A scalable, spin-free approach to generate enhanced induced pluripotent stem cell-derived natural killer cells for cancer immunotherapy.

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges.

One Health: Urban birds peck up resistant pathogens.

A spatial-genomic analysis reveals that bird species living closer to humans have higher diversity of the pathogen Campylobacter and its antimicrobial resistance genes. This suggests that urbanization could promote pathogen transmission among wild animals and, potentially, humans.

Breathy Voice as a Compensatory Strategy for Essential Vocal Tremor: A Single Case Experiment Across Participants.

Objective: Essential vocal tremor (EVT) manifests as nearly rhythmic modulations of fundamental frequency (f) and intensity and causes a shaky voice. Although research on behavioral therapy for EVT is limited, previous studies have shown that a breathy voice reduces the perception of simulated EVT and might be an effective compensatory strategy. The current study aimed to measure the acoustical and perceptual effects of a breathy voice strategy in speakers with EVT.

AR eGFP reporter mouse enables elucidation of AR expression dynamics during anti-tumor immune responses.

There is significant clinical interest in targeting adenosine-mediated immunosuppression, with several small molecule inhibitors having been developed for targeting the AR receptor. Understanding of the mechanism by which AR is regulated has been hindered by difficulty in identifying the cell types that express AR due to a lack of robust antibodies for these receptors. To overcome this limitation, here an AR eGFP reporter mouse is developed, enabling the expression of AR during ongoing anti-tumor immune responses to be assessed.

Defect characterization in optical coatings using scattered light.

Optical coatings play a vital role in sensing technologies. The development of new coatings that exhibit minimal optical losses requires a detailed understanding of the development of defects within them. Current methods of defect characterization involve direct microscope imaging or x-ray diffraction studies in the case of crystallites.

CRISPR-Cas9 screening identifies an IRF1-SOCS1-mediated negative feedback loop that limits CXCL9 expression and antitumor immunity.

CXCL9 expression is a strong predictor of response to immune checkpoint blockade therapy. Accordingly, we sought to develop therapeutic strategies to enhance the expression of CXCL9 and augment antitumor immunity. To perform whole-genome CRISPR-Cas9 screening for regulators of CXCL9 expression, a CXCL9-GFP reporter line is generated using a CRISPR knockin strategy.

Distinct modulation of IFNγ-induced transcription by BET bromodomain and catalytic P300/CBP inhibition in breast cancer.

Background: Interferon gamma (IFNγ) is a pro-inflammatory cytokine that directly activates the JAK/STAT pathway. However, the temporal dynamics of chromatin remodeling and transcriptional activation initiated by IFNγ have not been systematically profiled in an unbiased manner. Herein, we integrated transcriptomic and epigenomic profiling to characterize the acute epigenetic changes induced by IFNγ stimulation in a murine breast cancer model.

CD4 chimeric antigen receptor T cells in for the long journey.

In a recently published article, Melenhorst et al. performed a longitudinal analysis on chimeric antigen receptor (CAR) T cells isolated from patients over 10 years after therapy, revealing expansion of a long-lived CD4 CAR T-cell population with a cytotoxic phenotype.

Characterization of Source-Filter Interactions in Vocal Vibrato Using a Neck-Surface Vibration Sensor: A Pilot Study.

Purpose: Vocal vibrato is a singing technique that involves periodic modulation of fundamental frequency (f) and intensity. The physiological sources of modulation within the speech mechanism and the interactions between the laryngeal source and vocal tract filter in vibrato are not fully understood. Therefore, the purpose of this study was to determine if differences in the rate and extent of f and intensity modulation could be captured using simultaneously recorded signals from a neck-surface vibration sensor and a microphone, which represent features of the source before and after supraglottal vocal tract filtering.

Impact of a Devastating Brain Injury Pathway on Outcomes, Resources, and Organ Donation: 3 Years' Experience in a Regional Neurosciences ICU.

