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1.
Heliyon ; 10(12): e33222, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39022093

ABSTRACT

The Twangiza-Namoya Gold Deposit within the Kibaran Belt of the Democratic Republic of the Congo represents a crucial manifestation of the hydrothermal gold system. This review investigates its intricate origin and the subsequent metallogenic evolution that has shaped its present-day characteristics and offers a systematic categorization based on its deposition processes and geotectonic settings. The findings reveal that the gold deposits are predominantly derived from sedimentary fluid sources. Within this vast metallogenic province, two stages of gold deposition have been constrained: (a) the early-stage formation related to the accretion of Rodinia assembly with subduction-collisional event where diagenesis cemented the syngenetic pyrite carbonaceous sediments and (b) the later stage deposition related to the continent-collisional event during the last stage of Rodinia supercontinent amalgamation. Previous isotopic investigations, with a particular emphasis on pyrite sulfur isotopes on both host rocks and vein-bearing sulfides, have been instrumental in tracing the origins of gold-bearing fluids in the study region. The isotopic variance in the four deposits: Twangiza (-5.2 % to +3 %, avg. -0.3 %), Kamituga (-0.6 % to -0.9.1 %, avg. -5%), Lugushwa (+3.0 % to -18.4 %), and Namoya, on the southernmost end, has a vast range but with much heavier isotope compositions, ranging between +1.3 % and to +22.6 %, with an average of +12.2 %. The data predominantly points to the sedimentary origins of ore fluids in the Twangiza-Namoya Gold belt, highlighting the pivotal role of sedimentary processes in shaping the metallogenic landscape of the region. The fluids inclusions depicted the deposits to be formed from H2O-Nacl-H2O with abundant CH4 and N2 ore-forming fluid, moderate temperature (350-500 °C), and low salinity. The overall results confirm the genetic style of the Twangiza-Namoya Gold Belt to be an orogenic gold-style deposit that was emplaced during the early Neoproterozoic era in low greenschist facies terrain.

2.
Anal Chem ; 96(16): 6209-6217, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38607319

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but dangerous side effect of adenoviral-vectored COVID-19 vaccines. VITT had been linked to production of autoantibodies recognizing platelet factor 4 (PF4). Here, we characterize anti-PF4 antibodies obtained from a VITT patient's blood. Intact mass measurements indicate that a significant fraction of these antibodies represent a limited number of clones. MS analysis of large antibody fragments (the light chain and the Fc/2 and Fd fragments of the heavy chain) confirms the monoclonal nature of this component of the anti-PF4 antibodies repertoire and reveals the presence of a mature complex biantennary N-glycan within the Fd segment. Peptide mapping using two complementary proteases and LC-MS/MS was used to determine the amino acid sequence of the entire light chain and over 98% of the heavy chain (excluding a short N-terminal segment). The sequence analysis allows the monoclonal antibody to be assigned to the IgG2 subclass and verifies that the light chain belongs to the λ-type. Incorporation of enzymatic de-N-glycosylation into the peptide mapping routine allows the N-glycan in the Fab region of the antibody to be localized to the framework 3 region of the VH domain. This novel N-glycosylation site is the result of a single mutation within the germline sequence. Peptide mapping also provides information on lower-abundance (polyclonal) components of the anti-PF4 antibody ensemble, revealing the presence of all four subclasses (IgG1-IgG4) and both types of the light chain (λ and κ). This case study demonstrates the power of combining the intact, middle-down, and bottom-up MS approaches for meaningful characterization of ultralow quantities of pathogenic antibodies extracted directly from patients' blood.


Subject(s)
Platelet Factor 4 , Humans , Platelet Factor 4/immunology , Platelet Factor 4/chemistry , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/chemistry , Autoantibodies/immunology , Autoantibodies/blood , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/chemistry , Amino Acid Sequence , Purpura, Thrombotic Thrombocytopenic/chemically induced , Purpura, Thrombotic Thrombocytopenic/immunology
3.
Ophthalmol Sci ; 4(4): 100504, 2024.
Article in English | MEDLINE | ID: mdl-38682030

