EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data.

Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice.

Random errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy.

Sperm cryopreservation in adolescents with cancer.

Objective: To evaluate whether sperm banking is under-used in adolescents with cancer.

Study Design: We reviewed our 33 years long experience of semen cryopreservation and identified male subjects with cancer aged 14-21 years who banked their sperm. We hypothesized as a referring model a constant rate of referral in every age category (uniform distribution).

Oral Vitamin D supplementation impacts gene expression in granulosa cells in women undergoing IVF.

Study Question: Does oral Vitamin D supplementation alter the hormonal milieu of follicular fluid (FF) and the transcriptomic profile of luteinised granulosa cells (GCs) in women with Vitamin D deficiency undergoing IVF?

Summary Answer: A transcriptomic signature relevant to oral Vitamin D supplementation in luteinised GCs was demonstrated, although Vitamin D supplementation did not alter hormone levels in FF.

What Is Known Already: Vitamin D deficiency is linked to lower live birth rates among women undergoing IVF. It is unclear whether Vitamin D elicits a targeted action in reproductive physiology or is a surrogate marker of overall well-being.

Mitochondrial misreading in skeletal muscle accelerates metabolic aging and confers lipid accumulation and increased inflammation.

We have recently reported on an experimental model of mitochondrial mistranslation conferred by amino acid exchange V338Y in the mitochondrial ribosomal protein MrpS5. Here we used a combination of RNA-Seq and metabolic profiling of homozygous transgenic MrpS5V338Y/V338Y mice to analyze the changes associated with the V338Y mutation in post-mitotic skeletal muscle. Metabolic profiling demonstrated age-dependent metabolic changes in the mutant V338Y animals, which included enhanced levels of age-associated metabolites and which were accompanied by increased glycolysis, lipid desaturation and eicosanoid biosynthesis, and alterations of the pentose phosphate pathway.

ALADDIN study: does assisted hatching of vitrified/warmed blastocysts improve live birth rate? Protocol for a multicentric randomised controlled trial.

Introduction: Recent data suggest a higher clinical pregnancy rate performing assisted hatching (AH) on previously cryopreserved embryos but fail to demonstrate significant effects on live birth rate. However, current evidence is based on studies with a small sample size and may hide a type II error. Moreover, poor attention has been given to the specific effect of AH on frozen/thawed blastocysts.

The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols.

The advent of random start protocols to shorten the time needed to store oocytes in women with malignancies has represented an important improvement in the field of fertility preservation. However, Randomized Controlled Trials are difficult to implement in this area and available evidence that supports this approach remains modest. To shed more light on this issue, we compared the follicular development between the ovary carrying the dominant follicle or the corpus luteum and the contralateral resting ovary in 90 women who underwent random start controlled ovarian stimulation (COS).

Dysregulated Interorganellar Crosstalk of Mitochondria in the Pathogenesis of Parkinson's Disease.

The pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder, is complex and involves the impairment of crucial intracellular physiological processes. Importantly, in addition to abnormal α-synuclein aggregation, the dysfunction of various mitochondria-dependent processes has been prominently implicated in PD pathogenesis. Besides the long-known loss of the organelles' bioenergetics function resulting in diminished ATP synthesis, more recent studies in the field have increasingly focused on compromised mitochondrial quality control as well as impaired biochemical processes specifically localized to ER-mitochondria interfaces (such as lipid biosynthesis and calcium homeostasis).

Upregulation of Peroxiredoxin 3 Protects 2-KO Cortical Neurons from Oxidative Stress: A Paradigm for Neuronal Cell Survival under Neurodegenerative Conditions.

Several neurodegenerative disorders exhibit selective vulnerability, with subsets of neurons more affected than others, possibly because of the high expression of an altered gene or the presence of particular features that make them more susceptible to insults. On the other hand, resilient neurons may display the ability to develop antioxidant defenses, particularly in diseases of mitochondrial origin, where oxidative stress might contribute to the neurodegenerative process. In this work, we investigated the oxidative stress response of embryonic fibroblasts and cortical neurons obtained from -KO mice.

Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21.

Stress adaptation is essential for neuronal health. While the fundamental role of mitochondria in neuronal development has been demonstrated, it is still not clear how adult neurons respond to alterations in mitochondrial function and how neurons sense, signal, and respond to dysfunction of mitochondria and their interacting organelles. Here, we show that neuron-specific, inducible in vivo ablation of the mitochondrial fission protein Drp1 causes ER stress, resulting in activation of the integrated stress response to culminate in neuronal expression of the cytokine Fgf21.

Clinical comparison between conventional and microdissection testicular sperm extraction for non-obstructive azoospermia: Understanding which treatment works for which patient.

Objectives: The superiority of microdissection testicular sperm extraction (mTESE) over conventional TESE (cTESE) for men with non-obstructive azoospermia (NOA) is debated. We aimed to compare the sperm retrieval rate (SRR) of mTESE to cTESE and to identify candidates who would most benefit from mTESE in a cohort of Caucasian-European men with primary couple's infertility.

Material And Methods: Data from 49 mTESE and 96 cTESE patients were analysed.

Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics.

Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin fibroblasts and DRP1-deficient or clock-deficient mice, to show that these dynamics are clock controlled via circadian regulation of DRP1.

