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JPRAS Open Dec 2022Nerve injury of the saphenous nerve or infrapatellar branch seems to be a frequent complication following knee surgery or trauma. Denervation results vary, and in some...
Nerve injury of the saphenous nerve or infrapatellar branch seems to be a frequent complication following knee surgery or trauma. Denervation results vary, and in some cases, no pain relief is achieved. This might be due to anatomic variation. The purpose of this anatomical study is to identify the variation in the course of the infrapatellar branch and saphenous nerve. We dissected 18 cadavers from adult donors. Medial to the knee, the saphenous nerve and infrapatellar branch were identified and followed proximally to the point where the infrapatellar branch branched from the saphenous nerve. The location where the infrapatellar branch came off from the saphenous nerve relative to the knee joint and where it passed the knee joint were measured. A total of 23 infrapatellar branches were found. We identified 10 branches between 0-10 cm proximal to the knee joint, 3 branches at 10-20 cm, and 9 branches at >20 cm. Between the patella and semitendinosus tendon, the knee joint was crossed by 5 branches in the anterior, 15 in the middle, and 2 in the posterior one-third. The origin of the infrapatellar branch and the location at which it passes the knee are highly variable. This, in addition to people having multiple branches, might explain why denervation is frequently unsuccessful. Based on the anatomical findings, we propose a more proximal diagnostic nerve block to help differentiate between a distal-middle or proximal origin of the infrapatellar branch. Appropriate placement of the nerve block might help identify people who benefit from denervation.
PubMed: 36304072
DOI: 10.1016/j.jpra.2022.08.006 -
Cancers Jul 2022Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with...
Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with cancer cells and other stromal cell types. CAFs are composed of heterogeneous subpopulations of activated fibroblasts, including myofibroblastic, inflammatory, and immunosuppressive CAFs. In this study, we sought to identify subpopulations of CAFs isolated from human lung adenocarcinomas and describe their transcriptomic and functional characteristics through single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatics analyses. Cell trajectory analysis of combined total and THY1 + CAFs revealed two branching points with five distinct branches. Based on Gene Ontology analysis, we denoted Branch 1 as "immunosuppressive", Branch 2 as "neoantigen presenting", Branch 4 as "myofibroblastic", and Branch 5 as "proliferative" CAFs. We selected representative branch-specific markers and measured their expression levels in total and THY1 + CAFs. We also investigated the effects of these markers on CAF activity under coculture with lung cancer cells. This study describes novel subpopulations of CAFs in lung adenocarcinoma, highlighting their potential value as therapeutic targets.
PubMed: 35884546
DOI: 10.3390/cancers14143486 -
Frontiers in Plant Science 2023Vessel traits are key in understanding trees' hydraulic efficiency, and related characteristics like growth performance and drought tolerance. While most plant hydraulic...
Vessel traits are key in understanding trees' hydraulic efficiency, and related characteristics like growth performance and drought tolerance. While most plant hydraulic studies have focused on aboveground organs, our understanding of root hydraulic functioning and trait coordination across organs remains limited. Furthermore, studies from seasonally dry (sub-)tropical ecosystems and mountain forests are virtually lacking and uncertainties remain regarding potentially different hydraulic strategies of plants differing in leaf habit. Here, we compared wood anatomical traits and specific hydraulic conductivities between coarse roots and small branches of five drought-deciduous and eight evergreen angiosperm tree species in a seasonally dry subtropical Afromontane forest in Ethiopia. We hypothesized that largest vessels and highest hydraulic conductivities are found in roots, with greater vessel tapering between roots and equally-sized branches in evergreen angiosperms due to their drought-tolerating strategy. We further hypothesized that the hydraulic efficiencies of root and branches cannot be predicted from wood density, but that wood densities across organs are generally related. Root-to-branch ratios of conduit diameters varied between 0.8 and 2.8, indicating considerable differences in tapering from coarse roots to small branches. While deciduous trees showed larger branch xylem vessels compared to evergreen angiosperms, root-to-branch ratios were highly variable within both leaf habit types, and evergreen species did not show a more pronounced degree of tapering. Empirically determined hydraulic conductivity and corresponding root-to-branch ratios were similar between both leaf habit types. Wood density of angiosperm roots was negatively related to hydraulic efficiency and vessel dimensions; weaker relationships were found in branches. Wood density of small branches was neither related to stem nor coarse root wood densities. We conclude that in seasonally dry subtropical forests, similar-sized coarse roots hold larger xylem vessels than small branches, but the degree of tapering from roots to branches is highly variable. Our results indicate that leaf habit does not necessarily influence the relationship between coarse root and branch hydraulic traits. However, larger conduits in branches and a low carbon investment in less dense wood may be a prerequisite for high growth rates of drought-deciduous trees during their shortened growing season. The correlation of stem and root wood densities with root hydraulic traits but not branch wood points toward large trade-offs in branch xylem towards mechanical properties.
