilitate coping.
Influence of AI-based decision support on shared decision making in hemodialysis: a Wizard of Oz experiment
Authors: Osmanodja Bilgin , Samhammer David , Roller Roland , Beck Susanne , Burchardt Aljoscha , Duettmann Wiebke , Dabrock Peter , Gerndt Simon , Moeller Sebastian , Ronicke Simon , Budde Klemens
Published: January 2023

Artificial Intelligence-based decision support systems (AI-DSS) to improve hemodialysis therapy are currently under development. However, the influence of AI-DSS on shared decision making (SDM) in hemodialysis patients has not been studied so far. We performed a Wizard of Oz experiment, using a sham AI-DSS suggesting ultrafiltration volume at the beginning of each dialysis session. We performed 10 patient interviews in 5 patients, and investigated views towards AI, different aspects of the SDM, and the influence of an AI-DSS on SDM in a real-life scenario.

Five main topics were identified: (1) the patient as self-determined, (2) role of the medical staff, (3) other forms of automation, (4) attitude towards AI, (5) needs and preferences for future use of AI. The patients describe novel AI-DSS in dialysis as an opportunity to promote self-determination and to ensure more efficient therapy. At the same time, they describe the special relationship with the nursing staff and physicians, who, from the patients’ point of view, must be given control over an AI-DSS.

This study provides first evidence regarding the influence of AI-DSS on SDM in the context of hemodialysis. Further studies should focus on other aspects that require SDM such as initiation of dialysis, and selection of dialysis modality.
Primate-conserved Carbonic Anhydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier
Authors: Shay Timothy F. , Sullivan Erin E. , Ding Xiaozhe , Chen Xinhong , Kumar Sripriya Ravindra , Goertsen David , Brown David , Vielmetter Jost , Borsos Máté , Lam Annie W. , Gradinaru Viviana
Published: January 2023

The blood-brain barrier (BBB) presents a major challenge to delivering large molecules to study and treat the central nervous system (CNS). This is due in part to the scarcity of effective targets for BBB crossing, the identification of which is the crucial first step of drug development. Here, we leveraged a panel of adeno-associated viruses (AAVs) previously identified through directed evolution for improved BBB transport to reverse engineer protein targets for enhanced BBB crossing. We identify both murine-restricted Ly6c1 and primate-conserved carbonic anhydrase IV (Car4; CA4) as novel receptors for crossing the BBB. We demonstrate how these receptors can unlock new experimental and computational target-focused engineering strategies by creating the enhanced Ly6c1-binding vector AAV-PHP.eC and by applying AlphaFold2-enabled in silico methods to rank capsids against identified receptors and generate capsid-receptor binding models. Here, with Car4, we add a completely new receptor to the very short list currently available for crossing the BBB in humans and, with Ly6c1, we validate a pipeline for receptor-targeted engineering. The identification of Car4/CA4 and structural insights from computational modeling provide new paths toward human brain-penetrant chemicals (drugs) and biologicals (including gene delivery).
Temporal pattern recognition in retinal ganglion cells is mediated by dynamical inhibitory synapses
Authors: Ebert Simone , Buffet Thomas , Sermet B.Semihcan , Marre Olivier , Cessac Bruno
Published: January 2023

A fundamental task for the brain is to generate predictions of future sensory inputs, and signal errors in these predictions. Many neurons have been shown to signal omitted stimuli during periodic stimulation, even in the retina. However, the mechanisms of this error signaling are unclear. Here we show that depressing inhibitory synapses enable the retina to signal an omitted stimulus in a flash sequence. While ganglion cells, the retinal output, responded to an omitted flash with a constant latency over many frequencies of the flash sequence, we found that this was not the case once inhibition was blocked. We built a simple circuit model and showed that depressing inhibitory synapses were a necessary component to reproduce our experimental findings. We also generated new predictions with this model, that we confirmed experimentally. Depressing inhibitory synapses could thus be a key component to generate the predictive responses observed in many brain areas.
Persistent Extrasynaptic Hyperdopaminergia in the mouse Hippocampus Induces Plasticity and Recognition Memory Deficits Reversed by Antipsychotics
Authors: Rocchetti Jill , Fasano Caroline , Dal-Bo Gregory , Guma Elisa , El Mestikawy Salah , Wong Tak Pan , Fakhfouri Gohar , Giros Bruno
Published: January 2023

