Harvest of Vestibular End-Organs under Physiologic Conditions during Labyrinthectomy.

The living human inner ear is challenging to study because it is encased within dense otic capsule bone that limits access to biological tissue. Traditional temporal bone histopathology methods rely on lengthy, expensive decalcification protocols that take 9-10 months and reduce the types of tissue analysis possible due to RNA degradation. There is a critical need to develop methods to access fresh human inner ear tissue to better understand otologic diseases, such as Ménière's disease, at the cellular and molecular level.

Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.

The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1 disease.

Lockbox enrichment facilitates manipulative and cognitive activities for mice.

Background: Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing (CH) and super-environmental enrichment (SEE).

Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors - a biomarker analysis of the ALICE and ICON trials.

Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy.

Peripheral immune cells in metastatic breast cancer patients display a systemic immunosuppressed signature consistent with chronic inflammation.

Immunotherapies blocking the PD-1/PD-L1 checkpoint show some efficacy in metastatic breast cancer (mBC) but are often hindered by immunosuppressive mechanisms. Understanding these mechanisms is crucial for personalized treatments, with peripheral blood monitoring representing a practical alternative to repeated biopsies. In the present study, we performed a comprehensive mass cytometry analysis of peripheral blood immune cells in 104 patients with HER2 negative mBC and 20 healthy donors (HD).

Traumatic Events Preceding the Development of Superior Canal Dehiscence Syndrome.

Objective: To describe the features of antecedent head trauma in patients with superior canal dehiscence syndrome (SCDS).

Study Design: Cross-sectional survey.

Setting: Tertiary referral center.

Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: a randomized phase 2b trial.

Background: Immune checkpoint inhibitors have shown minimal clinical activity in hormone receptor-positive metastatic breast cancer (HRmBC). Doxorubicin and low-dose cyclophosphamide are reported to induce immune responses and counter regulatory T cells (Tregs). Here, we report the efficacy and safety of combined programmed cell death protein-1/cytotoxic T-lymphocyte-associated protein 4 blockade concomitant with or after immunomodulatory chemotherapy for HRmBC.

Cochlear Implant Electrode Array Design and Speech Understanding.

Objective: Cochlear implant electrode arrays are categorized based on their design as lateral wall (LW) and perimodiolar (PM) electrode arrays. The objective of this study was to investigate the effect of LW versus PM designs on postoperative speech perception across multiple manufacturers and over long follow-up durations.

Design: Retrospective cohort study.

Association Between Retinal Pathology and Hearing in Older Adults.

We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions.

Relativistic ultrafast electron diffraction at high repetition rates.

The ability to resolve the dynamics of matter on its native temporal and spatial scales constitutes a key challenge and convergent theme across chemistry, biology, and materials science. The last couple of decades have witnessed ultrafast electron diffraction (UED) emerge as one of the forefront techniques with the sensitivity to resolve atomic motions. Increasingly sophisticated UED instruments are being developed that are aimed at increasing the beam brightness in order to observe structural signatures, but so far they have been limited to low average current beams.

Development of deflector mode for spin-resolved time-of-flight photoemission spectroscopy.

Spin- and angle-resolved photoemission spectroscopy ("spin-ARPES") is a powerful technique for probing the spin degree-of-freedom in materials with nontrivial topology, magnetism, and strong correlations. Spin-ARPES faces severe experimental challenges compared to conventional ARPES attributed to the dramatically lower efficiency of its detection mechanism, making it crucial for instrumentation developments that improve the overall performance of the technique. In this paper, we demonstrate the functionality of our spin-ARPES setup based on time-of-flight spectroscopy and introduce our recent development of an electrostatic deflector mode to map out spin-resolved band structures without sample rotation.

Challenges and advanced concepts for the assessment of learning and memory function in mice.

The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments.

Longitudinal Auditory Benefit for Elderly Patients After Cochlear Implant for Bilateral Hearing Loss, Including Those Meeting Expanded Centers for Medicare & Medicaid Services Criteria.

Objective: To examine the effect of patient age on longitudinal speech understanding outcomes after cochlear implantation (CI) in bilateral hearing loss.

