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The Journal of Physical Chemistry. B Sep 2023Describing protein dynamical networks through amino acid contacts is a powerful way to analyze complex biomolecular systems. However, due to the size of the systems,...
Describing protein dynamical networks through amino acid contacts is a powerful way to analyze complex biomolecular systems. However, due to the size of the systems, identifying the relevant features of protein-weighted graphs can be a difficult task. To address this issue, we present the connected component analysis (CCA) approach that allows for fast, robust, and unbiased analysis of dynamical perturbation contact networks (DPCNs). We first illustrate the CCA method as applied to a prototypical allosteric enzyme, the imidazoleglycerol phosphate synthase (IGPS) enzyme from bacteria. This approach was shown to outperform the clustering methods applied to DPCNs, which could not capture the propagation of the allosteric signal within the protein graph. On the other hand, CCA reduced the DPCN size, providing connected components that nicely describe the allosteric propagation of the signal from the effector to the active sites of the protein. By applying the CCA to the IGPS enzyme in different conditions, i.e., at high temperature and from another organism (yeast IGPS), and to a different enzyme, i.e., a protein kinase, we demonstrated how CCA of DPCNs is an effective and transferable tool that facilitates the analysis of protein-weighted networks.
Topics: Amino Acids; Cluster Analysis; Phosphates; Saccharomyces cerevisiae; Thermotoga maritima
PubMed: 37641933
DOI: 10.1021/acs.jpcb.3c04592 -
Orthopaedics & Traumatology, Surgery &... Dec 2021Superior capsular reconstruction (SCR) is a treatment option for patients with massive irreparable rotator cuff tears. Different types of grafts from various donor sites...
AIMS
Superior capsular reconstruction (SCR) is a treatment option for patients with massive irreparable rotator cuff tears. Different types of grafts from various donor sites have been described. There are no clinical studies comparing the different grafts available. The aim of this study is to compare the early clinical outcomes of patients who have undergone arthroscopic SCR with different types of grafts (allograft vs. autograft).
MATERIAL AND METHODS
This study is a retrospective analysis of data collected prospectively, from patients who underwent arthroscopic SCR with either a long head of biceps autograft (LHB) (n=40) or an acellular dermal allograft (n=40), between March 2015 and April 2018. The pre- and postoperative clinical data were compared between the 2 groups, as well as the incidence and type of complications.
RESULTS
All patients were monitored with a minimum follow-up of one year. Three patients (7.5%) in the autograft group, and 14 (35%) in the allograft group (p=0.005) had a complication, of which 2 (5%) and 5 (12.5%) respectively, required revision surgery (p=0.432). Linear regression ruled out any significant difference between the 2 groups, with respect to clinical scores. However, patients with a history of prior rotator cuff surgery had poorer results with regard to active elevation (β, -29.3; p=0.020), internal rotation (β, -3.4; p=0.003) and Subjective Shoulder Value (SSV) (β, -17.2; p=0.023). Older patients, as well as men, are associated with poorer postoperative internal rotation (β, -0.1; p=0.003 and β, -1.9; p=0.039 respectively), and type D lesions are associated with poorer external rotation and postoperative SSV (β, -11.3; p=0.012 and β, -12.4; p=0.048 respectively), compared to type C lesions. Postoperative graft integrity was improved in the autograft group compared to the allograft group. (Grade 1: 65.8% vs. 2.9%; Grade 5: 5.3% vs. 28.6%; p<0.001).
CONCLUSIONS
In both groups, clinical scores improved after SCR in patients with irreparable rotator cuff tears. Fewer complications and revisions were observed with the autograft compared to the allograft. If the LHB was still in place during surgery, its use appears valid, given the reasonable cost and low rate of complications associated with it. If absent, an allograft is also an option, considering the potential clinical improvement.
LEVEL OF EVIDENCE
III; Case-control study.
Topics: Allografts; Arthroscopy; Autografts; Case-Control Studies; Humans; Male; Range of Motion, Articular; Retrospective Studies; Rotator Cuff Injuries; Shoulder Joint; Treatment Outcome
PubMed: 34537391
DOI: 10.1016/j.otsr.2021.103059 -
Nature Communications Aug 2023Electrochemical conversion of CO to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to...