Evidence suggests that subcortical hyperdopaminergia alters cognitive function in schizophrenia and antipsychotic drugs (APD) fail at rescuing cognitive deficits in patients. In a previous study, we showed that blocking D2 dopamine receptors (D2R), a core action of APD, led to profound reshaping of mesohippocampal fibers, deficits in synaptic transmission and impairments in learning and memory in the mouse hippocampus (HP). However, it is currently unknown how excessive dopamine affects HP-related cognitive functions, and how APD would impact HP functions in such a state. After verifying the presence of DAT-positive neuronal projections in the ventral (temporal), but not in the dorsal (septal), part of the HP, GBR12935, a blocker of dopamine transporter (DAT), was infused in the CA1 of adult C57Bl/6 mice to produce local hyperdopaminergia. Chronic GBR12935 infusion in temporal CA1 induced a mild learning impairment in the Morris Water Maze and abolished long-term recognition memory in novel-object (NORT) and object-place recognition tasks (OPRT). Deficits were accompanied by a significant decrease in DAT+mesohippocampal fibers. Intrahippocampal or systemic treatment with sulpiride during GBR infusions improved the NORT deficit but not that of OPRT.In vitroapplication of GBR on hippocampal slices abolished long-term depression (LTD) of fEPSP in temporal CA1. LTD was rescued by co-application with sulpiride. In conclusion, chronic DAT blockade in temporal CA1 profoundly altered mesohippocampal modulation of hippocampal functions. Contrary to previous observations in normodopaminergic mice, antagonising D2Rs was beneficial for cognitive functions in the context of hippocampal hyperdopaminergia.
Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates
Authors: Chen Xinhong , Wolfe Damien A. , Sivadasan Bindu Dhanesh , Zhang Mengying , Taskin Naz , Goertsen David , Shay Timothy F. , Sullivan Erin , Huang Sheng-Fu , Ravindra Kumar Sripriya , Arokiaraj Cynthia M. , Plattner Viktor , Campos Lillian J. , Mich John , Monet Deja , Ngo Victoria , Ding Xiaozhe , Omstead Victoria , Weed Natalie , Bishaw Yeme , Gore Bryan , Lein Ed S , Akrami Athena , Miller Cory , Levi Boaz P. , Keller Annika , Ting Jonathan T. , Fox Andrew S. , Eroglu Cagla , Gradinaru Viviana
Published: January 2023

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds and rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), andex vivohuman brain slices although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. Vasculature-secreted Hevin (a synaptogenic protein) rescued synaptic deficits in a mouse model.
Occupational determinants of COVID-19 cases and vaccination: an ecological analysis of counties in the United States as of December 2021
Authors: Ji John S. , Wang Yucheng , Duncan Dustin T.
Published: January 2023

Objective

We aim to study the relationship between occupation distribution within each county and COVID-19 cumulative incidence and vaccination rate in the United States.

Methods

We collected county-level data from January 22, 2020 up to December 25, 2021. We fit multivariate linear models to find the relationship of the percentage of people employed by 23 main occupations.

Results

Counties with more health-related jobs, office support roles, community service, sales, production and material moving occupations had higher COVID-19 cumulative incidence. During the uptick of the “Delta” COVID variant (stratified period July 1-Dec 25), counties with more transportation occupations had significantly more COVID-19 cumulative incidence than before.

Significance

Understanding the association between occupations and COVID-19 cumulative incidence on an ecological level can provide information for precision public health strategies for prevention and protecting vulnerable workers.

