Understanding Follicular Output Rate (FORT) and its Implications for POSEIDON Criteria.

The management of low prognosis patients in ART represents a challenge for reproductive specialists. Different profiles and biologic characteristics have been identified among these patients. Indeed, while poor ovarian response can be seen in patients with impaired ovarian reserve, others, identified as hypo-responders, show unexpected poor or suboptimal response to controlled ovarian stimulation despite satisfying ovarian parameters.

Melatonin Levels in Preterm and Term Infants and Their Mothers.

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants.

Robust designs in longitudinal studies accounting for parameter and model uncertainties - application to count data.

Nonlinear mixed effect models (NLMEMs) are widely used for the analysis of longitudinal data. To design these studies, optimal designs based on the expected Fisher information matrix (FIM) can be used. A method evaluating the FIM using Monte-Carlo Hamiltonian Monte-Carlo (MC-HMC) has been proposed and implemented in the R package MIXFIM using Stan.

Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons.

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.

Characteristic and outcomes of patients with pathologic complete response after preoperative treatment in borderline and locally advanced pancreatic adenocarcinoma: An AGEO multicentric retrospective cohort.

Introduction: Following publication of improved patients' outcome using first line FOLFIRINOX for metastatic pancreatic adenocarcinoma, many physicians now prescribe it as neo-adjuvant or induction treatment for borderline and locally advanced pancreatic cancer. A pathologic complete response, rarely seen with previous preoperative regimens, is sometimes observed in these patients. The aim of this study was to assess long-term outcomes of patients presenting pathologic complete response after preoperative FOLFIRINOX usually followed by chemo-radiation therapy for non-metastatic pancreatic adenocarcinoma.

Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score.

Background: About 5% of pancreatic ductal adenocarcinomas are inherited due to a deleterious germline mutation detected in 20% or fewer families. Pancreatic screening in high-risk individuals is proposed to allow early surgical treatment of (pre)malignant lesions. The outcomes of pancreatic surgery in high-risk individuals have never been correctly explored.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad.

Imaging localized neuronal activity at fast time scales through biomechanics.

Mapping neuronal activity noninvasively is a key requirement for in vivo human neuroscience. Traditional functional magnetic resonance (MR) imaging, with a temporal response of seconds, cannot measure high-level cognitive processes evolving in tens of milliseconds. To advance neuroscience, imaging of fast neuronal processes is required.

Influence of Baseline Anemia on Dual Antiplatelet Therapy Cessation and Risk of Adverse Events After Percutaneous Coronary Intervention.

Background: Anemia is a well-recognized risk factor for both bleeding and ischemic events after percutaneous coronary intervention (PCI). We sought to determine the impact of baseline anemia on dual antiplatelet therapy (DAPT) cessation patterns ≤2 years after PCI and the subsequent risk of clinical adverse events.

Methods And Results: PARIS (Patterns of Non-Adherence to Dual Anti-Platelet Regimen in Stented Patients) was a prospective multicenter observational registry of PCI-treated patients (n=5018).

Hepatorenal Syndrome.

Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified.

Linking Bisphenol S to Adverse Outcome Pathways Using a Combined Text Mining and Systems Biology Approach.

Background: Available toxicity data can be optimally interpreted if they are integrated using computational approaches such as systems biology modeling. Such approaches are particularly warranted in cases where regulatory decisions have to be made rapidly.

Objectives: The study aims at developing and applying a new integrative computational strategy to identify associations between bisphenol S (BPS), a substitute for bisphenol A (BPA), and components of adverse outcome pathways (AOPs).

How a well-adapting immune system remembers.

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a midlife plateau to the ease of learning salient features of sparse environments.

Body Surface Area-Based Dosing Regimen of Caspofungin in Children: a Population Pharmacokinetics Confirmatory Study.

We evaluated the population pharmacokinetics of caspofungin in children (2 to 12 years of age). The real-world data from 48 children were best fit by a two-compartment model with first-order elimination. Subsequent covariate analysis demonstrated that body surface area had a significant correlation with caspofungin pharmacokinetics, compared to body weight.

