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1.
Medicine (Baltimore) ; 103(20): e38163, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758888

ABSTRACT

Prolonged ventilation is a complication of spontaneous supratentorial hemorrhage patients, but the predictive relationship with successful weaning in this patient cohort is not understood. Here, we evaluate the incidence and factors of ventilation weaning in case of spontaneous supratentorial hemorrhage. We retrospectively studied data from 166 patients in the same hospital from January 2015 to March 2021 and analyzed factors for ventilation weaning. The clinical data recorded included patient age, gender, timing of operation, initial Glasgow Coma Scale (GCS), Intracranial hemorrhage (ICH) score, alcohol drinking, cigarette smoking, medical comorbidity, and the blood data. Predictors of patient outcomes were determined by the Student t test, chi-square test, and logistic regression. We recruited and followed 166 patients who received operation for spontaneous supratentorial hemorrhage with cerebral herniation. The group of successful weaning had 84 patients and the group of weaning failed had 82 patients. The patient's age, type of operation, GCS on admission to the Intensive care unit (ICU), GCS at discharge from the ICU, medical comorbidity was significantly associated with successful weaning, according to Student t test and the chi-square test. According to our findings, patients with stereotaxic surgery, less history of cardiovascular or prior cerebral infarction, GCS >8 before admission to the hospital for craniotomy, and a blood albumin value >3.5 g/dL have a higher chance of being successfully weaned off the ventilator within 14 days.


Subject(s)
Ventilator Weaning , Humans , Female , Male , Ventilator Weaning/methods , Middle Aged , Retrospective Studies , Aged , Intracranial Hemorrhages/epidemiology , Glasgow Coma Scale , Adult , Time Factors
3.
Commun Biol ; 6(1): 911, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37670137

ABSTRACT

The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.


Subject(s)
Antibodies , Phosphoric Monoester Hydrolases , Phosphatidylinositols , Receptors, Antigen, T-Cell
4.
Front Neurol ; 14: 1219372, 2023.
Article in English | MEDLINE | ID: mdl-37602248

ABSTRACT

Pituitary adenomas are benign tumors of the anterior pituitary gland for which surgery or pharmacological treatment is the primary treatment. When initial treatment fails, radiation therapy should be considered. There are several case reports demonstrating radiation-induced vascular injury. We report an adult patient who presented with headache and diplopia for 6 months and a sellar tumor with optic chiasm compression. The patient received transnasal surgery, and the tumor was partially removed, which demonstrated adenoma. Stereotactic radiosurgery (SRS) was arranged. However, owing to progressive tumor growth, the patient received further transnasal surgery and stereotactic radiosurgery (SRS). After 14 years, the patient reported the sudden onset of headache and diplopia, and a ruptured fusiform aneurysm from the left internal carotid artery with pituitary apoplexy was diagnosed. The patient received transarterial embolization of the aneurysm. There were no complications after embolization, and this patient was ambulatory on discharge with blindness in the left eye and cranial nerve palsies. Aneurysm formation may be a complication of SRS, and it may occur after several years. Further research is needed to investigate the pathogenesis of radiosurgery and the development of cerebral aneurysms.

