Role of Imaging in Predicting the Deep Surgical Margin in Gingivobuccal Complex Cancers: A Pilot Study.

Cancers arising from the gingivobuccal complex are one of the most common types of cancer in the oral cavity and are associated with poor prognosis. Among the various prognostic factors, positive surgical margin is the most important one that can be controlled by the operating surgeon. The deep surgical margins for buccal mucosa cancers is normally assessed by palpating the skin for induration and skin pinchability. The present study evaluates the role of imaging in assessing the deep surgical margin and its efficacy for skin preservation in buccal mucosa/ gingivobuccal carcinomas. The patients of gingivobuccal complex squamous cell carcinomas after histopathological confirmation were selected for the study. In imaging, the distance between the base of the tumour and skin (epidermis) of the cheek was measured by a senior radiologist preoperatively. The frozen section findings were confirmed by histopathological examination and the depth of invasion of the tumour was measured and the clearance of the deep surgical margin was confirmed. The correlation between imaging, skin pinch test and histopathological examination of the specimen was assessed. The sensitivity and specificity of imaging to predict the skin preservation (deep surgical margin more than 5 mm) is 100% and 75% respectively compared to sensitivity and specificity of skin pinch test of 82.6% and 50% respectively. Imaging is an effective tool in predicting the skin preservation and skin excision compared to skin pinch test. Compared to the skin pinch test, imaging appears to be a useful tool for advising surgeons on skin preservation vs excision.

The correlation between quality of recovery and parturient outcomes after Cesarean delivery: a cohort study.

PURPOSE: Recent studies have reported the use of the obstetric-specific quality of recovery tool (ObsQoR-10) to assess the quality of recovery in parturients after childbirth; however, the correlation between ObsQoR-10 scores and important postpartum outcomes are unclear. The primary aim of the present study was to investigate the correlations between ObsQoR-10 scores at 24 hr after Cesarean delivery and breastfeeding, depressive symptomatology, overall health, and pain at seven days postpartum. METHODS: We recruited parturients who underwent elective Cesarean delivery at KK Hospital in Singapore. Parturients provided responses to post-Cesarean questionnaires at 1) 24 hr (ObsQoR-10, EuroQol EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale), 2) 48 hr (ObsQoR-10, EQ-Visual Analogue Scale), and 3) seven days after Cesarean delivery (ObsQoR-10, Breastfeeding Self-Efficacy Scale-Short form, EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale, pain survey). RESULTS: We enrolled 222 participants, 200 (90%) of whom completed the seven-day follow-up between September 2022 and April 2023. There was limited correlation between ObsQoR-10 at 24 hr with the Edinburgh Postnatal Depression Scale (r = 0.135), EQ-Visual Analogue Scale (r = 0.158), Breastfeeding Self-Efficacy Scale-Short form (r = 0.225), and averaged pain scores (r = -0.107) at seven days postpartum. ObsQoR-10 breastfeeding sub-score at 24 hr was weakly correlated with Breastfeeding Self-Efficacy Scale-Short form at seven days postpartum (r = 0.307). CONCLUSION: ObsQoR-10 at 24 hr postpartum had limited correlation with breastfeeding, depressive symptomatology, overall health, and pain at seven days. STUDY REGISTRATION: ClinicalTrials.gov ( NCT04989894 ); first submitted 4 July 2021.

RéSUMé: OBJECTIF: Des études récentes ont rapporté l'utilisation de l'outil de qualité de récupération spécifique à l'obstétrique (ObsQoR-10) pour évaluer la qualité de la récupération chez les personnes parturientes après l'accouchement; cependant, la corrélation entre les scores sur l'outil ObsQoR-10 et les devenirs post-partum importants n'est pas claire. L'objectif principal de la présente étude était d'examiner les corrélations entre les scores ObsQoR-10 obtenus 24 heures après l'accouchement par césarienne et l'allaitement, la symptomatologie dépressive, l'état de santé général et la douleur sept jours après l'accouchement. MéTHODE: Nous avons recruté des personnes parturientes qui ont bénéficié d'un accouchement par césarienne programmée à l'Hôpital KK de Singapour. Les personnes parturientes ont répondu aux questionnaires post-césarienne à 1) 24 heures (ObsQoR-10, échelle visuelle analogique EuroQol EQ-Visual Analogue Scale, Échelle de dépression postnatale d'Édimbourg), 2) 48 heures (ObsQoR-10, EQ-Visual Analogue Scale), et 3) sept jours après la césarienne (ObsQoR-10, Échelle abrégée d'auto-efficacité de l'allaitement [Breastfeeding Self-Efficacy Scale-Short form], EQ-Visual Analogue Scale, Échelle de dépression postnatale d'Edimbourg, enquête sur la douleur). RéSULTATS: Nous avons recruté 222 participant·es, dont 200 (90 %) ont terminé le suivi de sept jours entre septembre 2022 et avril 2023. Il y avait une corrélation limitée entre l'ObsQoR-10 à 24 heures et l'Échelle de dépression postnatale d'Édimbourg (r = 0,135), l'échelle EQ-Visual Analogue Scale (r = 0,158), l'échelle d'auto-efficacité de l'allaitement maternel forme courte (r = 0,225) et les scores moyens de douleur (r = -0,107) sept jours après l'accouchement. Le sous-score d'allaitement ObsQoR-10 à 24 heures était faiblement corrélé à l'échelle d'auto-efficacité de l'allaitement maternel à sept jours après l'accouchement (r = 0,307). CONCLUSION: L'ObsQoR-10 à 24 heures après l'accouchement avait une corrélation limitée avec l'allaitement, la symptomatologie dépressive, l'état de santé général et la douleur à sept jours. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT04989894 ); première soumission le 4 juillet 2021.

