Chromatic fusion: Generative multimodal neuroimaging data fusion provides multi-informed insights into schizophrenia.

This work proposes a novel generative multimodal approach to jointly analyze multimodal data while linking the multimodal information to colors. We apply our proposed framework, which disentangles multimodal data into private and shared sets of features from pairs of structural (sMRI), functional (sFNC and ICA), and diffusion MRI data (FA maps). With our approach, we find that heterogeneity in schizophrenia is potentially a function of modality pairs. Results show (1) schizophrenia is highly multimodal and includes changes in specific networks, (2) non-linear relationships with schizophrenia are observed when interpolating among shared latent dimensions, and (3) we observe a decrease in the modularity of functional connectivity and decreased visual-sensorimotor connectivity for schizophrenia patients for the FA-sFNC and sMRI-sFNC modality pairs, respectively. Additionally, our results generally indicate decreased fractional corpus callosum anisotropy, and decreased spatial ICA map and voxel-based morphometry strength in the superior frontal lobe as found in the FA-sFNC, sMRI-FA, and sMRI-ICA modality pair clusters. In sum, we introduce a powerful new multimodal neuroimaging framework designed to provide a rich and intuitive understanding of the data which we hope challenges the reader to think differently about how modalities interact.

Chromatic fusion: generative multimodal neuroimaging data fusion provides multi-informed insights into schizophrenia.

This work proposes a novel generative multimodal approach to jointly analyze multimodal data while linking the multimodal information to colors. By linking colors to private and shared information from modalities, we introduce chromatic fusion, a framework that allows for intuitively interpreting multimodal data. We test our framework on structural, functional, and diffusion modality pairs. In this framework, we use a multimodal variational autoencoder to learn separate latent subspaces; a private space for each modality, and a shared space between both modalities. These subspaces are then used to cluster subjects, and colored based on their distance from the variational prior, to obtain meta-chromatic patterns (MCPs). Each subspace corresponds to a different color, red is the private space of the first modality, green is the shared space, and blue is the private space of the second modality. We further analyze the most schizophrenia-enriched MCPs for each modality pair and find that distinct schizophrenia subgroups are captured by schizophrenia-enriched MCPs for different modality pairs, emphasizing schizophrenia's heterogeneity. For the FA-sFNC, sMRI-ICA, and sMRI-ICA MCPs, we generally find decreased fractional corpus callosum anisotropy and decreased spatial ICA map and voxel-based morphometry strength in the superior frontal lobe for schizophrenia patients. To additionally highlight the importance of the shared space between modalities, we perform a robustness analysis of the latent dimensions in the shared space across folds. These robust latent dimensions are subsequently correlated with schizophrenia to reveal that for each modality pair, multiple shared latent dimensions strongly correlate with schizophrenia. In particular, for FA-sFNC and sMRI-sFNC shared latent dimensions, we respectively observe a reduction in the modularity of the functional connectivity and a decrease in visual-sensorimotor connectivity for schizophrenia patients. The reduction in modularity couples with increased fractional anisotropy in the left part of the cerebellum dorsally. The reduction in the visual-sensorimotor connectivity couples with a reduction in the voxel-based morphometry generally but increased dorsal cerebellum voxel-based morphometry. Since the modalities are trained jointly, we can also use the shared space to try and reconstruct one modality from the other. We show that cross-reconstruction is possible with our network and is generally much better than depending on the variational prior. In sum, we introduce a powerful new multimodal neuroimaging framework designed to provide a rich and intuitive understanding of the data that we hope challenges the reader to think differently about how modalities interact.

Vapor-Assisted Conversion of Heterobimetallic Titanium-Organic Framework Thin Films.

Heterobimetallic Metal-Organic Frameworks (MOFs) synergically combine the properties of two metal ions, thus offering significant advantages over homometallic MOFs in gas storage, separation, and catalysis, among other applications. However, these remain centered on bulk materials, while applications that require functional coatings on solid supports are not developed. We explore for the first time the deposition of heterometallic Ti-based MOF thin films using vapor-assisted conversion on substrates functionalized with a self-assembled monolayer. Furthermore, metal-induced dynamic topological transformation allows the conversion of MUV-10(Ca) films into MUV-101(Co) and MUV-102(Cu), which is not accessible through direct synthesis, without morphologically altering the films. These nonconventional thin-film deposition techniques enable homogeneous and crystalline coatings of heterometallic titanium MOFs that also maintain their corresponding porosity.

