Abstract: Methods are provided for the adjuvant treatment of operable HER2-positive primary breast cancer in human patients by administration of pertuzumab in addition to chemotherapy and trastuzumab. The methods reduce the risk of recurrence of invasive breast cancer or death for a patient diagnosed with HER2-positive early breast cancer (eBC) compared to administration of trastuzumab and chemotherapy, without pertuzumab.

Abstract: The present invention relates to compounds of formula (I), (I), wherein R1, R2 and R3 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

Abstract: The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

Abstract: The method includes generating, for each of a plurality of original images, a first artificially degraded image by applying a first image-artifact-generation logic on each of the original images; and generating the program logic by training an untrained version of a first machine-learning logic that encodes a first artifacts-removal logic on the original images and their respectively generated first degraded images; and returning the trained first machine-learning logic as the program logic or as a component thereof. The first image-artifact-generation logic is A) an image-acquisition-system-specific image-artifact-generation logic or B) a tissue-staining-artifact-generation logic.

Abstract: The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

Abstract: The invention relates to a method of identifying a biomarker in a tissue sample. The method comprises receiving an acquired image depicting a tissue sample, the pixel intensity values of the acquired image correlating with an autofluorescence signal or of an X-ray induced signal or a signal of a non-biomarker specific stain or a signal of a first biomarker specific stain adapted to selectively stain a first biomarker. The acquired image is input into a trained machine learning logic—MLL which automatically transforms the acquired image into an output image highlighting tissue regions predicted to comprise a second biomarker.

Abstract: Methods and systems disclosed herein relate generally to systems and methods for predicting a future visual acuity of a subject by using machine-learning models. An image of at least part of a retina of a subject can be processed by one or more first machine-learning models to detect a set of retina-related segments. Segment-specific metrics that characterize a retina-related segment of the set of retina-related segments can be generated. The segment-specific metrics can be processed by using a second machine-learning model to generate a result corresponding to a prediction corresponding to a future visual acuity of the subject.

Abstract: A force testing machine (FTM) validation apparatus is disclosed for validating a test process involving a force testing machine to measure forces involved in operation of a syringe arrangement. Particularly a syringe arrangement that includes a staked-in needle prefilled syringe and a needle safety device cooperating with the staked-in needle prefilled syringe. The FTM validation apparatus includes a syringe arrangement surrogate, and a holder arranged to support the syringe arrangement surrogate in a predefined position and orientation in the force testing machine. The syringe arrangement surrogate includes a break loose part arranged to mimic a break loose force of the syringe arrangement and an injection force part arranged to mimic an injection force of the syringe arrangement. Methods are also disclosed for validating a test process that measures forces involved in operation of a syringe arrangement and for measuring forces involved in operation of the syringe arrangement.

Abstract: Genotyping methods and compositions for selecting patients with cardiovascular disease who will benefit from treatment with HDL-raising or HDL mimicking agent, in particular with a CETP inhibitor/modulator.

Abstract: Herein is reported a method for the production of an immunoglobulin comprising the following steps: a) providing a eukaryotic cell comprising a nucleic acid encoding the immunoglobulin, b) cultivating the eukaryotic cell in a cultivation medium wherein the amount of glucose available in the cultivation medium per time unit is kept constant and limited to less than 80% of the amount that could maximally be utilized by the cells in the cultivation medium per time unit, and c) recovering the immunoglobulin from the culture.

Abstract: The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for: —receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102); —receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured a

Abstract: Methods and systems for online sampling an aliquot from a mobile phase comprising an analyte for producing a pharmaceutical or chemical product, wherein the apparatus comprises an analytical device and a tube between an inlet and an outlet, wherein the outlet is in fluid communication with the analytical device, the method comprising: providing a sample device comprising a needle with a needle tip, a septum pierceable by the needle and a pump, wherein the needle is moveable between an extended position in which the septum is pierced by the needle, and a retracted position, in which the septum is not pierced, disposing the sample device at the curved portion of the tube, moving the needle to the extended position such that the needle tip faces the flow direction, and drawing out an aliquot out of the mobile phase.

Abstract: The present invention provides substituted isoindole compounds which are selective allosteric EGFR inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances, generally of Formula: or a pharmaceutically acceptable salt thereof.

Abstract: A method of preparing a double chamber container is disclosed that includes filling a substance into the container, freeze-drying the substance therein, inserting a middle plunger in the container to form distal and proximal chambers, wherein the middle plunger seals the distal chamber from the proximal chamber and the freeze-dried substance is inside the distal chamber. The method includes filling a reconstitution medium in the proximal chamber, and sealing distal and proximal openings of the container. The method includes providing a holder having a seat and arranging the container in the seat in an upright position wherein a distal end side of the container extends downwardly and a proximal end side of the container extends upwardly. The container is arranged in the seat while the substance is filled, the substance is freeze-dried, the middle plunger is inserted, the reconstitution medium is filled, and the proximal opening is sealed.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, A, X and R11 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: An image processing system configured to receive a first fluorescence image generically indicating the presence of biological matter; transform the first image into a transformed first image having a first color; for each of the biomarkers, receive a respective second fluorescence image indicating signals emitted by fluorescence stain selectively staining the biomarker, transforming the second images into a respective transformed second images having a respective second color; overlaying and combining the transformed first and second images; storing and/or displaying the combined image as the simulated digital bright field IHC or ISH image. The first image is created using an autofluorescence reference spectrum of the tissue sample or of a similar tissue sample or by using a fluorescence reference spectrum of a first stain which generically binds to biological matter of the tissue sample for spectrally unmixing of a multi-spectral digital image of the tissue sample.

Abstract: Herein is reported a feed mixing device for adding feed solutions with a non-physiologically pH value to a cell cultivation vessel comprising a chamber for mixing the feed solutions prior to their addition to the cell cultivation vessel as well as its use. With the feed mixing device as reported herein feed components can be provided in solution at a pH value at which they have good solubility and/or good stability whereby the pH value can be clearly different from the pH value of the cultivation medium, i.e. different from the physiological pH value. This allows performing the cultivation with more flexibility compared to a cultivation in which the pH value of the feed solution is limited to a small range around the pH value of the cultivation.

Abstract: The present invention relates to antisense oligonucleotides that are capable of reducing expression of PD-L1 in a target cell. The oligonucleotides hybridize to PD-L1 mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of viral liver infections such as HBV, HCV and HDV; parasite infections such as malaria, toxoplasmosis, leishmaniasis and trypanosomiasis or liver cancer or metastases in the liver using the oligonucleotide.

Abstract: An image analysis method for analyzing an IHC tissue sample includes storing, for each of one or more sets of digital images, a set-ID in a spatial database of a spatial DBMS, the images of each set depicting the same or adjacent layers of the IHC tissue sample; storing, for each of the, a plurality of spatial data objects in the database in association with the set-ID; creating, by the spatial DBMS, at least one spatial index covering the objects of the images contained in the one or more sets; applying, by the spatial DBMS, a spatial database operation on the at least one spatial index for determining the relative positions of objects of two or more images of a selected set; and providing the relative positions as input for determining the distance and/or relative position of the biomedical features of the tissue sample.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.