Adeno-associated virus genome quantification with amplification-free CRISPR-Cas12a.

Efficient manufacturing of recombinant Adeno-Associated Viral (rAAV) vectors to meet rising clinical demand remains a major hurdle. One of the most significant challenges is the generation of large amounts of empty capsids without the therapeutic genome. There is no standardized analytical method to accurately quantify the viral genes, and subsequently the empty-to-full ratio, making the manufacturing challenges even more complex.

Development and Delivery of a Hands-On Short Course in Adeno-Associated Virus Manufacturing to Support Growing Workforce Needs in Gene Therapy.

The manufacturing of gene therapy products is a rapidly growing industry bolstered by the tremendous potential of these therapies to provide lifesaving treatment for rare and complex genetic diseases. The industry's steep rise has resulted in a high demand for skilled staff required to manufacture gene therapy products of the expected high quality. To address this skill shortage, more opportunities for education and training in all aspects of gene therapy manufacturing are needed.

Flexible sensor patch for continuous carbon dioxide monitoring.

Monitoring and measurement of carbon dioxide (CO) is critical for many fields. The gold standard CO sensor, the Severinghaus electrode, has remained unchanged for decades. In recent years, many other CO sensor formats, such as detection based upon pH-sensitive dyes, have been demonstrated, opening the door for relatively simple optical detection schemes.

An Integrated Model to Accelerate Patient Satisfaction Improvement.

Patient satisfaction is gaining traction in the strategic direction and daily operations of hospital executives. The financial penalty/incentive tied to patient satisfaction scores creates a burning platform to accelerate progress. Previous studies have shown the effectiveness of various improvement strategies including leadership rounding and employee training, among others.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.

BacMam production and crystal structure of nonglycosylated apo human furin at 1.89 Å resolution.

Furin, also called proprotein convertase subtilisin/kexin 3 (PCSK3), is a calcium-dependent serine endoprotease that processes a wide variety of proproteins involved in cell function and homeostasis. Dysregulation of furin has been implicated in numerous disease states, including cancer and fibrosis. Mammalian cell expression of the furin ectodomain typically produces a highly glycosylated, heterogeneous protein, which can make crystallographic studies difficult.

Sex-based outcomes in type I thyroplasty for nonparalytic glottic incompetence.

Objective: Clinical outcomes for type I Gore-Tex thyroplasty (GMT) for nonparalytic glottic incompetence (GI) have been reported in the literature. Given differences in male and female laryngeal anatomy, sex-based outcomes should also be evaluated. We endeavored to evaluate sex-specific post-GMT voice outcomes.

Analysis of anterior and posterior maneuvers to enhance intraconal exposure.

Background: The medial and inferior recti encompass the ideal surgical corridor to approach the intraconal space endonasally. Here, we describe 3 different maneuvers to achieve greater access to orbital contents through an expanded endonasal approach (EEA).

Methods: Four human cadaver heads were dissected bilaterally (n = 8).

Maintenance avelumab versus continuation of first-line chemotherapy in gastric cancer: JAVELIN Gastric 100 study design.

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastatic gastric/gastroesophageal junction cancer, including as first-line maintenance therapy. Here, we describe the design of JAVELIN Gastric 100 (NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2- gastric/gastroesophageal junction cancer adenocarcinoma, who had achieved at least stable disease following 12 weeks of first-line oxaliplatin/fluoropyrimidine chemotherapy, have been randomized 1:1 to receive avelumab maintenance therapy or continue chemotherapy.

Conscious Perception of Facial Asymmetry in a Unilateral Cleft Lip Model.

Objective: Lip asymmetry after a unilateral cleft lip repair can be perceived as an unsatisfactory result. The objective of this study is to determine the degree of upper lip asymmetry and/or nasal alar hooding required for recognition of asymmetry in a simulated model of unilateral cleft lip.

Design: A model of unilateral cleft lip was created using digital morphing software to simulate asymmetries in vermilion height and nasal hooding in photographs of children.

Hypovolemic shock after labial and lingual frenulectomy: A report of two cases.

Lingual and labial frenulectomy are commonly performed as an outpatient procedure, either in an office setting or under general anesthesia. Frenulectomy is generally regarded by both otolaryngologists and dentists as a straightforward and low-risk procedure with limited evidence-based indications and similarly few contraindications. We describe two cases of hypovolemic shock occurring after outpatient frenulectomy requiring emergent interventions of cardiopulmonary resuscitation and blood transfusion.

Trial Vocal Fold Injection Predicts Thyroplasty Outcomes in Nonparalytic Glottic Incompetence.

Objectives: Trial vocal fold injection (TVFI) may be used prior to permanent medialization when voice outcome is uncertain. We aimed to determine whether voice outcomes of TVFI are predictive of, or correlate with outcomes after type I Gore-Tex medialization thyroplasty (GMT) in patients with nonparalytic glottic incompetence (GI).

Methods: Thirty-five patients with nonparalytic GI who underwent TVFI followed by GMT were retrospectively reviewed.

Longitudinal Voice Outcomes After Type I Gore-tex Thyroplasty for Nonparalytic Glottic Incompetence.

Objective: Type I Gore-tex thyroplasty (GTP) for nonparalytic glottic incompetence (GI) results in significantly improved subjective and perceptual voice outcomes. We endeavored to investigate the longitudinal course of voice outcomes measuring the same patients across time points stratified by diagnostic subgroup.

Methods: Seventy-five patients with nonparalytic GI treated with GTP in the past 9 years were retrospectively reviewed and grouped according to their primary diagnoses (atrophy, scar, hypomobility, and paresis).

