Location Of Onset Research Articles

A comparative analysis of the role of interplanetary magnetic field (IMF) and sudden impulse (SI) in triggering a substorm

During a typical Akasofu-type of substorm, the southward component of IMF Bz is necessary prior to the onset. However, a sudden compression of solar wind, if intense enough, can also sometimes trigger a substorm, and is independent of the IMF orientation. The Akasofu-type substorm and the Impulse-induced substorm may differ in their occurrence mechanism and ground-based observations. This is shown using the initial four substorm events discussed in this paper having distinctly different IMF and sudden impulse conditions. A question then arises is how will these signatures vary when both sudden impulse and a southward component of IMF Bz are present prior to the onset. To account for the same, we analyze two substorm events of 05th April 2010 and 22nd June 2015. The substorm onsets on these days not just coincided with the sudden impulse but also a southward component of IMF Bz was present prior to the onsets. The present study accounts for the similarities and differences among isolated IMF induced substorms, isolated impulse-induced substorms and when both sudden impulse and a southward component of IMF Bz are present. We examined the relative dominance between the two factors in triggering a substorm using ground-based and satellite-based observations. If IMF Bz is near zero, a strong pressure pulse and/or large IMF By can lead to particle precipitation away from the usual midnight. To further ensure whether a pressure pulse or IMF By predominantly influences the substorm onset location, a statistical analysis of isolated substorms will be needed.

Solar Wind Energy Input: The Primary Control Factor of Magnetotail Reconnection Site

AbstractIn this paper, we examine the solar wind energy input (expressed by −Vx × Bs, where Vx is the x component of the solar wind velocity and Bs is the southward component of the interplanetary magnetic field IMF Bz) for an onset of magnetic reconnection in the near‐Earth magnetotail. There are 41 events in which in situ observations of magnetic reconnection were made by Geotail. Magnetic reconnection in the postmidnight (premidnight) sector of the plasma sheet occurred under strong (weak) solar wind energy input conditions. Furthermore, we study temporal variations in the solar wind energy input with two different approaches using ground magnetic field observations and proton injections at geosynchronous altitude. These two analyses confirmed the preference of the postmidnight sector for the onset of magnetic reconnection under the strong solar wind energy input conditions. It is also found that the medium and weak solar wind energy input may move the onset location to earlier magnetic local times. The onset location of magnetic reconnection in the near‐Earth magnetotail is controlled by the solar wind energy input through the global magnetospheric dynamics during the loading period.

Verification of Substorm Onset From Intruding Flow Channels With High‐Resolution SuperDARN Radar Flow Maps

AbstractAuroral observations were first to identify the substorm, and later used to propose that substorm onset is triggered in the inner plasma sheet (equatorward portion of the auroral oval) by an intrusion of low entropy plasma comprising plasma sheet flow channels. Longitudinal localization makes the intruding flow channels difficult to observe with spacecraft. However, they are detectable in the ionosphere via the broader, two‐dimensional coverage by radars. Line‐of‐sight radar flow measurements have provided considerable support for the onset proposal. Here we use two‐dimensional, ionospheric flow maps for further testing. Since these maps are derived without the smoothing from global fits typically used for global convection maps, their spatial resolution is significantly improved, allowing representation of localized spatial structures. These maps show channels of enhanced ionospheric flow intruding to the time and location of substorm onset. We also see evidence that these intruding flows enter the plasma sheet from the polar cap, and that azimuthal spread of the reduced entropy plasma in the inner plasma sheet contributes to azimuthal onset spreading after initial onset. Identified events with appropriate radar data remain limited, but we have found no exceptions to consistency with flow channel triggering. Thus, these analyses strongly support the proposal that substorm onset is due to the intrusion of new plasma to the onset region. The lower entropy of the new plasma likely changes the entropy distribution of inner plasma sheet, a change possibly important for the substorm onset instability seen via the growing waves that demarcate substorm auroral onset.