ABSTRACT

Purpose: Genome-wide association studies have recently uncovered many loci associated with variation in intraocular pressure (IOP). Artificial intelligence (AI) can be used to interrogate the effect of specific genetic knockouts on the morphology of trabecular meshwork cells (TMCs) and thus, IOP regulation. Design: Experimental study. Subjects: Primary TMCs collected from human donors. Methods: Sixty-two genes at 55 loci associated with IOP variation were knocked out in primary TMC lines. All cells underwent high-throughput microscopy imaging after being stained with a 5-channel fluorescent cell staining protocol. A convolutional neural network was trained to distinguish between gene knockout and normal control cell images. The area under the receiver operator curve (AUC) metric was used to quantify morphological variation in gene knockouts to identify potential pathological perturbations. Main Outcome Measures: Degree of morphological variation as measured by deep learning algorithm accuracy of differentiation from normal controls. Results: Cells where LTBP2 or BCAS3 had been perturbed demonstrated the greatest morphological variation from normal TMCs (AUC 0.851, standard deviation [SD] 0.030; and AUC 0.845, SD 0.020, respectively). Of 7 multigene loci, 5 had statistically significant differences in AUC (P < 0.05) between genes, allowing for pathological gene prioritization. The mitochondrial channel most frequently showed the greatest degree of morphological variation (33.9% of cell lines). Conclusions: We demonstrate a robust method for functionally interrogating genome-wide association signals using high-throughput microscopy and AI. Genetic variations inducing marked morphological variation can be readily identified, allowing for the gene-based dissection of loci associated with complex traits. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

4.
Alzheimers Dement ; 20(1): 173-182, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37519032

ABSTRACT

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Memory, Episodic , Humans , Female , Aged , Middle Aged , Male , Cross-Sectional Studies , Cognitive Dysfunction/psychology , Memory Disorders/diagnosis , Alzheimer Disease/complications , Neuropsychological Tests
5.
J Am Chem Soc ; 145(46): 25203-25213, 2023 11 22.
Article in English | MEDLINE | ID: mdl-37949820

ABSTRACT

The massive COVID-19 vaccine roll-out campaign illuminated a range of rare side effects, the most dangerous of which─vaccine-induced immune thrombotic thrombocytopenia (VITT)─is caused by adenoviral (Ad)-vectored vaccines. VITT occurrence had been linked to the production of pathogenic antibodies that recognize an endogenous chemokine, platelet factor 4 (PF4). Mass spectrometry (MS)-based evaluation of the ensemble of anti-PF4 antibodies obtained from a VITT patient's blood indicates that the major component is a monoclonal antibody. Structural characterization of this antibody reveals several unusual characteristics, such as the presence of an N-glycan in the Fab segment and high density of acidic amino acid residues in the complementarity-determining regions. A recombinant version of this antibody (RVT1) was generated by transient expression in mammalian cells based on the newly determined sequence. It captures the key properties of VITT antibodies such as their ability to activate platelets in a PF4 concentration-dependent fashion. Homology modeling of the Fab segment reveals a well-defined polyanionic paratope, and the docking studies indicate that the polycationic segment of PF4 readily accommodates two Fab segments, cross-linking the antibodies to yield polymerized immune complexes. Their existence was verified with native MS by detecting assemblies as large as (RVT1)3(PF4)2, pointing out at FcγRIIa-mediated platelet activation as the molecular mechanism underlying VITT clinical manifestations. In addition to the high PF4 affinity, RVT1 readily binds other polycationic targets, indicating a polyreactive nature of this antibody. This surprising promiscuity not only sheds light on VITT etiology but also opens up a range of opportunities to manage this pathology.


Subject(s)
COVID-19 Vaccines , Thrombocytopenia , Humans , Antibodies, Monoclonal , COVID-19 Vaccines/adverse effects , Thrombocytopenia/chemically induced
6.
bioRxiv ; 2023 May 29.
Article in English | MEDLINE | ID: mdl-37398203