Framework Adaptability and Concerted Structural Response in a Bismuth Metal-Organic Framework Catalyst.

Bismuth metal-organic frameworks (MOFs) as heterogeneous catalysts are scarce, and there is little knowledge on the influence of the MOF features on their resulting activity and behavior. Here, we present the synthesis, characterization, and catalytic activity in the one-pot multicomponent Strecker reaction with ketones of three new MOFs prepared with the combination of indium or bismuth and 4,4',4'',4'''-methanetetrayltetrabenzoic acid. One of them, denoted BiPF-7, is very robust and chemically stable, and demonstrates a high activity in the formation of the desired α-aminonitriles. The interaction of the catalytic substrates with the metal centers in this MOF has been crystallographically characterized, showcasing a concerted framework adaptability process that involves structural changes in framework components that are not directly involved in the binding of the guests.

Building a Green, Robust, and Efficient Bi-MOF Heterogeneous Catalyst for the Strecker Reaction of Ketones.

In this work, we present the new [Bi14(µ3-O)9(µ4-O)2(µ3-OH)5(3,5-DSB)5(H2O)3]·7H2O, BiPF-4 (bismuth polymeric framework─4) MOF, its microwave hydrothermal synthesis, as well as its behavior as a heterogeneous catalyst in the multicomponent organic Strecker reaction. The BiPF-4 material shows a three-dimensional (3D) framework formed by peculiar inorganic oxo-hydroxo-bismutate layers connected among them through the 3,5-dsb (3,5-disulfobenzoic acid) linker. These two-dimensional (2D) layers, built by junctions of Bi7 polyhedra SBU, provide the material of many Lewis acid catalytic sites because of the mixing in the metal coordination number. BiPF-4 is a highly robust, green, and stable material that demonstrates an excellent heterogeneous catalytic activity in the multicomponent Strecker reaction of ketones carried out in one-pot synthesis, bringing a reliable platform of novel green materials based on nontoxic and abundant metal sources such as bismuth.

Neurodevelopmental Trajectories in Children With Internalizing, Externalizing and Emotion Dysregulation Symptoms.

Introduction: Childhood and adolescence are crucial periods for brain and behavioral development. However, it is not yet clear how and when deviations from typical brain development are related to broad domains of psychopathology. Methods: Using three waves of neuroimaging data within the population-based Generation R Study sample, spanning a total age range of 6-16 years, we applied normative modeling to establish typical development curves for (sub-)cortical volume in 37 brain regions, and cortical thickness in 32 brain regions. Z-scores representing deviations from typical development were extracted and related to internalizing, externalizing and dysregulation profile (DP) symptoms. Results: Normative modeling showed regional differences in developmental trajectories. Psychopathology symptoms were related to negative deviations from typical development for cortical volume in widespread regions of the cortex and subcortex, and to positive deviations from typical development for cortical thickness in the orbitofrontal, frontal pole, pericalcarine and posterior cingulate regions of the cortex. Discussion: Taken together, this study charts developmental curves across the cerebrum for (sub-)cortical volume and cortical thickness. Our findings show that psychopathology symptoms, are associated with widespread differences in brain development, in which those with DP symptoms are most heavily affected.

Protein-polyelectrolyte complexes to improve the biological activity of proteins in layer-by-layer assemblies.

A standard method of protein immobilization is proposed, based on the use of protein-polyelectrolyte complexes (PPCs) as building blocks for layer-by-layer assembly. Thicker multilayers, with a higher polyelectrolyte fraction, are obtained with PPCs compared to single protein molecules. Biological activity is not only maintained, but specific activity is also higher, as demonstrated for lysozyme-poly(styrene sulfonate) complexes. This is attributed to the more hydrated state of the assemblies. This new method of protein immobilization opens up perspectives for biotechnology and biomedical applications.

Central skull base osteomyelitis: a rare but life-threatening disease.