Impact Statement

We used data from US Census and COVID-19 data to explore the association between occupations and COVID-19 cumulative incidence and vaccination rate on an ecological level, which can provide information for precision public health strategies for prevention of spread of disease and protecting vulnerable workers.
SARS-CoV-2 VARIANT PREVALENCE ESTIMATION USING WASTEWATER SAMPLES
Authors: López-de-Ullibarri I. , Tomás L. , Trigo-Tasende N. , Freire B. , Vaamonde M. , Gallego-García P. , Barbeito I. , Vallejo J.A. , Tarrío-Saavedra J. , Alvariño P. , Beade E. , Estévez N. , Rumbo-Feal S. , Conde-Pérez K. , de Chiara L. , Iglesias-Corrás I. , Poza M. , Ladra S. , Posada D. , Cao R.
Published: January 2023

The present work describes a statistical model to account for sequencing information of SARS-CoV-2 variants in wastewater samples. The model expresses the joint probability distribution of the number of genomic reads corresponding to mutations and non-mutations in every locus in terms of the variant proportions and the joint mutation distribution within every variant. Since the variant joint mutation distribution can be estimated using GISAID data, the only unknown parameters in the model are the variant proportions. These are estimated using maximum likelihood. The method is applied to monitor the evolution of variant proportions using genomic data coming from wastewater samples collected in A Coruña (NW Spain) in the period May 2021 – March 2022. Although the procedure is applied assuming independence among the number of reads along the genome, it is also extended to account for Markovian dependence of counts along loci in the aggregated information coming from wastewater samples.
Consistency of left ventricular ejection fraction measurements in the early time course of STEMI
Authors: Georgieva Lilyana , Nienhaus Fabian T. , Haberkorn Sebastian , Erkens Ralf , Polzin Amin , Wischmann Patricia , Ipek Rojda , Marjani Kian , Christidi Aikaterini , Roden Michael , Jung Christian , Bönner Florian , Kelm Malte , Perings Stefan , Gastl Mareike
Published: January 2023

Structured Abstract

Background

Assessment of left ventricular (LV) function and volume after ST-segment elevation myocardial infarction (STEMI) is recommended to guide clinical decision within and after hospitalization. Early after STEMI, initial LV reshaping and hypokinesia may affect analysis of LV function. A comparative evaluation of left ventricular ejection fraction (LVEF) and stroke volume (SV) by different imaging modalities to assess LV function early after STEMI has not been performed so far.

Methods

LV function was assessed by LVEF and SV using serial imaging within 24h and 5 days after STEMI with cineventriculography (CVG), 2-dimensional echocardiography (2DE), 2D and 3D cardiovascular magnetic resonance (2D/3D) in 82 patients. Respective parameters were compared between modalities and to 3D gold standard CMR.

Results

2D analyses of LVEF using CVG and 2DE as well as 2D CMR yielded uniform results within 24h and 5 days of STEMI. SV assessment between CVG and 2DE at day 1 after STEMI was comparable, whereas values for SV were higher using 2D CMR on all occasions (p<0.01 all). This was due to higher LVEDV measurements. LVEF by 2D versus 3D CMR was comparable, 3D CMR yielded consistently higher volumetric values. This was not influenced by infarct location or infarct size.

Conclusions

Early after STEMI, 2D analysis of LVEF yielded robust results across all imaging techniques implying that CVG, 2DE, and 2D CMR can be used interchangeably in this setting. SV measurements to assess cardiac function differed substantially between imaging techniques due to higher intermodality-differences of absolute volumetric measurements.
Uncertainty aversion predicts the neural expansion of semantic representations
Authors: Vives Marc-Lluís , de Bruin Daantje , van Baar Jeroen M. , FeldmanHall Oriel , Bhandari Apoorva
Published: January 2023

Correctly identifying the meaning of a stimulus requires activating the appropriate semantic representation among many alternatives. One way to reduce this uncertainty is to differentiate semantic representations from each other, thereby expanding the semantic space. In four experiments, we test this semantic-expansion hypothesis, finding that uncertainty averse individuals exhibit increasingly differentiated and separated semantic representations. This effect is mirrored at the neural level, where uncertainty aversion predicts greater distances between activity patterns in the left inferior frontal gyrus when reading words, and enhanced sensitivity to the semantic ambiguity of these words in the ventromedial prefrontal cortex. Two direct tests of the behavioral consequences of semantic-expansion further reveal that uncertainty averse individuals exhibit reduced semantic interference and poorer generalization. Together, these findings demonstrate that the internal structure of our semantic representations is shaped in a principled manner: aversion to uncertainty acts as an organizing principle to make the world more identifiable.
Enhancing glymphatic function with very low-intensity ultrasound via the transient receptor potential vanilloid-4-aquaporin-4 pathway
Authors: Liao Wei-Hao , Wu Chueh-Hung , Chu Ya-Cherng , Hsiao Ming-Yen , Kung Yi , Wang Jaw-Lin , Chen Wen-Shiang
Published: January 2023

