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Psychedelic drug use along with schizotypy throughout adults.
b was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.Lynch syndrome is a heritable cancer syndrome caused by a heterozygous germline mutation in DNA mismatch repair (MMR) genes. MMR-deficient (dMMR) tumors are particularly sensitive to immune checkpoint inhibitors, an effect attributed to the higher mutation rate in these cancers. However, approximately 15% to 30% of patients with dMMR cancers do not respond to immunotherapy. This report describes 3 patients with Lynch syndrome who each had 2 primary malignancies 1 with dMMR and a high tumor mutational burden (TMB), and 1 with dMMR but, unexpectedly, a low TMB. Two of these patients received immunotherapy for their TMB-low tumors but experienced no response. We have found that not all Lynch-associated dMMR tumors have a high TMB and propose that tumors with dMMR and TMB discordance may be resistant to immunotherapy. The possibility of dMMR/TMB discordance should be considered, particularly in less-typical Lynch cancers, in which TMB evaluation could guide the use of immune checkpoint inhibitors.
Translation of basic discoveries to clinical care for patients with cancer is a difficult process greatly enabled by physician-trained researchers. Selleckchem MMAF Three categories of physicians, with responsibilities spanning from laboratory and preclinical research to direct patient care, are involved in the translational research continuum physician-scientist (PS), clinician investigator (CI), and academic clinician (AC).

To define how protected time for research efforts is supported, the Association of American Cancer Institutes (AACI) conducted a survey of their member institutions, obtaining 56 responses documenting time spent in research and clinical activities across multiple cancer disciplines, and providing information about funding streams for the different categories of cancer physicians.

Responses showed that PSs and ACs are minimally involved in clinical research activities; the driver or clinical research in academic cancer centers is the CI. A significant concern was a lack of stable funding streams for nonbillable clinical research activities, putting the sustainability of the CI in jeopardy. Limited funding was derived from hospital sources, with most support derived from cancer center sources.

This study highlights the importance of the CI in translational cancer medicine and represents a call to action for institutions and research funding agencies to develop new programs targeted toward CI support to ensure continued progress against cancer.
This study highlights the importance of the CI in translational cancer medicine and represents a call to action for institutions and research funding agencies to develop new programs targeted toward CI support to ensure continued progress against cancer.Transorbital surgery has gained recent notoriety because of its incorporation into endoscopic skull base surgery. The use of this surgical corridor has been pervasive throughout the 20th century. It has been utilized by multiple disciplines for both clinical and experimental purposes, although its historical origin is medically and ethically controversial. Hermann Knapp first introduced the orbital surgical technique in 1874, and Rudolf Krönlein introduced his procedure in 1889. Rivalry between Walter Dandy in neurosurgery and Raynold Berke in ophthalmology further influenced methods of tackling intracranial and intraorbital pathologies. In 1946, Walter Freeman revolutionized psychosurgery by completing seemingly successful transorbital leucotomies and promoting their minimally invasive and benign surgical characteristics. However, as Freeman's legacy came into disrepute, so did the transorbital brain access corridor, again resulting in its stunted evolution. Microsurgery and endoscopy further influenced the use, or lack thereof, of the transorbital corridor in neurosurgical approaches. Historical analysis of present goals in modern skull base surgery echoes the principles established through an approach described almost 150 years ago minimal invasion, minimal morbidity, and priority of patient satisfaction. The progression of the transorbital approach not only reflects psychosocial influences on medical therapy, as well as the competition of surgical pioneers for supremacy, but also describes the diversification of skull base techniques, the impact of microsurgical mastery on circumferential neurosurgical corridors, the influence of technology on modernizing skull base surgery, and the advancing trend of multidisciplinary surgical excellence.
Surgical treatment for nonforaminal syringomyelia related to spinal arachnoiditis is still controversial. The authors sought to assess respective outcomes and rates of reintervention for shunting and spinal cord untethering (arachnolysis) in spinal arachnoiditis with syringomyelia.

This retrospective cohort study was conducted at a single reference center for syringomyelia. Patients undergoing arachnolysis and/or shunting interventions for nonforaminal syringomyelia were screened.

The study included 75 patients undergoing 130 interventions. Arachnolysis without shunting was performed in 48 patients, while 27 patients underwent shunting. The mean follow-up between the first surgery and the last outpatient visit was 65.0 months (range 12-379 months, median 53 months). At the last follow-up, the modified McCormick score was improved or stabilized in 83.4% of patients after arachnolysis versus 66.7% after shunting. Thirty-one (41.3%) patients underwent reintervention during follow-up, with a mean delay of 3opathies, irrespective of the surgical technique.
The objective of this study was to evaluate a novel connector design and compare it with traditional side connectors, such as a fixed-angle connector (FAC) and a variable-angle connector (VAC), with respect to lumbosacral stability and instrumentation strain.