Understanding Lactatemia in Human Sepsis. Potential Impact for Early Management.

Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy. To understand the relationship among central venous oxygen saturation (Scv), lactate, and base excess to better determine the origin of lactate.

Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock - Results from the Cardshock Study.

Introduction: Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment.

Methods And Results: This is a secondary analysis of the CardShock study.

Severe Arterial Hypertension from Cullin 3 Mutations Is Caused by Both Renal and Vascular Effects.

Background: Mutations in four genes, WNK lysine deficient protein kinase 1 and 4 ( and ), kelch like family member 3 (), or Cullin 3 (), can result in familial hyperkalemic hypertension (FHHt), a rare Mendelian form of human arterial hypertension. Although all mutations result in an increased abundance of WNK1 or WNK4, all FHHt-causing mutations, resulting in the skipping of exon 9, lead to a more severe phenotype.

Methods: We created and compared two mouse models, one expressing the mutant Cul3 protein ubiquitously () and the other specifically in vascular smooth muscle cells ().

Population Pharmacokinetics and Dosing Optimization of Imipenem in Children with Hematological Malignancies.

Imipenem is widely used for the treatment of children with serious infections. Currently, studies on the pharmacokinetics of imipenem in children with hematological malignancies are lacking. Given the significant impact of disease on pharmacokinetics and increased resistance, we aimed to conduct a population pharmacokinetic study of imipenem and optimize the dosage regimens for this vulnerable population.

Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas.

Background: Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors.

Aim Of The Study: To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8 infiltrate, and metastatic evolution.

Materials And Methods: Eighty-three adnexal carcinomas were included.

Single-molecule characterization of extrinsic transcription termination by Sen1 helicase.

Extrinsic transcription termination typically involves remodeling of RNA polymerase by an accessory helicase. In yeast this is accomplished by the Sen1 helicase homologous to human senataxin (SETX). To gain insight into these processes we develop a DNA scaffold construct compatible with magnetic-trapping assays and from which S.

Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia.

Outcomes for adults with relapsed/refractory acute lymphoblastic leukemia (ALL) are poor with chemotherapy, particularly in later salvage. The TOWER study examined survival, remission, bridge to allogeneic hematopoietic stem cell transplantation (HSCT), and safety with blinatumomab versus chemotherapy. This report examined outcomes separately for study treatment as first or later salvage.

The parapharyngeal adipose corpus: anatomic and radiologic study.

Purpose: Although the morphology of the parapharyngeal adipose corpus (PAC) has been already described, the clinical interest of its volume and weight in the genesis of obstructive sleep apnea syndrome (OSAS) is still controversial. The volume of the PAC has been determined in OSAS patients but not in a normal population. The aim of our study was to investigate the morphology of the PAC by dissection and MRI in a normal population and to determine if there is a relation between the dimensions and volume of the PAC and the Body Mass Index (BMI).

Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.

Purpose: This study was conducted in order to evaluate if iso- or hyperintensity of HCAs on HBP is systematically related to a high uptake of hepatospecific contrast agent, using a quantitative approach.

Methods: This bicentric retrospective study included all patients with histologically confirmed and subtyped HCA from 2009 to 2017 who underwent MRI with HBP after Gd-BOPTA injection and who showed iso- or hyperintensity on HBP. The signal intensity of tumors on pre- and postcontrast images and the presence of hepatic steatosis were noted.

Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity.

CAR T cells represent a potentially curative strategy for B cell malignancies. However, the outcome and dynamics of CAR T cell interactions in distinct anatomical sites are poorly understood. Using intravital imaging, we tracked interactions established by anti-CD19 CAR T cells in B cell lymphoma-bearing mice.

Receptor crosstalk improves concentration sensing of multiple ligands.

Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems, leading to crosstalk between ligand-receptor pairs. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of noncognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway.