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2.
BMC Biol ; 22(1): 108, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714997

ABSTRACT

BACKGROUND: Populations of the plant pathogenic fungus Verticillium dahliae display a complex and rich genetic diversity, yet the existence of sexual reproduction in the fungus remains contested. As pivotal genes, MAT genes play a crucial role in regulating cell differentiation, morphological development, and mating of compatible cells. However, the functions of the two mating type genes in V. dahliae, VdMAT1-1-1, and VdMAT1-2-1, remain poorly understood. RESULTS: In this study, we confirmed that the MAT loci in V. dahliae are highly conserved, including both VdMAT1-1-1 and VdMAT1-2-1 which share high collinearity. The conserved core transcription factor encoded by the two MAT loci may facilitate the regulation of pheromone precursor and pheromone receptor genes by directly binding to their promoter regions. Additionally, peptide activity assays demonstrated that the signal peptide of the pheromone VdPpg1 possessed secretory activity, while VdPpg2, lacked a predicted signal peptide. Chemotactic growth assays revealed that V. dahliae senses and grows towards the pheromones FO-a and FO-α of Fusarium oxysporum, as well as towards VdPpg2 of V. dahliae, but not in response to VdPpg1. The findings herein also revealed that VdMAT1-1-1 and VdMAT1-2-1 regulate vegetative growth, carbon source utilization, and resistance to stressors in V. dahliae, while negatively regulating virulence. CONCLUSIONS: These findings underscore the potential roles of VdMAT1-1-1 and VdMAT1-2-1 in sexual reproduction and confirm their involvement in various asexual processes of V. dahliae, offering novel insights into the functions of mating type genes in this species.


Subject(s)
Genes, Mating Type, Fungal , Genes, Mating Type, Fungal/genetics , Ascomycota/genetics , Ascomycota/physiology , Pheromones/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Verticillium
3.
JCI Insight ; 9(9)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602775

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog of triptolide, has demonstrated potent antiinflammatory and antitumor activity in several preclinical models and has proven both safe and efficacious in clinical trials for advanced gastrointestinal malignancies. Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared with posttransplant cyclophosphamide (PTCy). Strikingly, we found Minnelide improved survival, weight loss, and clinical scores in an MHC-mismatched model of aHSCT. These benefits were also apparent in minor MHC-matched aHSCT and xenogeneic HSCT models. Minnelide was comparable to PTCy in terms of survival, GVHD clinical score, and colonic length. Notably, in addition to decreased donor T cell infiltration early after aHSCT, several regulatory cell populations, including Tregs, ILC2s, and myeloid-derived stem cells in the colon were increased, which together may account for Minnelide's GVHD suppression after aHSCT. Importantly, Minnelide's GVHD prevention was accompanied by preservation of graft-versus-tumor activity. As Minnelide possesses anti-acute myeloid leukemia (anti-AML) activity and is being applied in clinical trials, together with the present findings, we conclude that this compound might provide a new approach for patients with AML undergoing aHSCT.


Subject(s)
Diterpenes , Epoxy Compounds , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Phenanthrenes , Graft vs Host Disease/prevention & control , Graft vs Host Disease/drug therapy , Animals , Mice , Hematopoietic Stem Cell Transplantation/methods , Diterpenes/pharmacology , Diterpenes/therapeutic use , Epoxy Compounds/pharmacology , Epoxy Compounds/therapeutic use , Phenanthrenes/pharmacology , Phenanthrenes/therapeutic use , Humans , Transplantation, Homologous , Female , Cyclophosphamide/pharmacology , Cyclophosphamide/therapeutic use , Disease Models, Animal , Graft vs Leukemia Effect/drug effects , Mice, Inbred C57BL , Male
4.
J Clin Oncol ; : JCO2301019, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640453

ABSTRACT

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

5.
Front Neurosci ; 18: 1249783, 2024.
Article in English | MEDLINE | ID: mdl-38562307

ABSTRACT

Introduction: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs. Methods: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, synched with the lateral board sway. Electrotactile feedback was given in two different modes: 1) Discrete-mode E-stim as the stimulation on/off by a predefined threshold of lateral board sway and 2) Proportional-mode E-stim as the stimulation frequency proportional to the amount of lateral board sway. All subjects were distracted from the balancing task by the n-back counting task, to test subjects' balancing capability with minimal cognitive involvement. Results: Proportional-mode E-stim, along with the n-back counting task, increased the balance time from 1.86 ± 0.03 s to 1.98 ± 0.04 s (p = 0.010). However, discrete-mode E-stim did not change the balance time (p = 0.669). Proportional-mode E-stim also increased the time duration per each swayed state (p = 0.035) while discrete-mode E-stim did not (p = 0.053). Discussion: These results suggest that proportional-mode E-stim is more effective than discrete-mode E-stim on improving standing balance. It is perhaps because the proportional electrotactile feedback better mimics the natural tactile sensation of foot pressure than its discrete counterpart.

6.
J Pharm Bioallied Sci ; 16(Suppl 1): S215-S218, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595612

ABSTRACT

Antidepressants have anti-inflammatory effects and boost immunity, and dentists should be aware. This case-control study included only those patients who consented to take part and had a ham-d score of at least 16 and a diagnosis of moderate-to-severe depression. Inclusion criteria included adults, those experiencing moderate to severe depression, taking fluoxetine or venlafaxine, and those with twenty or more teeth. Exclusion criteria included tobacco chewers, smokers, women expecting or nursing, periodontal treatment, antibiotics, anti-inflammatory medication, or vitamin/nutritional supplements. Patients who had had surgery or other therapy were excluded from the study. Three groups of patients were created: Control, venlafaxine, and fluoxetine. A periodontist assisted in the dental examination, and indices were observed. The analysis was done using Statistical Package for the Social Sciences (SPSS) version 24.0. Number, percentage, mean, and standard deviation were used to present the values. Results showed that antidepressants may be a risk factor for periodontal health, with increased periodontal parameters, and concluded that It is crucial to frequently check the periodontal health of depressed people using fluoxetine or venlafaxine since these drugs put good periodontal tissues at risk.

7.
ESMO Open ; 9(2): 102226, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38458658

ABSTRACT

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/therapy , Follow-Up Studies , Asia , Medical Oncology , Societies, Medical
8.
Nat Rev Neurosci ; 25(4): 213-236, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38443626

ABSTRACT

The study of the cortical control of movement experienced a conceptual shift over recent decades, as the basic currency of understanding shifted from single-neuron tuning towards population-level factors and their dynamics. This transition was informed by a maturing understanding of recurrent networks, where mechanism is often characterized in terms of population-level factors. By estimating factors from data, experimenters could test network-inspired hypotheses. Central to such hypotheses are 'output-null' factors that do not directly drive motor outputs yet are essential to the overall computation. In this Review, we highlight how the hypothesis of output-null factors was motivated by the venerable observation that motor-cortex neurons are active during movement preparation, well before movement begins. We discuss how output-null factors then became similarly central to understanding neural activity during movement. We discuss how this conceptual framework provided key analysis tools, making it possible for experimenters to address long-standing questions regarding motor control. We highlight an intriguing trend: as experimental and theoretical discoveries accumulate, the range of computational roles hypothesized to be subserved by output-null factors continues to expand.