Toward Interpretable Sleep Stage Classification Using Cross-Modal Transformers.

Accurate sleep stage classification is significant for sleep health assessment. In recent years, several machine-learning based sleep staging algorithms have been developed, and in particular, deep-learning based algorithms have achieved performance on par with human annotation. Despite improved performance, a limitation of most deep-learning based algorithms is their black-box behavior, which have limited their use in clinical settings. Here, we propose a cross-modal transformer, which is a transformer-based method for sleep stage classification. The proposed cross-modal transformer consists of a cross-modal transformer encoder architecture along with a multi-scale one-dimensional convolutional neural network for automatic representation learning. The performance of our method is on-par with the state-of-the-art methods and eliminates the black-box behavior of deep-learning models by utilizing the interpretability aspect of the attention modules. Furthermore, our method provides considerable reductions in the number of parameters and training time compared to the state-of-the-art methods. Our code is available at https://github.com/Jathurshan0330/Cross-Modal-Transformer. A demo of our work can be found at https://bit.ly/Cross_modal_transformer_demo.

CARDS - Computer Access to Research on Dietary Supplements

CARDS is a database that contains information on federally funded research projects related to dietary supplements. It includes projects funded by the United States Department of Agriculture (USDA), the Department of Defense (DOD), and the Institutes and Centers (ICs) of the National Institutes of Health (NIH), beginning from the fiscal year 1999, the first year federal agencies started reporting research related to dietary supplements. It is provides detailed records of research projects funded by these federal agencies. It serves as an resource for tracking the progress and outcomes of dietary supplement research funded by the government.

DSID - Dietary Supplement Ingredient Database

The Dietary Supplement Ingredient Database (DSID) provides estimated levels of ingredients in dietary supplement products sold in the United States. These estimates, which are based on chemical analysis of nationally representative products, may differ from the labeled amounts. The DSID offers data for understanding the actual content of dietary supplements, supporting research, regulation, and consumer awareness regarding the accuracy and quality of supplement ingredients.

DTP’s Natural Products Repository - The National Cancer Institute Natural Products Repository

DTP’s Natural Products Repository is a storehouse of natural products. It houses extracts from samples of plants and marine organisms collected from more than 25 countries andextracts of diverse bacteria and fungi. Access to this Repository will be subject to meeting the conditions and signing a Material Transfer Agreement (pdf file for download) protecting the rights of all parties.

IBIDS database - International Bibliographic Information on Dietary Supplements

The International Bibliographic Information on Dietary Supplements (IBIDS,) database is a resource that provides bibliographic citations and abstracts from published international and scientific literature on dietary supplements. It is designed to support researchers, healthcare professionals, and students in accessing reliable information on dietary supplements. This includes international and scientific publications, providing a thorough and diverse collection of references on the subject.

Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

The natural menstrual cycle revisited - can natural cycle be trusted.

BACKGROUND: The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)? RESULTS: This observational prospective cohort study analysed 26 healthy women with a cycle length between 21-35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L. The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels. CONCLUSIONS: A significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.

Optofluidic photonic crystal fiber platform for sensitive and reliable fluorescence based biosensing.