PubMed: 37377798
DOI: 10.3389/fpls.2023.1127292 -
Frontiers in Molecular Biosciences 2023Protein ubiquitylation is an essential post-translational modification that regulates nearly all aspects of eukaryotic cell biology. A diverse collection of... (Review)
Review
Protein ubiquitylation is an essential post-translational modification that regulates nearly all aspects of eukaryotic cell biology. A diverse collection of ubiquitylation signals, including an extensive repertoire of polymeric ubiquitin chains, leads to a range of different functional outcomes for the target protein. Recent studies have shown that ubiquitin chains can be branched and that branched chains have a direct impact on the stability or the activity of the target proteins they are attached to. In this mini review, we discuss the mechanisms that control the assembly and disassembly of branched chains by the enzymes of the ubiquitylation and deubiquitylation machinery. Existing knowledge regarding the activities of chain branching ubiquitin ligases and the deubiquitylases responsible for cleaving branched chains is summarized. We also highlight new findings concerning the formation of branched chains in response to small molecules that induce the degradation of otherwise stable proteins and examine the selective debranching of heterotypic chains by the proteasome-bound deubiquitylase UCH37.
PubMed: 37325469
DOI: 10.3389/fmolb.2023.1197272 -
Frontiers in Medical Technology 2022Nanoparticles (NP) are being increasingly explored as vehicles for targeted drug delivery because they can overcome free therapeutic limitations by drug encapsulation,...
Nanoparticles (NP) are being increasingly explored as vehicles for targeted drug delivery because they can overcome free therapeutic limitations by drug encapsulation, thereby increasing solubility and transport across cell membranes. However, a translational gap exists from animal to human studies resulting in only several NP having FDA approval. Because of this, researchers have begun to turn toward physiologically based pharmacokinetic (PBPK) models to guide NP experimentation. However, typical PBPK models use an empirically derived framework that cannot be universally applied to varying NP constructs and experimental settings. The purpose of this study was to develop a physics-based multiscale PBPK compartmental model for determining continuous NP biodistribution. We successfully developed two versions of a physics-based compartmental model, models A and B, and validated the models with experimental data. The more physiologically relevant model (model B) had an output that more closely resembled experimental data as determined by normalized root mean squared deviation (NRMSD) analysis. A branched model was developed to enable the model to account for varying NP sizes. With the help of the branched model, we were able to show that branching in vasculature causes enhanced uptake of NP in the organ tissue. The models were solved using two of the most popular computational platforms, MATLAB and Julia. Our experimentation with the two suggests the highly optimized ODE solver package DifferentialEquations.jl in Julia outperforms MATLAB when solving a stiff system of ordinary differential equations (ODEs). We experimented with solving our PBPK model with a neural network using Julia's Flux.jl package. We were able to demonstrate that a neural network can learn to solve a system of ODEs when the system can be made non-stiff quasi-steady-state approximation (QSSA). Our model incorporates modules that account for varying NP surface chemistries, multiscale vascular hydrodynamic effects, and effects of the immune system to create a more comprehensive and modular model for predicting NP biodistribution in a variety of NP constructs.
PubMed: 35909883
DOI: 10.3389/fmedt.2022.934015 -
Genes Mar 2021Minimum free energy prediction of RNA secondary structures is based on the Nearest Neighbor Thermodynamics Model. While such predictions are typically good, the accuracy...
Minimum free energy prediction of RNA secondary structures is based on the Nearest Neighbor Thermodynamics Model. While such predictions are typically good, the accuracy can vary widely even for short sequences, and the branching thermodynamics are an important factor in this variance. Recently, the simplest model for multiloop energetics-a linear function of the number of branches and unpaired nucleotides-was found to be the best. Subsequently, a parametric analysis demonstrated that per family accuracy can be improved by changing the weightings in this linear function. However, the extent of improvement was not known due to the ad hoc method used to find the new parameters. Here we develop a branch-and-bound algorithm that finds the set of optimal parameters with the highest average accuracy for a given set of sequences. Our analysis shows that the previous ad hoc parameters are nearly optimal for tRNA and 5S rRNA sequences on both training and testing sets. Moreover, cross-family improvement is possible but more difficult because competing parameter regions favor different families. The results also indicate that restricting the unpaired nucleotide penalty to small values is warranted. This reduction makes analyzing longer sequences using the present techniques more feasible.