We present the case of a 70-year-old non-diabetic patient who presented to the emergency department with unrelenting otalgia. A severe otitis externa (OE) and mastoiditis were treated with broad spectrum antibiotics and surgical drainage. No bacteria was isolated from surgical samples. Because the otalgia persisted, a magnetic resonance (MR) was performed and showed an infiltrating process at the skull base. Biopsies failed to prove malignancy or granulomatosis. The patient's neurological state deteriorated. The suspicion of a skull base osteomyelitis (SBO) was raised and proven by CT-guided biopsies that grew Pseudomonas aeruginosa. Meropenem and ciprofloxacin, given for 8 weeks, lead to a fast clinical improvement and a full recovery. SBO is uncommon, often complicating severe OE. Pseudomonas aeruginosa is the main pathogen. Prompt diagnosis and adequate antibiotherapy are required to lower mortality and morbidity. The diagnosis may be delayed because of unawareness and large differential diagnosis including solid neoplasic tumours, malignant hemopathies and granulomatosis.

Worsening pneumonitis due to a pharmacokinetic drug-drug interaction between everolimus and voriconazole in a renal transplant patient.

WHAT IS KNOWN AND OBJECTIVE: Azole antifungals, prescribed prophylactically to avoid severe infections in immunosuppressed organ transplant recipients, can interact with drug substrates of CYP3A4. We report serious adverse effects due to interaction between orally administered voriconazole and everolimus in a renal transplant recipient. CASE DESCRIPTION: Despite reduction of the dose of everolimus by a third, the blood trough concentration of everolimus increased considerably in a kidney transplant recipient upon oral administration of voriconazole. Everolimus was then discontinued. Pneumonia secondary to pulmonary aspergillosis worsened, possibly due to the excessive immunosuppression. WHAT IS NEW AND CONCLUSION: Orally administered voriconazole inhibits intestinal and hepatic cytochrome P450-3A4 activity and thereby reduces everolimus metabolism. An 80% decrease in dose or discontinuation of everolimus is required when concomitant voriconazole is introduced. Daily blood monitoring of everolimus is warranted until a steady state of concentrations is reached.

French adaptation and validation of the sino-nasal outcome test-22: a prospective cohort study on quality of life among 422 subjects.

OBJECTIVES: ENT surgeons are facing an ever-increasing demand to demonstrate their efficacy. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a fully validated and easy-to-use outcome measure in rhinology. Our goal was to translate and validate the SNOT-22 in a cohort of 422 French-speaking subjects. DESIGN, SETTING AND PARTICIPANTS: The French version of the SNOT-22 was obtained by forward and backward translations by six independent interpreters. Five experienced rhinologists compared the translations to each other, and a group of 12 naive patients selected the most appropriate translation of each item. To evaluate this questionnaire, we conducted a prospective cohort study on 376 rhinological patients and 46 healthy volunteers in three University-affiliated teaching Hospitals. MAIN OUTCOME MEASURES: Reproducibility (test-retest reliability), internal consistency, known-group differences, responsiveness to treatment, validity and correlation to other clinical instruments (visual analogue scale, Nasal Obstruction Symptoms Evaluation score and Lund-Mackay score). RESULTS: The test-retest reliability coefficient was 0.78, indicating a good reliability when administering the instrument on two different occasions. The internal consistency was high with a Cronbach's α value of 0.93. Our questionnaire was able to detect differences between rhinological patients and control subjects (P < 0.0001) and improved significantly after nose and sinus surgery (P < 0.0001), indicating a good responsiveness. There was a relative correlation with visual analogue scale and Nasal Obstruction Symptoms Evaluation (NOSE) score, but no correlation with Lund-Mackay score. CONCLUSION: The SNOT-22 is a reliable and valid tool to assess quality of life in French-speaking patients and correlates well with known indices of disease severity.

Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients.

INTRODUCTION AND AIM: There is a high prevalence of olfactory dysfunction in the general population. Several causes of olfactory dysfunction have been reported and this disorder is classically divided into sinonasal and non-sinonasal-related olfactory dysfunction. The aims of this study were firstly, to evaluate the frequency of the various aetiologies of olfactory dysfunction in a population of patients with non-sinonasal-related olfactory dysfunction and secondly, to evaluate the degree of olfactory impairment associated with these various aetiologies. MATERIAL AND METHODS: We retrospectively reviewed a cohort of 496 patients with non-sinonasal-related olfactory dysfunction. The aetiology of the olfactory dysfunction was recorded for each patient. The aetiology was determined by a complete clinical assessment, including medical history, complete otorhinolaryngological examination, psychophysical testing of olfactory function, recording of olfactory event-related potentials and brain magnetic resonance imaging. Six groups of patients were defined on the basis of the aetiology of the disease and orthonasal and retronasal psychophysical olfactory performances were evaluated in each group. RESULTS: Post-infectious and post-traumatic aetiologies were the most common causes, representing 37.9% and 33.1% of patients, respectively, followed by idiopathic (16.3%), congenital (5.9%), toxic (3.4%) and neurological (3.4%) olfactory dysfunction. Anosmia was significantly more frequent in congenital (93.1%) and post-traumatic (62.8%) olfactory dysfunction, whereas hyposmia was more frequent in the post-infectious group (59.6%). Orthonasal and retronasal olfactory function tests were significantly correlated in all groups except for the congenital group. CONCLUSIONS: The data of this study confirm that the most common causes of non-sinonasal-related olfactory dysfunction are post-infectious and post-traumatic. Post-infectious olfactory dysfunction is mainly observed in middle-aged women and is mainly associated with hyposmia, whereas post-traumatic olfactory dysfunction is mainly observed in young men and is associated with a high rate of anosmia.