5.
In Vivo ; 37(4): 1838-1846, 2023.
Article in English | MEDLINE | ID: mdl-37369487

ABSTRACT

BACKGROUND/AIM: To investigate the radiographic and clinical outcomes in patients diagnosed with multilevel lumbar spine degeneration, undergoing hybrid stabilization with an interspinous device (IPD) adjacent to spine fusion, as compared with those experiencing three-segment or two-segment transforaminal lumbar interbody fusion (TLIF) via minimally invasive surgery (MIS). PATIENTS AND METHODS: Between 2015-2017, 51 consecutive patients who received three-segment TLIF, interspinous dynamic stabilization combined with two-segment TLIF (topping-off surgery), and two-segment TLIF coupled with adjacent level lumbar discectomy (two-segment TLIF+discectomy) were studied. These three operative procedures were performed by one neurosurgeon at the same hospital. Post-operative analysis of the two-year analysis was conducted by another neurosurgeon. Radiographic and clinical outcomes were compared among the three groups. RESULTS: Duration of surgery was significantly shorter in the topping-off surgery and TLIF+discectomy compared to three-segment TLIF group. Although there was no difference in hospital stay among the three groups, visual analogue scale (VAS) and Oswestry disability index (ODI) were less in the topping-off group than in the three-segment TLIF or two-segment TLIF+discectomy groups after one week and three months follow-up, respectively. Disc high index (DHI) in adjacent segment decreased from before the operation to two years follow-up postoperatively in the two-segment TLIF+discectomy group. In contrast, DHI in the segment adjacent to spondylolisthesis increased from before the operation to last follow-up post-operatively in the three-segment TLIF group. Compared with the two-segment TLIF+discectomy group, the topping-off group showed higher foramen high index at the IPD level. While there was no difference in segment range of motion among the three groups, the topping-off group showed preserved total range of motion at a two-year follow-up, as compared with the three-segment TLIF group. CONCLUSION: Under strict indications, topping-off surgery is an acceptable alternative to fusion surgery for spondylolisthesis combined with adjacent disc degeneration.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Spinal Fusion , Spondylolisthesis , Humans , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Spondylolisthesis/diagnostic imaging , Spondylolisthesis/surgery , Follow-Up Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Treatment Outcome , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/surgery , Retrospective Studies
6.
J Comput Biol ; 30(1): 3-20, 2023 01.
Article in English | MEDLINE | ID: mdl-36125448

ABSTRACT

An accurate understanding of the evolutionary history of rapidly-evolving viruses like SARS-CoV-2, responsible for the COVID-19 pandemic, is crucial to tracking and preventing the spread of emerging pathogens. However, viruses undergo frequent recombination, which makes it difficult to trace their evolutionary history using traditional phylogenetic methods. In this study, we present a phylogenetic workflow, virDTL, for analyzing viral evolution in the presence of recombination. Our approach leverages reconciliation methods developed for inferring horizontal gene transfer in prokaryotes and, compared to existing tools, is uniquely able to identify ancestral recombinations while accounting for several sources of inference uncertainty, including in the construction of a strain tree, estimation and rooting of gene family trees, and reconciliation itself. We apply this workflow to the Sarbecovirus subgenus and demonstrate how a principled analysis of predicted recombination gives insight into the evolution of SARS-CoV-2. In addition to providing confirming evidence for the horseshoe bat as its zoonotic origin, we identify several ancestral recombination events that merit further study.


Subject(s)
COVID-19 , Chiroptera , Severe acute respiratory syndrome-related coronavirus , Animals , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/genetics , Phylogeny , Pandemics , Gene Transfer, Horizontal/genetics , Chiroptera/genetics , Genome, Viral/genetics , Evolution, Molecular
7.
Medicine (Baltimore) ; 101(41): e31086, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36254070

ABSTRACT

INTRODUCTION: Hydrocephalus is a complication of spontaneous intracerebral hemorrhage; however, its predictive relationship with hydrocephalus in this patient cohort is not understood. Here, we evaluated the incidence and risk factors of hydrocephalus after craniectomy. METHODS: Retrospectively studied data from 39 patients in the same hospital from 2016/01 to 2020/12 and analyzed risk factors for hydrocephalus. The clinical data recorded included patient age, sex, timing of surgery, initial Glasgow Coma Scale score, intracerebral hemorrhage (ICH) score, alcohol consumption, cigarette smoking, medical comorbidity, and blood data. Predictors of patient outcomes were determined using Student t test, chi-square test, and logistic regression. RESULTS: We recruited 39 patients with cerebral herniation who underwent craniectomy for spontaneous supratentorial hemorrhage. Persistent hydrocephalus was observed in 17 patients. The development of hydrocephalus was significantly associated with the timing of operation, cigarette smoking, and alcohol consumption according to the Student t test and chi-square test. Univariate and multivariate analyses suggested that postoperative hydrocephalus was significantly associated with the timing of surgery (P = .031) and cigarette smoking (P = .041). DISCUSSION: The incidence of hydrocephalus in patients who underwent delayed operation (more than 4 hours) was lower than that in patients who underwent an operation after less than 4 hours. nonsmoking groups also have lower incidence of hydrocephalus. Among patients who suffered from spontaneous supratentorial hemorrhage and need to receive emergent craniectomy, physicians should be reminded that postoperative hydrocephalus followed by ventriculoperitoneal shunting may be necessary in the future.


