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: A method of recovering lithium from a lithium-containing material comprises introducing a lithium-containing material to an electrochemical cell, transporting lithium ions from the lithium-containing material through a cation exchange membrane to a catholyte within a cathode chamber of the electrochemical cell, reacting the lithium ions with bicarbonate ions in the cathode chamber to form lithium carbonate, and removing the lithium carbonate from the catholyte. Related methods of recovering lithium from lithium-containing, materials, and related systems are disclosed.

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.

Abstract: TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.

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: 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: 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: 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 genomic data processing systems and methods described herein can accurately detect mutations in nucleic acid (e.g., cell free DNA (cfDNA) sequence reads associated with plasma nucleic acid samples. The genomic data processing system of the present disclosure distinguishes mutations derived from a tumor from mutations derived of clonal hematopoietic (CH) origin. The origin of mutated DNA fragments can be more accurately determined by analyzing fragment sizes in cfDNA to generate tumor and CH regions of interest (ROIs) in corresponding size profiles. A mutation can be more accurately classified using a metric based on proportions of fragments in the ROIs.

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: A system and method for comparing zones for different versions of a website based on performance metrics are provided. The method includes collecting comparison versions of at least one website specified in a received comparison request; identifying at least one comparison zone in the collected comparison versions, wherein a comparison zone is a zone included in the at least one specified website; collecting at least one comparison zone metric for each of the at least one comparison zones for the collected comparison versions, wherein the at least one comparison zone metric is a numerical value related to a user interaction metric with the at least one comparison zone; analyzing the collected comparison zone metrics to determine zone performance; and returning the analysis results.

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.