Electrochemical conversion of CO to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to achieve high formic acid production at wide voltage intervals and industrial current densities because the Bi catalysts are often poisoned by oxygenated species. Herein, we report a BiS nanowire-ascorbic acid hybrid catalyst that simultaneously improves formic acid selectivity, activity, and stability at high applied voltages. Specifically, a more than 95% faraday efficiency was achieved for the formate formation over a wide potential range above 1.0 V and at ampere-level current densities. The observed excellent catalytic performance was attributable to a unique reconstruction mechanism to form more defective sites while the ascorbic acid layer further stabilized the defective sites by trapping the poisoning hydroxyl groups. When used in an all-solid-state reactor system, the newly developed catalyst achieved efficient production of pure formic acid over 120 hours at 50 mA cm (200 mA cell current).
PubMed: 37537180
DOI: 10.1038/s41467-023-40342-6 -
Orthopaedics & Traumatology, Surgery &... Dec 2021The early postoperative period after anterior cruciate ligament reconstruction (ACL) is critical for optimal functional recovery. Despite an abundance of literature,...
INTRODUCTION
The early postoperative period after anterior cruciate ligament reconstruction (ACL) is critical for optimal functional recovery. Despite an abundance of literature, there is no consensus regarding good practices. This period is often under-considered by orthopedic surgeons. The aim of this study was to identify early postoperative practices after ACL reconstruction in France.
HYPOTHESIS
The hypothesis was that there was a discrepancy between validated data in the literature and the current practices of orthopedic surgeons in France.
MATERIAL AND METHODS
In 2019, a questionnaire was sent to all the members of the French Arthroscopy Society to investigate their postoperative practices after ACL reconstruction. Two hundred sixty-nine members responded. Surgeons were divided into two groups of experienced (n=137) and less experienced (n=132) surgeons, according to the number of ACL reconstructions performed per year (
RESULTS
ACL reconstruction was performed as an outpatient procedure in 72.9% of cases. This rate increased with surgical experience (p=0.009×10). Among measures to prevent effusion, cryotherapy was recommended in 97.8% of cases. The experienced group more often used compressive cryotherapy devices (p=0.004). Rehabilitation was started immediately in 75.5% of cases, with as main objective recovery of full extension (89.6%). Weight-bearing was allowed in 98.5% of cases and a brace was prescribed in 69.9% of cases. In the experienced group, braces were less frequent (p=0.02) and self-rehabilitation was preferred (p=0.0006).
CONCLUSION
Early postoperative practices after ACL reconstruction in France are related to surgical experience. The greater the surgical experience, the greater the role of joint effusion prevention and self-rehabilitation. Despite recommendations in the literature, a quarter of the French orthopedic surgeons who responded to this survey did not perform this procedure on an outpatient basis and more than two-thirds prescribed braces.
LEVEL OF EVIDENCE
IV.
Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Braces; Humans; Postoperative Period; Weight-Bearing
PubMed: 34537390
DOI: 10.1016/j.otsr.2021.103065 -
Microbiology Spectrum Aug 2022Dicyandiamide (DCD) and nitrapyrin (NP) are nitrification inhibitors (NIs) used in agriculture for over 40 years. Recently, ethoxyquin (EQ) was proposed as a novel...
Dicyandiamide (DCD) and nitrapyrin (NP) are nitrification inhibitors (NIs) used in agriculture for over 40 years. Recently, ethoxyquin (EQ) was proposed as a novel potential NI, acting through its derivative quinone imine (QI). Still, the specific activity of these NIs on the different groups of ammonia-oxidizing microorganisms (AOM), and mostly their effects on other soil microbiota remain unknown. We determined the impact of QI, and comparatively of DCD and NP, applied at two doses (regular versus high), on the function, diversity, and dynamics of target (AOM), functionally associated (nitrite-oxidizing bacteria-NOB), and off-target prokaryotic and fungal communities in two soils mainly differing in pH (5.4 versus 7.9). QI was equally effective to DCD but more effective than NP in inhibiting nitrification in the acidic soil, while in the alkaline soil QI was less efficient than DCD and NP. This was attributed to the higher activity of QI toward AOA prevailing in the acidic soil. All NIs induced significant effects on the composition of the AOB community in both soils, unlike AOA, which were less responsive. Beyond on-target effects, we noted an inhibitory effect of all NIs on the abundance of NOB in the alkaline soil, with being more sensitive than . QI, unlike the other NIs, induced significant changes in the composition of the bacterial and fungal communities in both soils. Our findings have serious implications for the efficiency and future use of NIs on agriculture and provide unprecedented evidence for the potential off-target effects of NIs on soil microbiota. NIs could improve N use efficiency and decelerate N cycling. Still, we know little about their activity on the distinct AOM groups and about their effects on off-target soil microorganisms. Here, we studied the behavior of a new potent NI, QI, compared to established NIs. We show that (i) the variable efficacy of NIs across soils with different pH reflects differences in the inherent specific activity of the NIs to AOA and AOB; (ii) beyond AOM, NIs exhibit negative effects on other nitrifiers, like NOB; (iii) QI was the sole NI that significantly affected prokaryotic and fungal diversity. Our findings (i) highlight the need for novel NI strategies that consider the variable sensitivity of AOM groups to the different NIs (ii) identify QI as a potent AOA inhibitor, and (iii) stress the need for monitoring NIs' impact on off-target soil microorganisms to ensure sustainable N fertilizers use and soil ecosystem functioning.
