A novel frameshift TBX4 variant in a family with ischio-coxo-podo-patellar syndrome and variable severity.

Background: Congenital anomalies of the knee are a spectrum of rare disorders with wide clinical and genetic variability, which are mainly due to the complex processes underlying knee development. Despite progresses in understanding pathomechanisms and associated genes, many patients remain undiagnosed.

Objective: To uncover the genetic bases of a congenital patellar dislocation affecting multiple family members with variable severity.

Characterizing local pig breeds as reservoirs for the domestic pig genetic variability worldwide via contributions to gene diversity and allelic richness.

Contributions to gene diversity and allelic richness were computed in a total of 2,260 domestic pig genotypes, sharing 53,626 autosomal SNPs, belonging to 98 pig subpopulations worldwide (41 Asian, 696 genotypes; 20 American, 262 genotypes; and 37 European, 686 genotypes), using 616 pig samples belonging to 5 different Cosmopolitan pig breeds as an outgroup, to ascertain if local pig subpopulation can be considered reservoirs of genetic diversity for the whole domestic pig species worldwide. Assessments were carried out for the whole dataset and separately for the American-European and Asian subsets. Effective population size was computed at the subpopulation level using molecular coancestry and linkage disequilibrium information to ensure that estimates of contributions to diversity were not affected by demographic issues.

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

Robust machine learning challenge: An AIFM multicentric competition to spread knowledge, identify common pitfalls and recommend best practice.

Purpose: A novel and unconventional approach to a machine learning challenge was designed to spread knowledge, identify robust methods and highlight potential pitfalls about machine learning within the Medical Physics community.

Methods: A public dataset comprising 41 radiomic features and 535 patients was employed to assess the potential of radiomics in distinguishing between primary lung tumors and metastases. Each participant developed two classification models using: (i) all features (base model); (ii) only robust features (robust model).

Novel benzenesulfonamide-aroylhydrazone conjugates as carbonic anhydrase inhibitors that induce MAPK/ERK-mediated cell cycle arrest and mitochondrial-associated apoptosis in MCF-7 breast cancer cells.

A series of novel 4-alkylthio-2-chloro-5-[(2-arylmethylidene)hydrazinecarbonyl]benzenesulfonamide derivatives 3-22 were synthesized and evaluated for their inhibitory activity against human carbonic anhydrase isozymes hCA I, hCA II, hCA IX, and hCA XII. These compounds showed varying degrees of activity against the studied isoenzymes. However, the importance of substituent choice in designing potent carbonic anhydrase inhibitors is highlighted by the strong inhibition profiles of compounds 3 and 10 against hCA IX and the low average K values for compounds 9 and 10 (134 nM and 77 nM, respectively).

Survival analysis of the metastatic cohort of Italian Association of Medical Oncology (AIOM) GARIBALDI survey.

This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Treatment-naïve patients ≥18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause.

Magneto-Chiral Dichroism of Chiral Lanthanide Complexes in the Context of Richardson's Theory of Optical Activity.

Here we report on the Magneto-Chiral Dichroism (MChD) detected through visible and near-infrared light absorption of two enantiomeric pairs of Er and Tm chiral complexes featuring a propeller-like molecular structure. The magnetic properties show typical features of isolated paramagnetic ions associated with I and H ground state terms. MChD spectroscopy shows high g dissymmetry factors of ca.

Mott Transition for a Lieb-Liniger Gas in a Shallow Quasiperiodic Potential: Delocalization Induced by Disorder.

Disorder or quasidisorder is known to favor localization in many-body Bose systems. Here, in contrast, we demonstrate an anomalous delocalization effect induced by incommensurability in quasiperiodic lattices. Loading ultracold atoms in two shallow periodic lattices with equal amplitude and either equal or incommensurate spatial periods, we show the onset of a Mott transition not only in the periodic case but also in the quasiperiodic case.

Large Scale Simulations of Photosynthetic Antenna Systems: Interplay of Cooperativity and Disorder.

Large-scale simulations of light-matter interaction in natural photosynthetic antenna complexes containing more than one hundred thousands of chlorophyll molecules, comparable with natural size, have been performed. Photosynthetic antenna complexes present in Green sulfur bacteria and Purple bacteria have been analyzed using a radiative non-Hermitian Hamiltonian, well-known in the field of quantum optics, instead of the widely used dipole-dipole Frenkel Hamiltonian. This approach allows us to study ensembles of emitters beyond the small volume limit (system size much smaller than the absorbed wavelength), where the Frenkel Hamiltonian fails.

Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors.

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms.