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but extremely dangerous side effect that has been reported for several adenoviral (Ad)-vectored COVID-19 vaccines. VITT pathology had been linked to production of antibodies that recognize platelet factor 4 (PF4), an endogenous chemokine. In this work we characterize anti-PF4 antibodies obtained from a VITT patient's blood. Intact-mass MS measurements indicate that a significant fraction of this ensemble is comprised of antibodies representing a limited number of clones. MS analysis of large antibody fragments (the light chain, as well as the Fc/2 and Fd fragments of the heavy chain) confirms the monoclonal nature of this component of the anti-PF4 antibodies repertoire, and reveals the presence of a fully mature complex biantennary N-glycan within its Fd segment. Peptide mapping using two complementary proteases and LC-MS/MS analysis were used to determine the amino acid sequence of the entire light chain and over 98% of the heavy chain (excluding a short N-terminal segment). The sequence analysis allows the monoclonal antibody to be assigned to IgG2 subclass and verify that the light chain belongs to the λ-type. Incorporation of enzymatic de- N -glycosylation into the peptide mapping routine allows the N -glycan in the Fab region of the antibody to be localized to the framework 3 region of the V H domain. This novel N -glycosylation site (absent in the germline sequence) is a result of a single mutation giving rise to an NDT motif in the antibody sequence. Peptide mapping also provides a wealth of information on lower-abundance proteolytic fragments derived from the polyclonal component of the anti-PF4 antibody ensemble, revealing the presence of all four subclasses (IgG1 through IgG4) and both types of the light chain (λ and κ). The structural information reported in this work will be indispensable for understanding the molecular mechanism of VITT pathogenesis.

7.
Clin Radiol ; 78(8): 616-621, 2023 08.
Article in English | MEDLINE | ID: mdl-37149417

ABSTRACT

AIM: To evaluate the reliability of synthetic diffusion-weighted imaging (DWI) using a high b-value in comparison to conventional DWI for paediatric abdominal MRI. MATERIALS AND METHODS: Paediatric patients (<19 years old) who underwent liver or pancreatobiliary MRI with DWI using 10 b-values (b = 0, 25, 50, 75, 100, 200, 400, 600, 800, 1,500 s/mm2) from March to October 2021 were included in this retrospective study. Using the software, synthetic DWI using b = 1,500 s/mm2 was generated automatically by selecting the b-value required as output. Conventional and synthetic DWI values for b = 1,500 s/mm2 were measured at the liver, spleen, paraspinal muscle, and mass lesions, if present, and apparent diffusion coefficient (ADC) values were calculated using the mono-exponential model. Intraclass correlation coefficients (ICCs) were calculated to assess the reliability of conventional and synthetic DWI and ADC values with b = 1,500 s/mm2. RESULTS: Thirty paediatric patients (M:F = 22:8, mean 10.8 ± 3.1 years old) were included and four had tumours on abdominal MRI. ICC values were 0.906-0.995 between conventional and synthetic DWI and ADC with b = 1,500 s/mm2 in the liver, spleen and muscle. For mass lesions, ICC values were 0.997-0.999 for both synthetic DWI and ADC images. CONCLUSIONS: Synthetic DWI and ADC values obtained using a high b-value showed excellent agreement with conventional DWI for the liver, spleen, muscle, and mass in paediatric MRI.


Subject(s)
Diffusion Magnetic Resonance Imaging , Neoplasms , Humans , Child , Young Adult , Adult , Adolescent , Retrospective Studies , Reproducibility of Results , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/methods
8.
Neural Comput Appl ; 35(11): 8143-8156, 2023.
Article in English | MEDLINE | ID: mdl-36532882

ABSTRACT

There is an urgent need, accelerated by the COVID-19 pandemic, for methods that allow clinicians and neuroscientists to remotely evaluate hand movements. This would help detect and monitor degenerative brain disorders that are particularly prevalent in older adults. With the wide accessibility of computer cameras, a vision-based real-time hand gesture detection method would facilitate online assessments in home and clinical settings. However, motion blur is one of the most challenging problems in the fast-moving hands data collection. The objective of this study was to develop a computer vision-based method that accurately detects older adults' hand gestures using video data collected in real-life settings. We invited adults over 50 years old to complete validated hand movement tests (fast finger tapping and hand opening-closing) at home or in clinic. Data were collected without researcher supervision via a website programme using standard laptop and desktop cameras. We processed and labelled images, split the data into training, validation and testing, respectively, and then analysed how well different network structures detected hand gestures. We recruited 1,900 adults (age range 50-90 years) as part of the TAS Test project and developed UTAS7k-a new dataset of 7071 hand gesture images, split 4:1 into clear: motion-blurred images. Our new network, RGRNet, achieved 0.782 mean average precision (mAP) on clear images, outperforming the state-of-the-art network structure (YOLOV5-P6, mAP 0.776), and mAP 0.771 on blurred images. A new robust real-time automated network that detects static gestures from a single camera, RGRNet, and a new database comprising the largest range of individual hands, UTAS7k, both show strong potential for medical and research applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s00521-022-08090-8.