Topics: Ammonia; Archaea; Bacteria; Guanidines; Imines; Microbiota; Nitrification; Oxidation-Reduction; Phylogeny; Picolines; Quinones; Soil; Soil Microbiology
PubMed: 35856708
DOI: 10.1128/spectrum.02403-21 -
Scientific Reports Oct 2019The atmosphere is an important route for transporting and disseminating microorganisms over short and long distances. Understanding how microorganisms are distributed in...
The atmosphere is an important route for transporting and disseminating microorganisms over short and long distances. Understanding how microorganisms are distributed in the atmosphere is critical due to their role in public health, meteorology and atmospheric chemistry. In order to determine the dominant processes that structure airborne microbial communities, we investigated the diversity and abundance of both bacteria and fungi from the PM10 particle size (particulate matter of 10 micrometers or less in diameter) as well as particulate matter chemistry and local meteorological characteristics over time at nine different meteorological stations around the world. The bacterial genera Bacillus and Sphingomonas as well as the fungal species Pseudotaeniolina globaosa and Cladophialophora proteae were the most abundant taxa of the dataset, although their relative abundances varied greatly based on sampling site. Bacterial and fungal concentration was the highest at the high-altitude and semi-arid plateau of Namco (China; 3.56 × 10 ± 3.01 × 10 cells/m) and at the high-altitude and vegetated mountain peak Storm-Peak (Colorado, USA; 8.78 × 10 ± 6.49 × 10 cells/m), respectively. Surrounding ecosystems, especially within a 50 km perimeter of our sampling stations, were the main contributors to the composition of airborne microbial communities. Temporal stability in the composition of airborne microbial communities was mainly explained by the diversity and evenness of the surrounding landscapes and the wind direction variability over time. Airborne microbial communities appear to be the result of large inputs from nearby sources with possible low and diluted inputs from distant sources.
Topics: Air Microbiology; Bacteria; Biodiversity; Fungi; Phylogeography; Wind
PubMed: 31595018
DOI: 10.1038/s41598-019-51073-4 -
HardwareX Mar 2023Transcranial magnetic stimulation (TMS) is increasingly applied in basic neuroscience while its field of usage for diagnosing and treating various neurological diseases...
Transcranial magnetic stimulation (TMS) is increasingly applied in basic neuroscience while its field of usage for diagnosing and treating various neurological diseases broadens steadily. A TMS device generates a current pulse in the reach of several thousand ampére to produce a magnetic pulse which induces an electric field around neurons. This electric field, if high enough to depolarize the neuron membrane, generates an action potential at the neuron which travels down the neurons connected to it. The PLUSPULS TMS generates this magnetic pulse by pre-charging a pulse capacitor with the voltage and connecting it with a stimulation coil . The oscillation of the resonance circuit is cut off after one period and is called a biphasic pulse. PLUSPULS is a high frequency stimulator with inter stimulus intervals (ISI) down to 1ms which enables different pulse protocols as paired pulse or quadri theta burst stimulation. A GUI on PC allows a flexible control of PLUSPULS with varying amplitudes and ISI in one burst. The modular hardware and the control via GUI on PC allows for an easier adjustment on requirements to come. The article provides design considerations, hardware, firmware and software to reconstruct a modular biphasic TMS with enhanced charging network to enable extended pulse protocols.
PubMed: 36578972
DOI: 10.1016/j.ohx.2022.e00380 -
Therapeutic Advances in Medical Oncology 2023The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment...
BACKGROUND
The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment durations in cornerstone phase 3 clinical trials vary between a fixed 2-year duration and pursuit until disease progression. Clinical practices may thus differ according to the attending physician.
OBJECTIVES
Here we provide real-world data about treatment decisions at 2 years, with subsequent clinical outcomes.