Objective: To assess the impact of introducing a devastating brain injury (DBI) pathway on patient outcome, intensive care unit (ICU) resources, and organ donation practice in the first 3 years of implementation in a regional neurosciences ICU in the South West of England.

Methods: Patients with DBI admitted to our ICU between 2015 and 2018 were identified from our ICU database and their outcomes compared to those of non-DBI patients. Data were also obtained from the national potential donor audit to compare organ donation metrics before and after the introduction of the DBI pathway.

Ewing Sarcoma of the Pelvis with an Atypical Radiographic Appearance: A Mimicker of Non-malignant Etiologies.

Ewing sarcoma (ES) is a primary malignant bone tumor which most commonly arises in children and young adults. The common clinical presentation with ES includes nighttime pain or pain related to activity, though patients may also present with a combination of localized swelling, a palpable mass, pathologic fracture, and constitutional symptoms. Clinical diagnosis may be delayed when a patient presents with clinical or imaging findings that overlap with non-malignant etiologies, such as fibrous dysplasia (FD) or osteomyelitis.

Effectiveness of a Medical vs Revascularization Intervention for Intermittent Leg Claudication Based on Patient-Reported Outcomes.

Importance: Intermittent claudication (IC) is the most common presentation of infrainguinal peripheral artery disease. Both medical and revascularization interventions for IC aim to increase walking comfort and distance, but there is inconclusive evidence of the comparative benefit of revascularization given the possible risk of limb loss.

Objective: To compare the effectiveness of a medical (walking program, smoking cessation counseling, and medications) vs revascularization (endovascular or surgical) intervention for IC in the community, focusing on outcomes of greatest importance to patients.

Myocardial Fatty Foci in Tuberous Sclerosis Complex: Imaging Findings.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic syndrome. The hallmark of the disease is multiple hamartomatous lesions in multiple organ systems. Common cardiac manifestations of TSC are rhabdomyomas, which are a benign tumor of striated muscle.

Peroneus Tertius Tendon Tear: A Rare Cause of Lateral Ankle Pain.

The peroneus tertius (PT) muscle is a variably present muscle, uncommonly found in humans. Injury to the PT tendon is rare with virtually no cases reported in the literature. As a consequence of the rarity of this injury, there is little clinical information regarding injury or rupture of the PT muscle and tendon.

Unilateral Absence of the Left Pulmonary Artery With an Associated Vascular Anomaly in Adulthood.

Left-sided pulmonary artery agenesis is a rare malformation that commonly requires childhood intervention secondary to associated congenital cardiovascular anomalies. We present an uncommon case of left-sided agenesis with an associated right-sided aortic arch and significant hypoplasia of the ipsilateral lung. Additionally, there is radiographic evidence of emphysema and pulmonary artery hypertension.

Solitary Fibrous Tumor of the Kidney: A Case Report and Literature Review.

Solitary fibrous tumors are neoplasms of mesenchymal origin that may occur virtually in any body part, most commonly arising from the pleura. Solitary fibrous tumor of the kidney is exceptionally rare, and limited clinical knowledge regarding its behavior makes prognosis of the neoplasm difficult. We report a case of solitary fibrous tumor of the left kidney and describe its clinical, imaging, and pathological features.

RNAi Screening with Self-Delivering, Synthetic siRNAs for Identification of Genes That Regulate Primary Human T Cell Migration.

Screening of RNA interference (RNAi) libraries in primary T cells is labor-intensive and technically challenging because these cells are hard to transfect. Chemically modified, self-delivering small interfering RNAs (siRNAs) offer a solution to this problem, because they enter hard-to-transfect cell types without needing a delivery reagent and are available in library format for RNAi screening. In this study, we have screened a library of chemically modified, self-delivering siRNAs targeting the expression of 72 distinct genes in conjunction with an image-based high-content-analysis platform as a proof-of-principle strategy to identify genes involved in lymphocyte function-associated antigen-1 (LFA-1)-mediated migration in primary human T cells.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

Background: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV).

Objectives: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K.