Spontaneous blinking and brain health in aging: Large-scale evaluation of blink-related oscillations across the lifespan.

Blink-related oscillations (BROs) are newly discovered neurophysiological brainwave responses associated with spontaneous blinking, and represent environmental monitoring and awareness processes as the brain evaluates new visual information appearing after eye re-opening. BRO responses have been demonstrated in healthy young adults across multiple task states and are modulated by both task and environmental factors, but little is known about this phenomenon in aging. To address this, we undertook the first large-scale evaluation of BRO responses in healthy aging using the Cambridge Centre for Aging and Neuroscience (Cam-CAN) repository, which contains magnetoencephalography (MEG) data from a large sample ( = 457) of healthy adults across a broad age range (18-88) during the performance of a simple target detection task.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

Clinical Validation of a Prenatal Cell-Free DNA Screening Test for Fetal RHD in a Large U.S. Cohort.

Objective: To present a large U.S. clinical validation of a next-generation sequencing-based, noninvasive prenatal cell-free DNA test for fetal RHD .

Tau, synapse loss and gliosis progress in an Alzheimer's mouse model after amyloid-β immunotherapy.

While preclinical studies assessing drugs for Alzheimer's disease (AD) are conducted in animal models that usually display only one neuropathological feature of AD, patients present with a complex combination of comorbidities and neuropathologies. Importantly, it is well-established that amyloid (Aβ) plaque and tau tangle accumulation interact in a phase-dependent manner, making it difficult to predict how targeting one might influence the other, as well as downstream degeneration. We developed a transgenic mouse model, APP/PS1xTau22, with progressive cortical Aβ deposition and hippocampal tau neurofibrillary inclusions to investigate how both neuropathologies act jointly to bring about neural degeneration, synapse loss, and glial phenotypes.

Secondary thalamic dysfunction underlies abnormal large-scale neural dynamics in chronic stroke.

Stroke causes pronounced and widespread slowing of neural activity. Despite decades of work exploring these abnormal neural dynamics and their associated functional impairments, their causes remain largely unclear. To close this gap in understanding, we applied a neurophysiological corticothalamic circuit model to simulate magnetoencephalography (MEG) power spectra recorded from chronic stroke patients.

A program for real-time surveillance of SARS-CoV-2 genetics.

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.

Protocol for assessing GD2 on formalin-fixed paraffin-embedded tissue sections using immunofluorescence staining.

The detection of disialoganglioside GD2 on tumor biopsies, especially in paraffin-embedded tissues, has been challenging due to the glycolipid structure of GD2 and its membrane anchorage. Here, we present an immunofluorescence protocol for the reliable assessment of GD2 on formalin-fixed paraffin-embedded (FFPE) tissues. We describe steps for antigen retrieval with Tris-EDTA buffer and staining with unconjugated anti-GD2 antibody (clone 14.

Determinants of remote measurement-based care uptake in a safety net outpatient psychiatry department as part of learning health system transition.

Introduction: Behavioral measurement-based care (MBC) can improve patient outcomes and has also been advanced as a critical learning health system (LHS) tool for identifying and mitigating potential disparities in mental health treatment. However, little is known about the uptake of remote behavioral MBC in safety net settings, or possible disparities occurring in remote MBC implementation.

Methods: This study uses electronic health record data to study variation in completion rates at the clinic and patient level of a remote MBC symptom measure tool during the first 6 months of implementation at three adult outpatient psychiatry clinics in a safety net health system.

APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease.

Epidemiological studies show that individuals who carry the relatively uncommon APOE ε2 allele rarely develop Alzheimer disease, and if they do, they have a later age of onset, milder clinical course, and less severe neuropathological findings than people without this allele. The contrast is especially stark when compared with the major genetic risk factor for Alzheimer disease, APOE ε4, which has an age of onset several decades earlier, a more aggressive clinical course and more severe neuropathological findings, especially in terms of the amount of amyloid deposition. Here, we demonstrate that brain exposure to APOE ε2 via a gene therapy approach, which bathes the entire cortical mantle in the gene product after transduction of the ependyma, reduces Aβ plaque deposition, neurodegenerative synaptic loss, and, remarkably, reduces microglial activation in an APP/PS1 mouse model despite continued expression of human APOE ε4.

Blink-Related Oscillations Provide Naturalistic Assessments of Brain Function and Cognitive Workload within Complex Real-World Multitasking Environments.

Background: There is a significant need to monitor human cognitive performance in complex environments, with one example being pilot performance. However, existing assessments largely focus on subjective experiences (e.g.

Contrasting MEG effects of anodal and cathodal high-definition TDCS on sensorimotor activity during voluntary finger movements.

Introduction: Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation.

Cognitive components of aging-related increase in word-finding difficulty.

Word-finding difficulty (WFD) is a common cognitive complaint in aging, manifesting both in natural speech and in controlled laboratory tests. Various theories of cognitive aging have addressed WFD, and understanding its underlying mechanisms can help to clarify whether it has diagnostic value for neurodegenerative disease. Two influential "information-universal" theories attribute it to rather broad changes in cognition.