9.
RSC Adv ; 12(54): 34831-34836, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36540248

ABSTRACT

Methods for direct functionalization of C(sp2)-H bonds in pyrrolo[1,2-a]quinoxalines have witnessed emerging development over the last decade. Herein we report a new tactic to afford a selective sulfenylation of 4-aryl pyrrolo[1,2-a]quinoxalines with diaryl disulfides. The reactions proceeded in the presence of a copper catalyst and potassium iodide promoter. Functionalities including nitro, ester, amide, methylthio, and halogen groups were all tolerated. Our method offers a convenient route to obtain highly substituted pyrrolo[1,2-a]quinoxalines-based thioethers in moderate to good yields.

10.
J Neurol Sci ; 440: 120336, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35843178

ABSTRACT

Across the world, Essential Tremor (ET) is the most common tremor diagnosis but up to half of these diagnoses are inaccurate. The misdiagnosis rate is particularly high in late-onset ET, when tremor begins after the age of 60 years. Currently, ET is reported to affect 5.5% of those over 65 years old and 21.7% aged over 95 but there is emerging evidence that late-onset ET has associations with dementia, mortality and more rapid progression. With ageing populations, and a range of new surgical treatments for ET, there is urgent need to clarify whether the clinical manifestations of late-onset ET are the same as for earlier-onset ET. This scoping review used MEDLINE, EMBASE and CINAHL as the information sources of published peer-reviewed research articles between 2011 and 2021. Analysis was done by narrative synthesis. 14 relevant papers were retrieved from studies conducted in Denmark, India, Italy, Germany, Spain and the US and, together, they comprised 7684 participants in total. Compared to older adults with earlier-onset ET, there is evidence that late-onset ET is associated with higher risk of cognitive impairment and dementia, higher mortality rate, faster rate of progression, lack of family history, altered cortical electrical activity, prolonged pupillary responses, and less propensity to demonstrate characteristic alcohol sensitivity. There is evidence that late-onset ET has different clinical manifestations to earlier-onset ET; in particular there is higher risk of dementia and mortality. The prognosis is important for clinicians to consider when selecting candidates for deep brain stimulation surgery and also for advanced care planning.


Subject(s)
Dementia , Essential Tremor , Aged , Aging , Dementia/diagnosis , Dementia/epidemiology , Dementia/etiology , Essential Tremor/diagnosis , Essential Tremor/epidemiology , Essential Tremor/therapy , Germany , Humans , Middle Aged , Tremor/complications
11.
Health Inf Sci Syst ; 9(1): 30, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34276971

ABSTRACT

With the increasing prevalence of neurodegenerative diseases, including Parkinson's disease, hand tremor detection has become a popular research topic because it helps with the diagnosis and tracking of disease progression. Conventional hand tremor detection algorithms involved wearable sensors. A non-invasive hand tremor detection algorithm using videos as input is desirable but the existing video-based algorithms are sensitive to environmental conditions. An algorithm, with the capability of detecting hand tremor from videos with a cluttered background, would allow the videos recorded in a non-research environment to be used. Clinicians and researchers could use videos collected from patients and participants in their own home environment or standard clinical settings. Neural network based machine learning architectures provide high accuracy classification results in related fields including hand gesture recognition and body movement detection systems. We thus investigated the accuracy of advanced neural network architectures to automatically detect hand tremor in videos with a cluttered background. We examined configurations with different sets of features and neural network based classification models. We compared the performance of different combinations of features and classification models and then selected the combination which provided the highest accuracy of hand tremor detection. We used cross validation to test the accuracy of the trained model predictions. The highest classification accuracy for automatically detecting tremor (vs non tremor) was 80.6% and this was obtained using Convolutional Neural Network-Long Short-Term Memory and features based on measures of frequency and amplitude change.