Study Design: Retrospective cohort study.

Setting: Tertiary academic center.

Cochlear Implant Revisions Over Three Decades of Experience.

Importance: The indications, technology, and surgical technique for cochlear implantation have evolved over the last three decades. Understanding the risk of cochlear implant revision (CIR) is important for patient counseling.

Objective: The objective of this study was to analyze the rates, indications, and audiologic outcomes for CIR over three decades of experience at a single academic medical center.

Outcomes after revision of Advanced Bionics Clarion 1.2 cochlear implants.

Introduction: Cochlear implant reimplantation (CIR) for external processor upgrade or device failure is becoming increasingly common as the population of cochlear implant recipients ages. Patients with Advanced Bionics (AB) Clarion 1.2 cochlear implants may undergo CIR for device age/failure or desired technology upgrade so that they may use newer external processors that have improved connectivity features.

Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens.

Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in EOC.

Sex and Race Representation in Temporal Bone Histopathology Studies in the United States: A Systematic Review.

Objectives: The author's objective was to evaluate sex and race representation in temporal bone histopathology studies.

Design: PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for studies written in English examining temporal bone histopathology specimens from U.S.

Otolith Membrane Herniation, not Semicircular Canal Duct Dilation, Is Associated with Decreased Caloric Responses in Ménière's Disease.

Ménière's disease (MD) is a debilitating disorder with unclear pathophysiology whose diagnosis often relies on clinical judgment rather than objective testing. To complicate matters further, a dissociation has emerged between two vestibular function tests commonly used in patients with MD to examine the same end-organ (the semicircular canals): the caloric test and video head impulse testing (vHIT). Caloric responses are often abnormal, while vHIT results remain normal.

Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial.

Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1 disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 , 24 May 2017) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28).

Are Speech Perception Scores in Cochlear Implant Recipients Consistent Across Different Tests?

Objective: Cochlear implant (CI) candidacy and postoperative outcomes are assessed using sets of speech perception tests that vary from center to center, limiting comparisons across institutions and time periods. The objective of this study was to determine if scores on one speech perception test could be reliably predicted from scores on another test.

Study Design: Arizona Biomedical (AzBio) Sentence Test, Consonant-Nucleus-Consonant word (CNCw), and Hearing in Noise Test (HINT) scores in quiet for the implanted ear were collected for individuals who received a CI between 1985 and 2019.

The History of Otology and What We Can Learn from It: Putting Historical Research in Context.

Why study the history of scientific discovery in otology and neurotology? This is an especially important question in our surgical field, where standard mechanisms of medical science such as the randomized controlled trial are not feasible. Here, we discuss the benefits of engaging with the history of science including 1) gaining a fuller understanding of scientific methodology, 2) becoming critically aware of current knowledge and its gaps, 3) aiding diagnostic and therapeutic discovery, and 4) humanizing innovative thinking. Science is a human endeavor, and it is subject to the constraints inherent to humans.

Positioning for Middle Cranial Fossa Repair of Superior Semicircular Canal Dehiscence.

Superior semicircular canal dehiscence (SCD) repair through the middle cranial fossa approach is typically performed on a patient in the supine position and the patient’s head is turned to the contralateral side and secured with surgical pinions or supported on a headrest. However, traditional supine positioning method may place strain on the patient’s neck, limit the surgeon’s visualization of the dehiscence due to inadequate head rotation, and compromise the ergonomic positioning of the surgeon. Here, we present a novel positioning method for middle fossa SCD repair that allows for optimal head rotation in a semi-supine position, requires less set-up and patient manipulation than the park bench position, and does not require the use of surgical pins.

High-Speed Human Temporal Bone Sectioning for the Assessment of COVID-19-Associated Middle Ear Pathology.

Histopathologic analysis of human temporal bone sections is a fundamental technique for studying inner and middle ear pathology. Temporal bone sections are prepared by postmortem temporal bone harvest, fixation, decalcification, embedding, and staining. Due to the density of the temporal bone, decalcification is a time-consuming and resource-intensive process; complete tissue preparation may take 9-10 months on average.