Recently, the glymphatic system has been proposed as a mechanism for waste clearance from the brain parenchyma. Glymphatic dysfunction has been associated with several neurological diseases such as Alzheimer’s disease, traumatic brain injury, and stroke. Therefore, it may be an important target for therapeutic interventions. In this study, we demonstrated that very low intensity ultrasound (VLIUS) (center frequency = 1 MHz; pulse repetition frequency = 1 kHz; duty factor = 1%, and spatial peak temporal average intensity [Ispta] = 3.68 mW/cm2; duration = 5 min) could significantly enhance the influx of cerebrospinal fluid tracers into the perivascular spaces of the brain and also facilitate interstitial substance clearance from the brain parenchyma. Notably, no evidence of brain damage was observed after VLIUS stimulation. We also demonstrated that VLIUS enhanced the glymphatic influx via the transient receptor potential vanilloid-4-aquaporin-4 pathway in the astrocytes. This mechanism may provide insights into VLIUS-regulated glymphatic function that modifies the natural course of central nervous system disorders related to waste clearance dysfunction.

One Sentence Summary

Very low-intensity ultrasound enhances glymphatic influx via the TRPV4-AQP4 pathway in the astrocytes, without observable brain damage.
2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified
Authors: Neto Nuno GB , Suku Meenakshi , Hoey David A. , Monaghan Michael G.
Published: January 2023

Human mesenchymal stem cells (hMSCs) fuel discrete biosynthetic pathways to multiply and differentiate into specific cell lineages; with undifferentiated hMSCs showing reliance on glycolysis. hMSCs differentiating towards an osteogenic phenotype rely on oxidative phosphorylation as an energy source. Here, the metabolic profile of hMSCs was profiled during osteogenic differentiation over 14 days using a non-invasive live-cell imaging platform- two-photon fluorescence lifetime imaging microscopy (2P-FLIM) which images and measures NADH fluorescence. During osteogenesis, we observe a higher dependence on oxidative phosphorylation for cellular energy; concomitant with an increased reliance on anabolic pathways. We validated this metabolic profile using qPCR and extracellular metabolite analysis and observed a higher reliance on glutaminolysis in the earlier time-points of osteogenic differentiation. Based on the results obtained, we sought to promote glutaminolysis further during osteogenic differentiation. An indirect method of promoting glutaminolysis was explored so as to not impact cellular differentiation. As Lactate has been shown to promote glutamine uptake via c-Myc activation triggering expression of glutamine transmembrane transporters and glutaminase 1; we chose to increase extracellular lactate concentrations to drive increased glutaminolysis rates leading to higher levels of mineral deposition and osteogenic gene expression. Lactate supplementation of osteogenic medium also promoted upregulation of lactate metabolism and increased the expression of transmembrane cellular lactate transporters. Higher rates of lactate dehydrogenase gene expression coupled with higher NADH fluorescence intensity demonstrate a conversion of lactate to pyruvate. During this conversion, NADH is formed by the reverse enzymatic reaction of lactate dehydrogenase resulting in increased NADH fluorescence intensity. In order to evaluate the importance of glutaminolysis and lactate metabolism in osteogenic differentiation, these metabolic pathways were shut down using BPTES and α-CHC respectively which led to reduced hMSC mineralisation. In summary, we demonstrate that hMSCs osteogenic differentiation has a temporal metabolic profile and shift that is observed as early as day 3 of cell culture. Osteogenic differentiation was demonstrated to be directly dependent on OxPhos and on glutaminolysis and validated using biochemical assays. Furthermore, extracellular lactate is an essential metabolite to ensure osteogenic differentiation as a metabolic fuel and signalling molecule to promote glutaminolysis. These findings have significant impact in generating potent approaches towards bone tissue engineeringin vitroandin vivoby engaging directly with metabolite driven osteogenesis.