mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in .

A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas.

Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7).

Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring.

Purpose: Activation of Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K) represent parallel, synergistic pathways in lymphoma pathogenesis. As predominant PI3Kδ inhibition is a possible mechanism of tumor escape, we proposed a clinical trial of dual BTK and pan-PI3K inhibition.

Patients And Methods: We conducted a single-center phase I/Ib trial combining a BTK inhibitor (ibrutinib) and a pan-PI3K inhibitor (buparlisib) in 37 patients with relapsed/refractory (R/R) B-cell lymphoma.

The effect of overweight/obesity on diastolic function in children and adolescents: A meta-analysis.

Left ventricular diastolic function (LVDF) is an important marker of early cardiovascular remodelling, which has not been well summarized in young people with overweight/obesity. Weighted, random-effects regression was used to determine the strength of associations of both body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) with LVDF measures, adjusting for age and sex. Six databases were searched after PROSPERO registration (CRD42020177470) from inception to July 2020 for studies that compared LVDF between overweight/obesity and control groups aged ≤24 years, yielding 70 studies (9983 individuals).

Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts.

Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD.

Dominant monoallelic variant in the PAK2 gene causes Knobloch syndrome type 2.

Knobloch syndrome is an autosomal recessive phenotype mainly characterized by retinal detachment and encephalocele caused by biallelic pathogenic variants in the COL18A1 gene. However, there are patients clinically diagnosed as Knobloch syndrome with unknown molecular etiology not linked to COL18A1. We studied an historical pedigree (published in 1998) designated as KNO2 (Knobloch type 2 syndrome with intellectual disability, autistic behavior, retinal degeneration, encephalocele).

Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism.

Background: Hypogonadotropic hypogonadism (HH) is hypogonadism due to either hypothalamic or pituitary dysfunction. While gonadotropin-releasing hormone (GnRH) can directly test pituitary function, no specific test of hypothalamic function exists. Kisspeptin-54 (KP54) is a neuropeptide that directly stimulates hypothalamic GnRH release and thus could be used to specifically interrogate hypothalamic function.

Pathogenic mosaic variants in congenital hypogonadotropic hypogonadism.

Purpose: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder resulting in absent puberty and infertility. The genetic architecture is complex with multiple loci involved, variable expressivity, and incomplete penetrance. The majority of cases are sporadic, consistent with a disease affecting fertility.

Reprogramming of the cambium regulators during adventitious root development upon wounding of storage tap roots in radish ( L.).

Cambium contains a stem cell population that produces xylem and phloem tissues in a radial direction during the secondary growth stage. The growth of many storage roots, including in the radish, L., also depends on cambium.

Autologous CD19-Targeted CAR T Cells in Patients with Residual CLL following Initial Purine Analog-Based Therapy.

Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-based chemoimmunotherapy exhibit a shorter duration of response and may benefit from novel therapeutic strategies. We and others have previously described the safety and efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors (CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL. Here we report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 (19-28z) as a consolidative therapy in 8 patients with residual CLL following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab.

Predicting enteric methane emission of dairy cows with milk Fourier-transform infrared spectra and gas chromatography-based milk fatty acid profiles.

The objective of the present study was to compare the prediction potential of milk Fourier-transform infrared spectroscopy (FTIR) for CH emissions of dairy cows with that of gas chromatography (GC)-based milk fatty acids (MFA). Data from 9 experiments with lactating Holstein-Friesian cows, with a total of 30 dietary treatments and 218 observations, were used. Methane emissions were measured for 3 consecutive days in climate respiration chambers and expressed as production (g/d), yield (g/kg of dry matter intake; DMI), and intensity (g/kg of fat- and protein-corrected milk; FPCM).

The analysis of tetracyclines, quinolones, macrolides, lincosamides, pleuromutilins, and sulfonamides in chicken feathers using UHPLC-MS/MS in order to monitor antibiotic use in the poultry sector.

In The Netherlands, all antibiotic treatments should be registered at the farm and in a central database. To enforce correct antibiotic use and registration, and to enforce prudent use of antibiotics, there is a need for methods that are able to detect antibiotic treatments. Ideally, such a method is able to detect antibiotic applications during the entire lifespan of an animal, including treatments administered during the first days of the animals' lives.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma.

Imaging for Staging and Response Assessment in Lymphoma.

Lymphoma comprises a heterogeneous group of diseases; remarkable advances have been made in diagnosis and treatment. Diagnostic imaging provides important information for staging and response assessment in patients with lymphoma. Over the years, staging systems have been refined, and dedicated criteria have been developed for evaluating response to therapy with both computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT.

Verification of fresh grass feeding, pasture grazing and organic farming by cows farm milk fatty acid profile.

