Isolation and Characterization of Neutralizing Monoclonal Antibodies from a Large Panel of Murine Antibodies against RBD of the SARS-CoV-2 Spike Protein.

The COVID-19 pandemic, once a global crisis, is now largely under control, a testament to the extraordinary global efforts involving vaccination and public health measures. However, the relentless evolution of SARS-CoV-2, leading to the emergence of new variants, continues to underscore the importance of remaining vigilant and adaptable. Monoclonal antibodies (mAbs) have stood out as a powerful and immediate therapeutic response to COVID-19.

High throughput surface plasmon resonance imaging method for clinical detection of presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infection.

Surface Plasmon Resonance imaging (SPRi) was used to determine the presence and strength of binding of IgG, IgM and IgA against the Receptor Binding Domain (RBD) of SARS-CoV-2 in sera of 102 CoViD-19 and non-CoViD-19 patients. The SPRi assay simultaneously measures the antibody isotype levels and the strength of binding to the RBD of ultimate 384 patient samples in one run. It turns out that during the course of the disease, the IgG levels and strength of binding increased while generally the IgM and IgA levels go down.

Presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infection.

Surface Plasmon Resonance imaging (SPRi) was used to determine the presence and strength of binding of IgG, IgM and IgA against the Receptor Binding Domain (RBD) of SARS-CoV-2 in sera of 119 CoViD-19 patients. The SPRi assay measures the antibody isotype levels and the strength of binding to the RBD of ultimate 384 patient samples in one run. It turns out that during the course of the disease, the IgG levels and strength of binding increased while generally the IgM and IgA levels go down.

Identification of the origin of infantile saturnism based on lead isotopic and elemental ratios.

Background: In France, the prevalence of childhood lead poisoning is becoming rare since the avoidance of lead in paints in 1949 and the gradual replacement of water pipes. Chronic lead toxicity is well known and is well correlated to blood lead concentration.

Aim: Here we report a case of severe lead poisoning occurring in a young female child with a pica behavior.

Pre-launch radiometric calibration of the infrared spectrometer onboard SuperCam for the Mars2020 rover.

Near-infrared spectroscopy has become a well-known remote sensing technique for the surface characterization of planetary objects. Among them, Mars was observed in the past by three imaging spectrometers from orbit. The Infrared Spectrometer/SuperCam instrument performs near-infrared spectroscopy from the martian surface for the first time, with a 1.

The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease.

Transcription factors are expressed in a dynamic fashion both in time and space during brain development, and exert their roles by activating a cascade of multiple target genes. This implies that understanding the precise function of a transcription factor becomes a challenging task. In this review, we will focus on COUP-TFI (or NR2F1), a nuclear receptor belonging to the superfamily of the steroid/thyroid hormone receptors, and considered to be one of the major transcriptional regulators orchestrating cortical arealization, cell-type specification and maturation.

COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons.

C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study.

After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival.

White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years.

Background: To assess the prevalence of early confluent/confluent white matter lesions (ec/cWMLs) in asymptomatic individuals aged ≥50 years and to identify associated clinical phenotypes.

Methods: Cross-sectional analysis of 141 asymptomatic individuals aged ≥50 years assessed at an outpatient department in France. Brain magnetic resonance imaging was rated using the Fazekas scale.

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored.

"Cancer 2015": A Prospective, Population-Based Cancer Cohort-Phase 1: Feasibility of Genomics-Guided Precision Medicine in the Clinic.

"Cancer 2015" is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data.

Cancer 2015: a longitudinal whole-of-system study of genomic cancer medicine.

Genomic cancer medicine promises revolutionary change in oncology. The impacts of 'personalized medicine', based upon a molecular classification of cancer and linked to targeted therapies, will extend from individual patient outcomes to the health economy at large. To address the 'whole-of-system' impact of genomic cancer medicine, we have established a prospective cohort of patients with newly diagnosed cancer in the state of Victoria, Australia, about whom we have collected a broad range of clinical, demographic, molecular, and patient-reported data, as well as data on health resource utilization.

HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators.

Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis.

[Outpatient expectations in dermatology consultations: A pilot study].