12.
Orthop Surg ; 13(4): 1437-1442, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33942980

ABSTRACT

BACKGROUND: The traumatic dislocation of the radial head in children is commonly treated by closed reduction. Sometimes, however, this strategy of treatment may not be effective due to the location of soft tissues in the radio-shoulder joint. The literature presents a few cases of the irreducible radial head dislocation with ulnar plastic deformation. Because it is a relatively rare condition, such a traumatic dislocation can be easily missed. Neglected injuries can lead to unwanted complications and unpredictable surgical outcomes. CASE PRESENTATION: This study presents a relatively rare case of traumatic radial head dislocation with ulnar plastic deformation in a 3-year-old child, which was successfully treated by open reduction. The examined case did not require osteotomy and ligamentous reconstruction. The initial attempt of closed reduction failed due to annular ligament interposition, which has been detected on MRI. After 3 months of treatment, the range of motion of the operated arm gradually improved. At the 6-month follow-up, the Mayo elbow-performance score indicated an excellent treatment outcome. CONCLUSIONS: The delayed treatment of radial head dislocation with ulnar plastic deformation can hinder the supination and pronation of the forearm, resulting in elbow/forearm deformity. The earlier this condition is detected, the easier it will be to treat it and the better the treatment outcome will be. The examined case of irreversible traumatic dislocation, successfully treated by open reduction, may help to treat radial head dislocation better.


Subject(s)
Elbow Joint/surgery , Joint Dislocations/surgery , Ligaments, Articular/surgery , Radius/surgery , Child, Preschool , Female , Humans , Ligaments, Articular/injuries , Radius/injuries , Range of Motion, Articular , Ulna/injuries , Elbow Injuries
13.
Bull World Health Organ ; 99(1): 50-61, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33658734

ABSTRACT

OBJECTIVE: To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. METHODS: We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. FINDINGS: Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). CONCLUSION: Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.


Subject(s)
Out-of-Hospital Cardiac Arrest/mortality , Out-of-Hospital Cardiac Arrest/therapy , Emergency Medical Services , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Survival Analysis , Transportation of Patients , Vietnam/epidemiology
15.
J Comp Pathol ; 178: 32-40, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32800106

ABSTRACT

Histiocytic sarcoma (HS) is a haematopoietic tumour of histiocyte origin that has been sporadically reported in four-toed hedgehogs (Atelerix albiventris). The present study aimed to investigate clinical, gross, histopathological and immunohistochemical features of HS in eight hedgehogs. Histological and immunohistochemical features of normal histiocytes and Langerhans cells (LCs) of hedgehogs were also investigated. HLA-DR-, Iba-1- and E-cadherin-positive LCs were observed in the epidermis, while Iba-1- and CD204-positive histiocytes were detected in the lymph nodes and spleen of normal hedgehogs. Localized HS (six cases) developed in the skin and spleen, while disseminated HS (two cases) occurred in the intestine. Tumour cells of disseminated HS were also distributed within the mesenteric lymph nodes, liver, kidney, spleen, lung and adrenal glands. Tumour cells of both localized and disseminated HS were composed of histiocytic cells, spindle to pleomorphic cells, multinucleated giant cells and erythrophagocytic cells. Most tumour cells were immunopositive for Iba-1, CD204 and lysozyme. A small number of tumour cells were positive for E-cadherin and CD208, and the tumour cells in one case were positive for HLA-DR. These results suggest that the tumour cells have variable features of histiocyte origin, including dendritic cells, LCs and macrophages. The behaviour of HS in the hedgehog was very aggressive, and 50% of cases died within 90 days of resection. The present study also highlighted the tendency for local tumour recurrence in localized cutaneous HS cases, suggesting a requirement for a long-term follow-up after excision.


Subject(s)
Hedgehogs , Histiocytes , Histiocytic Sarcoma/veterinary , Langerhans Cells , Neoplasm Recurrence, Local/veterinary , Animals , Animals, Wild , Biomarkers, Tumor , Dendritic Cells/pathology , Histiocytes/pathology , Histiocytic Sarcoma/diagnosis , Histiocytic Sarcoma/pathology , Immunohistochemistry/veterinary , Intestines/cytology , Intestines/pathology , Kidney/cytology , Kidney/pathology , Langerhans Cells/pathology , Macrophages/pathology , Skin/cytology , Skin/pathology , Skin Neoplasms/pathology , Skin Neoplasms/veterinary , Spleen/cytology , Spleen/pathology , Splenic Neoplasms/pathology , Splenic Neoplasms/veterinary
16.
BJS Open ; 4(2): 268-273, 2020 04.
Article in English | MEDLINE | ID: mdl-32207572

