Understanding TCR T cell knockout behavior using interpretable machine learning.

Genetic perturbation of T cell receptor (TCR) T cells is a promising method to unlock better TCR T cell performance to create more powerful cancer immunotherapies, but understanding the changes to T cell behavior induced by genetic perturbations remains a challenge. Prior studies have evaluated the effect of different genetic modifications with cytokine production and metabolic activity assays. Live-cell imaging is an inexpensive and robust approach to capture TCR T cell responses to cancer.

Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Development and Implementation of a Basic Veterinary Ultrasound Curriculum.

Diagnostic ultrasound is an important imaging modality in veterinary medicine. Surveys of veterinarians suggest that ultrasound is a desired clinical competence and that new graduates are expected to practice basic ultrasound skills. This report describes the development and implementation of a basic ultrasound training program in the core curriculum at Iowa State University College of Veterinary Medicine (ISU-CVM).

Fulfilling moral duty or prioritizing moral image? The moral self-regulatory consequences of ethical voice.

Previous research on the consequences of ethical voice has largely focused on the performance or social relational consequences of ethical voice on multiple organizational stakeholders. The present research provides an important extension to the ethical voice literature by investigating the distinct intrapersonal and interpersonal moral self-regulatory processes that shape ethical voicers' own psychological experiences and their subsequent purposeful efforts to maintain a positive sense of moral self. On one hand, we argue that ethical voice heightens voicers' sense of responsibility over ethical matters at work (i.

Future Directions and Innovations in Venous Sinus Stenting.

This review explores the future role of venous sinus stenting (VSS) in the management of idiopathic intracranial hypertension and pulsatile tinnitus. Despite its favorable safety profile and clinical outcomes compared with traditional treatments, VSS is not yet the standard of care for these conditions, lacking high-level evidence data and guidelines for patient selection and indications. Current and recently completed clinical trials are expected to provide data to support the adoption of VSS as a primary treatment option.

Challenges in the use of Venous Sinus Stenting in the Treatment of Idiopathic Intracranial Hypertension and Pulsatile Tinnitus.

Although numerous case series and meta-analyses have shown the efficacy of venous sinus stenting (VSS) in the treatment of idiopathic intracranial hypertension and idiopathic intracranial hypertension-associated pulsatile tinnitus, there remain numerous challenges to be resolved. There is no widespread agreement on candidacy; pressure gradient and failed medical treatment are common indications, but not all clinicians require medical refractoriness as a criterion. Venous manometry, venography, and cerebral angiography are essential tools for patient assessment, but again disagreements exist regarding the best, or most appropriate, diagnostic imaging choice.

Foundations of the Diagnosis and Management of Idiopathic Intracranial Hypertension and Pulsatile Tinnitus.

Venous sinus stenosis has garnered increasing academic attention as a potential etiology of idiopathic intracranial hypertension (IIH) and pulsatile tinnitus (PT). The complex anatomy of the cerebral venous sinuses and veins plays a crucial role in the pathophysiology of these conditions. Venous sinus stenosis, often found in the superior sagittal or transverse sinus, can lead to elevated intracranial pressure (ICP) and characteristic IIH symptoms.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

Background: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms.

The Endoscopic Lateral Transorbital Approach for the Removal of Select Sphenoid Wing and Middle Fossa Meningiomas. Surgical Technique and Short-Term Outcomes.

Background And Objective: The endoscopic lateral transorbital approach (eLTOA) is a relatively new approach to the skull base that has only recently been applied in vivo in the management of complex skull base pathology. Most meningiomas removed with this approach have been in the spheno-orbital location. We present a series of select purely sphenoid wing and middle fossa meningiomas removed through eLTOA.

Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.

Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors.

Minimizing blood loss with direct percutaneous polymethylmethacrylate embolization before corpectomy for vascular spinal tumors.

Background: Standard surgical treatment for vascular spinal tumors, including renal cell carcinomas and hemangiomas, may result in significant blood loss despite preoperative arterial tumor embolization.

Methods: This is a retrospective review of 12 patients who underwent direct percutaneous polymethylmethacrylate embolization (DPPE) with or without feeding artery embolization before partial or complete corpectomy for the resection of vascular spinal tumors (2013-2018). Estimated blood loss (EBL) was compared to the blood loss reported in the literature and to patients receiving standard arterial embolization before surgery.

Atrophy and Severe Kinking of Trigeminal Nerve Root by Duplicate Trunks of Superior Cerebellar Artery in an Elderly Patient with Trigeminal Neuralgia.

Trigeminal neuralgia, or tic douloureux, clinically presents as a unilateral paroxysmal, stabbing, intense pain of the face, lasting for seconds but occurring frequently. Alternative causes including multiple sclerosis or mass of the brainstem or cranial nerves must be ruled out. Medical treatment, most commonly with carbamazepine, remains an effective first-line treatment.

The butt of the joke: Understanding the social evaluations of leader humor targets.

Research on humor at work has tended to focus on either the social evaluations formed about the source of humor or the interpersonal consequences that accompany the use of humor. Yet, research suggests that the targets of humor - such as a follower who is the punchline of her leader's jokes - face their own unique judgements and impressions from the social environment. Indeed, humor directed toward another person can communicate important information about the individual and can shape how others perceive and evaluate them.

Lateral Transorbital Endoscope-Assisted Approach to the Cavernous Sinus.

Background And Objectives: Surgical access to the cavernous sinus (CS) poses a unique challenge to the neurosurgeon given the concentration of delicate structures in the confines of a very small anatomic space. The lateral transorbital approach (LTOA) is a minimally invasive, keyhole approach that can provide direct access to the lateral CS.

Methods: A retrospective review of CS lesions treated by a LTOA at a single institution was performed between 2020 and 2023.

Endonasal, supraorbital, and transorbital approaches: minimal access endoscope-assisted surgical approaches for meningiomas in the anterior and middle cranial fossae.

Objective: Minimally invasive endoscope-assisted approaches to the anterior skull base offer an alternative to traditional open craniotomies. Given the restrictive operative corridor, appropriate case selection is critical for success. In this paper, the authors present the results of three different minimal access approaches to meningiomas of the anterior and middle fossae and examine the differences in the target areas considered appropriate for each approach, as well as the outcomes, to determine whether the surgical goals were achieved.