.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups.
 
  Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults.
 
  ClinicalTrials.gov Identifier NCT03183908.
 ClinicalTrials.gov Identifier NCT03183908.Few large cohorts have examined histoplasmosis in both immunocompromised and immunocompetent patients. We describe the differences in presentations and outcomes of histoplasmosis by immune and dissemination status. We assembled a retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Patients were grouped by immune status people living with HIV (PLWH), patients who were HIV negative but had other-immunocompromise (OIC), and immunocompetent patients. Patients were further classified into asymptomatic lung nodule (ALN), localized and disseminated disease groups, and outcomes were compared across patients by these immune status categories We identified 261 patients with histoplasmosis 54 (21%) PLWH, 98 (38%) OIC, and 109 (42%) immunocompetent. Disseminated disease was more common among PLWH than among other groups (P 
  This article examines how the signs and symptoms of histoplasmosis vary by immune status and dissemination status. Immunocompetent patients with localized disease present with fewer typical signs and symptoms, are diagnosed later, but despite this have lower 90-day mortality.
 This article examines how the signs and symptoms of histoplasmosis vary by immune status and dissemination status. Immunocompetent patients with localized disease present with fewer typical signs and symptoms, are diagnosed later, but despite this have lower 90-day mortality.The pericentriolar material (PCM) that accumulates around the centriole expands during mitosis and nucleates microtubules. Here, we show the cooperative roles of the centriole and PCM scaffold proteins, pericentrin and CDK5RAP2, in the recruitment of CEP192 to spindle poles during mitosis. Systematic depletion of PCM proteins revealed that CEP192, but not pericentrin and/or CDK5RAP2, was crucial for bipolar spindle assembly in HeLa, RPE1, and A549 cells with centrioles. Upon double depletion of pericentrin and CDK5RAP2, CEP192 that remained at centriole walls was sufficient for bipolar spindle formation. In contrast, through centriole removal, we found that pericentrin and CDK5RAP2 recruited CEP192 at the acentriolar spindle pole and facilitated bipolar spindle formation in mitotic cells with one centrosome. Furthermore, the perturbation of PLK1, a critical kinase for PCM assembly, efficiently suppressed bipolar spindle formation in mitotic cells with one centrosome. Overall, these data suggest that the centriole and PCM scaffold proteins cooperatively recruit CEP192 to spindle poles and facilitate bipolar spindle formation.Glioblastoma is the most common and deadly malignant brain cancer. We now demonstrate that loss of function of the endosomal GTPase Rab35 in human brain tumor initiating cells (BTICs) increases glioblastoma growth and decreases animal survival following BTIC implantation in mouse brains. Mechanistically, we identify that the GTPase Arf5 interacts with the guanine nucleotide exchange factor (GEF) for Rab35, DENND1/connecdenn, and allosterically enhances its GEF activity toward Rab35. Knockdown of either Rab35 or Arf5 increases cell migration, invasiveness, and self-renewal in culture and enhances the growth and invasiveness of BTIC-initiated brain tumors in mice. RNAseq of the tumors reveals up-regulation of the tumor-promoting transcription factor SPOCD1, and disruption of the Arf5/Rab35 axis in glioblastoma cells leads to strong activation of the epidermal growth factor receptor, with resulting enhancement of SPOCD1 levels. These discoveries reveal an unexpected cascade between an Arf and a Rab and indicate a role for the cascade, and thus endosomal trafficking, in brain tumors.JGP study reveals that insufficient reuptake of calcium into the sarcoplasmic reticulum underlies arrhythmogenic variations in cardiac calcium transients.Human centromeres form primarily on α-satellite DNA but sporadically arise de novo at naive ectopic loci, creating neocentromeres. Centromere inheritance is driven primarily by chromatin containing the histone H3 variant CENP-A. Here, we report a chromosome engineering system for neocentromere formation in human cells and characterize the first experimentally induced human neocentromere at a naive locus. The spontaneously formed neocentromere spans a gene-poor 100-kb domain enriched in histone H3 lysine 9 trimethylated (H3K9me3). Long-read sequencing revealed this neocentromere was formed by purely epigenetic means and assembly of a functional kinetochore correlated with CENP-A seeding, eviction of H3K9me3 and local accumulation of mitotic cohesin and RNA polymerase II. At formation, the young neocentromere showed markedly reduced chromosomal passenger complex (CPC) occupancy and poor sister chromatin cohesion. However, long-term tracking revealed increased CPC assembly and low-level transcription providing evidence for centromere maturation over time.
  Venous thromboembolism (VTE) is associated with substantial morbidity and is the most common factor associated with preventable death among hospitalized patients. Data from otolaryngologic studies suggest that the risk of VTE may be underestimated among high-risk patients, particularly among those undergoing oncologic procedures. The incorporation of prolonged-duration chemoprophylaxis (PDC) into preventive therapy has been associated with substantial decreases in VTE incidence among patients undergoing oncologic surgery.  https://www.selleckchem.com/CDK.html  However, bleeding remains a major concern among otolaryngologists, and substantial variation exists in the use of thromboprophylaxis.
 
  To assess the association between PDC and VTE in high-risk patients with head and neck cancer undergoing oncologic procedures.
 
  This retrospective cohort study identified 750 patients with biopsy-confirmed head and neck cancer and a Caprini risk score of 8 or higher who underwent inpatient oncologic surgery at a tertiary care referral center between January 1, 2014, and February 1, 2020.