Subject(s)
Motor Cortex , Humans , Motor Cortex/physiology , Movement/physiology , Neurons/physiology
9.
Plant Dis ; 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38506911

ABSTRACT

Verticillium wilt, caused by Verticillium dahliae, is one of the most devastating soilborne diseases of lettuce (Lactuca sativa L.). There are three races of V. dahliae and each race has been characterized by markers representing race-specific effectors. Race 1 is differentiated by the presence of the functional secretory Ave1 effector. Similarly, races 2 and 3 are differentiated by effectors VdR2e and VdR3e, respectively. While the presence of race 1 in coastal California was well-established, the presence of effector-based races 2 and 3 was uncertain. This study therefore focused on characterizing 727 isolates collected from 142 ranches of symptomatic lettuce and other crops from coastal California. Based on this evaluation, 523 isolates were designated as race 1, 20 isolates as race 2, 23 isolates as race 3, and 17 as race undefined. Isolates representing other Verticillium species totaled 110, and 34 were non-Verticillium fungal species. Since the use of resistant cultivars is a key strategy to manage this disease, we evaluated 48 lettuce germplasm lines and one endive (Cichorium endivia L.) line, comprised of commercial cultivars (cv.) and breeding lines, including the race 1-resistant heirloom cv. La Brillante and the susceptible cv. Salinas as controls. Resistance against races 1, 2, and 3 along with VdLs17, a virulent isolate of V. dahliae from lettuce that is currently not assigned to a race was evaluated in replicated greenhouse experiments. Two crisphead lettuce lines, HL28 and HL29, exhibited resistance against race 1 and a partial resistance against race 2 while all other lines were highly susceptible to races 1 and 2 and VdLs17. The majority of lines exhibited higher resistance to race 3 relative to the other two races. This study documents the current distribution of the different races in coastal California. In addition, the sources of resistance currently being developed should be effective or partially effective against these races for targeted deployment as soon as they are available. Keywords: Lactuca sativa, avirulence, effectors, host resistance, disease severity.

10.
Toxicon ; 241: 107679, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38447765

ABSTRACT

The search for mechanism-based anti-inflammatory therapies is of fundamental importance to avoid undesired off-target effects. Phospholipase A2 (PLA2) activity is a potential molecular target for anti-inflammatory drugs because it fuels arachidonic acid needed to synthesize inflammation mediators, such as prostaglandins. Herein, we aim to investigate the molecular mechanism by which ß-keto amyrin isolated from a methanolic extract of Cryptostegia grandiflora R. Br. Leaves can inhibit inflammation caused by Daboia russellii viper (DR) venom that mainly contains PLA2. We found that ß-keto amyrin neutralizes DR venom-induced paw-edema in a mouse model. Molecular docking of PLA2 with ß-keto amyrin complex resulted in a higher binding energy score of -8.86 kcal/mol and an inhibition constant of 611.7 nM. Diclofenac had a binding energy of -7.04 kcal/mol and an IC50 value of 620 nM, which predicts a poorer binding interaction than ß-keto amyrin. The higher conformational stability of ß-keto amyrin interaction compared to diclofenac is confirmed by molecular dynamics simulation. ß-keto amyrin isolated from C. grandiflora inhibits the PLA2 activity contained in Daboia russellii viper venom. The anti-inflammatory property of ß-keto amyrin is due to its direct binding into the active site of PLA2, thus inhibiting its enzyme activity.


Subject(s)
Apocynaceae , Daboia , Inflammation , Oleanolic Acid , Viper Venoms , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Apocynaceae/chemistry , Diclofenac/pharmacology , Diclofenac/therapeutic use , Inflammation/chemically induced , Inflammation/drug therapy , Molecular Docking Simulation , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/pharmacology , Oleanolic Acid/therapeutic use , Phospholipases A2/drug effects , Phospholipases A2/metabolism , Viper Venoms/chemistry , Viper Venoms/toxicity
11.
J Am Acad Orthop Surg ; 32(5): 220-227, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38175998

ABSTRACT

INTRODUCTION: The 2022 to 2023 orthopaedic residency cycle implemented a preference signaling program (PSP), allowing applicants to send "signals" to up to 30 programs to demonstrate their genuine interest. With the conclusion of the 2022 to 2023 cycle, the primary purpose of this study was to analyze program director (PD) perceptions of the PSP after the match cycle and provide a retrospective evaluation of the effects of the PSP on the orthopaedic resident selection process. METHODS: A 21-question survey was distributed to 98 PDs (32.7% response rate). Contact information was obtained from a national database. RESULTS: Most respondents (96.9%) participated in the American Orthopaedic Association's PSP. The majority (93.7%) view preference signaling as a positive change. Most PDs (56.2%) reported a decreased number in applications received compared with previous years. Receiving a preference signal was ranked among the most important factors in resident selection, and most PDs agreed that preference signaling should be used to screen applicants (84.4%) and differentiate similar applicants (96.8%). Moreover, 65.6% of PDs indicated that they would not rank or invite applicants to interview without a signal or completion of a formal away rotation. PDs report that in the 2022 to 2023 cycle, 98.5% of applicants who matched at their program had sent a preference signal. DISCUSSION: Preference signaling was one of the most important factors assessed during its inaugural application cycle and is anticipated to remain a key tool for screening and differentiating candidates. Applicants should strategically select signal recipients to enhance their success in the match.


Subject(s)
Internship and Residency , Orthopedics , Humans , United States , Retrospective Studies , Surveys and Questionnaires , Databases, Factual
12.
Sci Rep ; 14(1): 1598, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238386

ABSTRACT

Brain-computer interfaces have so far focused largely on enabling the control of a single effector, for example a single computer cursor or robotic arm. Restoring multi-effector motion could unlock greater functionality for people with paralysis (e.g., bimanual movement). However, it may prove challenging to decode the simultaneous motion of multiple effectors, as we recently found that a compositional neural code links movements across all limbs and that neural tuning changes nonlinearly during dual-effector motion. Here, we demonstrate the feasibility of high-quality bimanual control of two cursors via neural network (NN) decoders. Through simulations, we show that NNs leverage a neural 'laterality' dimension to distinguish between left and right-hand movements as neural tuning to both hands become increasingly correlated. In training recurrent neural networks (RNNs) for two-cursor control, we developed a method that alters the temporal structure of the training data by dilating/compressing it in time and re-ordering it, which we show helps RNNs successfully generalize to the online setting. With this method, we demonstrate that a person with paralysis can control two computer cursors simultaneously. Our results suggest that neural network decoders may be advantageous for multi-effector decoding, provided they are designed to transfer to the online setting.


Subject(s)
Brain-Computer Interfaces , Neural Networks, Computer , Humans , Movement , Functional Laterality , Hand , Paralysis , Brain
13.
Ann Thorac Surg ; 117(4): 829-837, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37279827

ABSTRACT

BACKGROUND: Pain control after minimally invasive repair of pectus excavatum (MIRPE) can be challenging, especially in adult patients undergoing surgical repair. This study reviewed different analgesic modalities used over ≥10 years after pectus repair. METHODS: A retrospective analysis was performed of adult patients (≥18 years) who underwent uncomplicated primary MIRPE at a single institution from October 2010 to December 2021. Patients were classified by analgesic modality used: epidural, elastomeric continuous infusion subcutaneous catheters (SC-Caths), and intercostal nerve cryoablation. Comparisons among the 3 groups were performed. RESULTS: In total, 729 patients were included (mean age, 30.9 ±10.3 years; 67% male; mean Haller index, 4.9 ±3.0). Patients in the cryoablation group required significantly lower doses of morphine equivalents (P < .001) and had overall the shortest hospital stay (mean, 1.9 ±1.5 days; P < .001) with <17% staying >2 days (vs epidural at 94% and SC-Cath at 48%; P < .001). The cryoablation group had a lower incidence of ileus and constipation (P < .001) but a higher incidence of pleural effusion requiring thoracentesis (P = .024). Mean pain scores among groups were minor (<3), and differences were insignificant. CONCLUSIONS: The use of cryoablation in conjunction with enhanced recovery pathways provided significant benefit to our patients undergoing MIRPE compared with previous analgesic modalities. These benefits included a decrease in length of hospital stay, a reduction of in-hospital opioid use, and a lower incidence of opioid-related complications associated with constipation and ileus. Further studies to assess additional potential benefits with long-term follow-up after discharge are warranted.