Fibro-Osseous Lesion of the Nose and Paranasal Sinus: A Retrospective Study With Literature Review

BackgroundFibro-osseous (FO) lesions are slow-growing benign lesions in the paranasal sinuses. They include osteomas, fibrous dysplasia (FD), and ossifying fibro­ma (OF). Fibro-osseous (FO) lesions are frequently asymptomatic, and they are incidentally found on imaging. They are characterized by different histological, radiological, and clinical variants. Depending on symptoms, size, location, and extension, the treatment strategy varies significantly for these lesions.ObjectiveWe aim to compare the age, onset, gender, clinical presentation, postoperative improvement, and complications of a fibro-osseous lesion in the paranasal sinuses.MethodsA retrospective analysis was done targeting patients diagnosed with benign fibro-osseous (FO) lesions, and the incidence among 403 patients who underwent functional endoscopic sinus surgery (FESS) at Aseer Central Hospital, Kingdom of Saudi Arabia, was reviewed from January 2013 to January 2022.ResultsA total of seven patients were found; five patients were diagnosed with osteoma, and two were diagnosed with fibrous dysplasia. There were no ossifying fibroma cases. The patients’ mean age was 25.5 ± 12.9 years old. Four (57.1%) patients were males, and three (42.9%) were females, with a male/female ratio of 1.25:1. The most common locations were the frontal sinus and ethmoid sinus, and the two cases of fibrous dysplasia involved almost all facial bones. The endonasal endoscopic approach was chosen to treat all seven patients.ConclusionsThere are differences in the onset age, location, and complications postoperatively among osteoma and fibrous dysplasia patients. Osteoma most commonly occurs in the frontal sinus, while fibrous dysplasia involved all facial bones in our study. Endoscopic surgery is currently the primary strategy for treatment.

Efficient and lightweight detection of PPG onset and systolic peaks using implementable time-domain strategies

A majority of clinically reliable Photoplethysmogram (PPG) signal features necessitate exact location of PPG onset and systolic peaks. So far, state-of-the-art researches in the field of PPG peak detection is lagging due to the use of amplitude thresholding, complicated techniques or pathophysiologically limited datasets. In this paper, a robust algorithm is developed that primarily uses a novel combination of PPG-derivative, trigonometric area of the curve (TAOC), slope reversal and time-domain based lightweight methodologies to uncover the precise location of PPG onset and systolic peaks. Rigorous evaluation of the algorithm is conducted over 2,16,374 beats, collected from standard databases together with the PPG signal acquired from healthy and cardiac subjects. Superiority of the algorithm is presented by high average accuracy, sensitivity, predictivity and error as 99.69%, 99.77%, 99.92% and 0.31%. The adopted lightweight methodologies and high-speed execution over a wide pathophysiological variety presents immense promises for implementation in standard healthcare applications.

Association of Mesoscale Auroral Structures and Breakups With Energetic Particle Injections at Geosynchronous Orbit

Geomagnetic substorms are associated with characteristic energetic particle injection signatures at geosynchronous orbit that are often dispersionless in both electrons and ions near the magnetic local time sector of auroral onset locations and are dispersed farther away from this region. Although the precise mechanism responsible for the coherent injection signatures at geosynchronous orbit have been the topic on considerable ongoing debate for decades, recent work on bursty bulk flows (BBFs) in the tail have led to the hypothesis that they may be the result of multiple, overlapping flow bursts penetrating into the inner magnetosphere from more distant downtail reconnection sites. Since auroral streamers are thought to be ionospheric signatures of BBFs in the tail, they can be used as proxies for testing this hypothesis. Using high resolution auroral imagery from the POLAR/VIS instrument combined with multi-spacecraft observations of energetic particle injections at geosynchronous orbit, we examine the association of mesoscale auroral structures with particle injection signatures over many hours during the 9 November 1998 storm. We find that the explosive types of auroral activations, such as pseudo-breakups and substorm onset breakups, are associated with the more intense and well-defined dispersed injection signatures, while intervals of isolated streamer activity appear to be associated with smaller dispersed “injectionlet” signatures. Furthermore, intervals of sustained, intense, and late expansion phase/recovery phase streamer activity appear to be associated with sustained elevated dispersed particle fluxes. These results are consistent with the hypothesis that it is the overlapping effects of sustained, intense multiple flow bursts penetrating toward the Earth that result in classical substorm particle injection signatures at geosynchronous orbit. However, it is also suggested that torches/omega-band tongues are the prime fate of braking isolated flow bursts (streamers) rather than the development of breakups, bulges, and substorm current wedge formation. A statistical analysis is presented showing that 93% of the observed torches evolved from streamers, 93% of streamers arriving in the equatorward regions of the bulge led to torches, 10.5% of such streamers led to breakups (either pseudo-breakups or substorm onsets), and only 3.5% of such streamers led to substorm onsets.