Standard nondestructive flexibility tests (7.5 Nm) and compression tests (400 N) were performed using 7 human cadaveric specimens (L1-ilium) to compare range of motion (ROM) stability, posterior rod strain (RS), and sacral screw bending moment (SM). Directions of motion included flexion, extension, left and right lateral bending, left and right axial rotation, and compression. Conditions included 1) the standard 2-rod construct (2R); 2) the dual-tulip head (DTH) with 4-rod construct (4R); 3) FACs with 4R; and 4) VACs with 4R. Data were analyzed using repeated-measures ANOVA.

Overall, there were no statistically significant differences in ROM across the lumbosacral junction among conditions (p > 0.07). Compared with 2R, DTH and FAC significantly across the lumbosacral junction. However, the greatest reduction in RS and SM was achieved with a VAC that allowed for straight (uncontoured) accessory rod placement.
The aim of this study was to investigate diffusion tensor imaging (DTI), an objective and noninvasive neuroimaging technique, for its potential as an imaging biomarker to predict the need and timing of CSF diversion surgery in patients after prenatal myelomeningocele (MMC) repair.

This was a retrospective analysis of data based on 35 pediatric patients after prenatal MMC repair (gestational age at birth 32.68 ± 3.42 weeks, range 24-38 weeks; 15 females and 20 males). A logistic regression analysis was used to classify patients to determine the need for CSF diversion surgery. The model performance was compared between using the frontooccipital horn ratio (FOHR) alone and using the FOHR combined with DTI values (the genu of the corpus callosum [gCC] and the posterior limb of the internal capsule [PLIC]). For patients who needed to be treated surgically, timing of the procedure was used as the clinical outcome to test the predictive value of DTI acquired prior to surgery based on a linear regression analysis = -0.6830, p = 0.010; both adjusted for age and FOHR).

The authors' data demonstrated that DTI could potentially serve as an objective biomarker differentiating patients after prenatal MMC repair regarding those who may require surgery for MMC-associated hydrocephalus. The predictive value for the need and timing of CSF diversion surgery is highly clinically relevant for improving and optimizing decision-making for the treatment of hydrocephalus in this patient population.
The authors' data demonstrated that DTI could potentially serve as an objective biomarker differentiating patients after prenatal MMC repair regarding those who may require surgery for MMC-associated hydrocephalus. The predictive value for the need and timing of CSF diversion surgery is highly clinically relevant for improving and optimizing decision-making for the treatment of hydrocephalus in this patient population.
Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and group 3 (Myc driven) subtypes that are associated with the activity of eukaryotic initiation factor 4E (eIF4E), a critical mediator of translation, and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and master regulator of transcription. Recent drug repurposing efforts in multiple solid and hematologic malignancies have demonstrated that eIF4E and EZH2 are both pharmacologically inhibited by the FDA-approved antiviral drug ribavirin. Given the molecular overlap between medulloblastoma biology and known ribavirin activity, the authors investigated the preclinical efficacy of repurposing ribavirin as a targeted therapeutic in cell and animal models of medulloblastoma.

Multiple in vitro assays were performed using human ONS-76 (a primitive SHH model) and D425 (an aggressive group 3 model) cells. The impacts of ribavirin on cellular growth, death, migration, and invasion were quantified using proliferatin multiple preclinical models of medulloblastoma, including an aggressive group 3 animal model. Ribavirin may represent a promising targeted therapeutic in medulloblastoma.
The authors demonstrate that ribavirin, a clinically used drug known to inhibit eIF4E and EZH2, has significant antitumor effects in multiple preclinical models of medulloblastoma, including an aggressive group 3 animal model. Ribavirin may represent a promising targeted therapeutic in medulloblastoma.
Hydrocephalus and seizures greatly impact outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH); however, reliable tools to predict these outcomes are lacking. The authors used a volumetric quantitative analysis tool to evaluate the association of total aSAH volume with the outcomes of shunt-dependent hydrocephalus and seizures.

Total hemorrhage volume following aneurysm rupture was retrospectively analyzed on presentation CT imaging using a custom semiautomated computer program developed in MATLAB that employs intensity-based k-means clustering to automatically separate blood voxels from other tissues. Volume data were added to a prospectively maintained aSAH database. The association of hemorrhage volume with shunted hydrocephalus and seizures was evaluated through logistic regression analysis and the diagnostic accuracy through analysis of the area under the receiver operating characteristic curve (AUC).

The study population comprised 288 consecutive patients with aSAH. The mean total hemorrhage volume was 74.
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