Cystic dilation of the distal end of the nasolacrimal duct: underrated cause of epiphora in adults and its endoscopic treatment.

Epiphora is a frequent reason for ophthalmologic consultation. Among the multiple causes, obstructions of the lacrimal excretory system are common. Sacal and postsacal obstructions are much more frequent than presacal obstructions. Obstruction at the level of the Hasner's valve is rare and likely underestimated. The authors report the clinical history and the imaging of 3 patients with a cystic dilation of the distal end of the nasolacrimal duct (NLD). These patients were easily managed by an ENT surgeon. In one case, the surgery consisted of an endonasal DCR where in the 2 other cases, a marsupialisation of the cystic expansion of the nasolacrimal duct was successfully performed with the micro- debrider. The authors review the world literature on this specific topic. They conclude that a coronal sinus CT scan and an inferior meatus endoscopy should be included in the ophthalmologic work-up performed in all cases of low obstruction of the lacrimal system. When there is a dilation of the distal end of the NLD the marsupialisation of the cystic expansion in the inferior meatus is the option of treatment instead of performing a DCR. ENTs must play a role in the assessment and treatment of low obstructions of the lacrimal excretory system.

Biological conditions affecting chronic inflammation in upper airways in children.

PROBLEMS/OBJECTIVES: A child's immune system cannot depend on a memory-type immune response and it also induces cytokine responses less efficiently. Biological conditions like allergy or cystic fibrosis, immune deficiency or gastrooesophageal reflux can induce and maintain background inflammation in children's upper airways, making newborns and children more susceptible to upper airway infections and inflammations. This paper will describe in brief how allergy, cystic fibrosis, immune deficiency, nasal and paranasal anatomical variants, and gastro-oesophageal reflux (GOR) can affect the immune and inflammatory responses in upper airways and how they could interfere with immunity development and maturation in children. METHODOLOGY: Literature review. RESULTS: Chronic inflammation induced by infection, allergy, cystic fibrosis or immune deficiency is multifactorial in origin and is strongly influenced by physiological, immunological, anatomical, environmental and, above all, genetic parameters. Finally, the direct role played by nasal and paranasal anatomical variants and GOR is also discussed. CONCLUSIONS: These conditions should be screened systematically in all children presenting chronic clinical features of upper airway inflammation.

Specific medical and surgical treatment for chronic inflammatory diseases in children.

Treatment for chronic inflammatory conditions in children should take into account the specific pathophysiological and clinical processes underlying these disorders. These guidelines provide a framework for both the medical and surgical treatment of chronic inflammatory diseases such as otitis media, allergic rhinitis and chronic rhinosinusitis, chronic inflammation of tonsils and adenoids, and laryngitis. In addition, the role of vaccinations and immunomodulatory therapies is discussed. Whenever possible, the evidence levels for specific treatments comply with the Oxford Levels of Evidence.

Type III frontal sinusotomy: surgical technique, indications, outcomes, a multi-university retrospective study of 120 cases.

Draf in 1991. The procedure--which is also known as the modified endoscopic Lothrop procedure--aims to create the largest possible anteroposterior and lateral to lateral opening between both frontal sinuses and the nasal cavities. This requires the resection of the medial floor of both frontal sinuses, the intersinus septum and the superior nasal septum. The authors present a retrospective study including a cohort of 120 patients who underwent surgery in six Belgian university ENT departments. Mean follow-up was 24.6 months (range: 5-36 months). This paper describes the surgical procedure and reviews the indications, comorbidities, outcomes and complications of the type III frontal sinusotomy. Some correlations are also established with the data published in the worldwide literature. The authors conclude that the Draf III is a demanding procedure requiring considerable expertise in endoscopic sinus surgery. The procedure is effective with a success rate of 87.5%. Indeed, 12.5% of patients only experienced closure of the neoostium while 20% of all the patients had unchanged or worse symptomatology. The percentage of post-operative complications is 7.5%. All complications were managed successfully.

