Personalized whole-brain neural mass models reveal combined Aß and tau hyperexcitable influences in Alzheimer's disease.

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-ß (Aß) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aß and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aß-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

Is perioperative COVID-19 really associated with worse surgical outcomes among vaccinated patients?

INTRODUCTION: During the surge of the SARS-CoV-2 pandemic, studies revealed high complication and morbidity rates following surgical procedures in COVID-19 positive patients. Anesthetic and surgical societies swiftly developed strategies to mitigate these risks, including a recommended postponement of elective surgeries for a minimum of 7 weeks post-COVID infection. Nowadays, with a predominantly vaccinated population, it has become crucial to discern the influencing factors on post-COVID morbidity and mortality and a reevaluation of the existing recommendations pertaining to elective surgery. METHODS: A single-center case-control study was conducted, including patients who underwent surgery between November 2021 and March 2022 and met the inclusion criteria. Eighty COVID-19 positive patients were matched 1:1 with 80 controls, each undergoing an identical intervention within a 2-week time frame. The primary outcome was 30-day postoperative mortality and secondary outcome postoperative complications (respiratory and thromboembolic). RESULTS: At the time of surgery, 88.8% of patients in the case group and 92.5% in the control group had received at least one vaccine dose. Mortality and morbidity did not show a significant difference when comparing the case and control groups (7.5% vs 6.2%, p = 0.755; 11.3% vs 8.9%, p = 0.541 respectively). In the COVID-positive group, mortality was significantly associated with age over 70 years, ASA score over III, RCRI over 1, emergency procedures, and absence of thromboembolic prophylaxis. CONCLUSIONS: In contrast to previously reported findings, we did not observe an increased morbi-mortality in patients with perioperative COVID-19 infection. It may not be necessary to delay elective interventions, except in cases with a high-risk.

Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques.

Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite's biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library encoded 99.6% of 119,747 58-mer peptides, providing comprehensive coverage of the parasite's proteome. Library screening with rhesus macaques' antibodies, from the early phase of establishment of parasite infection, identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during the late phase of parasite clearance. Immunization of mice with a selected pool of PhIP-Seq-enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden in a vaccination assay. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine.

The importance of cell uptake in photothermal treatments mediated by biomimetic magnetic nanoparticles.

Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.

Revealing the combined roles of Aß and tau in Alzheimer's disease via a pathophysiological activity decoder.

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, evidence in humans remains scarce, necessitating improved non-invasive techniques and integrative mechanistic models. Here, we introduce personalized brain activity models incorporating functional MRI, amyloid-ß (Aß) and tau-PET from AD-related participants (N=132). Within the model assumptions, electrophysiological activity is mediated by toxic protein deposition. Our integrative subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aß and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP). Furthermore, our results reproduce hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aß-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

Relationship between nutritional treatment compliance and nutritional status improvements in patients with gastrointestinal impairment taking an oral peptide-based supplement.

OBJECTIVES: Compliance in outpatients with gastrointestinal (GI) malabsorption is key in nutritional treatment. The objective of this study was to assess compliance in patients with GI impairment and malnutrition taking a high-calorie, high-protein, peptide-based oral nutritional supplement (ONS-PBD). METHODS: A prospective, multicenter, observational study was conducted in 19 medical sites in Spain where ONS-PBD were prescribed as standard of care. Patients consumed ONS-PBD daily for 12 wk. Compliance was calculated as the percentage consumed of the prescribed amount of ONS per day. RESULTS: A total of 90 adult patients were included in the study, of whom 64 completed the 12-wk regimine. Mean compliance was 78.8% ± 24.5%. Risk of malnutrition decreased in 56.3% of patients at 12 wk, as measured with the malnutrition universal screening tool. A reduction in abdominal pain was observed and stool consistency improved, with a mean of 54.7% and 27.5%, respectively. Improvements in quality of life and a decrease in percentage of patients with severe functional impairment were observed. CONCLUSIONS: These data show that ONS-PBD compliance in malnourished patients with GI symptoms is high, reducing GI symptoms and improving patients' nutritional status.

SEOM-GECP-GETTHI Clinical Guidelines for the treatment of patients with thymic epithelial tumours (2021)

Thymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions.MethodologyThese guidelines are based on leading studies published in peer review journals. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.

SEOM-GECP-GETTHI Clinical Guidelines for the treatment of patients with thymic epithelial tumours (2021).

Thymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions.

Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días? / Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

Objetivo: Como hay poca literatura sobre el tema, nos propusimos comparar la utilidad diagnóstica del análisis semicuantitativo versus el análisis visual en la escintigrafía de glóbulos blancos etiquetados (WBCS) para la infección osteoarticular. Se evaluaron protocolos de uno y dos días, en particular en los dispositivos ortopédicos.Material y métodos: Estudio prospectivo de 79 pacientes consecutivos con sospecha de infección osteoarticular. En todos los pacientes, la SCBM se realizó a los 30 min, 4 h, 8 h y 24 h. Las imágenes se analizaron agrupándolas en dos protocolos: protocolo de un día (los expertos evaluaron imágenes planas de 30 min, 4 h y 8 h) y protocolo de dos días (los expertos evaluaron imágenes planas de 30 min, 4 h y 24 h). Las imágenes planas se interpretaron cualitativa y semicuantitativamente y también se compararon agrupando a los pacientes con y sin dispositivos ortopédicos. Para determinar qué valor de corte de la variación porcentual podía predecir la infección osteoarticular, se calcularon múltiples valores de corte en ambos protocolos a partir del índice de Youden. Tres lectores ciegos analizaron las imágenes.Resultados: Comparando el diagnóstico final, el análisis visual del protocolo de un día proporcionó mejores resultados con una sensibilidad del 95,5%, una especificidad del 93% y una precisión diagnóstica del 93,7% (p < 0,01) que el protocolo de dos días con valores del 86,4%, 94,7% y 92,4%, respectivamente (p < 0,01). Para el análisis semicuantitativo, el protocolo de un día también obtuvo mejores resultados con una sensibilidad del 72,7%, una especificidad del 78,9% y una precisión del 77,2% (p < 0,01) que el protocolo de dos días (sin resultados significativos; p = 0,14), especialmente en el grupo de pacientes con aparatos ortopédicos (sensibilidad del 100%, especificidad del 79,5% y precisión del 82,7%; p < 0,01)

Objective: As scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices.Material and methods: Prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images.Results: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01).Conclusions: Most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful

Second-virial theory for shape-persistent living polymers templated by disks.

Living polymers composed of noncovalently bonded building blocks with weak backbone flexibility may self-assemble into thermoresponsive lyotropic liquid crystals. We demonstrate that the reversible polymer assembly and phase behavior can be controlled by the addition of (nonadsorbing) rigid colloidal disks which act as an entropic reorienting "template" onto the supramolecular polymers. Using a particle-based second-virial theory that correlates the various entropies associated with the polymers and disks, we demonstrate that small fractions of discotic additives promote the formation of a polymer nematic phase. At larger disk concentrations, however, the phase is disrupted by collective disk alignment in favor of a discotic nematic fluid in which the polymers are dispersed antinematically. We show that the antinematic arrangement of the polymers generates a nonexponential molecular-weight distribution and stimulates the formation of oligomeric species. At sufficient concentrations the disks facilitate a liquid-liquid phase separation which can be brought into simultaneously coexistence with the two fractionated nematic phases, providing evidence for a four-fluid coexistence in reversible shape-dissimilar hard-core mixtures without cohesive interparticle forces. We stipulate the conditions under which such a phenomenon could be found in experiment.

Effect of the type of specialized nutrition support on the course of the patient with amyotrophic lateral sclerosis (ALS). Interhospital registry SCLEDyN.

INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which specialized nutritional support is essential. The objectives of our study were to describe nutritional support at the beginning of follow-up and its impact on anthropometry and survival. METHODS: An interhospital registry was created for the hospitals of Castilla-León through a web platform designed for this purpose. An anamnesis was carried out on the evolution and nutritional history of the disease; and classical anthropometry was determined. The prescribed nutritional treatment was recorded. The parameters were measured at the beginning, at six and twelve months of nutritional follow-up. RESULTS: A total of 93 patients [49 (52.7%) spinal; 44 (47.3%) bulbar)] were analyzed. The nutritional support route at the beginning was oral diet in 36 (38.7%) patients; oral nutritional supplementation (SON) in 46 (49.5%) patients; and in 11 (11.8%) patients percutaneous endoscopic gastrostomy (PEG). A decrease in the body mass index (BMI) was observed between the first and second visit [Start: 24.18 (3.29) kg/m2; 6 months: 23.69 (4.12) kg/m2; P < .05]. Less weight loss was observed at 6 months compared to the start of nutritional follow-up [Start: 8.09 (8.72)%; 6 months: 1.4 (6.29)%; P < .01]. 36 (38.7%) patients died but with no differences according to when nutritional support was started. Survival from the onset of symptoms was higher in the group of patients with artificial nutrition, although without reaching statistical significance [Oral: 28 (20.25) months; SON: 30 (16.75-48.25) months; PEG: 39 (27-52) months; P = .90]. CONCLUSIONS: Patients with ALS present a severe deterioration in nutritional status before the start of nutritional support. After the nutritional intervention, a slowdown in weight loss and nutritional deterioration was observed.

Thirty years of recombinant BCG: new trends for a centenary vaccine.