Background: Understanding patients' expectations with regard to medical care is critical as it guarantees an efficient therapeutic process. Our aim was to determine outpatients' expectations concerning clinical encounters in a dermatology clinic and to study how these matched the opinions of dermatologists regarding them.

Patients And Methods: Consecutive outpatients consulting in five dermatology centres in the Paris suburbs between February 2013 and March 2013 were prospectively included.

Sleep-disordered breathing in chronic heart failure: development and validation of a clinical screening score.

Aims: Sleep-disordered breathing (SDB) is highly prevalent and of adverse prognostic significance in patients with chronic heart failure (CHF). Polygraphy is used for diagnosing SDB but polygraphy resources fall short of needs. Here, our aim was to develop a score for SDB screening in patients with CHF.

Is it worth continuing sexual rehabilitation after radical prostatectomy with intracavernous injection of alprostadil for more than 1 year?

Introduction: Intracavernous alprostadil injection (IAI) is a widely used treatment for sexual rehabilitation (SR) after radical prostatectomy (RP). It is unknown whether the continuation of IAI beyond 1 year continues to improve erectile function.

Aims: To assess evolution of sexual function in patients using IAI who are nonresponsive to phosphodiesterase type 5 inhibitors (PDE5i) between 12 (M12) and 24 (M24) months after RP.

Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

Introduction: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system.

Methods: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited.

Update on 2-year outcomes of the TOMS™ transobturator male sling for the treatment of male stress urinary incontinence.

Aims: To update the 2-year outcomes of the TOMS™ transobturator male sling for treating post-prostatectomy urinary incontinence (pRP-UI) in a group of patients previously evaluated at 1 year.

Methods: We prospectively followed 40 patients with pRP-UI before and 6, 12, and 24 months after implantation of the TOMS™ transobturator male sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA-PCI (urinary bother domain), PGI-I, and daily pad use.

In situ reconstruction in native and prosthetic aortic infections using cryopreserved arterial allografts.

Objectives: To evaluate overall survival and complications of cryopreserved arterial allografts in aortic graft infections and infected aortic aneurysms.

Methods: A retrospective review of consecutive patients was conducted with native or prosthetic aortic infections, who underwent local debridement and in situ implantation of a cryopreserved aortic allograft from September 2004 to June 2012 at the Henri Mondor University Hospital. Patient characteristics, indications for allograft implantation, perioperative events, bacteriological data, and events related to follow-up were identified.

Sequence artefacts in a prospective series of formalin-fixed tumours tested for mutations in hotspot regions by massively parallel sequencing.

Background: Clinical specimens undergoing diagnostic molecular pathology testing are fixed in formalin due to the necessity for detailed morphological assessment. However, formalin fixation can cause major issues with molecular testing, as it causes DNA damage such as fragmentation and non-reproducible sequencing artefacts after PCR amplification. In the context of massively parallel sequencing (MPS), distinguishing true low frequency variants from sequencing artefacts remains challenging.

Erection hardness score for the evaluation of erectile dysfunction: further psychometric assessment in patients treated by intracavernous prostaglandins injections after radical prostatectomy.

Introduction: Erectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested.

Aim: This study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections.

De-novo designed library of benzoylureas as inhibitors of BCL-XL: synthesis, structural and biochemical characterization.

The prosurvival BCL-2 proteins are attractive yet challenging targets for medicinal chemists. Their involvement in the initiation and progression of many, if not all, tumors makes them prime targets for developing new anticancer therapies. We present our approach based on de novo structure-based drug design.

Discovery of potent and selective benzothiazole hydrazone inhibitors of Bcl-XL.

Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-XL inhibitors originating from a high-throughput screening campaign. Small structural changes to the hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM).

Structure-guided design of a selective BCL-X(L) inhibitor.

The prosurvival BCL-2 family protein BCL-X(L) is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-X(L) will most likely have widespread utility in cancer treatment and, instead of inhibiting multiple prosurvival BCL-2 family members, a BCL-X(L)-selective inhibitor would be expected to minimize the toxicity to normal tissues. We describe the use of a high-throughput screen to discover a new series of small molecules targeting BCL-X(L) and their structure-guided development by medicinal chemistry.