Subject(s)
Funnel Chest , Ileus , Adult , Humans , Male , Young Adult , Female , Analgesics, Opioid/therapeutic use , Retrospective Studies , Funnel Chest/surgery , Pain, Postoperative/prevention & control , Analgesics , Constipation , Minimally Invasive Surgical Procedures
14.
Phytopathology ; 114(1): 61-72, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37530500

ABSTRACT

Endophytes play important roles in promoting plant growth and controlling plant diseases. Verticillium wilt is a vascular wilt disease caused by Verticillium dahliae, a widely distributed soilborne pathogen that causes significant economic losses on cotton each year. In this study, an endophyte KRS015, isolated from the seed of the Verticillium wilt-resistant Gossypium hirsutum 'Zhongzhimian No. 2', was identified as Bacillus subtilis by morphological, phylogenetic, physiological, and biochemical analyses. The volatile organic compounds (VOCs) produced by KRS015 or its cell-free fermentation extract had significant antagonistic effects on various pathogenic fungi, including V. dahliae. KRS015 reduced Verticillium wilt index and colonization of V. dahliae in treated cotton seedlings significantly; the disease reduction rate was ∼62%. KRS015 also promoted plant growth, potentially mediated by the growth-related cotton genes GhACL5 and GhCPD-3. The cell-free fermentation extract of KRS015 triggered a hypersensitivity response, including reactive oxygen species (ROS) and expression of resistance-related plant genes. VOCs from KRS015 also inhibited germination of conidia and the mycelial growth of V. dahliae, and were mediated by growth and development-related genes such as VdHapX, VdMcm1, Vdpf, and Vel1. These results suggest that KRS015 is a potential agent for controlling Verticillium wilt and promoting growth of cotton.


Subject(s)
Acremonium , Ascomycota , Verticillium , Bacillus subtilis/genetics , Phylogeny , Plant Diseases/microbiology , Verticillium/physiology , Gossypium/genetics , Plant Extracts , Disease Resistance/physiology , Gene Expression Regulation, Plant
15.
Langmuir ; 39(50): 18663-18671, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38063076

ABSTRACT

The generation of clean and drinkable fresh water from seawater and contaminated water holds great potential to mitigate water scarcity. Herein, a floating spherical hydrogel evaporator (SHE) is designed to achieve sunlight-driven desalination, self-salt cleaning, and removal of environmental contaminants. The spherical lightweight polystyrene is coated with a porous carbon-embedded sodium alginate/PVA/CMC photothermal hydrogel to generate a spherical hydrogel evaporator (SHE) that floats naturally. The SHE is very sensitive to the weight imbalance (500 mg) and can respond quickly to the accumulation of salt by rotation to the fresh evaporation surface, realizing excellent antisalt fouling performance. Remarkably, with energy localization by porous carbon, the spherical floating evaporator achieved a high evaporation rate of 2.65 kg m-2 h-1 with an evaporation efficiency of 98%. At the same time, SHE is also capable of adsorbing both organic contaminants and heavy metal ions through functional groups of the hydrogel, attaining 99% removal efficiency. Overall, this low-cost spherical floating evaporator may offer solution for eco-friendly and sustainable production of fresh water on a large scale.