Introduction: Global perception of the potential for Bacille Calmette-Guérin (BCG), and consequently recombinant BCG (rBCG), in a variety of prophylactic and therapeutic applications has been increasing. A century of information on BCG, and three decades of experience with rBCG, has generated solid knowledge in this field.Area covered: Here, we review the current state of knowledge of BCG and rBCG development. Molecular tools have facilitated the expression of a variety of molecules in BCG, with the aim of improving its efficacy as a tuberculosis vaccine, generating polyvalent vaccines against other pathogens, including viruses, bacteria, and parasites, and developing immunotherapy approaches against noninvasive bladder cancer. BCG's recently appraised heterologous effects and prospects for expanding its application to other diseases are also addressed.Expert opinion: There are high expectations for new tuberculosis vaccines currently undergoing advanced clinical trials, which could change the prospects of the field. Systems biology could reveal effective biomarkers of protection, which would greatly support vaccine development. The development of appropriate large-scale production processes would further support implementation of new vaccines and rBCG products. The next few years should consolidate the broader applications of BCG and produce insights into improvements using the recombinant BCG technology.

Effect of the type of specialized nutrition support on the course of the patient with amyotrophic lateral sclerosis (ALS). Interhospital registry SCLEDyN. / Efecto del tipo de soporte nutricional especializado sobre la evolución del paciente con esclerosis lateral amiotrófica (ELA). Registro interhospitalario SCLEDyN.

INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which specialized nutritional support is essential. The objectives of our study were to describe nutritional support at the beginning of follow-up and its impact on anthropometry and survival. METHODS: An interhospital registry was created for the hospitals of Castilla-León through a web platform designed for this purpose. An anamnesis was carried out on the evolution and nutritional history of the disease; and classical anthropometry was determined. The prescribed nutritional treatment was recorded. The parameters were measured at the beginning, at six and twelve months of nutritional follow-up. RESULTS: A total of 93 patients [49 (52.7%) spinal; 44 (47.3%) bulbar)] were analyzed. The nutritional support route at the beginning was oral diet in 36 (38.7%) patients; oral nutritional supplementation (SON) in 46 (49.5%) patients; and in 11 (11.8%) patients percutaneous endoscopic gastrostomy (PEG). A decrease in the body mass index (BMI) was observed between the first and second visit [Start: 24.18 (3.29) kg/m2; 6 months: 23.69 (4.12) kg/m2; P<.05]. Less weight loss was observed at 6 months compared to the start of nutritional follow-up [Start: 8.09 (8.72)%; 6 months: 1.4 (6.29)%; P<.01]. 36 (38.7%) patients died but with no differences according to when nutritional support was started. Survival from the onset of symptoms was higher in the group of patients with artificial nutrition, although without reaching statistical significance [Oral: 28 (20.25) months; SON: 30 (16.75-48.25) months; PEG: 39 (27-52) months; P=.90]. CONCLUSIONS: Patients with ALS present a severe deterioration in nutritional status before the start of nutritional support. After the nutritional intervention, a slowdown in weight loss and nutritional deterioration was observed.

Effect of Oral CNSA-001 (sepiapterin, PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized, placebo-controlled, Phase 2 trial.

AIMS: Diabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH4) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH4 levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis. METHODS: Non-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10mg/kg BID CNSA-001 or matching placebo for 14days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up. RESULTS: Gastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p=0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events. CONCLUSIONS: CNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted; ClinicalTrials.gov number, NCT03712124.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol? / Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días?

OBJECTIVE: As scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: Prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01). CONCLUSIONS: Most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma.

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

Detecting brain network communities: Considering the role of information flow and its different temporal scales.

The identification of community structure in graphs continues to attract great interest in several fields. Network neuroscience is particularly concerned with this problem considering the key roles communities play in brain processes and functionality. Most methods used for community detection in brain graphs are based on the maximization of a parameter-dependent modularity function that often obscures the physical meaning and hierarchical organization of the partitions of network nodes. In this work, we present a new method able to detect communities at different scales in a natural, unrestricted way. First, to obtain an estimation of the information flow in the network we release random walkers to freely move over it. The activity of the walkers is separated into oscillatory modes by using empirical mode decomposition. After grouping nodes by their co-occurrence at each time scale, k-modes clustering returns the desired partitions. Our algorithm was first tested on benchmark graphs with favorable performance. Next, it was applied to real and simulated anatomical and/or functional connectomes in the macaque and human brains. We found a clear hierarchical repertoire of community structures in both the anatomical and the functional networks. The observed partitions range from the evident division in two hemispheres -in which all processes are managed globally- to specialized communities seemingly shaped by physical proximity and shared function. Additionally, the spatial scales of a network's community structure (characterized by a measure we term within-communities path length) appear inversely proportional to the oscillatory modes' average frequencies. The proportionality constant may constitute a network-specific propagation velocity for the information flow. Our results stimulate the research of hierarchical community organization in terms of temporal scales of information flow in the brain network.