DESIGN AND METHODS
This multicentric observational study included patients with advanced NSCLC whose disease was controlled after 2 years of pembrolizumab or nivolumab. The primary outcome was the decision to discontinue ICI treatment or not, along with factors motivating this decision. Secondary outcomes included progression-free survival (PFS) (according to treatment continuation or not) and adverse events.
RESULTS
A total of 91 patients were included, of which 60 (66%) had been pre-treated. The programmed death-ligand 1 expression level was ⩾50% in 43 patients (47%). In 61 patients (67%), ICI was continued after 2 years of treatment. This decision was significantly associated with the care center ( < 0.001) but neither with the tumor response at 2 years, as evaluated by CT scan or PET scan, nor with clinical status, immune-related adverse events, or previous locally treated oligo-progressive disease under ICI. Two years after the 2-year decision, PFS was 68.5%, [95% confidence interval (CI) (53.3-88.0)] in the 'ICI discontinuation' group and 64.1% [95% CI (51.9-79.2)] in the 'ICI pursuit' group; hazard ratio for relapse was 1.14 [95% CI (0.54-2.30), = 0.77]. The overall survival rate at 24 months after discontinuation was 89.2% [95% CI (78.4-100)] for the 'discontinuation' group and 93.1% [95% CI (85.8-100)] for the 'pursuit' group. Given insufficient power, overall survival could not be compared.
CONCLUSION
The decision to continue ICI or not after 2 years of treatment depends mainly on the care center and does not seem to impact survival. Larger, randomized data sets are required to confirm this result.
PubMed: 37720494
DOI: 10.1177/17588359231195600 -
Frontiers in Neuroimaging 2022tDCS is a non-invasive neuromodulation technique that has been widely studied both as a therapy for neuropsychiatric diseases and for cognitive enhancement. However,...
INTRODUCTION
tDCS is a non-invasive neuromodulation technique that has been widely studied both as a therapy for neuropsychiatric diseases and for cognitive enhancement. However, recent meta-analyses have reported significant inconsistencies amongst tDCS studies. Enhancing empirical understanding of current flow in the brain may help elucidate some of these inconsistencies.
METHODS
We investigated tDCS-induced current distribution by injecting a low frequency current waveform in a phantom and . MR phase images were collected during the stimulation and a time-series analysis was used to reconstruct the magnetic field. A current distribution map was derived from the field map using Ampere's law.
RESULTS
The current distribution map in the phantom showed a clear path of current flow between the two electrodes, with more than 75% of the injected current accounted for. However, in brain, the results did evidence a current path between the two target electrodes but only some portion ( 25%) of injected current reached the cortex demonstrating that a significant fraction of the current is bypassing the brain and traveling from one electrode to the other external to the brain, probably due to conductivity differences in brain tissue types. Substantial inter-subject and intra-subject (across consecutive scans) variability in current distribution maps were also observed in human but not in phantom scans.
DISCUSSIONS
An current mapping technique proposed in this study demonstrated that much of the injected current in tDCS was not accounted for in human brain and deviated to the edge of the brain. These findings would have ramifications in the use of tDCS as a neuromodulator and may help explain some of the inconsistencies reported in other studies.
PubMed: 37555148
DOI: 10.3389/fnimg.2022.1069500 -
Advanced Science (Weinheim,... May 2022For valence change memory (VCM)-type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of...
For valence change memory (VCM)-type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of vacancies enables low-voltage operation. However, a large number of vacancies increases the current of artificial synapses by acting like dopants, which aggravates low-energy operation and device scalability. Here, mixed-dimensional formamidinium bismuth iodides featuring in-situ formed type-I band structure are reported for the VCM-type synapse. As compared to the pure 2D and 0D phases, the mixed phase increases defect density, which induces a better dynamic range and higher linearity. In addition, the mixed phase decreases conductivity for non-paths despite a large number of defects providing lots of conducting paths. Thus, the mixed phase-based memristor devices exhibit excellent potentiation/depression characteristics with asymmetricity of 3.15, 500 conductance states, a dynamic range of 15, pico ampere-scale current level, and energy consumption per spike of 61.08 aJ. A convolutional neural network (CNN) simulation with the Canadian Institute for Advanced Research-10 (CIFAR-10) dataset is also performed, confirming a maximum recognition rate of approximately 87%. This study is expected to lay the groundwork for future research on organic bismuth halide-based memristor synapses usable for a neuromorphic computing system.
Topics: Amidines; Bismuth; Canada; Iodides; Neural Networks, Computer
PubMed: 35307991
DOI: 10.1002/advs.202200168