Saturated or unsaturated fat supplemented maternal diets influence omental adipose tissue proteome of suckling goat-kids.

The aim of the present study was to investigate how maternal diet can influence the adipose tissue of goat kids. Omental adipose tissue proteomes of goat-kids from mothers fed with diet enriched with stearic acid (ST-kids), fish oil (FO-kids) and standard diets (CTRL) were determined by quantitative iTRAQ 2D-LC-MS/MS analysis. Twenty proteins were found to be differentially expressed in suckling kids' omental adipose tissue.

Comprehensive protocol of traceability during IVF: the result of a multicentre failure mode and effect analysis.

Study Question: Can traceability of gametes and embryos be ensured during IVF?

Summary Answer: The use of a simple and comprehensive traceability system that includes the most susceptible phases during the IVF process minimizes the risk of mismatches.

What Is Known Already: Mismatches in IVF are very rare but unfortunately possible with dramatic consequences for both patients and health care professionals. Traceability is thus a fundamental aspect of the treatment.

Frozen-thawed blastocyst transfer in natural cycle: feasibility in everyday clinical practice.

Purpose: Transfer of frozen-thawed embryos in natural cycle is gaining consensus but evidence on this approach is scanty. The aim of this study is reporting on the feasibility of this type of policy in everyday clinical practice.

Methods: We retrospectively selected all women undergoing the procedure between July 2013 and December 2014.

Obstetric and neo-natal outcomes of ICSI cycles using pentoxifylline to identify viable spermatozoa in patients with immotile spermatozoa.

Pentoxifylline (PF) represents an effective tool in stimulating motility and identifying viable spermatozoa in intracytoplasmic sperm injection (ICSI) patients presenting exclusively with immotile spermatozoa. However, its use is not universally accepted for its possible detrimental effects on oocytes, embryos or newborns. To evaluate whether PF use may affect obstetrical/neo-natal outcomes, 102 patients achieving a clinical pregnancy after a PF-ICSI in four IVF units in Spain and Italy were followed up after delivery.

Application of failure mode and effect analysis in an assisted reproduction technology laboratory.

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment.

DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress.

During apoptosis mitochondria undergo cristae remodeling and fragmentation, but how the latter relates to outer membrane permeabilization and downstream caspase activation is unclear. Here we show that the mitochondrial fission protein Dynamin Related Protein (Drp) 1 participates in cytochrome c release by selected intrinsic death stimuli. While Bax, Bak double deficient (DKO) and Apaf1(-/-) mouse embryonic fibroblasts (MEFs) were less susceptible to apoptosis by Bcl-2 family member BID, H(2)O(2), staurosporine and thapsigargin, Drp1(-/-) MEFs were protected only from BID and H(2)O(2).

The impact of Alpha/ESHRE consensus regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in vitro fertilization outcome.

Purpose: The present study aimed to gather information on the impact of Alpha/European Society of Human Reproduction and Embryology (ESHRE) consensus regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in vitro fertilization outcome. In particular, we investigated if patients undergoing intracytoplasmic sperm injection (ICSI) and whose oocytes are discarded due to SERa have a higher chance of embryo transfer cancellation compared to patients without SERa oocytes.

Methods: This is a nested case-control study drawn from the cohort of women referring for in vitro fertilization with ICSI.

Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.

Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment.

Intrafollicular iron and ferritin in women with ovarian endometriomas.

Objective: To evaluate whether iron contained in ovarian endometriomas can diffuse through the cyst wall and negatively affect ovarian function.

Design: Prospective case series.

Setting: Infertility unit in an academic setting.

UCP1 and UCP2 expression in different subcutaneous and visceral adipose tissue deposits in 30 days old goat kids and effect of fatty acid enriched diets.

Beside its importance in the first hours of life, brown adipose tissue has also significant roles in the following stages of growth and in adults by regulating energy metabolism, but its identification in adult ruminants is still controversial. Quantitative PCR, followed by histological confirmation, was used to investigate UCP expression and brown and white adipocytes' distribution in 30-day-old goat kids. The influence of maternal diet enriched with either fish oil or stearic acid was investigated as well.

Expression of α1-acid glycoprotein and lipopolysaccharide binding protein in visceral and subcutaneous adipose tissue of dairy cattle.

Adipose tissue is an endocrine compartment that plays an important role in immune defence by producing and releasing a wide range of proteins, including acute phase proteins (APPs). The liver is the main organ of APP synthesis, although extrahepatic production has also been reported. In the present study, expression of two APPs in dairy cattle, lipopolysaccharide binding protein (LBP) and α1-acid glycoprotein (AGP), was determined in four visceral (pericardial, mesenteric, omental and retroperitoneal) and three subcutaneous (withers, tail head and sternum) adipose tissue depots.

Can we use incubators with atmospheric oxygen tension in the first phase of in vitro fertilization? A retrospective analysis.

Purpose: Aim of the present study was to compare two culture strategies used in our routine in vitro fertilization program.

Methods: This is a retrospective analysis. Two culture systems were used in parallel and analysed retrospectively: 1) Use of atmospheric oxygen tension (~20 %) until insemination followed by use of low (~5 %) oxygen concentration; 2) Exclusive use of low oxygen concentration.