Biosensing plays a pivotal role in various scientific domains, offering significant contributions to medical diagnostics, environmental monitoring, and biotechnology. Fluorescence biosensing relies on the fluorescence emission from labelled biomolecules to enable sensitive and selective identification and quantification of specific biological targets in various samples. Photonic crystal fibers (PCFs) have led to the development of optofluidic fibers enabling efficient light-liquid interaction within small liquid volume. Herein, we present the development of a user-friendly optofluidic-fiber platform with simple hardware requirements for sensitive and reliable fluorescence biosensing with high measurement repeatability. We demonstrate a sensitivity improvement of the fluorescence emission up to 17 times compared to standard cuvette measurement, with a limit of detection of Cy5 fluorophore as low as 100 pM. The improvement in measurement repeatability is exploited for detecting haptoglobin protein, a relevant biomarker to diagnose several diseases, by using commercially available Cy5 labelled antibodies. The study aims to showcase an optofluidic platform leveraging the benefits provided by optofluidic fibers, which encompass easy light injection, robustness, and high sensitivity.

Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach.

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.

Experimental study of local anesthetic and antiarrhythmic activities of fluorinated ethynylpiperidine derivatives.

The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Nav1.4 and Nav1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.

Innovative suspended ring core fiber for SERS application.

Solid core photonic crystal fibers (SC-PCFs) have garnered attention as probes for surface-enhanced Raman spectroscopy (SERS) due to their potential as optofluidic devices, offering heightened sensitivity and reliability compared to traditional planar/colloidal nanoparticle-based SERS platforms. A smaller core allows for more light interaction but might compromise sensitivity and reliability due to reduced surface area for interaction. Here, we introduce an innovative SC-PCF design aimed at resolving the trade-off between increasing the evanescent field fraction and the core surface area. By substituting a suspended silica rod with a suspended thin-silica ring, we augment the surface area for attached nanoparticles by one order of magnitude while retaining a substantial amount of evanescent light interaction with the analyte. Experimental findings showcase an improved sensitivity in SERS signal compared to previously reported top-performing PCF sensor designs. Importantly, with necessary refinement and optimization, this innovative fiber design extends beyond SERS applications, potentially amplifying the sensitivity of various other fiber-based sensing platforms.

Antimicrobial resistance of Streptococcus dysgalactiae, Streptococcus agalactiae, and Streptococcus canis in quarter milk samples from Bavaria, Southern Germany, between 2012 and 2022.

The objective of this study was to analyze the in vitro antimicrobial resistance (AMR) of Streptococcus (Sc.) dysgalactiae, Sc. agalactiae, and Sc. canis over a 10-year period from 2012 to 2022 against the most commonly used antimicrobial agents. For this purpose, all quarter milk samples (QMS) submitted to the milk laboratory of the Bavarian Animal Health Service (TGD) were analyzed. Each QMS was tested using the California Mastitis Test (CMT) and categorized as negative (N), subclinical (S), or clinical (C) mastitis if the milk character was abnormal. Samples with Sc. dysgalactiae, Sc. agalactiae, or Sc. canis were included and a subset of isolates were further tested for in vitro antimicrobial resistance by breakpoint analysis with broth microdilution. Sc. dysgalactiae (61%, n = 65,750) was the most abundant pathogen among those 3 species, followed by Sc. agalactiae (28%, n = 30,486), and Sc. canis (11%, n = 11,336). All 3 species showed the highest resistance to the same 4 antimicrobial agents: erythromycin, marbofloxacin, pirlimycin, and cefalexin/kanamycin with varying degrees of resistance. Throughout the study period, Sc. dysgalactiae, Sc. agalactiae, and Sc. canis were largely susceptible to the remaining antimicrobial agents tested (penicillin, amoxicillin-clavulanate, oxacillin, cefazolin, cefoperazone, cefquinome). Only less than 14% of isolates of Sc. dysgalactiae and Sc. canis were resistant against any of the antimicrobials tested. Sc. agalactiae was the species with the highest percentage of resistant isolates. While the percentage of resistant isolates from Sc. canis and Sc. dysgalactiae decreased, the percentage of resistant Sc. agalactiae isolates increased since 2017. In summary, most isolates were not resistant to the most commonly used antimicrobial agents for mastitis therapy, including ß-lactam antibiotics and penicillin should remain the first-choice therapy against streptococcal mastitis.

Fractured Metallic Tracheostomy Tube: A Rare Presentation of Bronchial Foreign Body.