Carotid artery and lower cranial nerve exposure with increasing surgical complexity to the parapharyngeal space.

Objectives/hypothesis: To investigate the extent of carotid artery exposure attained, including the identification of the external carotid branches and lower cranial nerves in five sequential external approaches to the parapharyngeal space, and to provide an anatomical algorithm.

Study Design: Anatomical study.

Methods: Six latex-injected adult cadaver heads were dissected in five consecutive approaches: transcervical approach with submandibular gland removal, posterior extension of the transcervical approach, transcervical approach with parotidectomy, parotidectomy with lateral mandibulotomy, and parotidectomy with mandibulectomy.

Protein Expression in Insect and Mammalian Cells Using Baculoviruses in Wave Bioreactors.

Many types of disposable bioreactors for protein expression in insect and mammalian cells are now available. They differ in design, capacity, and sensor options, with many selections available for either rocking platform, orbitally shaken, pneumatically mixed, or stirred-tank bioreactors lined with an integral disposable bag (Shukla and Gottschalk, Trends Biotechnol 31(3):147-154, 2013). WAVE Bioreactors™ were among the first disposable systems to be developed (Singh, Cytotechnology 30:149-158, 1999).

The Reverse-Flow Facial Artery Buccinator Flap for Skull Base Reconstruction: Key Anatomical and Technical Considerations.

Objective To highlight key anatomical and technical considerations for facial artery identification, and harvest and transposition of the facial artery buccinator (FAB) flap to facilitate its future use in anterior skull base reconstruction. Only a few studies have evaluated the reverse-flow FAB flap for skull base defects. Design Eight FAB flaps were raised in four cadaveric heads and divided into thirds; the facial artery's course at the superior and inferior borders of the flap was measured noting in which incisional third of the flap it laid.

Trends in chronic rhinosinusitis research in the past three decades.

Background: The objective of this work was to identify trends in chronic rhinosinusitis (CRS)-related publications for the past 3 decades.

Methods: Literature review was conducted using multiple terms, including sinusitis, chronic rhinosinusitis, chronic sinus disease, nasal polyposis, ethmoid sinusitis, frontal sinusitis, and maxillary sinusitis. Abstracts were divided into 3 decades: 1983 through 1992, 1993 through 2002, and 2003 through 2012.

Differences in skull base thickness in patients with spontaneous cerebrospinal fluid leaks.

Background: This study was designed to determine if differences in overall skull base thickness exist in patients with spontaneous cerebrospinal fluid (SCSF) leaks and to compare our institution's 10-year experience with the endoscopic repair of these leaks to the existing literature. A retrospective cohort study was performed in a tertiary rhinologic practice.

Methods: A retrospective study by two blinded independent reviewers compared the skull base thickness on computerized tomography (CT) imaging in our SCSF leak patients to nonleaking controls and patients with traumatic CSF leaks.

Regorafenib for treatment of advanced gastrointestinal stromal tumors.

Introduction: Gastrointestinal stromal tumors (GISTs) are abdominal sarcomas which are extremely refractory to chemotherapy treatment. The treatment of GISTs has been revolutionized by use of KIT/platelet-derived growth factor receptor-α (PDGFRA) kinase inhibitors. Unfortunately, most tumors develop resistance to front-line (imatinib) or second-line (sunitinib) therapy.

Sources and structures of mitotic crossovers that arise when BLM helicase is absent in Drosophila.

The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage.

Squamous cell carcinoma of the uvula: an analysis of factors affecting survival.

Objectives/hypothesis: Uvular squamous cell carcinoma (SCC) is usually considered with soft palate tumors as an oropharyngeal cancer subsite. This investigation aims to determine whether the uvula itself is a high-risk subsite in the oropharynx for primary squamous cell carcinomas.

Study Design: Retrospective analysis of a large population database.

Salivary morbidity and quality of life following radioactive iodine for well-differentiated thyroid cancer.

Objective: Determine the prevalence of sialadenitis in a group of patients treated with radioactive iodine (RAI) for well-differentiated thyroid cancer and assess whether RAI treatment is associated with a reduction in swallowing-related or global head and neck quality of life.

Study Design: Retrospective self-administered questionnaire study.

Setting: Academic, tertiary care, National Cancer Institute-designated cancer center.

Search for varicella zoster virus and herpes simplex virus-1 in normal human cerebral arteries.

Virological confirmation of varicella zoster virus (VZV) vasculopathy is provided by presence of virus in the cerebral arteries, frequently associated with inflammation. Yet, cerebral arteries from normal subjects have never been studied for VZV DNA or antigen. We analyzed 63 human cerebral arteries from 45 subjects for VZV DNA and antigen, control herpes simplex virus (HSV)-1 DNA and antigen, and leukocyte-specific CD45 antigen.

Head and neck soft tissue sarcomas: unique lack of significance of synchronous node metastases.

Background: Regional lymph node metastasis (RLNM) has been identified as a poor prognostic indicator for patients with soft tissue sarcomas (STS) of the extremities and trunk. However, the effect of RLNM on survival in patients with STS of the head and neck (HN) has not previously been explored. Our objective was to analyze RLNM as a prognostic indicator in HN-STS, and to compare this cohort to patients with STS of non-head and neck regions (NHN-STS).

Rosai Dorfman Disease presenting as unilateral chronic parotitis.

We report a 48-year-old man who presents with a 20-month history of left parotid enlargement despite treatment with antibiotics and steroids. He presented with a non-painful palpable mass in his left parotid without facial weakness or otologic symptoms. Fine needle aspiration was inconclusive, and an attempted excisional biopsy was aborted due to involvement of the facial nerve and suspicion of lymphoma.