16.
J Phys Chem B ; 127(50): 10912-10922, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38063349

ABSTRACT

Five molecular mesogens containing phenyl rings and thiophene are subjected to a detailed 13C NMR investigation. The first mesogen contains only phenyl rings, while the other four have thiophene with substitution at position 2 or 3. Two of these also have a spacer inserted between the thiophene and the rest of the core unit. The mesophase properties evaluated by complementary techniques reveal an enantiotropic nematic phase for all the cases and smectic C as well as Crystal J for a few mesogens. In addition to solution 13C NMR, the samples were studied using 1D and 2D solid-state 13C NMR experiments in the liquid crystalline phase. The chemical shifts and 13C-1H dipolar couplings obtained in the mesophase provided cutting-edge information about the molecular structure and orientation of the thiophene mesogens. Accordingly, dramatic differences in these parameters are noted for the mesogens, and consequently, the identification of 2- and 3-substituted thiophene mesogens is accomplished by a simple visual examination of the 2D spectra. Furthermore, for mesogens with a spacer between thiophene and the rest of the core, 13C chemical shifts and 13C-1H dipolar couplings showed remarkable variation, which was directly reflected in the order parameters. For instance, the order parameter (Szz) of thiophene in 2- and 3-substituted mesogens in which the spacer is absent is ∼0.63 whereas for those with spacer, it is reduced to ∼0.14-0.18. In comparison, the mesogen in which the core unit is made up of phenyl rings alone that is used to benchmark the characteristics of thiophene ordering showed an order parameter of ∼0.85. The study unambiguously demonstrates the supremacy of 13C NMR in extracting the structural and orientational information on mesogens in which thiophene is a constituent of the core unit.

18.
J Liver Transpl ; 9: 100131, 2023 Feb.
Article in English | MEDLINE | ID: mdl-38013774

ABSTRACT

Background: As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ''organ utilisation'' in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years. Methods: Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported. Results: The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638; 55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%. Conclusions: The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.

19.
ArXiv ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37986728

ABSTRACT

Intracortical brain-computer interfaces (iBCIs) have shown promise for restoring rapid communication to people with neurological disorders such as amyotrophic lateral sclerosis (ALS). However, to maintain high performance over time, iBCIs typically need frequent recalibration to combat changes in the neural recordings that accrue over days. This requires iBCI users to stop using the iBCI and engage in supervised data collection, making the iBCI system hard to use. In this paper, we propose a method that enables self-recalibration of communication iBCIs without interrupting the user. Our method leverages large language models (LMs) to automatically correct errors in iBCI outputs. The self-recalibration process uses these corrected outputs ("pseudo-labels") to continually update the iBCI decoder online. Over a period of more than one year (403 days), we evaluated our Continual Online Recalibration with Pseudo-labels (CORP) framework with one clinical trial participant. CORP achieved a stable decoding accuracy of 93.84% in an online handwriting iBCI task, significantly outperforming other baseline methods. Notably, this is the longest-running iBCI stability demonstration involving a human participant. Our results provide the first evidence for long-term stabilization of a plug-and-play, high-performance communication iBCI, addressing a major barrier for the clinical translation of iBCIs.

20.
Nat Commun ; 14(1): 6510, 2023 10 16.
Article in English | MEDLINE | ID: mdl-37845221

ABSTRACT

We used a dynamical systems perspective to understand decision-related neural activity, a fundamentally unresolved problem. This perspective posits that time-varying neural activity is described by a state equation with an initial condition and evolves in time by combining at each time step, recurrent activity and inputs. We hypothesized various dynamical mechanisms of decisions, simulated them in models to derive predictions, and evaluated these predictions by examining firing rates of neurons in the dorsal premotor cortex (PMd) of monkeys performing a perceptual decision-making task. Prestimulus neural activity (i.e., the initial condition) predicted poststimulus neural trajectories, covaried with RT and the outcome of the previous trial, but not with choice. Poststimulus dynamics depended on both the sensory evidence and initial condition, with easier stimuli and fast initial conditions leading to the fastest choice-related dynamics. Together, these results suggest that initial conditions combine with sensory evidence to induce decision-related dynamics in PMd.


Subject(s)
Motor Cortex , Motor Cortex/physiology , Neurons/physiology
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