Subject(s)
Decompressive Craniectomy , Hydrocephalus , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/surgery , Decompressive Craniectomy/adverse effects , Humans , Hydrocephalus/epidemiology , Hydrocephalus/etiology , Hydrocephalus/surgery , Intracranial Hemorrhages/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Risk Factors , Treatment Outcome
9.
J Pers Med ; 12(7)2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35887658

ABSTRACT

Primary brain malignancy is a rare tumor with a global incidence of less than 10 per 100,000 people. Hence, there is limited power for identifying risk loci in individual studies, especially for Han Chinese. We performed a genome-wide association study (GWAS) in Taiwan, including 195 cases and 195 controls. We identified five new genes for malignant neoplasms of the brain: EDARADD (rs645507, 1p31.3, p = 7.71 × 10-5, odds ratio (OR) = 1.893), RBFOX1 (rs8044700, p = 2.35 × 10-5, OR = 2.36), LMF1 (rs3751667, p = 7.24 × 10-7, OR = 2.17), DPP6 (rs67433368, p = 8.32 × 10-5, OR = 3.94), and NDUFB9 (rs7827791, p = 9.73 × 10-6, OR = 4.42). These data support that genetic susceptibility toward GBM or non-GBM tumors is highly distinct, likely reflecting different etiologies. Combined with signaling analysis, we found that RNA modification may be related to major risk factors in primary malignant neoplasms of the brain.

11.
ACS Appl Mater Interfaces ; 14(2): 3467-3475, 2022 Jan 19.
Article in English | MEDLINE | ID: mdl-34995438

ABSTRACT

A two-dimensional (2D) nonvolatile memory device architecture to improve the long-term charge retention with the minimum charge loss without compromising storage capacity and the extinction ratio for practical applications has been an imminent demand. To address the current issue, we adopted a novel type-II band-aligned heterobilayer channel comprising vertically stacked monolayer WSe2 nanodots on monolayer WS2. The band offset modulation leads to electron doping from WSe2 nanodots into the WS2 channel without any external driving electric field. As a result, the tested device outperformed with a memory window as high as 34 V and a negligible charge loss of 7% in a retention period of 10 years while maintaining a high extinction ratio of 106. The doping technique presented in this work provides a feasible route to modulate the electrical properties of 2D channel materials without hampering charge transport, paving the way for high-performance 2D memory devices.

12.
IEEE/ACM Trans Comput Biol Bioinform ; 19(5): 2642-2653, 2022.
Article in English | MEDLINE | ID: mdl-34406946

ABSTRACT

Phylogenetic analyses commonly assume that the species history can be represented as a tree. However, in the presence of hybridization, the species history is more accurately captured as a network. Despite several advances in modeling phylogenetic networks, there is no known polynomial-time algorithm for parsimoniously reconciling gene trees with species networks while accounting for incomplete lineage sorting. To address this issue, we present a polynomial-time algorithm for the case of level-1 networks, in which no hybrid species is the direct ancestor of another hybrid species. This work enables more efficient reconciliation of gene trees with species networks, which in turn, enables more efficient reconstruction of species networks.


Subject(s)
Evolution, Molecular , Gene Duplication , Algorithms , Hybridization, Genetic , Models, Genetic , Phylogeny
13.
Nat Commun ; 12(1): 2163, 2021 04 12.
Article in English | MEDLINE | ID: mdl-33846331

ABSTRACT

γδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.


Subject(s)
Cytoskeleton/metabolism , Cytotoxicity, Immunologic/genetics , Epigenesis, Genetic , Immunological Synapses/genetics , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/metabolism , Animals , Cell Line, Tumor , Cytoskeleton/drug effects , Cytotoxicity, Immunologic/drug effects , DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferases/metabolism , Decitabine/pharmacology , Enzyme Inhibitors/pharmacology , Epigenesis, Genetic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunological Synapses/drug effects , Isotope Labeling , Lymphocyte Activation/drug effects , Lymphocyte Activation/genetics , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/metabolism , Male , Mice, Inbred NOD , Phosphotyrosine/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Survival Analysis , Tumor Suppressor Protein p53/metabolism , Up-Regulation/drug effects , Xenograft Model Antitumor Assays
14.
IEEE/ACM Trans Comput Biol Bioinform ; 18(6): 2144-2156, 2021.
Article in English | MEDLINE | ID: mdl-31199267