ABSTRACT

BACKGROUND: This study investigated the results of transanal total mesorectal excision (TaTME) combined with laparoscopy for locally advanced mid-low rectal cancer. METHODS: Patients with mid-low locally advanced rectal cancer (T3 category or above and/or N+) who underwent rectal resection with TaTME technique were enrolled prospectively. Patients who had distant metastasis, multiple malignancies, intestinal obstruction or perforation, or a clinical complete response to chemoradiotherapy were excluded. Postoperative results, including morbidity, circumferential resection margin (CRM) assessment, short-term survival and functional outcomes, were analysed. RESULTS: Thirty-eight patients, with 25 mid and 13 low rectal tumours, who had elective resection by TaTME from March 2015 to September 2018 were included. There were 25 men and 13 women. Mean(s.d.) age was 58·2(16·4) years and mean(s.d.) BMI was 24·2(2·5) kg/m2 . Tumours were 3-9 cm from the anal verge. Mean(s.d.) duration of surgery was 210(42) min. All patients had hand-sewn anastomoses and protective ileostomies. There were no conversions, abdominal perineal resections or postoperative deaths. Four patients had a complication, including three presacral abscesses, all managed by transanastomotic drainage. At 3 months after ileostomy closure, all patients had perfect continence. Apart from a greater tumour diameter in patients with low rectal cancers (6·0 cm versus 4·6 cm in those with mid rectal tumours; P = 0·035), clinical features were similar in the two groups. CRM positivity was greater for low than for mid rectal tumours (3 of 13 versus 0 of 25 respectively; P = 0·034), and more patients with a low tumour had TME grade 2 (4 of 13 versus 1 of 25; P = 0·038). There was no difference in oncological outcomes at 17 months. CONCLUSION: Although this study cohort was small, special attention should be paid to bulky low rectal tumours to reduce the rate of CRM positivity.


ANTECEDENTES: La escisión total del mesorrecto transanal (transanal total mesorectal excision, TaTME) combinada con la laparoscopia convencional se ha descrito como un procedimiento prometedor para el tratamiento del cáncer de recto medio-inferior localmente avanzado. El objetivo de este estudio fue investigar los resultados de TaTME combinados con la laparoscopia para el cáncer de recto medio-inferior localmente avanzado. MÉTODOS: Se incluyeron de forma prospectiva los pacientes con cáncer de recto medio-inferior localmente avanzado (≥ T3 y/o N+) a los que se realizó una resección anterior de recto con la técnica TaTME. Se excluyeron aquellos pacientes con metástasis a distancia, neoplasias múltiples, obstrucción intestinal o perforación y aquellos que presentaron una respuesta clínica completa después de la quimiorradioterapia. Los pacientes recibieron tratamiento neoadyuvante de acuerdo con las guías de práctica clínica internacionales. Se analizaron los resultados postoperatorios entre los que se incluyen la morbilidad, la evaluación del margen de resección circunferencial (circumferential resection margin, CRM) y la supervivencia a corto plazo junto con los resultados funcionales. RESULTADOS: Se seleccionaron 38 pacientes, 25 con el tumor en el recto medio y 13 con el tumor en el recto inferior que se sometieron a una resección anterior de recto electiva por TaTME desde marzo de 2015 hasta septiembre de 2018. Las localizaciones de los tumores oscilaron entre 3 y 9 cm desde el margen anal. La relación varón/mujer fue de 1,93, la edad media fue de 58,2 ± 16,4 años y el IMC medio de 24,2 ± 2,5 kg/m2 . El tiempo medio operatorio fue de 210 ± 42 minutos. En la todos los pacientes se realizó una anastomosis manual y una ileostomía de protección. No se registró ninguna conversión, ninguna amputación abdomino-perineal y ninguna muerte postoperatoria en toda la cohorte. Cuatro pacientes (10,5%) presentaron alguna complicación, incluidos tres abscesos presacros (7,9%), todos tratados mediante drenaje a través de la anastomosis. La continencia a los 3 meses del cierre de la ileostomía fue grado I según la clasificación de Horgan en todos los pacientes. Las características clínicas fueron similares en los cánceres de recto medio e inferior, sin embargo, este último grupo presentó un diámetro tumoral medio mayor en la estadificación clínica (4,8 en el cáncer de recto medio versus 6,0 cm en el cáncer de recto inferior; P = 0,03). En comparación con los tumores del recto medio, aunque en una cohorte muy pequeña, los tumores del recto inferior presentaron una tasa de afectación del CRM significativamente mayor (3 casos de afectación del CRM versus ninguno, P = 0,02) y así como un mayor número con escisión completa del mesorrecto grado 2 (4 pacientes versus 1 paciente; P = 0,02). No se encontraron diferencias significativas en los resultados oncológicos después de una mediana de seguimiento de 17 meses. CONCLUSIÓN: Aunque este estudio es el resultado de una pequeña cohorte, se debe prestar especial atención a los tumores de recto inferior voluminosos para reducir la tasa de positividad de CRM.