BACKGROUND: Tracheostomy is an important life-saving surgical procedure that could be used to secure the lower airway. It can however serve as a source of airway compromise when fragments from it are deposited. This condition must be diagnosed early enough, and appropriate intervention should be done to forestall potential morbidity and mortality. CASE REPORT: A 56-year-old tracheostomized patient presented to the accident and emergency department with a 4-hour history of sudden onset choking cough and labored breathing. The shaft of his tracheostomy tube (TT) was fractured and subsequently aspirated while he was attempting to remove and clean the inner tube that morning. He has used the TT for about 6 years and lost to follow-up clinic visits. The chest radiograph showed the metallic foreign body lodged within the trachea. He had an emergency rigid bronchoscopy via the tracheostomy stoma, and the object was retrieved. All respiratory symptoms subsequently resolved, and a check radiograph showed normal findings. CONCLUSION: Tracheostomy tube fracture and aspiration should be ruled out in every tracheostomized patient with sudden onset acute respiratory symptoms. Otolaryngologists must always emphasize the need for proper handling of TT, regular follow-up, and tube replacement when due.

A dataset of unmanned aerial vehicle multispectral images acquired over a field to identify nitrogen requirements.

The technique of detecting and tracking an area's physical properties from a distance by measuring its reflected and emitted radiation is known as remote sensing. It gathered data accurately in near real-time. For this purpose, multispectral cameras mounted on UAVs that capture images with different bands can be used to generate vegetation indexes (NDVI, NDRE), which are useful in precision agriculture. In this study UAV image dataset contains 336 multispectral images from a 0.06 ha paddy field with three different phonological cycles of the crop (vegetative, reproductive, and ripening) in the north-western province of Sri Lanka. The selected sample rice variety is BG300. The images were taken over five days, starting from August 14 to October 5, 2023. The UAV flight took place at 30 m from the canopy level with the multispectral camera titled at an angle of 900. The SPAD Chlorophyll Meter was used to collect ground truth data, which is proportional to the nitrogen level of the leaf. There were 50 randomly selected readings throughout the paddy field. Relevant climate data for five days was provided by the Rice Research and Development Institute, Bathalagoda, which belongs to the paddy field. The purpose of this data creation was to aid researchers who are generally interested in disease diagnosis. Moreover, this dataset allows for studying the effect of using different tilt angles on the 3D reconstruction of the paddy fields and the generation of orthomosaics.

Structural and functional imaging of psoriasis for severity assessment and quantitative monitoring of treatment response using high-resolution optoacoustic imaging.

Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the quality of life significantly. Current disease severity assessment relies on semi-objective visual inspection based on the Psoriasis Area and Severity index (PASI) score that might not be sensitive to sub-clinical changes. Histology of psoriasis skin lesions necessitate invasive skin biopsies. This indicates an unmet need for a non-invasive, objective and quantitative approach to assess disease severity serially. Herein, we employ multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) derived structural and microvascular functional imaging metrics to examine the lesional and non-lesional skin in psoriasis subjects across different severities and also evaluate the treatment outcome in a subject with topical steroids and biologics, such as adalimumab. ms-RSOM derived structural metrics like epidermal thickness and total blood volume (TBV) and microvascular functional information such as oxygen saturation (sO2) are evaluated by spectrally resolving the endogenous chromophores like melanin, oxy-, and deoxy-hemoglobin. Initial findings reveal an elevated sO2 and TBV with severity in lesional and non-lesional psoriasis skin, thus representing increasing inflammation. An increase in epidermal thickness is also noted with the degree of severity, corresponding to the inflammation and increased abnormal cell growth. As a marker to evaluate the treatment response, we observed a decrease in epidermal thickness, sO2, and TBV in a psoriasis patient post-treatment, which is consistent with the decrease in the PASI score from 4.1 to 1.9. We envision that ms-RSOM has a huge potential to be translated into routine clinical setting for the diagnosis of severity and assessment of treatment monitoring in psoriasis subjects.

ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons.

Vaccinia-related kinase 1 (VRK1) is a gene which has been implicated in the pathological process of a broad range of neurodevelopmental disorders as well as neuropathies, such as Amyotrophic Lateral Sclerosis (ALS). Here we report a family presenting ALS in an autosomal recessive mode of inheritance, segregating with a homozygous missense mutation located in VRK1 gene (p.R321C; Arg321Cys). Proteomic analyses from iPSC-derived motor neurons identified 720 proteins eligible for subsequent investigation, and our exploration of protein profiles revealed significant enrichments in pathways such as mTOR signaling, E2F, MYC targets, DNA repair response, cell proliferation and energetic metabolism. Functional studies further validated such alterations, showing that affected motor neurons presented decreased levels of global protein output, ER stress and downregulation of mTOR signaling. Mitochondrial alterations also pointed to decreased reserve capacity and increased non-mitochondrial oxygen consumption. Taken together, our results present the main pathological alterations associated with VRK1 mutation in ALS.