Tag: pubmed

J Appl Crystallogr. 2023 Jul 20;56(Pt 4):910-926. doi: 10.1107/S1600576723005344. eCollection 2023 Aug 1.

ABSTRACT

By providing predicted protein structures from nearly all known protein sequences, the artificial intelligence program AlphaFold (AF) is having a major impact on structural biology. While a stunning accuracy has been achieved for many folding units, predicted unstructured regions and the arrangement of potentially flexible linkers connecting structured domains present challenges. Focusing on single-chain structures without prosthetic groups, an earlier comparison of features derived from small-angle X-ray scattering (SAXS) data taken from the Small-Angle Scattering Biological Data Bank (SASBDB) is extended to those calculated using the corresponding AF-predicted structures. Selected SASBDB entries were carefully examined to ensure that they represented data from monodisperse protein solutions and had sufficient statistical precision and q resolution for reliable structural evaluation. Three examples were identified where there is clear evidence that the single AF-predicted structure cannot account for the experimental SAXS data. Instead, excellent agreement is found with ensemble models generated by allowing for flexible linkers between high-confidence predicted structured domains. A pool of representative structures was generated using a Monte Carlo method that adjusts backbone dihedral allowed angles along potentially flexible regions. A fast ensemble modelling method was employed that optimizes the fit of pair distance distribution functions [P(r) versus r] and intensity profiles [I(q) versus q] computed from the pool to their experimental counterparts. These results highlight the complementarity between AF prediction, solution SAXS and molecular dynamics/conformational sampling for structural modelling of proteins having both structured and flexible regions.

PMID:37555230 | PMC:PMC10405597 | DOI:10.1107/S1600576723005344

J Orthop. 2023 Jul 26;43:64-68. doi: 10.1016/j.jor.2023.07.029. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: Cocaine use has surged in the past decade, with 4.8 million Americans (1.7% of the population greater than 12) reporting use in 2021, leading to a healthcare burden of 1.3 billion dollars. Cocaine users experience prolonged hospital stays, higher costs, worse surgical outcomes, increased risk of medical conditions, and inflammation-related osteoarthritis. The study aims to identify factors influencing length of stay, costs, and perioperative complications in cocaine users undergoing total hip arthroplasty (THA) to reduce these risks.

METHODS: This study utilized the NIS database, providing comprehensive information on patient demographics, length of stay, hospital costs, and complications. Statistical analyses were conducted using SPSS software, including propensity matching and significance testing, to compare outcomes between cocaine users (CU) and non-cocaine users (NCU) undergoing total hip arthroplasty.

RESULTS: After propensity matching, cocaine users had a significantly longer LOS (4.8 days) in comparison to non-cocaine users (2.6 days) (p < 0.001). Similarly, the CU group had a larger of care (87984.9) than the NCU group (69149.2) (p < 0.001). Cocaine users had significantly higher rates of blood loss anemia (OR: 3.24, 95% CI: 2.21, 4.73), blood loss anemia (OR: 1.59, 95% CI: 1.12, 2.24), blood transfusion (OR: 2.23, 95% CI: 1.04, 4.78), periprosthetic dislocation (OR: 6.57, 95% CI: 1.47, 29.32), and periprosthetic infection (OR: 4.59, 95% CI: 1.54, 13.68) than patients in the non-cocaine user’s group.

CONCLUSION: Cocaine users had a significantly longer length of stay, higher costs of care, and an increased number of post-operative complications compared to non-cocaine users. These data contribute to understanding the potential ramifications of cocaine users undergoing THA.

PMID:37555205 | PMC:PMC10404604 | DOI:10.1016/j.jor.2023.07.029

J Orthop. 2023 Jul 23;43:25-29. doi: 10.1016/j.jor.2023.07.011. eCollection 2023 Sep.

ABSTRACT

PURPOSE: Image-based Robotic Total knee Arthroplasty (RA-TKA)was developed with the purpose of enhancing the accuracy in determining the component sizes preoperatively and helping surgeons in minimizing errors and improve patient outcomes. The research aims to find the reliability of robotic-assisted TKR based on images in determining the correct component sizes using preoperative three-dimensional (3D) computer tomography.

METHOD: After ethical approval, we conducted a prospective study from March 2022 to December 2022. A total of 100 knees underwent image-based RA-TKA having grade 4 Osteoarthritis knee (Kellegren Lawrence classification). A single senior surgeon performed on all patients. Postoperative implant sizes and fit were assessed by five radiographic markers by an independent observer.

RESULTS: In our study, we found the mean age was (64.96 ± 7.3) years, with female to male ratio of 43:22. The preoperative 3D CT accuracy is 100% for femoral component sizing and 97% for the tibial component. There was a statistically significant improvement in varus deformity from preoperative 7.370 ± 3.70° to 1.24 0 ± 0.910° after surgery., p = 0.001. Improvement in flexion deformity correction was from preoperative 6.50 ± 6.30 to postoperative 1.640 ± 1.770, p = 0.001.

CONCLUSION: Our study concludes that the use of pre-operative 3D CT helps in predicting the component sizes, minimizes surgical time, and enhances implant position accuracy, as well as improves postoperative limb alignment in the coronal and sagittal planes.