TiO(2) doping by hydroxyurea at the nucleation stage: towards a new photocatalyst in the visible spectral range.

We report an original method of preparation of OCN-doped TiO(2) for photocatalysis in the visible spectral range. The preparation is achieved by a sol-gel route using titanium tetraisopropoxide precursor. Special attention was paid to fluid micromixing, which enables homogeneous reaction conditions in the reactor bulk and monodispersity of the produced clusters/nanoparticles. The dopant hydroxyurea (HyU, CH(4)N(2)O(2)) is injected into the reactive fluid at the nucleation stage, which lasts tens of milliseconds. The doping results in a strong yellow coloration of the nanocolloids due to the absorption band in the spectral range 380-550 nm and accelerates the aggregation kinetics of both nuclei at the induction stage and sub-nuclei units (clusters) at the nucleation stage. FTIR, Raman and UV-visible absorption analyses show the formation of a stable HyU-TiO(2) complex. EXAFS spectra indicate no appreciable changes of the first-shell Ti atom environment. The doping agent takes available surface sites of TiO(2) clusters/nanoparticles attaining ∼10% molar loading. The reaction kinetics then accelerates due to a longer collisional lifetime between nanoparticles induced by the formation of a weak [double bond, length as m-dash]OTi bond. The OCN-group bonding to titanium atoms produces a weakening of the C[double bond, length as m-dash]O double bond and a strengthening of the C-N and N-O bonds.

My surgery of the nasal valve.

We discuss the physiopathology and relevant anatomy of the nasal valves--internal and external--paying particular attention to the dynamics of the airflows in this area. We describe and comment on methods for medical examination, anterior rhinoscopy, endoscopy and fibrescopy of the valve, as well as the causes and sites of nasal valve dysfunction. We propose a review of the various treatments, medical and surgical, with a special emphasis on nasal valve surgery. Surgical techniques commonly used by the authors in daily practice for nasal valvuloplasty (such as spreader grafts and Z-plasty of the nostrils) are discussed and illustrated in depth. Some one-year postoperative results are presented and discussed.

Genetic evidence for a role of IL33 in nasal polyposis.

BACKGROUND: Little is known about the genetic factors that contribute to nasal polyposis (NP). A genome-wide association study identified 10 single nucleotide polymorphisms (SNPs) associated with eosinophilia. As eosinophils play a key role in the pathogenesis of NP, we assessed if any of these SNPs contribute to genetic susceptibility of NP. METHODS: We recruited 284 patients with NP in four participating hospitals in Belgium and 427 healthy controls, and genotyped 10 SNPs affecting eosinophilia (rs1420101 in IL1RL1, rs12619285 in IKZF2, rs4431128 in GATA2, rs4143832 in IL5, rs3184504 in SH2B3, rs2416257 in WDR36, rs2269426 in MHC, rs9494145 in MYB, rs748065 in GFRA2, and rs3939286 in IL33) using MALDI-TOF. A two-stage design was used while correcting for multiple testing. RESULTS: First stage analysis, involving 150 NP patients and 250 controls, identified rs3939286 nearby IL33 as a susceptibility factor for NP. Per at-risk A-allele, rs3939286 increased the risk for NP with an odds ratio (OR) of 1.60 (95% CI = 1.16-2.22; P = 0.0041). Second stage replication analysis in another 123 NP patients and 165 controls confirmed this association (OR = 1.43; CI = 1.00-2.06; P = 0.046). The combined analysis of both stages revealed an OR of 1.53 (CI = 1.21-1.96; P = 0.00041). Given the association of IL33 with NP, we also investigated rs1420101 in IL1RL1, which is the receptor for IL33. Although rs1420101 itself failed to associate with NP, a combined risk assessment of rs3939286 and rs1420101 further increased the risk for NP. CONCLUSION: We provide unprecedented genetic evidence suggesting a role for the IL33 pathway in the pathogenesis of NP.