The present study investigated the use of fatty acid (FA) profiling in combination with chemometric modelling to verify claims for cow milk in terms of fresh grass feeding, pasture grazing and organic/biodynamic farming. The FA profile was determined for 113 tank milk samples collected in the Netherlands from 30 farms over four different months, and used to develop classification models based on the PLS-DA algorithm. Milk from cows with daily rations of fresh grass could be successfully distinguished from milk from cows with no fresh grass in their diet.

Noncontrast perfusion single-photon emission CT/CT scanning: a new test for the expedited, high-accuracy diagnosis of acute pulmonary embolism.

Background: Standard ventilation and perfusion (V˙/Q˙) scintigraphy uses planar images for the diagnosis of pulmonary embolism (PE). To evaluate whether tomographic imaging improves the diagnostic accuracy of the procedure, we compared noncontrast perfusion single-photon emission CT (Q˙-SPECT)/CT scans with planar V˙/Q˙scans in patients at high risk for PE.

Methods: Between 2006 and 2010, most patients referred for diagnosis of PE underwent both Q˙-SPECT/CT scan and planar V˙/Q˙scintigraphy.

Recycling as a strategy against rare earth element criticality: a systemic evaluation of the potential yield of NdFeB magnet recycling.

End-of-life recycling is promoted by OECD countries as a promising strategy in the current global supply crisis surrounding rare earth elements (REEs) so that dependence on China, the dominant supplier, can be decreased. So far the feasibility and potential yield of REE recycling has not been systematically evaluated. This paper estimates the annual waste flows of neodymium and dysprosium from permanent magnets, the main deployment of these critical REEs, during the 2011-2030 period.

Shall we report cardiomegaly at routine computed tomography of the chest?

Purpose: To examine the accuracy of the cardiothoracic ratio (CTR) at routine computed tomography (CT) of the chest to diagnose cardiomegaly by using echocardiography (ECHO) as a criterion standard, and secondarily, to search for CT cardiac measurements correlating with left ventricular hypertrophy (LVH) at ECHO.

Materials And Methods: We searched 2 databases: cancer patients who had chest CT who also underwent routine ECHO by one experienced cardiologist, from January to March 2008. Consecutive patients were enrolled who had chest radiography (CXR) within 1 month and ECHO within 6 months of CT.

Competitive selection of lactic acid bacteria that persist in the human oral cavity.

Lactic acid bacteria (LAB) might offer opportunities as oral probiotics provided candidate strains persist in the mouth. After intake of a mixture of 69 LAB, strains of Lactobacillus fermentum and Lactobacillus salivarius were especially recovered. Coaggregation with other microbes is likely not a prerequisite for persistence since L.

Fine needle aspiration cytology of palpable and nonpalpable lymph nodes to detect metastatic melanoma.

Background: Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes.

Methods: FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes.

High-resolution amplified fragment length polymorphism typing of Lactococcus lactis strains enables identification of genetic markers for subspecies-related phenotypes.

A high-resolution amplified fragment length polymorphism (AFLP) methodology was developed to achieve the delineation of closely related Lactococcus lactis strains. The differentiation depth of 24 enzyme-primer-nucleotide combinations was experimentally evaluated to maximize the number of polymorphisms. The resolution depth was confirmed by performing diversity analysis on 82 L.

Primary systemic amyloidosis presenting as idiopathic inflammatory colitis.

A 75-year old-female was referred with chest pain. She was fully investigated and it was felt that her symptoms were non-cardiac. Four months later, she was seen in gastroenterology outpatients with bloody diarrhoea and abdominal pain.

Phenotypic and genomic diversity of Lactobacillus plantarum strains isolated from various environmental niches.

Lactobacillus plantarum is a ubiquitous microorganism that is able to colonize several ecological niches, including vegetables, meat, dairy substrates and the gastro-intestinal tract. An extensive phenotypic and genomic diversity analysis was conducted to elucidate the molecular basis of the high flexibility and versatility of this species. First, 185 isolates from diverse environments were phenotypically characterized by evaluating their fermentation and growth characteristics.

Regulatory phenotyping reveals important diversity within the species Lactococcus lactis.

The diversity in regulatory phenotypes among a collection of 84 Lactococcus lactis strains isolated from dairy and nondairy origin was explored. The specific activities of five enzymes were assessed in cell extracts of all strains grown in two different media, a nutritionally rich broth and a relatively poor chemically defined medium. The five investigated enzymes, branched chain aminotransferase (BcaT), aminopeptidase N (PepN), X-prolyl dipeptidyl peptidase (PepX), alpha-hydroxyisocaproic acid dehydrogenase (HicDH), and esterase, are involved in nitrogen and fatty acid metabolism and catalyze key steps in the production of important dairy flavor compounds.