[Registers as central real world data source: the experience of the Italian Multiple Sclerosis and Related Disorders Register].

Registers collecting data from clinical practice (real world data) have gained increasing interest in recent years in the scientific, administrative, and regulatory fields. The value of longitudinal data collection in deepening knowledge about a specific pathology and its healthcare complexity is increasingly recognized. This article describes the development, organizational structure, and technical characteristics of the Italian Multiple Sclerosis and Related Disorders Register (RISM).

Bucking the trend: understanding lipopolysaccharide structure and outer membrane dynamics in cold-adapted isolated from Enigma Lake, Antarctica.

Cold environments are predominant over the Earth and are inhabited by bacteria able to cope with a series of simultaneous environmental pressures. Gram-negative species of the genus are the predominant ones isolated from cold habitats, making them an excellent model for studying the mechanisms of bacterial adaptation to the most extreme habitats on our planet. Here we focused on the lipopolysaccharide (LPS) structure and the outer membrane dynamics of sp.

Late Miocene transformation of Mediterranean Sea biodiversity.

Understanding deep-time marine biodiversity change under the combined effects of climate and connectivity changes is fundamental for predicting the impacts of modern climate change in semi-enclosed seas. We quantify the Late Miocene-Early Pliocene [11.63 to 3.

Assessing Mechanochemical Properties of Acrylonitrile Butadiene Styrene (ABS) Items in Cultural Heritage Through a Multimodal Spectroscopic Approach.

A multimodal spectroscopic approach is proposed to correlate the mechanical and chemical properties of plastic materials in art and design objects, at both surface and subsurface levels, to obtain information about their conservation state and to monitor their degradation. The approach was used to investigate the photo-oxidation of acrylonitrile butadiene styrene (ABS), a plastic commonly found in many artistic and design applications, using ABS-based LEGO bricks as model samples. The modifications of the chemical and viscoelastic properties of ABS during photoaging were monitored by correlative Brillouin and Raman microspectroscopy (BRaMS), combined with portable and noninvasive broad-range external reflection infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) relaxometry, directly applicable in museums.

Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study.

This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m for 5-days with orally administered decitabine with cedazuridine (DEC-C), as well as the clinical efficacy and safety of DEC-C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC-IV or oral DEC-C (days 1-5 in a 28-day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC-C for subsequent treatment cycles until treatment discontinuation.

Exploration of 1,3,5-trisubstituted pyrazoline derivatives as human carbonic anhydrase inhibitors: Synthesis, biological evaluation and in silico studies.

The human carbonic anhydrase (hCA) IX and XII isoforms are overexpressed in hypoxic conditions, contributing to cancer. Lack of isoform selectivity has been one of the main challenges associated with the existing drugs targeting hCAs. Hence, the development of alternative approaches, such as tail approach to develop more selective hCA IX and XII inhibitors is need of the hour.

Many-Body Models for Chirality-Induced Spin Selectivity in Electron Transfer.

We present the first microscopic model for the chirality-induced spin selectivity effect in electron-transfer, in which the internal degrees of freedom of the chiral bridge are explicitly included. By exactly solving this model on short chiral chains we demonstrate that a sizable spin polarization on the acceptor arises from the interplay of coherent and incoherent dynamics, with strong electron-electron correlations yielding many-body states on the bridge as crucial ingredients. Moreover, we include the coherent and incoherent dynamics induced by interactions with vibrational modes and show that they can play an important role in determining the long-time polarized state probed in experiments.

Nickel release from 316L stainless steel following a Ni-free electroplating cycle.

Electroplating can induce nickel release even from 316L stainless steel, typically considered safe. In this work, the influence of different electroplating processes and surface treatments on nickel release was evaluated. The nickel release was tested according to the EN 1811 standard.

Gold(I)-Catalyzed Rautenstrauch/Hetero-Diels-Alder/Retro-aza-Michael Cascade Reaction for the Synthesis of α-Hydrazineyl-2-cyclopentenones.

A one-pot synthesis of ring-fused, α-hydrazineyl-2-cyclopentenone derivatives is achieved by a gold(I)-catalyzed Rautenstrauch/hetero Diels-Alder/ring opening tandem reaction of suitable propargyl esters. By mixing the latter with a dialkylazodicarboxylate in the presence of a gold(I) catalyst, the 1,2-acyloxy migration/cyclization process (Rautenstrauch reaction) leads to cyclopentadienyl ester intermediates which are trapped by the heterodienophile present in situ. This provides strained intermediates which spontaneously undergo highly regioselective ring opening by a retro aza-Michael reaction promoted by the gold(I) catalyst, eventually yielding the target compounds.