Utility of adding electrodes in patients undergoing invasive seizure localization: A case series

IntroductionSurgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage. MethodsElectrodes were placed according to a hypothesis derived from noninvasive monitoring techniques in adult patients with long term epilepsy. Seizure onset was not clearly localized at the end of the invasive monitoring period in ten patients, and additional electrodes were placed based on a new hypothesis that incorporated data from the invasive monitoring period. ResultsSuccessful localization was achieved in nine patients. There were no complications with adding additional electrodes. At final follow up, four patients were seizure free while four others had at least a 50% reduction in seizures after undergoing surgical intervention. ConclusionSeizure foci were localized safely in 90% of adult patients with long term epilepsy after implanting additional electrodes and expanding coverage. Patients undergoing invasive monitoring without clear localization should have additional electrodes placed to expand monitoring coverage as it is safe and effective.

Association between polarity of first episode and solar insolation in bipolar I disorder

ObjectiveCircadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. MethodsData from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. ResultsThe larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). ConclusionIncreased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Limited utility of structural MRI to identify the epileptogenic zone in young children with tuberous sclerosis.

The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC. We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, transmantle sign). They selected lesions suspect for the EZ based on structural MRI, and reselected after unblinding to seizure onset location on electroencephalography (EEG). None of the tuber characteristics and FCD features were distinctive for the EZ, indicated by resected lesions in seizure-free children. With structural MRI alone, the EZ was identified out of 10 lesions in 31%, and with addition of EEG data, this increased to 48%. However, rates of identification of resected lesions in non-seizure-free children were similar. Across 251 lesions, interrater agreement was moderate for large size (κ=.60), and fair (κ=.24) for all other features. In young children with TSC, the utility of structural MRI features is limited in the identification of the epileptogenic tuber, but improves when combined with EEG data.

Clostridioides difficile infection in a rural New Zealand secondary care centre: an incidence case-control study.

Clostridioides difficile infection (CDI) is a form of antibiotic-associated infectious diarrhoea resulting in significant morbidity and mortality. Community-acquired disease in low-risk individuals is increasingly recognised. There are limited New Zealand data published. To determine the incidence and location of onset of CDI cases in the Manawatu region, and further describe the demographics, risk factors and prevalent C. difficile ribotypes of the population. We performed an incidence case-control study of CDI in the Manawatu region between September 2018 and September 2019. Cases were matched to controls with a negative test for C. difficile. Demographic and comorbidity data, location of onset, drug exposure, disease recurrence and 30-day mortality were collected. Ribotype analysis was performed on C. difficile isolates. Thirty-two specimens tested toxin positive over 12 months, yielding an incidence of 18.3 cases per 100 000 person-years. Twenty-five percent of cases had community onset disease. Cases were more likely to have had amoxicillin/clavulanate or ceftriaxone prescribed. Elevated blood white cell count and lower HbA1c were significantly associated with CDI. The dominant ribotype was 014/020. Two cases were RT 023. Our data are similar to previous national data. RT 023 has not been previously reported in New Zealand and has been associated with severe colitis. We demonstrated a significant proportion of community-acquired cases and the true incidence might be higher. Vigilance for community onset disease is required. These data may allow observation of temporal changes in incidence and infection patterns of CDI in New Zealand.

Calibration of the Critical Amplification Factor for Reynolds-Averaged Navier–Stokes-Based Transition Modeling

The present study uses an adjoint-based gradient optimization framework to perform calibration of the critical amplification factor for transition models based on the linear stability theory. More specifically, the two-equation amplification factor transport model is used, and the critical amplification factor, which directly controls the onset of the transition via the source term of the intermittency equation, is calibrated for a set of canonical flat plate test cases in both bypass and natural transitional regimes. It is shown that, by utilizing a sigmoid fitting of the turbulence index profile, the transition onset location can be accurately predicted in a differentiable and smooth fashion, which is essential to the adjoint-based sensitivity analysis of the Reynolds-averaged Navier–Stokes solver. Subsequently, the results of these calibration studies are used for obtaining a new relation via a high-order polynomial regression model relating the critical amplification factor to the freestream turbulence intensity. Finally, the prediction capability of the calibrated relation is tested for natural transitional flows past NLF(1)-0416 and S809 airfoils. The numerical results show significant improvements in predicting the transition onset location as well as lift and drag predictions.