PMID:37555200 | PMC:PMC10405159 | DOI:10.1016/j.jor.2023.07.011

Front Neuroimaging. 2022 Jun 23;1:879098. doi: 10.3389/fnimg.2022.879098. eCollection 2022.

ABSTRACT

BACKGROUND: Understanding the relationship between cerebrospinal fluid (CSF) dynamics and intrathecal drug delivery (ITDD) injection parameters is essential to improve treatment of central nervous system (CNS) disorders.

METHODS: An anatomically detailed in vitro model of the complete CSF system was constructed. Patient-specific cardiac- and respiratory-induced CSF oscillations were input to the model in the subarachnoid space and within the ventricles. CSF production was input at the lateral ventricles and CSF absorption at the superior sagittal sinus. A model small molecule simulated drug product containing fluorescein was imaged within the system over a period of 3-h post-lumbar ITDD injections and used to quantify the impact of (a) bolus injection volume and rate, (b) post-injection flush volume, rate, and timing, (c) injection location, and (d) type of injection device. For each experiment, neuraxial distribution of fluorescein in terms of spatial temporal concentration, area-under-the-curve (AUC), and percent of injected dose (%ID) to the brain was quantified at a time point 3-h post-injection.

RESULTS: For all experiments conducted with ITDD administration in the lumbar spine, %ID to the brain did not exceed 11.6% at a time point 3-h post-injection. Addition of a 12 mL flush slightly increased solute transport to the brain up to +3.9%ID compared to without a flush (p < 0.01). Implantation of a lumbar catheter with the tip at an equivalent location to the lumbar placed needle, but with rostral tip orientation, resulted in a small improvement of 1.5%ID to the brain (p < 0.05). An increase of bolus volume from 5 to 20 mL improved solute transport to the brain from 5.0 to 6.3%ID, but this improvement was not statistically significant. Increasing bolus injection rate from 5 to 13.3 mL/min lacked improvement of solute transport to the brain, with a value of 6.3 compared to 5.7%ID.

CONCLUSION: The in vitro modeling approach allowed precisely controlled and repeatable parametric investigation of ITDD injection protocols and devices. In combination, the results predict that parametric changes in lumbar spine ITDD-injection related parameters and devices can alter %ID to the brain and be tuned to optimize therapeutic benefit to CNS targets.

PMID:37555174 | PMC:PMC10406265 | DOI:10.3389/fnimg.2022.879098

Front Neuroimaging. 2023 Jan 10;1:1070151. doi: 10.3389/fnimg.2022.1070151. eCollection 2022.

ABSTRACT

Functional MRI (fMRI) has become a popular technique to study brain functions and their alterations in psychiatric and neurological conditions. The sample sizes for fMRI studies have been increasing steadily, and growing studies are sourced from open-access brain imaging repositories. Quality control becomes critical to ensure successful data processing and valid statistical results. Here, we outline a simple protocol for fMRI data pre-processing and quality control based on statistical parametric mapping (SPM) and MATLAB. The focus of this protocol is not only to identify and remove data with artifacts and anomalies, but also to ensure the processing has been performed properly. We apply this protocol to the data from fMRI Open quality control (QC) Project, and illustrate how each quality control step can help to identify potential issues. We also show that simple steps such as skull stripping can improve coregistration between the functional and anatomical images.

PMID:37555150 | PMC:PMC10406300 | DOI:10.3389/fnimg.2022.1070151

Front Neuroimaging. 2022 Oct 26;1:981642. doi: 10.3389/fnimg.2022.981642. eCollection 2022.

ABSTRACT

Methods for the analysis of neuroimaging data have advanced significantly since the beginning of neuroscience as a scientific discipline. Today, sophisticated statistical procedures allow us to examine complex multivariate patterns, however most of them are still constrained by assuming inherent linearity of neural processes. Here, we discuss a group of machine learning methods, called deep learning, which have drawn much attention in and outside the field of neuroscience in recent years and hold the potential to surpass the mentioned limitations. Firstly, we describe and explain the essential concepts in deep learning: the structure and the computational operations that allow deep models to learn. After that, we move to the most common applications of deep learning in neuroimaging data analysis: prediction of outcome, interpretation of internal representations, generation of synthetic data and segmentation. In the next section we present issues that deep learning poses, which concerns multidimensionality and multimodality of data, overfitting and computational cost, and propose possible solutions. Lastly, we discuss the current reach of DL usage in all the common applications in neuroimaging data analysis, where we consider the promise of multimodality, capability of processing raw data, and advanced visualization strategies. We identify research gaps, such as focusing on a limited number of criterion variables and the lack of a well-defined strategy for choosing architecture and hyperparameters. Furthermore, we talk about the possibility of conducting research with constructs that have been ignored so far or/and moving toward frameworks, such as RDoC, the potential of transfer learning and generation of synthetic data.

PMID:37555142 | PMC:PMC10406264 | DOI:10.3389/fnimg.2022.981642

Iran Biomed J. 2023 Apr 26. doi: 10.52547/ibj.3885. Online ahead of print.