ABSTRACT

Gene trees can differ from species trees due to a variety of biological phenomena, the most prevalent being gene duplication, horizontal gene transfer, gene loss, and coalescence. To explain topological incongruence between the two trees, researchers apply reconciliation methods, often relying on a maximum parsimony framework. However, while several studies have investigated the space of maximum parsimony reconciliations (MPRs) under the duplication-loss and duplication-transfer-loss models, the space of MPRs under the duplication-loss-coalescence (DLC) model remains poorly understood. To address this problem, we present new algorithms for computing the size of MPR space under the DLC model and sampling from this space uniformly at random. Our algorithms are efficient in practice, with runtime polynomial in the size of the species and gene tree when the number of genes that map to any given species is fixed, thus proving that the MPR problem is fixed-parameter tractable. We have applied our methods to a biological data set of 16 fungal species to provide the first key insights in the space of MPRs under the DLC model. Our results show that a plurality reconciliation, and underlying events, are likely to be representative of MPR space.


Subject(s)
Algorithms , Gene Duplication/genetics , Genomics/methods , Models, Genetic , Phylogeny , Gene Transfer, Horizontal/genetics , Genes, Fungal/genetics
15.
Neurosurg Rev ; 44(4): 2171-2179, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32936389

ABSTRACT

This study introduces expanded application of the endoscopic transcanal approach with anterior petrosectomy (ETAP) in reaching the petroclival region, which was compared through a quantitative analysis to the middle fossa transpetrosal-transtentorial approach (Kawase approach). Anatomical dissections were performed in five cadaveric heads. For each head, the ETAP was performed on one side with a detailed description of each step, while the Kawase approach was performed on the contralateral side. Quantitative measurements of the exposed area over the ventrolateral surface of the brainstem, and of the angles of attack to the posterior margin of the trigeminal nerve root entry zone (CN V-REZ) and porus acusticus internus (PAI) were obtained for statistical comparison. The ETAP provided significantly larger exposure over the ventrolateral surface of the pons (93.03 ± 21.87 mm2) than did the Kawase approach (34.57 ± 11.78 mm2). In contrast to the ETAP, the Kawase approach afforded greater angles of attack to the CN V-REZ and PAI in the vertical and horizontal planes. The ETAP is a feasible and minimally invasive procedure for accessing the petroclival region. In comparison to the Kawase approach, the ETAP allows for fully anterior petrosectomy and larger exposure over the ventrolateral surface of the brainstem without passing through the cranial nerves or requiring traction of the temporal lobe.


Subject(s)
Cranial Fossa, Posterior , Endoscopy , Petrous Bone , Cadaver , Cranial Fossa, Posterior/anatomy & histology , Cranial Fossa, Posterior/surgery , Craniotomy , Humans , Petrous Bone/surgery
16.
Stereotact Funct Neurosurg ; 99(2): 135-139, 2021.
Article in English | MEDLINE | ID: mdl-33264794

ABSTRACT

Stereotactic radiosurgery is a treatment option for trigeminal neuralgia. This procedure is minimally invasive, but tumor development and facial numbness have been reported. Here, we report an unusual presentation after stereotactic radiosurgery to treat trigeminal neuralgia. A 60-year-old man demonstrated typical signs for type 1 trigeminal nerve neuralgia and was treated with medication for 5 years. Owing to an intolerance to that medication, he received stereotactic radiosurgery with 66 Gy. During a 9-year follow-up exam, dizziness with a spinning sensation was reported and a right superior cerebellar thrombosed aneurysm was diagnosed. He received transarterial embolization with coiling of aneurysm and subsequently reported no complications on follow-up exams. Although stereotactic radiosurgery is a promising treatment for trigeminal neuralgia, aneurysm development may be considered a possible complication. Long-term follow-up care of these patients should be considered. To understand the relationship between radiosurgery and the potential development of a cerebral aneurysm, further research is needed.