Subject(s)
Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Transanal Endoscopic Surgery/methods , Adult , Aged , Female , Humans , Laparoscopy/methods , Male , Margins of Excision , Middle Aged , Prospective Studies , Rectum/surgery , Vietnam
17.
IEEE Trans Neural Netw Learn Syst ; 31(11): 4806-4815, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31940559

ABSTRACT

For the classification of sequential data, dynamic Bayesian networks and recurrent neural networks (RNNs) are the preferred models. While the former can explicitly model the temporal dependences between the variables, and the latter have the capability of learning representations. The recurrent temporal restricted Boltzmann machine (RTRBM) is a model that combines these two features. However, learning and inference in RTRBMs can be difficult because of the exponential nature of its gradient computations when maximizing log likelihoods. In this article, first, we address this intractability by optimizing a conditional rather than a joint probability distribution when performing sequence classification. This results in the "sequence classification restricted Boltzmann machine" (SCRBM). Second, we introduce gated SCRBMs (gSCRBMs), which use an information processing gate, as an integration of SCRBMs with long short-term memory (LSTM) models. In the experiments reported in this article, we evaluate the proposed models on optical character recognition, chunking, and multiresident activity recognition in smart homes. The experimental results show that gSCRBMs achieve the performance comparable to that of the state of the art in all three tasks. gSCRBMs require far fewer parameters in comparison with other recurrent networks with memory gates, in particular, LSTMs and gated recurrent units (GRUs).

18.
Ann Burns Fire Disasters ; 32(2): 87-93, 2019 Jun 30.
Article in English | MEDLINE | ID: mdl-31528148

ABSTRACT

The aim of this study is to investigate characteristics, outcome and risk factors for death among elderly burn patients. A retrospective study was conducted on 416 elderly (≥ 65 years old) burn patients admitted to the National Burn Hospital, Hanoi, Vietnam from 1/1/2016 to 31/12/2018. Data on demographics, comorbidity, burn severity, complications and mortality were recorded. Bivariate and multivariate analyses were conducted to determine independent risk factors for death. Results indicated that elderly burn patients accounted for 4.2% of total admitted patients with an average age of 74.7 ± 8.1 years old. Significantly higher burn surface area (12.4% vs. 7.3%; p < .001) and deep burn area (5.5% vs. 2.5%; p < .001) were seen in the female group when compared to the male group. Pre-existing medical conditions were recorded in 20.9% of patients, the highest proportion (13.2%) represented by cardiovascular disease followed by neurological and diabetic disease (8.7% and 7% respectively). Over half (51.5%) of the patients had suffered deep burn and 6.3% developed complications, the most common being multiple organ failure and pneumonia. Overall mortality rate was 9.9%. However, death rate was extremely high in patients with inhalation injury (92.9%), burn extent > 40% total body surface area (TBSA) and deep burn > 10% TBSA (61.2% and 62.5% respectively). Comorbidity was not an independent risk factor for death, unlike increased age, burn extent and presence of inhalation injury. In conclusion, we show that despite advances in management, severe burn and inhalation injury in the elderly remains a big challenge in Vietnam.


Le but de cette étude est d'évaluer les caractéristiques, l'évolution et les facteurs de risque de décès chez des personnes âgées brûlées. Il s'agit d'une étude rétrospective concernant 416 patients âgés (≥ 65 ans) hospitalisés dans l'hôpital brûlologique national de Hanoi entre le 1/1/2016 et le 31/12/2018. Les données démographiques, comorbidités, sévérité de la brûlure, complications et mortalité ont été recueillies. Des analyses uni- et multivariées ont été réalisées pour rechercher les facteurs de risque de mortalité. Les patients âgés (74,7 +/- 8,1 ans) représentent 4,2% des admissions. Chez les femmes, la surface atteinte (12,4 VS 7,3% ; p < 0,001) et la surface profonde (5,5 VS 2,5% ; p < 0,001) sont plus étendues que chez les hommes. Des antécédents ont été notés chez 20,9% des patients. Ils étaient le plus souvent cardio-vasculaires (13,2%), neurologiques (8,7%) et diabétiques (7%). Plus de la moitié (51,5%) des patients avaient des brûlures profondes et 6,3% d'entre eux ont subi des complications, le plus souvent pneumonie et défaillance multiviscérale. La mortalité globale était de 9,9%. Elle était considérablement plus élevée en cas d'inhalation de fumées (92,9%), quand la surface totale dépassait 40% (61,2%) et quand plus de 10% de surface était profonde (62,5%). En analyse multivariée, les comorbidités ne sortaient pas, à la différence de l'âge, de la surface brûlée et de l'inhalation de fumées. Malgré les progrès de prise en charge, les brûlures étendues avec inhalation de fumées restent un gros défi au Vietnam.