Vortical characteristics of the corner separation flow in a high-speed compressor cascade

In aero-engine compressors, corner separations cause blockage, loss generation, and flow instabilities. The aim of the current study is to gain better knowledge of the vortical structures in corner separation flows and their resultant blockage and loss. Numerical simulations at different incidences have been performed for a high-speed linear compressor cascade. First, vortical structures have been visualized with the help of the Q-criterion and eigenvector method, and those associated with the corner separation have been focused on. It was found that the corner separation occurring on either the pressure surface or suction surface corner region was characterized by a large-scale streamwise vortex, named as the corner separation vortex in this paper. The pressure-side corner separation vortex is observed at a great negative incidence initiated from a focus point on the pressure surface, while the suction-side corner separation vortex observed at all concerned incidences originated from a focus on the endwall near the suction surface. Then, the mechanism by which corner separation vortices resulted in blockage and loss has been uncovered. The results showed that low-momentum fluids inside the core region of corner separation vortices led to the flow blockage and the viscous friction between them, and mainstream was responsible for the entropy generation. One major contributor of low-momentum fluids in the suction-side corner region was an off-wall reversed-flow region which was attributed to the breakdown of the suction-side corner separation vortex. Finally, multi-vortex structures in the leading region of the suction-side corner separation at two high positive incidences have been analyzed. It was found that the horseshoe vortex influenced the formation of the suction-side corner separation vortex, which induced a multi-vortex structure, and prevented the onset location of suction-side corner separation vortex from moving upstream with the increased incidence.

ATRT–SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT–TYR, ATRT–MYC and ATRT–SHH. ATRT–SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT–SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT–SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT–SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT–SHH has prognostic relevance and might aid to stratify patients within future clinical trials.

FABNet: Fusion Attention Block and Transfer Learning for Laryngeal Cancer Tumor Grading in P63 IHC Histopathology Images.

Laryngeal cancer tumor (LCT) grading is a challenging task in P63 Immunohistochemical (IHC) histopathology images due to small differences between LCT levels in pathology images, the lack of precision in lesion regions of interest (LROIs) and the paucity of LCT pathology image samples. The key to solving the LCT grading problem is to transfer knowledge from other images and to identify more accurate LROIs, but the following problems occur: 1) transferring knowledge without a priori experience often causes negative transfer and creates a heavy workload due to the abundance of image types, and 2) convolutional neural networks (CNNs) constructing deep models by stacking cannot sufficiently identify LROIs, often deviate significantly from the LROIs focused on by experienced pathologists, and are prone to providing misleading second opinions. So we propose a novel fusion attention block network (FABNet) to address these problems. First, we propose a model transfer method based on clinical a priori experience and sample analysis (CPESA) that analyzes the transfer ability by integrating clinical a priori experience using indicators such as the relationship between the cancer onset location and morphology and the texture and staining degree of cell nuclei in histopathology images; our method further validates these indicators by the probability distribution of cancer image samples. Then, we propose a fusion attention block (FAB) structure, which can both provide an advanced non-uniform sparse representation of images and extract spatial relationship information between nuclei; consequently, the LROI can be more accurate and more relevant to pathologists. We conducted extensive experiments, compared with the best Baseline model, the classification accuracy is improved 25%, and It is demonstrated that FABNet performs better on different cancer pathology image datasets and outperforms other state of the art (SOTA) models.

Experimental Measurements of Hypersonic Instabilities over Ogive-Cylinders at Mach 6

Hypersonic boundary-layer instability disturbance and transition experiments were performed in the Air Force Research Laboratory Mach-6 Ludwieg Tube on a 1-m-long ogive-cylinder model with interchangeable nose-tip geometries of varying ogive radii and nose bluntnesses. Boundary-layer disturbances were measured via focused laser differential interferometry, surface-mounted pressure sensors, and high-speed schlieren videography at unit Reynolds numbers ranging from to . Three primary disturbance structures were observed that were dependent on ogive radius and nose bluntness. Each disturbance structure exhibits unique characteristics that are closely tied to the leading-edge geometry of the model. The addition of nose bluntness is shown to have an overall delay in transition onset, and a possible blunt nose transition reversal is observed as bluntness is further increased. It is also shown that the effects of the ogive radius in addition to nose bluntness alter the flow instability disturbance and transition behaviors and are likely tied to a modification of the entropy layer structure. A novel curvature-based Reynolds number is proposed that successfully correlates the effects of multiple leading-edge radii of curvature to dominant downstream boundary-layer disturbances and transition onset locations.