Subject(s)
Intracranial Aneurysm , Radiosurgery , Trigeminal Neuralgia , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Male , Middle Aged , Radiosurgery/adverse effects , Trigeminal Nerve , Trigeminal Neuralgia/etiology , Trigeminal Neuralgia/surgery
17.
Bioinformatics ; 37(16): 2481-2482, 2021 08 25.
Article in English | MEDLINE | ID: mdl-33216126

ABSTRACT

SUMMARY: We describe eMPRess, a software program for phylogenetic tree reconciliation under the duplication-transfer-loss model that systematically addresses the problems of choosing event costs and selecting representative solutions, enabling users to make more robust inferences. AVAILABILITY AND IMPLEMENTATION: eMPRess is freely available at http://www.cs.hmc.edu/empress. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Algorithms , Evolution, Molecular , Phylogeny , Software
18.
BMC Bioinformatics ; 20(Suppl 20): 639, 2019 Dec 17.
Article in English | MEDLINE | ID: mdl-31842732

ABSTRACT

BACKGROUND: Reconciliation methods are widely used to explain incongruence between a gene tree and species tree. However, the common approach of inferring maximum parsimony reconciliations (MPRs) relies on user-defined costs for each type of event, which can be difficult to estimate. Prior work has explored the relationship between event costs and maximum parsimony reconciliations in the duplication-loss and duplication-transfer-loss models, but no studies have addressed this relationship in the more complicated duplication-loss-coalescence model. RESULTS: We provide a fixed-parameter tractable algorithm for computing Pareto-optimal reconciliations and recording all events that arise in those reconciliations, along with their frequencies. We apply this method to a case study of 16 fungi to systematically characterize the complexity of MPR space across event costs and identify events supported across this space. CONCLUSION: This work provides a new framework for studying the relationship between event costs and reconciliations that incorporates both macro-evolutionary events and population effects and is thus broadly applicable across eukaryotic species.


Subject(s)
Gene Duplication , Models, Genetic , Algorithms , Fungi/genetics , Phylogeny
19.
Article in English | MEDLINE | ID: mdl-29994484

ABSTRACT

Phylogenetic tree reconciliation is widely used in the fields of molecular evolution, cophylogenetics, parasitology, and biogeography to study the evolutionary histories of pairs of entities. In these contexts, reconciliation is often performed using maximum parsimony under the Duplication-Transfer-Loss (DTL) event model. In general, the number of maximum parsimony reconciliations (MPRs) can grow exponentially with the size of the trees. While a number of previous efforts have been made to count the number of MPRs, find representative MPRs, and compute the frequencies of events across the space of MPRs, little is known about the structure of MPR space. In particular, how different are MPRs in terms of the events that they comprise? One way to address this question is to compute the diameter of MPR space, defined to be the maximum number of DTL events that distinguish any two MPRs in the solution space. We show how to compute the diameter of MPR space in polynomial time and then apply this algorithm to a large biological dataset to study the variability of events.


Subject(s)
Gene Deletion , Gene Duplication/genetics , Models, Genetic , Phylogeny , Algorithms , Computational Biology
20.
BMC Bioinformatics ; 18(1): 292, 2017 Jun 05.
Article in English | MEDLINE | ID: mdl-28583091

ABSTRACT

BACKGROUND: In phylogenetics, we often seek to reconcile gene trees with species trees within the framework of an evolutionary model. While the most popular models for eukaryotic species allow for only gene duplication and gene loss or only multispecies coalescence, recent work has combined these phenomena through a reconciliation structure, the labeled coalescent tree (LCT), that simultaneously describes the duplication-loss and coalescent history of a gene family. However, the LCT makes the simplifying assumption that only one individual is sampled per species whereas, with advances in gene sequencing, we now have access to multiple samples per species. RESULTS: We demonstrate that with these additional samples, there exist gene tree topologies that are impossible to reconcile with any species tree. In particular, the multiple samples enforce new constraints on the placement of duplications within a valid reconciliation. To model these constraints, we extend the LCT to a new structure, the partially labeled coalescent tree (PLCT) and demonstrate how to use the PLCT to evaluate the feasibility of a gene tree topology. We apply our algorithm to two clades of apes and flies to characterize possible sources of infeasibility. CONCLUSION: Going forward, we believe that this model represents a first step towards understanding reconciliations in duplication-loss-coalescence models with multiple samples per species.


Subject(s)
Algorithms , Gene Duplication , Alleles , Animals , Computer Simulation , Databases, Genetic , Evolution, Molecular , Feasibility Studies , Genome , Hominidae/genetics , Models, Genetic , Phylogeny , Species Specificity
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