Safety and effectiveness of the radium-223-taxane treatment sequence in patients with metastatic castration-resistant prostate cancer in a global observational study (REASSURE).

Background: Radium-223 and taxane chemotherapy each improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). Whether the radium-223-taxane sequence could extend survival without cumulative toxicity was explored.

Methods: The global, prospective, observational REASSURE study (NCT02141438) assessed real-world safety and effectiveness of radium-223 in patients with mCRPC.

Enhanced mind-matter interactions following rTMS induced frontal lobe inhibition.

A major barrier to acceptance of psi is that effects are small and hard to replicate. To address this issue, we developed a novel neurobiological model to study this controversial phenomenon based upon the concept that the brain may act as a psi-inhibitory filter. Our previous research in individuals with frontal lobe damage suggests that this filter includes the left medial middle frontal region.

APOE2 gene therapy reduces amyloid deposition, and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease.

Unlabelled: Epidemiological studies show that individuals who carry the relatively uncommon APOE ε2 allele rarely develop Alzheimer disease, and if they do they have a later age of onset, milder clinical course, and less severe neuropathological findings than others with Alzheimer disease. The contrast is especially stark in comparison to the phenotype associated with the major genetic risk factor for Alzheimer disease, APOE ε4, which has an age of onset several decades earlier, as well as a more aggressive clinical course and notably more severe neuropathological findings, especially in terms of the amount of amyloid deposition. Even one APOE ε2 allele improves phenotype, but it is uncertain if that is due to the replacement of a more toxic allele by APOE ε2, or if APOE ε2 has a protective, neuro-modulatory effect.

CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process.

To enhance the potency of chimeric antigen receptor (CAR) engineered T cells in solid cancers, we designed a novel cell-based combination strategy with an additional therapeutic mode of action. CAR T cells are used as micropharmacies to produce a targeted pro-coagulatory fusion protein, truncated tissue factor (tTF)-NGR, which exerts pro-coagulatory activity and hypoxia upon relocalization to the vascular endothelial cells that invade tumor tissues. Delivery by CAR T cells aimed to induce locoregional tumor vascular infarction for combined immune-mediated and hypoxic tumor cell death.

Integrated CRISPR screening and drug profiling identifies combination opportunities for EGFR, ALK, and BRAF/MEK inhibitors.

Anti-tumor efficacy of targeted therapies is variable across patients and cancer types. Even in patients with initial deep response, tumors are typically not eradicated and eventually relapse. To address these challenges, we present a systematic screen for targets that limit the anti-tumor efficacy of EGFR and ALK inhibitors in non-small cell lung cancer and BRAF/MEK inhibitors in colorectal cancer.

Maternal Malignancy After Atypical Findings on Single-Nucleotide Polymorphism-Based Prenatal Cell-Free DNA Screening.

Objective: To evaluate the incidence and clinical outcomes of cell-free DNA results suspicious for maternal malignancy on prenatal cell-free DNA screening with single-nucleotide polymorphism (SNP)-based technology.

Methods: This retrospective cohort study included data from SNP-based, noninvasive prenatal screening samples from a commercial laboratory from January 2015 to October 2021. Maternal plasma was screened for trisomy 21, 18, and 13; monosomy X; and triploidy.

Success in Supporting Early Mobility and Exercise in a Cardiothoracic Intensive Care Unit.

Early mobility contributes to improved patient outcomes and reduced hospital length of stay during acute and intensive care hospitalization. The Bedside Mobility Assessment Tool was implemented in a cardiothoracic intensive care unit during participation in a nationwide evidence-based quality improvement initiative. One outcome included a high level of mobility that was sustained over time.

Surgical stabilization of rib fractures in patients with pulmonary comorbidities.

Introduction: Prior studies have shown that the surgical stabilization of rib fractures (SSRF) for patients with multiple rib fractures is associated with improved outcomes by restoring chest wall integrity and decreasing time to return to prior functional status. It is unclear if patients with pulmonary comorbidities (PCM) would benefit from this procedure.

Objective: To compare the difference in morbidity and mortality of patients with multiple rib fractures undergoing SSRF who have underlying PCM to those who do not have PCM.

Spectral slowing in chronic stroke reflects abnormalities in both periodic and aperiodic neural dynamics.

Decades of electrophysiological work have demonstrated the presence of "spectral slowing" in stroke patients - a prominent shift in the power spectrum towards lower frequencies, most evident in the vicinity of the lesion itself. Despite the reliability of this slowing as a marker of dysfunctional tissue across patient groups as well as animal models, it has yet to be explained in terms of the pathophysiological processes of stroke. To do so requires clear understanding of the neural dynamics that these differences represent, acknowledging the often overlooked fact that spectral power reflects more than just the amplitude of neural oscillations.

Asynchronous, online spaced-repetition training alleviates word-finding difficulties in aphasia.

Word-finding difficulties for naming everyday objects are often prevalent in aphasia. Traditionally, treating these difficulties has involved repeated drilling of troublesome items with a therapist. Spaced repetition schedules can improve the efficiency of such training.