Multi-Layered Numerical Model Development of a Standard Cylindrical Lithium-Ion Battery for the Impact Test

For safety issues in lithium-ion batteries (LIBs), international standards and regulations for various abusive environments have been developed, and UL1642 in Underwriters Laboratories (UL) currently covers electrical, mechanical, environmental, and fire exposure tests. An impact test is one of mechanical abuse tests in UL1642, which aims to determine the safe prevention of fire or explosion. As the energy density of a lithium-ion battery is continuously increasing, it is difficult to pass the regulation. Therefore, it is necessary to predict failure mode due to an internal short circuit in developing high-capacity cells. For a sudden and measured mechanical force, we speculate that damage to a separator consisting of LIBs makes the battery experience an exothermic phenomenon due to an internal short circuit because a separator is a key component for preventing the electrical contact between two electrodes. Therefore, if we can find mechanical stresses of each component in LIBs, we can evaluate whether each component is severely damaged or not. In the present study, we propose a finite element model consisting of a multi-layered structure, which will permit us to assess the possible onset location of the short circuit, and to predict the sequence of failure at a cell level. We applied the proposed method to a cylindrical cell, and the accuracy of the model was verified through the comparison of the experiment results. Additionally, simulation results showed that it is possible to track mechanical stress variations of each component progressively. Furthermore, we performed the numerical experiment evaluating the thickness effect of a center-pin. We expect the proposed finite element model to be used in order to devise cell level abuse-tolerant design from a mechanical point of view before conducting mechanical abuse tests as part of the product development process.

Meta-Analysis of the Factors Influencing the Restoration of Spontaneous Circulation After Cardiopulmonary Resuscitation

ObjectiveThis study aimed to systematically evaluate the factors influencing the restoration of spontaneous circulation (ROSC) after cardiopulmonary arrest (CA).MethodsRelevant papers on the factors influencing the ROSC in patients with CA were retrieved from PubMed, Embase, Cochrane Library, China Biology Medicine disk, China National Knowledge Infrastructure, Wanfang, and VIP databases. After screening, data extraction, and quality evaluation of the papers, a meta-analysis was carried out.ResultsA total of 36 papers, involving a total sample size of 2,305 cases, were included. The meta-analysis revealed that the location and time of onset of CA, the type of cardiac rhythm at first monitoring, the start time of cardiopulmonary resuscitation (CPR), the use of electric defibrillation, and the cumulative dose of adrenaline all significantly impacted the ROSC (p < 0.05) and may have affected its success rate. The pH value at CA onset, combined use of adrenaline and vasopressin, CPR duration, mechanical cardiac compression use, and whether CA was caused by heart disease had no significant effect on ROSC.ConclusionThe location and time of onset of CA, the cardiac rhythm at first monitoring, the start time of CPR, the use of electric defibrillation, and the cumulative dose of adrenaline significantly impacted the ROSC.

Possible Ionospheric Influence on Substorm Onset Location

AbstractAuroral substorm onset locations are highly unpredictable. Previous studies have shown that the By component of the interplanetary magnetic field (IMF) explains ∼5% of the variation in onset magnetic local time (MLT), while solar wind conditions and the other IMF components have even less explanatory power. In this study, we show that the level of geomagnetic activity before substorm onset, as indicated by the AL index, explains an additional ∼5% of the variation in onset MLT. We discuss our results with regard to recent modeling studies, which show that gradients in the ionospheric Hall conductance can lead to a duskward shift of the magnetotail dynamics. Our findings suggest that this magnetosphere‐ionosphere coupling effect may also influence the location of substorm onsets.

Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset

BackgroundPrior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field.MethodsALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R).ResultssALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS.ConclusionsWe found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

Understanding Language Reorganization With Neuroimaging: How Language Adapts to Different Focal Lesions and Insights Into Clinical Applications.

When the language-dominant hemisphere is damaged by a focal lesion, the brain may reorganize the language network through functional and structural changes known as adaptive plasticity. Adaptive plasticity is documented for triggers including ischemic, tumoral, and epileptic focal lesions, with effects in clinical practice. Many questions remain regarding language plasticity. Different lesions may induce different patterns of reorganization depending on pathologic features, location in the brain, and timing of onset. Neuroimaging provides insights into language plasticity due to its non-invasiveness, ability to image the whole brain, and large-scale implementation. This review provides an overview of language plasticity on MRI with insights for patient care. First, we describe the structural and functional language network as depicted by neuroimaging. Second, we explore language reorganization triggered by stroke, brain tumors, and epileptic lesions and analyze applications in clinical diagnosis and treatment planning. By comparing different focal lesions, we investigate determinants of language plasticity including lesion location and timing of onset, longitudinal evolution of reorganization, and the relationship between structural and functional changes.