Topics: Algorithms; Entropy; Humans; Nucleic Acid Conformation; RNA; RNA, Ribosomal, 5S; RNA, Transfer; Thermodynamics
PubMed: 33805944
DOI: 10.3390/genes12040469 -
Developmental Biology Jul 2019Dendrites are the input compartment of the neuron, receiving and integrating incoming information. Dendritic trees are often highly complex and branched. Their branch... (Review)
Review
Dendrites are the input compartment of the neuron, receiving and integrating incoming information. Dendritic trees are often highly complex and branched. Their branch extension and distribution are tightly correlated with their role and interactions within neuronal networks. Thus, intense research has focused on understanding the mechanisms that govern dendrite elaboration. Recent reports highlight the importance of specific lipids for these processes. In particular, glycerophospholipids and several of their interacting proteins are involved in various steps of dendrite growth, including the initiation and elongation of dendritic branches and dendritic spines. The aim of this review is to provide a general overview about which particular lipids are involved in shaping dendrite morphology during neuronal differentiation. Additionally, it summarizes recent studies, which helped to gain insights into the mechanisms by which glycerophospholipids and their associated proteins contribute to establishing correct dendritic morphologies.
Topics: Animals; Cell Differentiation; Dendritic Spines; Glycerophospholipids; Humans
PubMed: 30576627
DOI: 10.1016/j.ydbio.2018.12.009 -
The Journal of Thoracic and... Jul 2021The preliminary clinical outcomes of a novel branch stent-grafting for endovascular repair of chronic aortic arch dissection proved its safety and effectiveness.
BACKGROUND
The preliminary clinical outcomes of a novel branch stent-grafting for endovascular repair of chronic aortic arch dissection proved its safety and effectiveness.
OBJECTIVE
The purpose of this study is to present the long-term outcomes and evaluate the durability of this novel endovascular therapy.
METHODS
Between August 2009 and January 2014, 51 patients with aortic dissections involving arch branches were treated by the endovascular stent-grafting. There were 7 Stanford type A aortic dissections, 22 retrograde type A aortic dissections, and 22 Stanford type B aortic dissections. The supra-arch branch arteries were reconstructed by individualized strategies.
RESULTS
All the proximal entry tears in arch were successfully excluded, and no type I/III endoleaks occurred. The median follow-up period was 92 months (range, 62-114 months). A total of 7 complications, 4 deaths, and 3 reinterventions occurred. There were 2 deaths from retrograde type A aortic dissections, 1 death from cerebral infarction, and 1 death from malignant tumor. The incidence of complications, reintervention, all-cause mortality, and aorta-related mortality was 0.035%/patient-year, 0.015%/patient-year, 0.020%/patient-year, and 0.010%/patient-year, respectively. The patency rate of cervical bypass was 90.1%. The significant true lumen recovery and false lumen shrinkage were observed at the 4 designated levels of the thoracic aorta according to computed tomography angiography images.
CONCLUSIONS
Based on preoperatively adequate planning and accurate measurement, endovascular repair of chronic aortic arch dissection using this branched stent-graft showed a low and an acceptable incidence of complications and mortality with positive aortic remodeling, which provided a satisfactory and promising alternative treatment option.
Topics: Aged; Aortic Dissection; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chronic Disease; Databases, Factual; Endovascular Procedures; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Postoperative Complications; Reoperation; Stents; Treatment Outcome
PubMed: 31926697
DOI: 10.1016/j.jtcvs.2019.10.184 -
World Journal of Surgical Oncology Feb 2023Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse...
BACKGROUND
Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse colon. Although the vessels of the right colon have been investigated, middle colic artery (MCA) variation and the relationship with vessels around the transvers colon are unknown. We investigated variation of the MCA using computed tomography angiography (CTA) and cadaver specimen and the relationship between the superior mesenteric vein (SMV) and MCA using CTA. The classification of vessels around the transverse colon may lead to safer and reliable surgery.
METHODS
This study included 505 consecutive patients who underwent CTA in our institution from 2014 to 2020 and 44 cadaver specimens. Vascular anatomical classifications and relationships were analyzed using CT images.
RESULTS
The MCA was defined as the arteries arising from the superior mesenteric artery (SMA) that flowed into the transverse colon at the distal ends. The classifications were as follows: type I, branching right and left from common trunk; type II, the right and left branches bifurcated separately from the SMA; and type III, the MCA branched from a vessel other than the SMA. Type II was subclassified into two subtypes, type IIa with one left branch and type IIb with two or more left branches from SMA. In the CTA and cadaver studies, respectively, the classifications were as follows: type I, n = 290 and n = 31; type IIa, n = 211 and n = 13; type IIb, n = 3 and n = 0; and type III, n = 1 and n = 0. We classified the relationship between the MCA and left side of the SMV into three types: type A, a common trunk runs along the left edge of the SMV (n = 173; 59.7%); type B, a right branch of the MCA runs along the left edge of the SMV (n = 116; 40.0%); and type C, the MCA runs dorsal of the SMV (n = 1; 0.3%).
CONCLUSIONS
This study revealed that The MCA branching classifications and relationship between the SMV and MCA. Preoperative CT angiography may be able to reliably identify vessel variation, which may be useful in clinical practice.
Topics: Humans; Colon, Transverse; Computed Tomography Angiography; Colon; Colonic Neoplasms; Mesentery; Laparoscopy; Cadaver
PubMed: 36747176
DOI: 10.1186/s12957-023-02919-9