ABSTRACT

BACKGROUND: The majority of insecticides target sodium channels. The increasing emergence of resistance to the current insecticides has persuaded researchers to search for alternative compounds. Scorpion venom gland as a reservoir of peptides or proteins, which selectively target insect sodium channels. These proteins would be an appropriate source for finding new suitable anti-insect components.

METHODS: Transcriptome of venom gland of scorpion M. eupeus was obtained by RNA extraction and cDNA library synthesis. The obtained transcriptome was blasted against protein databases to find insect toxins against sodium channel based on the statistically significant similarity in sequence. Physicochemical properties of the identified protein were calculated using bioinformatics software. The 3D structure of this protein was determined using homology modeling, and the final structure was assessed by MD simulation.

RESULTS: The sodium channel blocker found in the transcriptome of M. eupeus venom gland was submitted to the GenBank under the name of meuNa10, a stable hydrophilic protein consisting of 69 amino acids, with the molecular weight of 7721.77 g/mol and pI of 8.7. The tertiary structure of meuNa10 revealed a conserved CS-alpha/beta domain stabilized by eight cysteine residues. The meuNa10 is a member of the 3FP superfamily consisting of three finger-like beta strands.

CONCLUSION: This study identified meuNa10 as a small insect sodium channel-interacting protein with some physicochemical properties, including stability and water-solubility, which make it a good candidate for further in vivo and in vitro experiments in order to develop a new bioinsecticide.

PMID:37553755 | DOI:10.52547/ibj.3885

Nutr Rev. 2023 Aug 8:nuad096. doi: 10.1093/nutrit/nuad096. Online ahead of print.

ABSTRACT

CONTEXT: The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency.

OBJECTIVE: This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU).

DATA SOURCES: Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022.

STUDY SELECTION: Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected.

DATA EXTRACTION: After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process.

RESULTS: Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P = .03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71) or the need for renal replacement therapy (P = .14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P = .39).

CONCLUSION: This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710).

PMID:37553224 | DOI:10.1093/nutrit/nuad096

Hum Reprod. 2023 Aug 8:dead154. doi: 10.1093/humrep/dead154. Online ahead of print.

ABSTRACT

STUDY QUESTION: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART?

SUMMARY ANSWER: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT.

WHAT IS KNOWN ALREADY: Anecdotal evidence suggests an association of ART with RT.

STUDY DESIGN, SIZE, DURATION: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age).

MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205).

LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART.

WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series.

STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the ‘Deutsche Kinderkrebsstiftung’ DKS 2020.10, by the ‘Deutsche Forschungsgemeinschaft’ DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the ‘Deutsche Kinderkrebsstiftung’ DKS 2020.05. We declare no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37553222 | DOI:10.1093/humrep/dead154

Respir Care. 2023 Aug 8:respcare.11037. doi: 10.4187/respcare.11037. Online ahead of print.

ABSTRACT

BACKGROUND: Progressive resistance inspiratory muscle training is the principle of inspiratory air-flow resistance loading training to restore diaphragm function, increase alveolar compliance, and further improve respiratory function. However, there is a lack of research on the effectiveness of progressive resistance inspiratory training in post-lobectomy rehabilitation and the accurate assessment of lung volumes.

METHODS: In this study, 79 subjects diagnosed with lung cancer and undergoing thoracoscopic lobectomy were retrospectively analyzed. The subjects were divided into a control group (n = 40) and an observation group (n =39) according to the different training modalities. The control group received conventional respiratory training. The observation group received progressive resistance inspiratory muscle training based on conventional breathing training. The primary outcome indicators were the following: lung function and lung volume. The secondary outcome indicators were the following: the number of postoperative hospital days, duration of drain retention, and incidence of postoperative pulmonary complications.

RESULTS: Baseline data on age, sex, body mass index, smoking history, education level, underlying disease, type of pathology, lung cancer stages, surgical site, preoperative lung volume, and preoperative lung function were not statistically different between the 2 groups (P > .05). The subjects in the observation group had median (interquartile range [IQR]) lung volumes at 1 month after surgery (3.22 [3.12-3.37] L vs 3.14 [2.95-3.24] L; P = .031), median (IQR) FEV₁ (2.11 [1.96-2.21] L vs 2.01 [1.81-2.12] L; P = .031), and mean ± SD peak expiratory flow (5.07 ± 0.62 L/s vs 4.66 ± 0.64 L/s; P = .005) were higher than those in the control group. The median (IQR) postoperative hospital stays (5 [4-5] d vs 5 [4-6] d; P = .030) and the median (IQR) chest drain retention times were shorter in the observation group versus the control group (74 [72-96] h vs 96 [84-96] h; P = .02). There was no significant difference in the incidence of postoperative atelectasis (5.1% vs 10.0%; P = .41) and pneumonia (7.7% vs 12.5%; P = .48).

CONCLUSIONS: Progressive resistance inspiratory muscle training was effective in improving lung volume and lung function, and in reducing the length of hospital stay and chest drain closure time after lobectomy.

PMID:37553214 | DOI:10.4187/respcare.11037