Abstract: We queried DNA from saliva or plasma of 93 HNSCC patients, searching for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% (95% CI, 84% to 99%) of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n=10) and 95% (n=37), respectively. Saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in the saliva and plasma is a valuable biomarker for detection of HNSCC.

Abstract: The present disclosure involves ctDNA assays that interrogate many regions from a single sample with high precision and accuracy, while evaluating multiple forms of cancer-related genomic alterations including sequence mutations and structural alterations. The disclosure provides simplified yet robust methods that achieve high sensitivity and specificity by analyzing cancer genes using a limited pool of non-unique barcodes in combination with endogenous barcodes. Samples are captured and sequenced using high coverage next-generation sequencing to allow tumor-specific somatic mutations, amplifications, and translocations to be identified.

Abstract: As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Abstract: A scoring functions is developed and used for identifying patients who might be responsive to a PD-1 axis directed therapy. The scoring functions are obtained by extracting features from multiplex-stained sections, selecting features that correlate with response to the therapy using a feature selection function, and fitting one or more of the selected features to a plurality of candidate scoring functions. A candidate scoring function showing the desired balance between predictive sensitivity and specificity may then selected for incorporation into a scoring system that includes at least an image analysis system.

Abstract: As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Abstract: The present invention relates to new 1H-pyrazole derivatives of formula (I) as sigma ligands having a great affinity for sigma receptors, especially the sigma-1 receptor (?1) and/or sigma-2 receptor (?2), as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: The present invention relates to new compounds of formula (I) as sigma ligands having a great affinity for sigma receptors, sigma-1 receptor (?1) and/or sigma-2 receptor (?2). The present invention also refers to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: The present invention relates to new 5,6,7,8-tetrahydropyrido[4?,3?:4,5]thieno[2,3d] pyrimidin-4(3H)-one derivatives as sigma ligands having a great affinity for sigma receptors, especially sigma-1 (?1), as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: The present invention relates to new 2,3-dihydro-1H-pyrrolo[3,2-b]pyridine derivatives of formula (I): as sigma ligands having a great affinity for sigma receptors, especially sigma-1 (?1) and/or sigma-2 (?2) receptors, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We generated single chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by human leukocyte antigen (HLA) molecules. These scFvs can be converted to full-length antibodies, termed MANAbodies, targeting “Mutation Associated Neo-Antigens” bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for peptides bound to pre-defined HLA types. In this way, we obtained scFvs, including one specific for a peptide encoded by a common KRAS mutant and another by a common EGFR mutant. Molecules targeting MANA can be developed that specifically react with mutant peptide-HLA complexes even when these peptides differ by only one amino acid from the normal, wild-type form.

Abstract: The present invention relates to pyrazolopyrimidine derivatives having dual pharmacological activity towards both the ?2? subunit of the voltage-gated calcium channel and the sigma-1 (?1) receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Abstract: DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.

Abstract: The present disclosure provides compositions comprising dostarlimab and methods of using the same to treat mismatch repair deficient (MMRd) rectal cancer (e.g., locally advanced rectal cancer).

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: Mandibular advancement measurement and positioning device provided with an instrument (1) with an upper slider (2) and a lower slider (3), means to measure and position the relative displacement of both sliders and two trays at one end of the instrument, one upper and one lower (11a, 11b), the trays being attached to each slider respectively, wherein the lower slider is divided into a fixed part (3a) and a pivoting part (3b) joined to the end of the fixed part (3a), being the upper and lower slider joined by means of a recess that allows a relative slide of both and wherein the pivoting part (3b) of the lower slider is provided with a vertical opening control (6). By means of the pivoting part and the opening control it is possible to measure and position the vertical opening.

Abstract: An improved system and method for pouring elevated concrete decking within a frame and backing surface area, wherein deck straps help hold the frame in position relative to the backing surface. The invention involves a bracket stand configured to elevate lower ends of deck straps above the backing surface such that wet concrete can enter the space between the lower end of the deck strap and the backing surface. The bracket stand has a platform elevated by a stable plurality of legs, the tips of which rest on the backing surface. The lower end of the deck strap and bracket stand are secured to the backing surface by one or more fasteners. When the backing surface is removed, a minimal portion of the bracket stand and fasteners is all that might protrude from the underside of the concrete decking. Depending upon the materials, these protruding portions are easily removed.

Abstract: A system and method for collection of a website in a past state and retroactive analysis thereof are provided. The method includes collecting, from a repository, at least one session replay; identifying, in the at least one collected session replay, at least one main state, wherein a main state is a portion of a session replay; selecting at least one webpage snapshot corresponding to a respective main state of the at least one identified main state, wherein each snapshot is a single-instant webpage state at a specific point in time; identifying, in the at least selected one snapshot, at least one webpage zone; and returning the at least one identified zone.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: The recently developed liquid-based Papanicolaou (Pap) smear allows not only cytologic evaluation but also collection of DNA for detection of HPV, the causative agent of cervical cancer. We tested these samples to detect somatic mutations present in rare tumor cells that might accumulate in the cervix once shed from endometrial and ovarian cancers. A panel of commonly mutated genes in endometrial and ovarian cancers was assembled and used to identify mutations in all 46 endometrial or cervical cancer tissue samples. We were able also able to identify the same mutations in the DNA from liquid Pap smears in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). We developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear without prior knowledge of the tumor's genotype.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.