19.
Anal Chem ; 91(18): 11629-11635, 2019 09 17.
Article in English | MEDLINE | ID: mdl-31412198

ABSTRACT

Lipids are a naturally occurring group of molecules that not only contribute to the structural integrity of the lung preventing alveolar collapse but also play important roles in the anti-inflammatory responses and antiviral protection. Alteration in the type and spatial localization of lipids in the lung plays a crucial role in various diseases, such as respiratory distress syndrome (RDS) in preterm infants and oxidative stress-influenced diseases, such as pneumonia, emphysema, and lung cancer following exposure to environmental stressors. The ability to accurately measure spatial distributions of lipids and metabolites in lung tissues provides important molecular insights related to lung function, development, and disease states. Nanospray desorption electrospray ionization (nano-DESI) and other ambient ionization mass spectrometry techniques enable label-free imaging of complex samples in their native state with minimal to absolutely no sample preparation. However, lipid coverage obtained in nano-DESI mass spectrometry imaging (MSI) experiments has not been previously characterized. In this work, the depth of lipid coverage in nano-DESI MSI of mouse lung tissues was compared to liquid chromatography tandem mass spectrometry (LC-MS/MS) lipidomics analysis of tissue extracts prepared using two different procedures: standard Folch extraction method of the whole lung samples and extraction into a 90% methanol/10% water mixture used in nano-DESI MSI experiments. A combination of positive and negative ionization mode nano-DESI MSI identified 265 unique lipids across 20 lipids subclasses and 19 metabolites (284 in total) in mouse lung tissues. Except for triacylglycerols (TG) species, nano-DESI MSI provided comparable coverage to LC-MS/MS experiments performed using methanol/water tissue extracts and up to 50% coverage in comparison with the Folch extraction-based whole lung lipidomics analysis. These results demonstrate the utility of nano-DESI MSI for comprehensive spatially resolved analysis of lipids in tissue sections. A combination of nano-DESI MSI and LC-MS/MS lipidomics is particularly useful for exploring changes in lipid distributions during lung development, as well as resulting from disease or exposure to environmental toxicants.


Subject(s)
Lipidomics/methods , Lipids/analysis , Lung/chemistry , Animals , Chromatography, Liquid , Mice, Inbred C57BL , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry
20.
Int J Tuberc Lung Dis ; 22(3): 246-251, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29471900

ABSTRACT

SETTING: The study was conducted in a randomly selected sample of persons aged 15 years living in Ca Mau Province, southern Viet Nam. OBJECTIVE: To estimate the prevalence of latent tuberculous infection (LTBI) in the general adult population of this province of Viet Nam. The secondary objective was to examine age and sex differences in prevalence. DESIGN: A cross-sectional survey was conducted in a cluster-random sample of the population. Clusters were subcommunes. The presence of LTBI was assessed using the QuantiFERON®-TB Gold In-Tube test system. RESULTS: QuantiFERON tests were performed among 1319 persons aged 15 years (77.7% of those selected). The overall prevalence of positive tests was 36.8% (95%CI 33.4-40.3). The prevalence of a positive test was lower in females than in males (31.0% vs. 44.7%, OR 0.57, 95%CI 0.45-0.72, P < 0.0001). The prevalence of positive tests increased with increasing age quintile (P < 0.0001). CONCLUSION: More than one third of the general adult population in a province in southern Viet Nam have evidence of LTBI. Although LTBI prevalence is higher in males, the sex difference is not as great as that for TB notification rates.


Subject(s)
Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Interferon-gamma/blood , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Prevalence , Sex Distribution , Sputum/microbiology , Vietnam/epidemiology , Young Adult
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